Pediatric Soft Tissue Lesions

Contents
Chapter Page No.
1. Introduction............................................................................................................07
2. Bacterial infections.................................................................................................09
3. Viral infections........................................................................................................27
4. Fungal infections.....................................................................................................45
5. Genetic diseases......................................................................................................50
6. Dermatological diseases..........................................................................................59
7. Trauma due to chronic frictional insult.....................................................................65
8. Inflammatory/Reactive lesions................................................................................67
9. Benign soft tissue tumors.........................................................................................74
10. Malignant soft tissue tumors....................................................................................89
11. Salivary gland tumors..............................................................................................99
12. References.............................................................................................................106
3
1 Introduction
O
ral cavity is responsible for many physiologic processes such as digestion, respiration and
speech. The mouth is a mirror to the body and acts as an early warning system as it is more or
less affected by many systemic diseases. Oral involvement may precede or follow the
manifestation of disease at other sites in body such as skin. Oral disease is broadly classified into soft or hard
tissue lesions. Children and adolescents demonstrate a wide spectrum of oral lesions including hard and soft
tissue lesions of the oral maxillofacial region. According to WHO criteria of 1986, childhood and
adolescence are the period comprising from 0 to 9 years and 10 to 19 years, respectively. Children and
adolescents in particular present a large variety and prevalence of oral pathology conditions, with clinical
features that are often different from those of adults. The information regarding prevalence of pediatric oral
lesions is insufficient but US places the prevalence rate in 4-10% excluding infants[1]. In Mexico, Espinoza-
Zapata (2006) conducted a study with a sample of 1165 patients between 1 and 16 years old. The prevalence
of oral mucosal lesions in children was 7.4 %. The most frequent lesions were: fibrous hyperplasia (3.18 %),
oral candidiasis (1.89 %), and ulcerative lesions (1.2 %)[2]. In india Ambika L conducted a study with a
sample of 1,003 children. The mucosal lesions were observed in 643 (64.11%) children, developmental
variations of mucosa were evident in 220 (21.93%) children and normal mucosal variations were present in
391 (38.98%) children. The most commonly observed mucosal lesions were gingivitis, gingival abscess
and traumatic ulcers[3]. Oral soft tissues are affected by a large number of pathologic conditions of variable
etiology and significance; their suitable management relies on their accurate diagnosis. Soft tissue lesions
of the oral cavity which are common in children, have various clinical presentations such as vesicles,
ulcers, macules, changes in color, size alterations, and configuration of the oral anatomy. Some lesions are
symptomatic and some are asymptomatic and can disturb the daily activity of the child. According to many
studies, children with systemic diseases are more prone to oral mucosal lesion than the healthy children.
Traumatic oral soft tissue lesions are usually due to habits that cause injuries such as food burns, lip and
cheek biting, orthodontic devices, Sharp ends of wires in space maintainer or habit breaker, and any
traumatic event. Considerable overlapping of the signs and symptoms produced by these diverse conditions
poses significant problems for their diagnosis, which can be resolved only through a thorough knowledge of
the clinicopathologic characteristics of each condition and a systematic approach to diagnosis. During the
evaluation of soft tissue lesions, it is necessary to distinguish the normal as well as abnormal findings,
which can suggest the pathological condition as well as normal anatomical variation. The correct
examination of the oral mucosa can give important tools in the field of diagnosis of developmental,
neoplastic, infectious, or inflammatory conditions. An essential component of the diagnostic process is the
formulation of a differential diagnosis, which encompasses the possible diseases and conditions that could
account for a specific collection of oral signs and symptoms[4].
Andres Pinto et al in 2014, divided the lesions into several categories according to lesion types and
anatomic variation in gingiva as well as frenum-
a) Developmental Lesions: Geographic tongue, Fissured tongue, Retro cuspid papillae ,Gingival
overgrowth.
b) Mucosal Changes (COLOR):
White Lesions such as Linea alba, Leukoedema, Pseudo membranous candidiasis, White sponge
nevus.
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Red and white lesions such as Petechiae, purpura, ecchymosis, erythematous candidiasis, Angular
chelitis, erythema migrans, median rhomboid glossitis.
c) Brown-black lesions: Physiological pigmentation, amalgam tattoo/graphite, melanotic nevus.
d) Soft tissue nodules: Inflammatory/reactive lesions Mucocele, Irritation fibroma, Peripheral
ossifying fibroma, pyogenic granuloma, peripheral giant cell granuloma.
e) Benign tumors: Hemangioma, lymphatic malformations, fibroma, benign neoplasm, squamous
papilloma.
f) Cysts: Eruption cyst.
g) Ulcerations: Traumatic ulcers, Apthous ulcers.
h) Infections: Herpes simplex virus, Coxsackievirus, Herpangina, Hand foot & mouth, Candida
albicans, HIV infection.
According to Martha Ann Keels pediatric soft tissue lesions are classified on the basis of their
location-
a) Lesions of gum include the eruption cyst or hematoma, pigmentation, retrocuspid papillae, parulis,
gingival overgrowth, gingival recession, HIV gingivitis, other lesions.
b) Lesions of tongue include Ankyloglossis, congenital lingual melanotic macules, geographic tongue,
fissured tongue, mucoceles, other lesions.
c) Lesions of lip include Herpes labialis, angular cheilitis, freckling, abnormalities of the labial frenum,
mucocele and ranula, other lesions.
d) Lesions of palate include herpangina and other lesions.
e) Lesions of buccal mucosa
f) Lesions that occur at multiple sites as benign tumor such as hemangiomas and lymphangiomas[5].
In the present review we try to set forth pediatric soft tissue lesions of oral cavity. The main focus is on
the clinical as well as the histopathological diagnosis which is important for the treatment of the lesion and
it determines the prognosis of lesion.
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2 Bacterial Infections
Acute necrotizing ulcerative gingivitis
?
Scarlet fever
?
Diphtheria
?
Bacterial sialadenitis
?
Oral tuberculosis and scrofula
?
Tetanus
?
Syphilis
?
NOMA
?
Juvenile periodontitis
?
Necrotizing ulcerative gingivitis
N UG is a well-defined and particular form of periodontal diseases, more common in children

below 10 years of age. It has been recognized for centuries. It is also known as acute
necrotizing ulcerative gingivitis, Vincent's disease, Fusospirochetal gingivitis, trench
mouth, acute ulcerative gingivitis, necrotizing gingivitis[6].
Etiopathogenesis:-
? The microbiota composition associated with NUG comprises Treponema spp., Selenomonas spp.,
Fusobacterium Spp., Prevotella intermedia.
? The risk factors associated with NUG are-
¬ Psychological stress- Psychological stress is a main predisposing factor, and the correlation
between the psychological stress and NUG are based on depletions of the gingival
microcirculation and salivary flow, rise in adrenocortical secretions which are linked with the
modifications in the function of polymorphonuclear leukocytes and lymphocytes.
Psychological stress modify not only the immune response but also the patient's behavior and
mood leading to poor oral hygiene, malnutrition, or increased tobacco consumption.
¬ Alcohol and tobacco consumption
¬ Trauma
¬ Poor nutritional status- Concerning the poor diet, diminishing dietary protein results in an
elevation in histamine concentration and that leads to a hyperemia of the gingival due to
elevated capillary permeability and reduced polymorphonuclear leukocytes chemotaxis.
¬ Poor oral hygiene
¬ Inadequate sleep
¬ Previous gingival infection as well as systemic condition primarily HIV infection.
? According to recent researches, Diabetes is a chief predictor in the causation of NUG, and it is
probably due to various features of the diabetic state comprising microangiopathy, delayed wound
healing, impaired function of neutrophils as well as disruption in collagen synthesis due to
glycation[7].
9
Clinical Features:-
¬ ANUG is seen most frequently in children and young adults. Some researchers have reported a
higher frequency in whites.
¬ Prevalence in the normal population is generally less than 0.1% and increased prevalence up to 7%
generally found in stressed population.
¬ The clinical presentation of ANUG painful ulceration necessitating the entire gingival, focal
necrosis of interdental papillae as well as hemorrhage.
¬ Due to the poor oral hygiene, halitosis is present with the necrotic debris[8].
¬ Due to the ulcerated and necrotic papillae and gingival margins, the punched out appearance can be
seen.
¬ Ulcers are covered by a yellow-white or grayish slough known as pseudomembrane. On the
removal of the slough, bleeding can be seen and the underlying tissue becomes exposed.
¬ Considerable gingival necrosis leads to the loss of crestal alveolar bone, which further give rise to
deep gingival pocket.
¬ An interposed necrotic depression is present
which divides the involved papillae into facial
and lingual portion.
¬ Enlargement of lymph nodes as well as greater
bleeding tendency are often present.
¬ Other clinical features include fever and Figure 2.1: Generalized punched out papillae Figure 2.2: Mild NUG case with erythematous
with pseudomembrane. Detached midline marginal & interproximal gingival with slightly
[9] papillae cratered papillae.
malaise .
Differential Diagnosis:-
w Sickle cell anemia- similar lesions can be seen in this disease, but this disease may be readily
identified by a special sickle cell blood preparation or by the electrophoretic examination of the
hemoglobin.
w Severe contact allergy can also mimic ANUG.
Diagnosis:-
Ø Smears of material from the gingival in case of necrotizing ulcerative gingivitis show vast numbers
of fusiform bacilli, an oral spirochete, various other spirochetes, filamentous organisms, vibrios,
cocci, desequamated epithelial cells and varying numbers of polymorphonuclear leukocytes.
Ø Although the bacterial smear may be of value as an aid in the diagnosis of atypical cases of
necrotizing ulcerative gingivitis, the final diagnosis is a clinical one.
Histopathologic Features:-
Four different layers have been described from the most outermost to innermost layers of the lesion.
Ø The bacterial area with an outermost fibrous mesh composed of degraded epithelial cells,
leukocytes, cellular rests, and an extensive variety of bacterial cells, comprising rods, fusiforms,
and spirochetes.
Ø The neutrophil-rich zone composed of a greater number of leukocytes, mostly neutrophilis, and
many spirochetes of dissimilar sizes as well as other bacterial morphocytes present between the
host cells.
Ø The necrotic zone, carrying degraded cells, together with medium and large sized spirochetes as
well as fusiform bacteria.
10
Ø
The spirochetal infiltration zone, where the tissue components are sufficiently preserved but are
infiltrated with large as well as medium-size spirochetes. Other bacterial morphotypes are not
found.
Treatment:-
The treatment of NUG should be organized in sequential stages:
Ø First stage- Treatment of the acute phase include two principle aims: To terminate the disease process
as well as tissue destruction and to control the patient's general feeling of irritation as well as pain that
influence the nutrition and oral hygiene practices. These aims can be accomplished by a superficial
ultrasonic debridement as well as by local oxygen therapy.
Systemic antibiotics can also be used in those cases, which show undesirable response to
debridement. Metronidazole (250 mg every 8 hr) is first choice of drug because it is useful against strict
anaerobes. Other systemic drugs such as peniciliin, tetracyclines, clindamycin, amoxicillin or amoxicillin
plus clavulanate are also useful in case of NUG
Ø Second stage- This stage includes treatment of the pre-existing condition, such as chronic gingivitis,
should be initiated, with professional prophylaxis, scaling and root planning. Predisposing local factors as
well as systemic factors should be evaluated and treated adequately. Gingivectomy as well as gingivoplasty
procedures can also be performed during this stage.
Ø Final phase- This is supportive as well as maintenance phase. The main goal of the final phase is to
observe the oral hygiene practices as well as controlling the predisposing factors. If adequate maintenance
is not carried out, relapses are likely to occur that lead to a loss of attachment[10].
Scarlet Fever
Scarlet fever is a most common systemic infection produced by the group A, beta hemolytic
streptococci which generally produces an endotoxin chiefly responsible for the skin manifestation of the
infection.
Etiopathogeneis:-
The causative agent of scarlet fever is Group A Streptococci (GAS), a gram positive coccus that grows
in chains. Bacteria release endotoxins and can cause complete red cell destruction. These toxins also cause
local inflammatory response on the skin and are known as erythrogenic toxins.
Clinical Features:-
Ø Scarlet fever is most common in children from the ages of 3 to 12 years due to ease of transmission
in the classrooms and nurseries.
Ø There is no gender preference for scarlet fever. Prevalence of scarlet fever is higher in undeveloped
countries.
Ø Scarlet fever is associated with an acute pharyngitis, as a result,
fever, sore throat, pain on swallowing, and cervical
lymphadenopathy is present.
Ø Other source of infection are infected wound or burn.
Ø The rash appear within 2 to 3 days after infection but can be delayed
up to 7 days.
Ø The rash of scarlet fever characterized as a blanching, papular rash Figure 2.3: Erythematous monomorphic rash on the inner
thighs and pubic region of a young boy with scarlet fever
that is classically described as a “sandpaper” rash.
11
Ø
It can be differentiated from the macular rash by the lack of confluence of the lesion. Because of the
lack of confluence in the rash of scarlet fever, it feels like sandpaper.
The trunk, underarms and groin are common sites, then the rash spreads to the extremities.
Ø
The rash is more intense in areas of pressure and skin folds such as the neck, antecubital fossa, and
Ø
groin, known as “pastia lines.”
The rash usually clears within 1week, and then a period of desquamation of the skin occurs and last
Ø
upto two weeks.
Oral Manifestations:-
Ø These rashes are also present in the oral mucosa and involves the tonsils,
pharynx, soft palate, and tongue.
Ø The tonsils, soft palate, and pharynx become erythematous and edematous,
and the tonsilar crypts may be filled with a yellowish exudates.
Ø During the first 2 days, the dorsal surface of the tongue demonstrates a white
coating of the tongue with hyperplastic papillae, and is termed as
“strawberry tongue.” Figure 2.4: Scarlet fever. (a) A white
strawberry tongueis usually followed by
(b) a red strawberry tongue as the ery-
throtoxin-mediated enanthema evolves
ü Impetigo or erysipelas- Pustules are more indicative of a these local infection.
ü Some viral illnesses which should be considered in the affected population are measles (rubeola),
chicken pox (herpes zoster), and hand-foot-and-mouth disease (Coxsackie), which all have specific
presentations that distinguish them from scarlet fever.
Histopathological Features:-
There are no specific histological changes in scarlet fever. Neutrophilic infiltration with spongiosis
and parakeratosis in the epidermis can be seen.
Diagnosis:-
Ø A proper history taking as well as clinical examination is very important, while evaluating a person
suspected of having scarlet fever.
Ø If the scarlet fever is associated with pharyngitis, lack of cough, exudates, cervical nodes,
temperature as well as age helps to determine the strep throat infection. This is known as CENTOR
criterion.
Ø A culture of throat secretions as well as rapid strep test can be used to confirm the diagnosis of
streptococcal infection. A throat culture is more specific but it usually takes longer time but the
rapid strep test is less specific and gives immediate results.
Ø Failure to respond to appropriate antibiotics should alert the clinician that the detected streptococci
may represent an intercurrent carrier state, and other cause of infection should be investigated.
Treatment:-
Treatment of scarlet fever as well as associated streptococcal pharyngitis is most important to prevent
the possibility of complications, such as peritonsillar or retropharyngeal abscess, sinusitis, or pneumonia.
Ø Antibiotics such as penicillin, amoxicillinare the first line drugs in case of scarlet fever. If the
infected person is allergic to penicillin then a first generation cephalosporin should be given.
Ø Ibuprofen can be given to reduce the fever and relieve the associated discomfort[11].
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Diphtheria
Diphtheria is an acute, life-threatening, infectious and communicable disease of skin as well as
mucous membrane.
Etiopathogenesis:-
It is caused by Corynebacterium diphtheria which is a non-motile, noncapsulated, club shaped, gram-
positive bacillus. The pathogenesis of diphtheria is based upon two primary factors-
I. The competence of a given strain of Corynebacterium diphtheriae to colonize in the
nasopharyngeal cavity or on the skin.
II. Competence of bacteria to generate diphtheria toxin.
The factors included in colonization of the host are encoded by the bacteria, as well as the toxin is
encoded by the corynebacteriophage. The organism's virulence is because of its exotoxin, these exotoxin
produce oropharyngeal pseudomembrane as well as the myocarditis and cranial nerve neuropathy
complications. The structural gene for diphtheria toxin is 'tox' which is carried by a family of closely related
corynebacteriophages. The expression of tox generally depends on the physiologic state of C diphtheriae
genome.
Clinical Features:-
Ø Diphtheria is commonly a disease of children and young adults.
Ø The signs as well as symptoms of diphtheria arise 1 to 5 days after exposure to the organism.
Ø The initial systemic symptoms generally involve low-grade fever, headache, malaise, anorexia,
sore throat and vomiting.
Ø Two type of clinical diphtheria can be seen- nasopharyngeal as well as cutaneous.
Ø The symptoms of nasopharyngeal diphtheria generally vary from mild pharyngitis to hypoxia,
because of airway obstruction by the pseudomembrane.
Ø The involvement of cervical lymph node is common which give rise to extreme swelling of neck
known as bull neck diphtheria.
Ø The symptoms of cutaneous diphtheria
involves the covering of effected area of the
skin with the gray-brown pseudomembrane.
Ø The systemic complication principally
involves the loss of motor functions
especially difficulty in swallowing,
congestive heart failure, these symptoms
generally develop because of the action of the
Figure 2.5: A child with Diptheria showing a Figure 2.6: An adherent, dense, grey pseudomem
diphtheria toxin on peripheral motor neurons characteristic swollen neck, sometimes referred -brane covering the tonsils is classically seen in
to as “bull neck”. diphtheria.
[12]
and on the myocardium .
w Streptococcal pharyngitis- This disease is characterized as a red throat and enlarged tonsils covered
by yellow or blood-tinged exudate.
w Acute epiglottis- Drolling is usually present in this disease, and patient maintains hyperextended
neck in attempt to maintain open airways.
w Acute necrotizing ulcerative gingivitis- This disease is characterized as a necrosis and ulceration of
the gingiva between the teeth, with adherent grayish pseudomembrane covering the gingiva.
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Histopathology:-
The organisms adhere to the epithelium of upper respiratory tract but may not invade the epithelium.
An acute inflammatory response specified by hyperemia, edema, focal hemorrhages as well as infiltration
of neutrophilis can be seen. A significant amount of fibrins can also be seen.
A few days after the acute inflammatory response, necrosis of epithelium with the debris of
inflammation can be seen, that entangled within the fibrin and forming a membrane that is attached to
underlying inflammatory tissues.
In the region of stratified squamous epithelium, the nature of membrane is firm as well as in areas of
thinner respiratory epithelium, the membrane is more easily separable[11].
Diagnosis:-
The clinical diagnosis of diphtheria demands bacteriologic laboratory confirmation of toxigenic C
diphtheriae in throat as well as in lesion cultures. Various laboratory investigations include-
? Culture medias- For primary segregation of diphtheriae various types of culture medias are
available such as Loeffler agar, Mueller-Miller tellurite agar, Tinsdale tellurite agar. Sterile cotton
tipped applicators can be used to collect the sample from pharyngeal tonsils as well as calcium
alginate swab can be used to collect nasopharyngeal sample for culture.
? Carbohydrate fermentation tests- After the initial isolation, various species of C diphtheriae can
be isolated on the basis of carbohydrate fermentation pattern as well as hemolysis on sheep blood
agar plates.
? In vivo and in vitro tests- Apart from this, the toxigenicity of C diphtheriae strains can be evaluated
by different in vivo and in vitro tests. The most popular in vitro test for the toxigenicity is the Elek
immunodiffusion test.
Diphtheria also must be kept in mind for any patient who has traveled to a disease-endemic area and
has chronic skin ulcerations. In these cases, wound swab specimens should be examined for C. diphtheriae.
Treatment:-
Treatment of the patient with diphtheria should be commenced at the time of the clinical diagnosis
and should not be delayed until the results of culture are collected.
§ The prevention of diphtheria depends upon appropriate immunization with diphtheria toxoid.
Diphtheria toxoid is used as a constituent in the DPT vaccine.
§ Antibiotics such as penicillin, erythromycin can also be used as a part of treatment of the patients.
§ If the patient is allergic to penicillin, erythromycin can be given to the patient[12].
Bacterial Sialadenitis
Sialadenitis can be defined as inflammation of the salivary glands.
Etiopathogenesis:-
Infectious sialadenitis generally occurs due to the bacterias such as Staphylococcus aureus,
streptococcus viridians, Haemophilus influenza, Peptostreptococcus spp, Streptococcus pneumoniae,
Escherichia coli, Bacteroides. Viral sialadenitis is most commonly caused by the paramyxovirus.
Most bacterial infections arise due to the ductal obstruction or decreased salivation flow, empowering
retrograde spread of bacteria throughout the ductal system. Submandibular as well as sublingual glands are
most commonly involved due to the tortuous anatomy of their ducts and anatomic position. Blockage of the
duct may be caused by- sialolithiasis, congenital strictures as well as compression by an adjacent tumor.
14
Decreased salivation flow can be due to the dehydration, debilitation, or medication that prevent secretions.
Clinical Features:-
Ø Sialadenitis is very common in pediatric population and it is approximately 10% of all salivary
gland disease.
Ø The most common clinical features of acute sialadenitis are swelling, pain, fever as well as
erythema overlying the affected glands.
Ø Symptoms may be unilateral as well as bilateral, but in bilateral cases, symptoms are more
distinguishable on one side.
Ø Pain usually evoked with mastication or swallowing, trismus is also present.
Ø Purulent mucus is also present in affected gland or duct, can be demonstrated with gentle palpation
over the affected gland or duct.
Ø Bacterial sialadenitis chiefly occurs in the parotid gland, involvement of parotid gland further
extend the infection to the angle of the mandible. Painful lymphadenopathy can be present as well.
Ø Bacterial sialadenitis can be distinguished from other inflammatory disease of the salivary glands,
due to the presence of pus.
Ø Chronic sialadenitis is related to the chronic
inflammation as well as obstruction of the
salivary glands. Patients commonly shows
the repeated episodes of the acute painful
gland swelling, which can be intricate by a
superimposed bacterial infection[13]. Figure 2.7: Child with parotid gland swelling Figure 2.8: Purulent exudate milked from the
parotid duct in a patient with a bacterial infection
of the parotid gland.
Diagnosis:-
In case of acute inflammation, suppurative sialadenitis can be distinguished from other inflammatory
disease of the salivary glands, by the presence of pus at the orifice of the duct. Any purulent should be sent to
the laboratory for gram staining or culture. Imaging
such as an occlusal radiograph as well as ultrasound
often can detect a sialolith. Ultrasonography can be
used to confirm the presence of an inflamed gland,
identify abscess as well as guide aspiration. Computed
tomography should be used if the systemic Figure 2.9: Sialolithiasis with acute sialadenitis. Figure 2.10: Chronic sialadenitis- The corresponding
Stone frag- ments (arrow) are blue, irregularly histologic specimen shows marked fibrosis, chronic
complications are suspected[8]. shaped, jagged structures of varying sizes that
are diagnostic of sialolithiasis. The presence of
inflammation, acinar atrophy, and residual ductal
elements (hematoxylin-eosin [H & E] stain).
numerous neutrophils signifies an accompany-
ing acute sialadenitis (Romanowsky stain).
Histopathology:-
In case of acute sialadenitis, collection of neutrophilis can be evaluated within the ductal system and
acini. Chronic sialadenitis usually involves the scattered as well as patchy infiltration of lymphocytes and
plasma cells in the salivary parenchyma[14].
Treatment:-
The treatment of acute sialadenitis involves –
§ Appropriate antibiotic therapy as well as rehydration of the patient to stimulate salivary flow. The
conservative management of acute sialadenitis composed of oral antibiotics, analgesics, adequate
hydration, warm massage as well as sialogogues.
15
§ If the conservative approach is not sufficient to resolve the acute symptoms, abscess formation
should be suspected. Abscess formation demands incision and drainage.
§ Treatment of the severe obstruction of the gland should involves, surgical intervention, primarily
when the obstruction is close to the gland.
Acute infection as well as inflammation is a relative contraindication to surgical intervention. In these
kind of cases, antibiotic therapy should start before any surgical intervention.
Oral Tuberculosis & Scrofula

Tuberculosis is a specific, lethal, infectious disease, resulting in high mortality in adults. It is caused
by Mycobacterium tuberculosis. M. tuberculosis organisms are also known as tubercle bacilli.
Etiopathogenesis:-
TB is airbone disease caused by the bacterium Mycobacterium tuberculosis. Infection oocurs when a
person inhales droplet nuclei containing tubercle bacilli that reach the alveoli of the lungs. Once the
tubercle bacilli entered in the alveoli further they ingested by alveolar macrophages. Macrophages inhibit
or destroy the bacilli. A small number of tubercle bacilli, which may not be destroyed by the macrophages,
will multiply intracellularly , and release when the macrophages die. Tubercle bacilli can also spread
through the lymphatic channels and bloodstream to more distant tissues and organs. This process of
dissemination prepares the immune system to give a systemic response[11].
Clinical Features:-
Ø Infants and young children are more prone to TB infection than older children and adults.
Ø It is more common in children less than 5 years of age and adolescents older than 10 years of age.
Ø M. Tuberculosis enter the alveoli of lung through aerosolized particle and cause coughing,
sneezing, speaking or singing, these are the initial signs and symptoms of the disease.
Ø The incubation period, usually lasts from 2 to 12 weeks.
Ø According to the WHO, the most common signs and symptoms of childhood TB are- chronic cough
persisting more than 21 days with or without wheezing. Mild dyspnea is common is childhood TB.
Ø Fever, weight loss, failure to thrive, feeling of sickness, lethargy, reduced playfulness, night sweats
are common clinical features of TB.
Ø Oral lesions of TB generally shows painful, ragged ulcers can be seen on the posterior aspect of the
tongue, palate.
Ø In some cases, bacteria that cause the TB causes symptoms outside the lung and this condition is
known as 'Scrofula'. This condition is also
known as 'cervical tuberculous lymphadenitis'.
Ø Swollen cervical lymph nodes are common
feature of scrofula, that may feel like a small,
round nodule. The lesion may start to get
bigger and may even drain pus or other fluid Figure 2.11: Tuberculosis (TB) Submandibular Figure 2.12: Chronic mucosal ulceration of
after several weeks[15]. fistula secondary to involvement of underlying the ventral surface of the tongue on the
cervical lymph nodes. right side
Oral TB will closely mimic several other important and well-known diseases, the most important of
which is squamous cell carcinoma. In addition, the chancres of primary syphilis and the oral lesions of
16
pulmonary fungal diseases such as histoplasmosis, coccidioidomycosis and blastomycosis will have a
similar appearance. If there is a history of trauma or a suspiciously sharp tooth edge exists, it is important to
remember that trauma Is still the leading cause of oral ulcers and should be included in the differential
diagnosis.
Histopathology:-
The histopathologic appearance is because of cell mediated hypersensitivity
reaction. Formation of granuloma showing foci of caseous necrosis
surrounded by macrophages, epitheloid cells, multinucleated giant cells
usually of langhans type, with peripheral lymphocytes, plasma cells as well
as fibroblasts. This may not seen in the intraoral lesions but may be an
Figure 2.13: Tuberculosis (TB). Histopathologic presentation
of the lesion showing sheets of histiocytes are intermixed important component in lymph node involvement and in the lung.
with multi nucleated giant cells and areas of necrosis.
Diagnosis:-
Oral TB ulcer can be diagnosed with the help of biopsy to rule out carcinoma as well as the fungal
lesions. Other laboratory investigations include-
Ziehl Neelsen staining-

® Acid fast organisms usually appears as red
bacilli, present within the cytoplasm of macrophages.
Figure 2.14: Tuberculosis (TB). Acid-fast stain of

specimen exhibiting scattered mycobacterial
organisms presenting as small red rods
Culture
® methods are also very useful for the diagnosis of M. Tuberculosis, Lowenstein-jensen
media is more preferable for culture method.
Another tissue specimen should also be sent for hematoxylin and eosin histopathology.
®
Oral TB is more closely associated to pulmonary TB, so a chest radiograph should be taken.
®
Mantoux
® test – it is an intradermal skin test, can also be used for the
detection of tubercle bacilli. It generally used in a dose of 5 tuberculin units
in a saline solution as the antigen.
Figure 2.15: Mantoux's test showing positive reaction
CT scan as well as MRI are more useful for the detection of extrapulmonary TB.
®
Recent
® advancements of the diagnosis of TB includes- radioimmunoassays(RIA), fluorescent
antibody test as well as ELISA[11].
Treatment:-
The principle goal of successful TB prevention are rehabilitation as well as preventing the
transmission of M. Tuberculosis in the community. The current recommended treatment regimen are
mostly the same for adults and children. Combination of some drugs can be given to the patient to prevent
the exposure of resistant organisms.
17
§First line bactericidal drugs for the M. Tuberculosis are- Isoniazid(INH) , rifampicin (RIF),
pyrazinamide(PZA) , ethambutol (EMB) or Streptomycin (S).
§Second-line TB drugs for infants and children are- Ethionamide, Cycloserine, Streptomycin, Para-
amino-salicylic, Amikacin and Kanamycin, Levofloxacin Moxifloxacin, Ciprofloxacin[15].
Tetanus (Lock Jaw)

Tetanus is an acute infection of central nervous system manifested by enormous activity of motor
neurons and followed by severe muscular spasm.
Etiopathogenesis:-
Tetanus is a life-threatening infection caused by the microorganism Clostridium tetani, which
produce a potent exotoxin, tetanospasmin. Tetanospasmin is a neurotoxin that produce the hyper-reactive
muscle as well as actual muscle spasms of this disease.
Most cases of tetanus are present in Unvaccinated individuals, newborns, elders, migrant workers as
well as in intravenous drug users.
Clinical Features:-
Ø Tetanus is more commonly present in neonates or infants. It can be diagnosed in an infant by
examining their capability to suck and cry in the first 2 days presents with inability to suck between
3 and 28 days of life due to rigidity or spasms.
Ø Tetanus is classified as- localized, cephalic as well as generalized.
Ø Children aged 5 years and above are more at risk with male predominance.
Ø Tetanus can also develop from the penetrating wound, these wounds can incubate C tetani.
Incubation period is generally 6-12 days.
Ø The first symptoms that would appear are- restricted jaw opening, stiffneck, diplopia as well as
dysphagia.
Ø Pain as well as the muscle spasm can be seen in the infected site.
Ø With the progression of the disease, tetanospasmin will also increase, and first involve the
masseter, external ocular as well as neck muscles and then involve
back muscles, leg muscles, diaphragm.
Ø As the disease advances further, contractions of the facial muscles
results in a sardonic smile.
Ø Spasms in the back muscle give rise to opisthotonos i.e. state of
severe hyperextension and spasticity in which an individual's head,
neck and spinal column enter into a complete bridging or arching
position.
Ø Involvement of the diaphragm and the intercostal muscles give rise
to apnea and death follows unless the individual is placed on a
Figure 2.16: Position of opistottons, characteristic of
ventilator and paralyzed with muscle relaxant[16]. generalized tetanus.
In the early stage of the disease, the jaw and neck stiffness as well as diplopia may suggest meningitis.
Diagnosis:-
Tetanus can be diagnosed on the basis of physical examination, medical and immunization history, as
18
well as the signs and symptoms of muscle spasm, stiffness and pain. Laboratory tests generally are not
helpful for diagnosing tetanus.
Treatment:-
Acute treatment of tetanus is generally based on wound cleaning, antibiotic as well as suppression of
Clostridium tetani.
§ Most commonly used antibiotics are metronidazole and penicillin.
§ The tetanus antitoxin can be given to deactivate any free tetanus toxin.
§ Muscles dysfunctions in case of tetanus can be corrected with benzodiazepines, which augment the
effect of GABA on the GABAA receptors of lower motor neuron. Baclofen can also be given, it
usually act on GABAB receptors. Propofol is an another GABAA receptor modulator, can also be
used as non-depolarizing muscle relaxant.
§ Other preventive measures- Patients suffering from tetanus should live in a calm environment to
avoid the triggering of the spasms by noise or other sensory stimulation. A good immunization status
in pregnant women leads to reduction in the prevalence of neonatal tetanus, because maternal anti-
tetanus toxin antibodies are transferred across the placenta to the child in utero[17].
Syphilis
Syphilis is a chronic sexually transmitted infectious disease.
Etiopathogenesis:-
It is an infectious disease and is caused by Treponema pallidum, belongs to the family
Spirochaetaceae and is a unicellular, spiral organism. Apart from T. pallidum subspecies pallidum, the
causative agent of venereal syphilis, other pathogenic treponemes that cause disease in humans include T.
pallidum subspecies pertenue, the causative agent of yaws; T. pallidum subspecies endemicum, the
causative agent of endemic syphilis.
T pallidum is a helically shaped micro-aerophilic bacterium, the outer membrane of T. pallidum does
not contain lipopolysaccharide and has relatively few surface exposed transmembrane proteins which has
the potential for virulence.
Pathogen causing the syphilis can enter into the body by various routes such as by- sexual intercourse,
blood transfusion, contaminated needles, vertical transmission, to hospital personnel by indiscriminate
handling of infected lesions. Organism enter into the body by penetrating the intact mucous membrane or
entering through breaks in the skin.
A family of T. pallidum repeat genes, which encode proteins homologus to the major surface proteins
of T. denticola that mediate attachment to host tissue, and function as porins. Tpr has shown to be a target for
opsonic antibody. Activated macrophages can phagocytize opsonized treponemes and clear them from
circulation[18].
Clinical Features:-
Syphilis traditionally is divided into- primary, secondary, latent as well as tertiary stages. The clinical
presentation of syphilis varies with the disease stage. It is usually present in infants and children.
Ø Primary Syphilis-
? Primary syphilis is commonly manifested by a single, painless papule that appears following a 3
week incubation period. This papule then transferred into a painless spirochete filled chancre,
which are presented as a smooth base with raised borders.
19
Chancre usually appears at the site of inoculation and is found
?
most commonly on the external genitalia. But can also be found on
the other areas such as cervix, perianal area as well as in mouth.
Approximately in 50% of cases, the chancre is accompanied by
?
painless regional lymphadenopathy.
Primary chancre are usually painless and sometimes it may not be
?
noted by the patient. So the spontaneous regression of the chancre &Figure 2.17: Chancre of Primary Syphilis. Erythematous
ulcerated mass of the right anterior buccal mucosa.
without treatment occurs in 3 to 6 weeks.
Secondary Syphilis-
Ø
? Secondary syphilis is integrated with extensive hematogenous as well as lymphatic spread of the
organism and represent the systemic manifestations associated with highly infectious
mucocutaneous lesions.
Systemic manifestations generally include fever, malaise, anorexia, weight loss as well as
?
generalized lymphadenopathy.
Skin lesions are another findings in secondary syphilis and usually begins as a nonpruritic,
?
symmetric, macular rash generally present on the trunk as well as proximal extremities that
progress into maculopapular as well as pustular rash.
In secondary syphilis, rashes are usually present on palms and soles.
?
Apart from this there are other skin manifestations includes eroded, popular lesion on the
?
genitalia.
A wart like lesions on the genitals can be seen and referred as
?
condyloma lata.
A grey colored mucous patches are also present on mucous
?
membrane.
Involvement of the scalp may give rise to alopecia in some cases.
?
Even without interference, symptoms of secondary syphilis
resolve thoroughly, and the patient passes into the latent period of Figure 2.18: Mucous Patch of Secondary Syphilis.
Irregular thickened white plaque of the right
soft palate
the disease.
Ø
Latent Syphilis-
Early latent syphilis is generally an asymptomatic phase because this phase generally appear in
?
first year after infection and is denoted by the absence of symptoms as well as the presence of
treponemal antibodies in blood.
Early latent period is followed by the late latent period, which usually start one year after the
?
acute infection and has a low rate of relapse than early latent syphilis.
Tertiary Syphilis-
Ø
? Tertiary syphilis is very uncommon in pediatric population, because there is very long duration
between the primary infection and emergence of tertiary syphilis, which is approximately 10 to
20 years.
The prevalence of tertiary syphilis is more in untreated patients of syphilis.
?
Congenital Syphilis-
Ø
? Congenital syphilis is generally transmitted to the offspring only by an infected mother and is not
inherited.
20
This type of syphilis is acquired in utero or may be acquired at the time of delivery.
?
Disease transmission is more common during the early stage of pregnancy.
?
Approximately the 20% of fetal infections results in stillbirth, neonatal death as well as many
?
infants may survive and show no symptoms of disease.
Congenital syphilis occur in two stages- early stage, late stage.
?
Early stage:- The early stage generally occur prior to 3 months of age and happens because of
?
infection existing earlier in pregnancy. Clinical manifestations include- fulminant disseminated
infection, mucocutaneous lesions, osteochondritis, anaemia, hepatosplenomegaly,
neurosyphlis.
Late stage:- The late stage of congenital
?
syphilis follows a latency period, in which
no clinical malformations are detectable
until after 2 years of age. Typical findings
include- interstitial keratitis,
lymphadenopathy, hepatosplenomegaly,
bone involvement, condylomata, anaemia, Figure 2.19: Hutchinson Incisors of Congenital Syphilis. Figure 2.20: Mulberry Molar of Congenital
Hutchinsonian teeth, eight nerve deafness, incisal
De ntition exhibiting crown s tapering towa rd the Syphilis. Maxillary molar demonstrating
edges occlusal surface with numerous globular
[19] projections.
recurrent arthropathy, neurosyphilis .
w An oral primary chancre should suggest the possibility of other serious diseases presenting with oral
ulcers, such as squamous cell carcinoma, TB, systemic fungal diseases.
w The oral mucous patches of secondary stage of disease, with or without the skin rash, may also
mimic reactive arthritis, diffuse candiiasis, erythema multiforme and lichem planus at times.
w The destruction of palate seen in the rare cases of oral tertiary syphilis must be distinguished from
the other entities known to cause palatal destruction such as natural killer/T cell lymphoma,
mucormycosis, nasopharyngeal carcinoma.
Laboratory Diagnosis:-
The laboratory diagnosis of syphilis is made primarily by serology or by direct antigen detection. For
the detection of syphilis, exudates from chancre, mucocutaneous lesion, nasal or ocular discharge can be
examined under dark-field, phase-contrast, or fluorescent microscopy. Three negative examinations can
confirm the absence of syphilis. Various laboratory tests can be performed for the diagnosis of syphilis-
§ Direct visualization techniques
Dark-field microscopy
Direct fluorescent antibody test for Treponema pallidum
§ Nontreponemal tests
Venereal disease research laboratory microscopic slide test (VDRL)
Rapid plasma reagin test
§ Treponemal tests
Fluorescent treponemal antibody absorption test (FTA-ABS)
Microhemagluttination assay for antibody to T pallidum
Patient suspected of having syphilis should undergo a screening VDRL test. This test is quick,
inexpensive, and easy to perform as well as an ideal test for screening numerous blood samples.
FTA-ABS is a confirmatory test for syphilis. It is highly specific, time-consuming, expensive test.
21
Histopathology:-
Ø The basic changes in syphilis are vascular, illustrated by a proliferative endarteritis which leads to
the swelling as well as proliferation of endothelial cells, resulting in
constriction of the vascular lumen.
Ø The early stages of syphilis are identified by dense perivascular
infiltrations of plasma cells as well as lymphocytes.
Ø In case of chancre, reaction is more dense at the center of the lesion
and endothelial proliferation is present at the periphery.
Ø Occlusion of vessels by the endothelium may cause necrosis and
Figure 2.21: Primary Syphilis. A chronic perivascular
ulceration of the chancre, as well as the epithelial margins may show inflammatory infiltrate of plasma cells & lymphocytes
a reactive acanthosis.
Ø Treponema pallidum can only be stained by a silver stain such as
Warthin-starry stain. Organisms usually appear as narrow, black,
thread like as well as with cork-screw configuration.
Ø Tertiary as well as late syphilis are identified by the presence of
epithelioid granuloma, which consist of the multinucleated giant
2.22: Secondary Syphilis, Low-power photo-
cells. Granulomas are more typically present in tertiary syphilis but Figure
micrograph of biopsy shows papillary epithelial
hyperplasia & a heavyplasmacytic infiltrate in the
sometimes can also be seen in secondary syphilis[11]. connective tissue.
Treatment:-
§ Parenteral Penicillin G is the drug of choice for all stages of syphilis and is only advocated for
congenital syphilis, syphilis during pregnancy as well as neurosyphilis.
§ Primary syphilis, secondary syphilis as well as the early latent syphilis can be cured with a single
injection of Benzathine penicillin G.
§ Jarisch-Herxheimer reaction is the systemic response to the ruination of large number of spirochetes
and usually occur upon the initiation of antimicrobial therapy. It is generally characterized by fever,
headache, myalgias, tachycardia, hypotension as well as tachypnea.
§ If the patient is allergic to penicillin, oral tetracycline, oral doxycycline or oral erythromycin can be
given to the patient.
NOMA
Also known as cancrum oris, gangrenous stomatitis.
This disease usually occurs in undernourished and immunosuppressed young children. NOMA is a
greek word, which means 'to devour' is an ancient disease having been described as long ago as by
Hippocrates and Galen.
Etiopathogenesis:-
NOMA generally occurs in debilitated or nutritionally deficient persons. Predisposing factors such as
malnutrition, infections like malaria, measles etc plays an important role in the development of this disease.
The lesion usually appear as a painful ulcer due to trauma or infection. The ulcer rapidly extends as
inflammation results in tissue necrosis which leads to the disintegration of mucosa and skin to expose
underlying bone, which may also become necrotic. It is generally a secondary complication of the systemic
disease rather than a primary disease. In many instances the infection begins as necrotizing ulcerative
gingivitis and several investigators believe that noma is merely an extension of the same process. Specific
22
infection by vincent's organism give rise to Acute necrotizing ulcerative gingivitis (ANUG), which is soon
complicated by secondary invasion of streptococci, staphylococci which further give rise to NOMA[20].
Clinical Features:-
Ø NOMA is more commonly occur in children or teenagers.
Ø Oral mucosa of affected child generally appear as gangrenous, black tissue slough. The lesion
usually appear as painful ulcer.
Ø The infection may either begins on the gingiva as NUG, or extend facially as well as lingually and it
comprises adjacent soft tissue and forms necrotizing ulcerative mucositis.
Ø Necrotic zone is the cone shaped which usually involve the skin and oral mucosa.
Ø This discolored zone break down into area of yellowish necrosis that extends in to adjacent bone
and give rise to osteomyelitis.
Ø Fetid odor, significant pain, fever, malaise, tachycardia, increased respiratory rate, anemia,
leukocytosis as well as regional lymphadenopathy are typical feature of NOMA.
Ø Other commonly involved sites are- scalp,
neck, ear, shoulder, chest, perineum as well as
vulva.
Ø Affected individuals also shown stunting
growth, high temperature as well as death
from toxemia.
Figure 2.23: Cancrum oris Figure 2.24: Facial involvement
The most important disease from which to distinguish noma is a rapidly progressing malignancy,
particularly entities such as immunoblastic lymphoma and leukemias. In addition, necrotizing fasciitis,
which is an analogous disease but localized to fascial planes, may in its early stages resemble noma.
Diagnosis:-
The diagnosis of NOMA usually based on the clinical recognition of growing ischemic alterations
with necrosis. Culture from the edge of necrotic tissue can distinguish the Vincent spirochetes as well as
fusiform bacilli, which makes the disease somewhat similar to acute necrotizing ulcerative periodontitis.
Histopathology:-
Ø In early stages the lesion shows acute inflammation with edema and infiltration of neutrophils,
followed by extensive necrosis.
Ø Granulation tissue usually appear around the foci of necrosis, and become infected.
Ø Masses of bacteria can also be seen.
Treatment:-
Two principal aspects of treatment are the reversal of the primary predisposing condition as well as
surgical procedure. Management of acute phase of NOMA includes-
§ Hydration (parenteral fluids)
§ Correction of anemia by blood transfusion
§ Antibiotics such as Penicillin, Metronidazole.
§ Corticosteroids in severe cases.
23
§Tube feeding
§Improvement of malnutrition by folic acid, ascorbic acid, vitamin B complex.
§Surgical procedure such as sequestrectomies, tooth extraction.
§Periodontal care
§Management of local wound infection[21].
Juvenile Periodontitis
Periodontitis is defined as an inflammatory disease of the supporting tissues of tooth caused by
specific microorganisms which leads to the continuous ruination of periodontal ligament as well as alveolar
bone with pocket formation or recession. It is further divided into chronic and aggressive type.
(1) Chronic Periodontitis (Periodontoclasia, Pyorrhea, Pyorrhea Alveolaris, Schmutz Pyorrhea)
This is the most common type of periodontitis and is related to local irritation. This usually starts as a
marginal gingivitis, which usually advances, if untreated or treated inadequately, to chronic periodontitis.
This is more commonly found in adults and occasionally seen in children.
(2) Aggressive periodontitis- This type of periodontitis is more common in children. It could be
localized and generalized[22].
Etiopathogenesis:-
Various factors are involved in the pathogenesis of JP-
(A) Bacteria- Plaque is the main factor in the etiology of the aggressive periodontitis. Gram
negative bacterias are more commonly found in the periodontal pocket of the individual suffering
from aggressive periodontitis apart from this some gram positive bacterias can also be seen. Bacterias
commonly found are- A. actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia,
Treponema denticola, Fusobacterium nucleatum, Prevotella intermedia, Prevotella nigrescens,
Campylobacter rectus, Eikenella corrodens and Parvimonas micra. Most common Gram positive
isolates are- streptococci, actinomycetes and peptostreptococci. A. actinomycetemcomitans gained
more importance because
? This bacteria is less common in periodontally healthy individuals.
? A. actinomycetemcomitans produce leukotoxin, that can cross the epithelial membrane and
induce the disease in experimental animals as well as in non-oral sites.
? These individuals usually show elevated level of serum antibodies to Aa. They also produce
antibodies against Aa at the site of infection.
? The subgingival load of Aa could not be reduced after treatment.
(B) Breakdown of Periodontium- Periodontal breakdown occurs via two related mechanisms-
(I) The quick action of microbes or their products on the host tissues.
(II) Due to inflammatory responses.
Many observations in the humans have improved that Aa could translocate across the junctional
epithelium and penetrate the connective tissue. Defense mechanism such as high turnover of
keratinocytes of junctional epithelium, the outward movement of crevicular fluid, the directed
movement of PMNs through the junctional epithelium; the capability is highly promoted by the
presence of specific antibodies as well as the complement fragment in the gingival crevicular fluid.
(C) Response of the host to bacteria- The acute enrollment of PMNs within the tissue as well as
into the periodontal pocket can give rise to local inflammatory response. B cells as well as antibody
producing plasma cells are present in appropriate proportion. IgG- producing cells, with a lower
proportion of IgA- producing cells. In case of aggressive periodontitis there is a depression of T-
24
helper to T-suppressor ratio in comparison to healthy gingival.
Local inflammatory responses are characterized by high levels of PGE2, IL-1a as well as IL-1b in
both gingival crevicular fluid and tissue. PGE2 production is also elevated in patients of aggressive
periodontitis as compared to the patients of healthy gingival.
(D) Environmental aspects of host susceptibility- Cigarette smoking is a risk factor for the
patients of generalized aggressive periodontitis. smoking can lead to the attachment loss of teeth in
the patients of aggressive periodontitis. smoking can also lead to the depression if IgG2 serum level as
well as antibody levels against the Aa that further leads to the increase in disease extent as well as
severity in patients of AP[23].
Clinical Features:-
Ø LAP is localized in nature and does not involve all teeth in the dentition. LAP starts at
circumpubertal age, and is confined to incisors and first molars.
Ø Lack of local factors such as plaque and calculus leads to lack of inflammation with presence of
deep periodontal pockets and advanced bone loss.
Ø Advanced bone loss can give rise to increased mobility of maxillary as well as mandibular incisors
and first molars.
Ø Distolabial migration of maxillary incisor with diastema formation can also occur in case of LAP.
Ø Sensitivity of the denuded root, deep dull radiating pain to the jaw as well as periodontal abscess,
lymph node enlargement are the secondary clinical features of the LAP.
Ø Blacks are more prevalent than whites in case of LAP, and females are more prone to suffer than
men. LAP usually occurs from puberty to 30 years of age.
Ø GAP has generalized involvement of the oral cavity. Most commonly involved teeth are the three
permanent teeth other than incisors and first
molars. There is an attachment loss in the
interproximal area of affected teeth.
Ø GAP usually affects the individual under age
30.
Ø In GAP, there is a presence of minimal
generalized factors such as plaque which is
Figure 2.25: A 14-year-old African-American female Figure 2.26: Patient presenting with flaring
incompatible with destruction as well as diagnosed with localized juvenile periodontitis. of the anterior teeth and deep pockets
presence of bacteria.
w Unexpected bone loss in a child or young adult, which will sometimes create the radiographic
appearance of a tooth floating in the alveolus, is a classic feature of several serious diseases, in
particular Langerhans cell histiocytosis, Papillon-Lefevre syndrome, acute lymphocytic leukemia
in children and preteens, and acute myelogenous leukemia in late teens and young adults.
w In addition, systemic diseases that suppress leukocyte function or cause immune suppression will
predispose patients to a more rapid progress of chronic periodontitis, which may resemble one of
the forms of juvenile periodontitis. Therefore, diabetes, HIV-AIDS and neutropenia-related
periodontitis among others, are also considerations.
Histopathology:-
? Histopathology of aggressive periodontitis is not well-documented than chronic periodontitis,
because of the less numbers of AP patients.
? Stambolieva and Bourkova establish that there is rise in numbers acid phosphatase positive
25
macrophages in AP patients.
Plasma cell inflammatory infiltration is predominantly present in the patients of AP as well as the
?
presence of neutrophils on the root surface of patients.
Neutrophils usually emigrate through the pocket lining epithelium and fabricating a layer between
?
the plaque and tisues[22].
Diagnosis:-
A) Assessment of systemic conditions:- firstly there should be adequate evaluation of the patient's
medical history. Risk factors such as smoking as well as psychosocial stress should be
determined. Any history of medication as well as the family history regarding periodontal
condition should be taken properly.
B) Periodontal clinical examination:- This usually includes the evaluation of- clinical attachment
levels, depth of periodontal pocket, bleeding on probing, furcation involvement, dental
mobility, suppuration as well as oral hygiene.
C) Radiological examination:- Radiological examination is very important in case of AP. The
following are recommended:
§ Periapical radiographic series
§ Radiovisiography
Treatment:
Treatment of AP can be done under various phases such as-
§ Systemic phase- This phase includes the medical reference as well as the medical interconsultation
for the modulation of risk factors.
§ Initial phase-
v This phase includes the emergency treatment if necessary. Education of patients regarding the
predisposing risk factors, triggers, oral hygiene habits etc.
v This phase also includes the evaluation as well as treatment of occlusal disharmony and
temporomandibular joints.
v Supragingival as well as subgingival scaling and root planning
v Atraumatic extraction of non-viable teeth.
v Local as well as systemic antibiotic treatment- combination of amoxicillin metronidazole can be
given by systemic administration. Other antibiotics- spiramycin, clindamycin can be
recommended. Systemic administration is very effective because this method has the advantage of
reaching all the areas of oral cavity. Antibiotics such as tetracycline, doxycycline as well as
minocycline can be administered locally.
§ Re-evaluation- This phase includes the re-evaluation of patients after treatment for reduced
probing depth, clinical attachment gain as well as resolution of inflammation, tooth mobility,
occlusal state and root sensitivity.
§ Surgical Phase- In AP, antimicrobial surgical as well as comprehensive mechanical therapy is an
adequate treatment protocol for long-term stabilization of periodontal health.
§ Maintenance Phase- If there is any refinement in the periodontal condition of the individual after
surgical treatment, maintenance will be carried out otherwise we should return the patient to the
initial phase. Medical appointments every three months have shown favorable results, this phase
usually help in the-
v Control of dental plaque
v Observation of clinical attachment level, probing depth, gingival bleeding as well as tooth
mobility.
26
3 Viral Infections
?Herpes simplex infections
?Herpangina
?Acute lymphonodular pharyngitis
?Hand-foot-and mouth disease
?Varicella
?Measles
?Rubella
?Mumps
?Heck's disease
Herpes simplex infections
I t is an acute infectious disease, is likely the most common viral disease affecting man, with the
exception of viral respiratory infections. Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-
2) are members of Herpes viridae family and distinguished by their potentiality to establish
latency after primary infection as well as subsequently reactivate. HSV-1 is identified primarily in
infections of the mouth, pharynx, face, eye as well as central nervous system. HSV-2 is identified in
infections of anogenital region.
Etiopathogenesis:-
Approximately more than 80 herpesvirus species are known, out of which 8 usually cause infection in
humans and they are- HSV-1, HSV-2, Varicella-zoster virus (VZV), Cytomegalovirus, Epstein-Barr virus,
human herpesviruses (HHV6 and HHV7), and Kaposi sarcoma-associated herpesvirus (HHV8). Infection
of herpes is transferred mainly through skin exposure to mucous membrane or skin that have active lesions
or to mucosal secretions of an individual who has an active HSV infection. The virus can be transmitted
through saliva as well as can remain secured outside of the host for short periods of time, permitting transfer
for sometime after direct mucocutaneous contact with the virus. Initially, there is primary HSV-1 and HSV-
2 infections occur, followed by an active viral shedding period which lasts for several weeks. Most patients
who are primarily infected with HSV are asymptomatic.
After the primary infection, virus remains latent within the sensory ganglia of autonomic nervous
system, now the infection cannot be curable. Replication of virus occurs within the sensory ganglia. HSV-1
resides most commonly within the trigeminal ganglion because the primary target site of this virus is oral
region. On the other hand HSV-2 mainly remain in sacral ganglia after infection of the genital area.
Many trigger factors are responsible for the reactivation of virus such as stress, exposure to sunlight, fever,
menstruation, now can virus can travel along the sensory nerve and can cause infection in the same area as
in primary infection. On average, reactivation of HSV occurs during approximately 1% of the days in the
life of patients infected previously[25].
27
Clinical Features:-
Clinical manifestations of HSV infection is unstable and generally depends on method of
transmission, age as well as immunocompetency of the host. It is most commonly seen in children and
young adults.
Cutaneous lesions usually includes- vesicles with erythematous base, ulcers with or without crusting.
Prodromal symptoms usually includes- burning, paresthesia at the site, lymphadenopathy, fever, malaise,
myalgia, headache as well as loss of appetite.
Recurrent infections usually occurs due to reactivation of viruses and these infection are more
localized, milder and shorter in duration.
ØHerpetic gingivostomatitis
w
It is generally caused by HSV-1
w
It usually presents as multiple round ulcers
mostly present on palate, tongue, gingivae.
w
Patient may present with prodromal
symptoms, followed by classic vesiculoul-
cerative lesion.
Figure 3.1 Acute Herpetic Gingivostomatitis. Figure 3.2 Acute Herpetic Gingivostomatitis.
w
Foul breathe, anorexia. Numerous coal escing, irregular, & yellowish
ulcerations of the dorsal surface of the tongue.
Painful, enlarged & erythematous facialgingiva.
Note erosions of the free gingival margin
Herpes labialis:-
Ø
w
It is the most common manifestation of HSV-1 infection, also known
as cold sores and fever blister a r e u s u a l l y s e e n a s i n i t i a l
manifestations in children.
w
It is most commonly occur on the outer vermillion border of lips
Figure 3.3 Herpes Labialis. Multiple
fluid-filled vesicles on the lip vermilion.
Genital Herpes:-
Ø
wIt is more commonly caused by HSV-2, although the proportion due to HSV-1 has been increasing
recently.
w
It is a sexually transmitted infection, other risk factors include- lower socioeconomic status,
geography, race, education.
w
Various complications include- urinary retention, psychological morbidity, and aseptic meningitis.
Herpetic Keratoconjunctivitis:-
Ø
w
Ocular HSV-1 infection is the second most common infectious that
cause blindness.
w
It usually cause vesicles followed by ulcerations of cornea which
further leads to purulent conjunctivitis.
w
Various complications include- permanent scarring, secondary
bacterial infection, meningoencephalitis as well as vision loss. Figure 3.4 Herpetic Whitlow. Recurrent herpetic infection
of the finger
Herpetic Whitlow:-
Ø
w
This infection occurs commonly in patients who have primary oral or genital herpes and health care
workers
28
Infection usually show deep-seated swelling, erythema as well as vesiculoulcerative lesions on
w
fingers.
Infection usually occurs in children by digital/oral contact and in adults with genital contact.
w
Herpes Gladiatorum:-
Ø
w
This infection most commonly occur in wrestlers, boxers, football, soccer as well as in rugby
players.
w
It most commonly affects exposed areas such as the face, ears, upper extremities, neck.
w
This infection mainly occurs due to HSV-1 than HSV-2.
Herpes Encephalitis and Meningitis:-

Ø
w
HSV encephalitis is the most common manifestation of primary and recurrent infections.
w
Common symptoms include- altered mental as well as personality status, seizures as well as focal
neurological findings.
w
HSV meningitis is characterized by CSF pleocytosis, with lymphocyte predominance as well as red
blood cells in the CSF.
w
Mollaret syndrome is usually associated with Herpes encephalitis, typical presentations of this
syndrome are- recurrent episodes of headache, meningismus, as well as fever that resolve
spontaneously.
w
General complications include- Bell's palsy, atypical pain syndrome, trigeminal neuralgia,
ascending myelitis.
Neonatal Herpes:-
Ø
w
Most neonatal herpes infections are due to HSV-2.
w
Neonatal infection mostly transmit from a pregnant women to the fetus during the third trimester of
gestation and usually manifests in the first 4 weeks after the birth.
w
Neonatal herpes generally affect the skin, eyes, mouth, CNS, liver,
adrenal glands as well as lungs.
w
Cutaneous lesions are most commonly present on scalp, mouth, nose,
eye etc.
w
Infection of the CNS usually give rise to neurological signs such as Figure 3.5 This neonates with AIDS also has disseminated
HSV-2 infection with lesions covering the entire body.
seizures.
Treatment- Antiviral therapy[26].
w
Congenital HSV:-
Ø
w
Congenital HSV usually occurs due to HSV2 and cause infection prenatally.
w
Infected fetus often die in utero, those that survive are typically present with vesicular lesions,
chorioretinitis, microphthalmia, microcephaly as well as abnormalities on brain scan.
w
In case of congenital HSV, there is an absence of signs of systemic toxicity and overwhelming
sepsis as well as presence of both fetal and maternal antibodies against HSV, on this basis
congenital HSV can be differentiated from neonatal HSV.
w
Treatment is similar to neonatal HSV.
Eczema Herpeticum:-
Ø
w
It is also known as Kaposi varicelliform eruption.
29
wIt is characterized by HSV infections of skin from an underlying barrier defect caused by atopic
dermatitis, pemphigus, Darier disease, burn trauma, and cosmetic procedures.
wThe lesions of eczema herpeticum usually fuse to form a large superficial lesion and often are
disseminated.
wTreatment- intravenous antiviral therapy, antibiotic therapy for secondary bacterial infection, anti-
inflammatory therapy.
Herpes in immunocompromised host:-

Ø
w
HSV infections are most commonly seen in immunocompromised individuals who are suffering
from hematological malignancy, immune deficiencies, AIDS.
w
Skin lesions have an atypical appearance and can be highly crusted, pustular, necrotic or exophytic.
w
Herpes in immunocompromised patients is very less responsive to therapy.
w
Complications are- Esophagitis, tracheobronchitis, pneumonitis, hepatitis, pancreatitis, adrenal
necrosis.
HSV associated Erythema Multiforme:-

Ø
w
It is the complication of HSV outbreaks that induce erythema multiforme skin lesions.
w
Lesions has “Bull's eye” appearance, scattered diffusely on the body, predominantly seen on palms
and soles.
w
These lesions occurs due to the reactivation of HSV-2 and does not give rise to any complications.
Treatment- Antiviral prophylaxis[25].
w
w The painful vesicular ulcerative lesions of acute herpetic gingivostomatitis may resemble
necrotizing ulcerative periodontitis or pemphigus vulgaris.
w The oral lesions by themselves might be suggestive of erythema multiforme, but without
concomitant skin lesions true erythema multiforme is not likely.
w In adults, erosive lichen planus is another consideration, as is streptococcal pharyngitis-mucositis
in younger patients.
w Lesions of recurrent herpes simplex, particularly on the palate and gingiva, can be confusing.
Intermittent episodes of “burning” lesions will occur. Their duration may be so brief that the
practitioner and the patient miss the acute stage.
w Aphthous ulcers and focal atrophic candida lesions are other prime considerations. Early herpes
zoster is also possible.
Diagnosis:-
? The most common diagnostic method is the detection of HSV circulating antibodies for primary
herpetic gingivostomatitis.
? Cytological smears are useful for the demonstration of virus particles and multinucleated epithelial
cells.
? H & E staining of tissue biopsy specimen are also very useful for the diagnosis of virus particles.
? Tzanck smear is a rapid as well as cheap diagnostic test that can assure the presence of HSV
infection. Cells should be scraped from the base of the opened vesicle and presence of HSV infected
cells including multinucleated giant cells, eosinophilic intranuclear inclusion can be confirmed with
the staining of the smear.
30
The presence of intracellular HSV in formalin fixed routine specimen could be identified by murine
?
monoclonal antibody immunohistochemistry.
Histopathology:-
? Basically in all vesiculobullous lesions, specific features may be seen only in early lesions, so the
biopsy of long standing as well as ruptured lesions should be avoided.
? A punch, shave, or wedge tissue biopsy also be used for the demonstration of HSV infection and is
especially helpful when a suspicious lesion is old or atypical.
? In the herpetic infections, the vesicle initially found in prickle cell layer secondary to degenerative
alterations prompted by the virus.
? These alterations are present in two forms- ballooning degenration as well as reticular degeneration.
These degenerative alterations are present in cells infected with HSV1 and HSV2
? Ballooning degeneration is most commonly present in the floor of the vesicle and cause expansion
of the cell. The cell has an eosinophilic cytoplasm as well as single nucleus or multiple nuclei. H & E
stain usually show the margination of nuclear material because of its washed out action. These cells
lose their intercellular bridges and acantholytic process give rise to the vesicles. The vesicle may
“bottom out,” so that it has a subepithelial rather than an intraepithelial location.
? The reticular degeneration occurs mainly in the superior as well as lateral aspects of the vesicle,
there is intracellular edema, such that the
epithelial cells rupture, leaving strands from
the cell walls to form a multilocular vesicle.
Eosinophilic inclusions (Lipschutz bodies),
about 3 to 8 um in diameter, may be seen within
the nucleus. The underlying connective tissue
shows an inflammatory reaction of varying Figure 3.6: Herpes simplex. Altered epithelial Figure 3.7: Herpes Simplex. Intraepithelial vesicle
cells exhibiting ballooning degeneration, demonstrating acantholytic & virally altered
intensity. margination of chromatin, & multinucleation epithelial cells.
Management:-
Management of HSV infection basically includes both treatment as well as prevention of recurrence.
Neonates as well as immunocompromised individuals are at greater risk so the prevention of recurrences is
important and should be practiced in every patient.
1. Prevention:- prevention of transmission is the first step in the management of HSV infection.
Education of the patient is very important in every aspect such as nature of disease, transmission of disease
through sexual as well as asexual contact etc. General precautions include-
? The avoidance of direct contact with other persons who have active lesions.
? Use of condoms as well as other barrier methods during sexual intercourse especially for the
pregnant women who are seronegative and whose partner is seropositive to prevent primary HSV
infections during the third trimester of pregnancy.
? Various risk factors that precipitate recurrence such as stress, exposure to sunlight, fever,
menustration, trauma should be addressed to patients.
? In the hospital, especially the health care staff should follow the precautions for all patients possibly
infected with HSV. These precautions are- using gloves at all times, washing hands after the removal
of gloves, wearing gowns etc.
2. Treatment:- Treatment of HSV infections usually reduce severity, prevent complications as well
as reduce the frequency of recurrence. Current treatments include supportive therapy and oral, parenteral,
and topical antiviral medications-
31
Supportive therapy- supportive therapy generally includes pain control as well as rehydration.
?
This supportive therapy is chiefly indicated for children who are suffering from herpes labialis and
gingivostomatitis. Because of pain patients usually refuse to eat or drink, resulting in dehydration.
Pain can be controlled with local anesthetics as well as oral or IV rehydration can be given to the
patient.
? Oral antiviral medications- The first line oral antiviral medication for children is acyclovir.
Alternatives such as famciclovir, valacyclovir are available, but their use in children had not been
approved by the United States Food and Drug Administration as of July 2008. Oral acyclovir is
usually indicated in primary genital HSV infection when treatment is initiated within 6 days of
disease onset and can shorten the duration by 3 to 5 days.
? Parenteral antiviral medication- IV acyclovir therapy is indicated in patients who are suffering
from severe complications of HSV infection such as HSV encephalitis.
? Topical antiviral medications- Topical therapy is recommended in immunocompromised patients
because it has been shown to accelerate the healing of lesions.
Topical antiviral therapy such as acyclovir is not indicated for mucocutaneous HSV lesions because it
does not reduce the severity as well as duration of the infections in immunocompromised hosts.
Ophthalmic antiviral medications,including 1% tri? uridine, 0.1% iododeoxyuridine, and 3% vidarabine,
are indicated for treatment of ocular HSV and neonatal HSV with SEM involvement[25].
Herpangina and hand-foot-and-mouth disease (HFMD)

Herpangina as well as hand-foot-and-mouth disease (HFMD) are specific viral infections and are
most commonly seen in pediatric population. These are two common related clinical syndromes. They are
both caused mainly by enteroviral infections. Herpangina usually shows a stereotypical
vesicular/ulcerative enanthem on the oropharyngeal mucosa. HFMD usually shows a similar rash on the
oral mucous membranes, hands and feet. Both syndromes are highly contagious, usually benign, can cause
remarkable temporary discomfort for patients.
Etiopathogenesis:-
Herpangina and HFMD are both caused by enteroviral infection. The genus Enterovirus belongs to
the Picornaviridae family. Within the genus, there are 12 species, which contain the coxsackievirus,
echovirus, human rhinovirus, and poliovirus serotypes. The principal strains which cause HFMD are
coxsackievirus A16 and enterovirus A71 on the other hand herpangina is caused by Coxsackievirus A1-6, 8,
10, and 22. Enteroviruses are mainly small, non-enveloped, single positive-strand RNA viruses which are
proficient to survive in a wide PH range as well as in temperature up to 50 C. Humans are the only natural
host of these viruses. These viruses are mostly transfer in the host's body via fecal-oral route. Transmission
could also be due to ingestion of infected saliva, respiratory droplets, or direct contact with fluid from
vesicle. The incubation period is 3 to 5 days. Viral shedding can also occur in asymptomatic patients.
Clinical Features:-
Ø Herpangina is associated with a painful enanthem that usually present on the soft palate, tonsils as
well as on posterior pharynx.
Ø The vesicles further transform into tiny yellow or white ulcers with red rims. These ulcers occurs
within 24 hours after the appearance of vesicles. Ulcers are approximately 3 to 4 mm in diameter.
Ø Rash further leads to the onset of high fever approximately 105 F.
Ø Other symptoms include- headache, malaise, odynophagia, sore throat etc.
32
Oral lesions of Herpangina as well as HFMD
Ø
are almost similar, HFMD generally shows an
exanthema of macules and papules on the
palms of hands and soles which are usually
non-painful and grow after the appearance of
oral ulcers.
Figure 3.8: Hand-foot-and-mouth Disease. Figure 3.9: Hand-foot-and- mouth Disease.
Dehydration is most common complications of
Ø Multiple vesicles of the skin of the toe Multiple aphthous-like ulcerations of the
mucobuccal fold
HFMD and herpangina
w Early varicella, rubeola will also present with concomitant oral lesions and skin lesions.
w In addition, one must be concerned about a developing Stevens-Johnson syndrome variant of
erythema multiforme, although the course of hand-foot-and-mouth disease would be less rapid and
the lesions less painful.
Diagnosis:-
? HFMD as well as herpangina can be evaluated clinically. Any laboratory testing as well as imaging
is not necessary in mild cases. So the confirmatory testing is necessary in complicated diseases.
? Viral culture is the gold standard for confirmatory testing but it takes more time to get the results of
viral culture.
? On the other hand Polymerase chain reaction (PCR) is the most reliable method for the
demonstration of enteroviruses. Samples from Stool, mucocutaneous ulcers, vesicular fluid as well
as cerebrospinal fluid can be taken for PCR.
? Enzyme-linked immunosorbent assays (ELISA) can also be used for the demonstration of
enteroviruses but it is less sensitive than PCR[27].
Histopathology:-
The histopathology does not play an important role in the diagnosis of herpangina but the oral lesions
can form the intraepithelial vesicles. But in case of herpangina intraepithelial vesicles are formed, and
reticular degeneration may cause multilocular vesicles. Ballooning degeneration can occur In the deep
epithelium and the intraepithelial vesicles can become subepithelial. Inflammatory cells such as
neutrophils as well as chronic inflammatory cells can be seen in the connective tissue and vesicles. But the
multinucleated giant cells as well as the inclusion bodies are generally absent[11].
Treatment:-
There is no prophylaxis for either HFMD and herpangina, nor is there specific management.
Treatment is predominantly supportive. Pain is usually associated with this disease, so ibuprofen as well as
acetaminophen can be given to the patient for pain control in conjunction with adequate oral hydration.
Acyclovir can also show more rapid symptomatic improvement by reducing the duration of symptoms.
Patients with more complicated conditions such as encephalitis or myocarditis should be admitted to the
intensive care unit (ICU) for more effective treatment and monitoring. Intravenous fluid therapy should be
given to the dehydrated patients[27].
Acute lymphonodular pharyngitis

It is generally an infection of the pharynx and tonsils. It is commonly seen in children and adolescents.
33
Etiopathogenesis:-
Generally the viruses are responsible for this condition but group A Streptococci can also cause acute
pharyngitis in children and adolescents. Other bacterial agents that cause pharyngitis are- Group C
Streptococcus (5% of total cases), C. pneumoniae (1%), M. pneumoniae (1%) and anaerobic species. Viral
agents that cause pharyngitis are- Rhinovirus, Coronavirus and Adenovirus account for the 30% of the total
cases, Epstein Barr virus for 1%, Influenza and Parainfluenza virus for about 4%. The infection is usually
transmitted through respiratory secretions and the incubation period is 2-5 days. Infection is more
communicable during the acute phase of the disease which generally ceases after 24 hours of antibiotic
therapy.
Clinical Features:-
Ø Common clinical manifestations are sore throat, fever, headache, red pharynx, enlarged tonsils
which are covered with a yellow, blood-tinged exudates.
Ø Soft palate as well as the tonsillar pillars are more commonly involved sites. There may be
petechiae on the soft palate and posterior pharynx.
Ø Anterior cervical nodes are swollen and shows enlargement.
Ø Gastrointestinal symptoms include- vomiting, abdominal pain.
Ø Oral lesions are raised, discrete, whitish or yellowish to dark pink solid papules or nodule,
surrounded by a narrow zone of erythema, most commonly present on uvula, soft palate, anterior
pillars and posterior oropharynx.
Ø Complications of the infections are further divided into- suppurative and nonsuppurative.
Ø Suppurative complications include- cervical lymphadenitis,
peritonsillar abscess, retropharyngeal abscess, otitis media,
mastoiditis and sinusitis. These type of complications can be
reduced by the use of antibiotics.
Ø Non-suppurative complications are- acute rheumatic fever (ARF),
acute post-streptococcal glomerulonephritis, Sydenham chorea,
reactive arthritis and Paediatric Autoimmune Neuropsychiatric Numerous Figure 3.10: Acute Lymphonodular Pharyngitis.
darkpink & yellow lymphoid aggregates.
Diseases.
The differential diagnosis must include herpangina, although lesions of lymphonodular pharyngitis
are not vesicular and do not ulcerate.
Diagnosis:-
The diagnosis generally depends on throat culture. Culture is the gold standard for diagnosis but
needs 18-24 hours of incubation at 37 C, causing a delay in diagnosis. Rapid antigen detection test is also
useful for the diagnostic purpose. Sensitivity as well as specificity of this test is 81% and 98% respectively.
Histopathology:-
The papules or nodules consist of hyperplastic lymphoid aggregates. In some cases the overlying
epithelium show inclusion of bodies, which in some instances are intranuclear but in others, cytoplasmic.
Treatment:-
No specific treatment is necessary as the disease is self-limiting. Antibiotic treatment is not routinely
34
recommended, due to the prevalent viral etiology of pharyngitis. However, when antimicrobial treatment is
indicated, it is important to choose a good therapeutic option. According to many authors and national
guidelines, penicillin is the first choice treatment. Penicillin V is the drug of choice for the treatment of this
disease. Other antibiotics such as ampicillin, amoxicillin, clindamycin, azithromycin, clarithromycin can
be given to the patients who are allergic to penicillin[28].
Varicella
Varicella-zoster virus is the herpes virus that causes varicella and zoster. Varicella usually referred as
chicken-pox, results from primary infection with the virus. Zoster also known as shingles, results from
reactivation of the latent virus. Varicella is more commonly seen in pediatric population, on the other side
zoster is more common in adults.
Etiopathogenesis:-
Chickenpox is caused by the varicella zoster virus (VZV), which is a type of herpes virus. The VZV,
like the HSV, is transmitted initially by direct water droplet transmission. The VZV penetrates the
epithelium and becomes engulfed by macrophages and other phagocytes. The virus proliferates within the
phagocytes, after proliferation virus leave the cell and disseminate via the circulation, which is referred as
incubation phase. The subsequent viremia associated dissemination implants viruses throughout the skin,
producing the characteristic skin lesions. IgM, IgG antibody production, T cell mediated reaction with
interferon production are usually associated with the host defense mechanism. This mechanism mainly
helps in the healing of the lesion and dissipation of the symptoms. VZV can cross the blood brain barrier and
remain dormant in the geniculate ganglion. When the immune system compromised, virus migrate outward
from the ganglia, enter the nerve endings to produce the lesions of herpes zoster.
Sources of significant exposure to varicella or zoster-

? Continuous household contact
? Playmate contact >I h of indoor play
? Hospital contact - same two- to four-bed room, adjacent beds in a large ward, prolonged face-to-face
contact with an infectious staff member or patient.
? Newborn contact- neonate whose mother had onset of varicella less than 5 days before delivery or
within 48 hours after delivery.
Clinical Features:-
Ø Primary infection of Varicella commonly occur in children, aged 3-6 years who are not immunized
at the time of their first exposure to the virus and is extremely contagious.
Ø Vericella is commonly present as a generalized, vesicular eruption that are irrelevant to any
systemic manifestations.
Ø In the early stage, lesions are more commonly present on the scalp and trunk. As the disease
progress, lesion spread centrifugally over the body.
Ø Apart from the skin, lesions are present on the other sites such as- mucous membranes of the mouth,
conjunctivae, vagina, and urethra.
Ø Lesions are generally small in size and superficial, pruritic in appearance.
Ø In early stages, lesion appear as a red papule, as the disease progess the lesion usually turns into
clear, teardrop-shaped vesicles on an erythematous base. After 24 hours, fluid in the vesicle gives
cloudy appearance, vesicles are easily broken and scab formation begins.
35
ØSerious systemic manifestations are usually not seen in the varicella but temperature elevation can
occur during early stage of the disease.
Other common features that a healthy children usually shows are- malaise, fever, anorexia,
Ø
headache, sore throat.
Intraoral as well as perioral vesicles occur more commonly on the vermilion border of lip and
Ø
palate, followed by buccal mucosa. Oral lesions are usually painless but the prevalence as well as
number of oral lesions generally depends on the severity of the infection.
Complications:- Complications of varicella usually involve the skin, central nervous system,
Ø
respiratory system-
? Skin complications are secondary staphylococcal or streptococcal infection, bullous and
hemorrhagic varicella, localized gangrene, necrotizing fasciitis, and purpura fulminans.
? Central nervous system complications are- Encephalitis, Reye's syndrome, aseptic meningitis,
transverse myelitis, and Guillain-Barre syndrome.
? Respiratory complications are- Viral and
bacterial pneumonia and upper respiratory
tract infections, especially otitis media.
? Other complications are- keratitis,
conjunctivitis, uveitis, iritis, arthritis,
appendicitis, glomerulonephritis,
myocarditis, Henoch-Schonlein purpura,
orchitis, thrombocytopenia, bleeding
diatheses, and hepatitis. Figure 3.11: Varicella. Infant with Figure 3.12: Varicella. White opaque vesicles on the hard palate
diffuse erythematous & vesicular rash.
w The main differential diagnoses of concern in a child with painful skin lesions with accompanying
fever are the other childhood diseases such as rubeola and rubella.
w A developing Stevens-Johnson form of erythema multiforme is another possibility.
w Less common today, scarlet fever and, if in the summer, hand foot and mouth disease may also show
skin rashes, associated fever and constitutional symptoms.
Diagnosis:-
w First step of varicella diagnosis is proper history taking and clinical findings.
w Apart from this, many laboratory tests are available for the confirmation of varicella-zoster
infection.
w In the healthy individuals, virus can be isolated from vesicular fluid for the first three to four days
following the onset of varicella.
w In immunocompromised individuals virus can be isolated for a longer period of time.
w üDirect electron microscopy and immunofluorescence staining can be used for the demonstration
of the virus.
w A Tzanck smear, prepared from the scraping of the base of a lesion, may also be used for diagnosis.
A positive Tzanck smear, demonstration of multinucleated giant cells, is a diagnostic feature of
herpes virus.
w Serum can be analyzed to detect an increase in varicella-zoster antibody. Antibody testing also may
be used to determine varicella susceptibility.
36
Histopathology:-
Ø The histopathological features of skin and mucous membrane are the same for the three infections
caused by herpes virus: Herpes simplex, varicella, herpes zoster. As in all vesiculobullous lesions,
the specific features may be seen only in early lesions; biopsy of long standing and ruptured lesions
should be avoided.
Ø In these herpetic infections, the vesicle initially present in the prickle cell layer secondary to
degenerative changes induced by the virus.
Ø Ballooning degeneration can be seen mainly in the floor of the vesicle, causes expansion of the cell.
Ø The cell has an eosinophilic cytoplasm and a single nucleus or multiple nuclei. The nucleus is
enlarged and may have an irregular contour. With H&E, it has a washed out, steelgray appearance
and shows margination of the nuclear material.
Ø These cells lose their intercellular bridges, and this acantholytic process creates the vesicle.
Ø These cells may be identified by cytologic smears. Subepithelial vesicles are predominant rather
than an intraepithelial vesicles.
Ø In reticular degeneration, which occurs essentially in the superior
and lateral aspects of the vesicle, there is intracellular edema such
that the epithelial cells rupture, leaving strands from the cell walls to
form a multilocular vesicle.
Ø Eosinophilic inclusions (Lipschutz bodies), about 3 to 8 um in
diameter, may be seen within the nucleus. Varying degree of Figure 3.13: Varicella zoster—balloon degeneration of
epithelial cell
Inflammatory cell infiltration is present in connective tissue.
Treatment:-
The treatment of vericella includes- supportive therapy and antiviral therapy.
? Supportive therapy is useful in the treatment of both healthy and immunocompromised children
with varicella. This therapy includes hydration, analgesics, antipyretics, rest during the course of the
disease.
? Antiviral therapy is useful for the immunocompromised individuals and HIV infected individuals.
Intravenous acyclovir can be given to immunocompromised individuals and pregnant women in the
third trimester. If the lesions are not responding to acyclovir, foscarnet can be administered.
? Varicella zoster immune globulin (VZIG) is effective in preventing varicella in exposed, susceptible
individuals with no natural or vaccine derived immunity. VZIG is not used to treat an active case of
varicella. Because VZIG binds directly to live attenuated virus in the varicella vaccine, so their
combined use is prohibited[29].
Measles (Rubeola)
The measles virus is a paramyxovirus and belongs to the morbillivirus genus. It is an acute, infectious,
highly contagious disease that frequently occurs in children.
Etiopathogenesis:-
Measles virus mainly cause infection in the human body via three stages. First stage includes the entry
of the virus into the susceptible host. Second stage includes the systemic dissemination of the virus. Third
stage includes the transmission of new virus particles via air into the body of the host.
? Measles usually spread through respiratory droplets. During first stage of transmission, virus enter
into a susceptible host via respiratory tract, where it binds to DC-SIGN+ DCs(Dendritic Cell-
37
Specific Intercellular adhesion molecule-3-Grabbing Non-integrin) or infects CD150+ myeloid or
lymphoid cells in the mucocilliary epithelium or the alveolar spaces. Virus can also enter through
conjunctiva, which is rich in DCs and CD150. Viruses which are deposited in the conjunctiva,
further enter the spaces between cornea and eyelids, where they can infect myeloid and lymphoid
stem cells. MV particles inhaled into the respiratory tract and, can either infect DC-SIGN+ dendritic
cells in the upper respiratory tract, with dendrites protruding into the respiratory mucosa, or
dendritic cells or macrophages in the alveolar lumina of the lower respiratory tract. The infected
immune cells subsequently migrate to nearby tertiary lymphoid tissues and draining lymph nodes.
In the second stage of MV infection, systemic dissemination occurs. The MV-infected myeloid cells
?
migrate to the draining lymph nodes, where they transmit the virus to CD150+ lymphocytes
(predominantly B-cells and memory CD4+ and CD8+ T-cells). During viremia infected cells enter
the circulation and migrate systemically to various organs and tissues, where the infection is further
amplified. Infection of skin-resident immune cells results in virus transmission to nectin-4+
epithelial cells, few days later, depletion of immune cells in lymphoid organs and tissues results in
transient immune suppression. MV-specific T-cells infiltrate the skin where they clear the infected
cells, which results in the typical measles skin rash.
The third stage of MV infection includes the transmission of new MV particles via the air. Nectin-4+
?
epithelial cells in the upper and lower respiratory tract epithelium produce new virus particles and
release them into the mucus lining the lumen of the respiratory tract. Epithelial damage in infected
lymphoid tissues, such as the tonsils, releases virus particles produced by lymphocytes into the
upper respiratory tract. Epithelial damage in the lower respiratory tract induces cough, enhancing
the discharge of aerosols containing MV particles[30].
Clinical Features:-
Ø There are three stages of infection, with each stage lasting 3 days, hence called as 9-day measles.
Ø In the early phase of the disease, patient generally experience low-grade fever, cough, photophobia
as well as coryza. Patient also show some gastrointestinal symptoms. These initial symptoms are
called prodromal symptoms.
Ø The child generally appear ill and irritable. Other common features are diffuse pharyngitis,
bilateral cervical lymphadenitis.
Ø The rash usually appear after 3 to 5 days of the disease. Common sites of rashes are- facial skin,
behind the ears, and the rashes further spread to the chest, trunk, extremities.
Ø At the later stages, rashes will convert into pinhead sized papules, which may further coalesce to
form a more uniform erythema over a large area.
Ø Oral Manifestations- Oral lesions of measles are known as koplik spots. These spots usually
appear during the prodromal phase. Koplik spots appear as flat, erythematous macules with tiny
white “salt crystal” centers. They will characteristically precede the skin rash by 1 or 2 days.
Koplik spots may also be seen on the conjunctiva. At this point, infection is highly contagious.
Ø Complications- During the course of illness, various complications can occur which can involve
the different organs. These are- Encephalitis
which leads to residual brain damage,
secondary bacterial infections as well as
autoimmune reaction.
Ø Case fatality rates are highest among children
Figure 3.14: Rubeola. Erythematous maculo Figure 3.15: Rubeola. Numerous blue-white Koplik
younger than 5 years. papular rash of the face. spots of buccal mucosa.
38
w Early varicella or chickenpox- clinical picture of the measles is somewhat similar to the varicella.
Oral lesions followed by a skin rashes are also present in varicella.
w Stevens-Johnson syndrome is a variant of erythema multiforme.
w Rubella
w Scarlet fever
w In rubella as well as scarlet fever, both have an oral and pharyngeal erythema but no true koplik
spots.
Diagnosis:-
? Adequate clinical history of the patient is the first step of the diagnosis.
? Throat swabs as well as serum samples can be collected from the patients for further laboratory tests.
? Laboratory confirmation includes the detection of rise in antibody titers in serum samples. The most
commonly used tests are- immunofluorescent antibody and complement fixation tests.
? Other investigations includes ELISA, RT-PCR which are useful for the detection of virus RNA,
Complete peripheral blood cell count, C-reactive protein (CRP), procalcitonin (PCT), serum
biochemical tests, blood culture, bacteria culture, and antigen test of respiratory pathogens of
nasopharyngeal aspirate or sputum and chest X-ray are also useful in the field of diagnosis[31].
Histopathology:-
? The infected epithelium of skin and mucosa shows intracellular vacuolization, hyperkeratosis, and
ultimately necrosis.
? Connective tissue show hyperemia as well as edema, perivascular
lymphocytes and macrophages are also present in connective tissue.
Koplik spots show more epithelial necrosis and infiltration by
neutrophils.
? The characteristic multinucleated giant cells of Warthin-Finkeldey
are seen in hyperplastic lymphoid tissues, including tonsils and
adenoids. They are usually present in the prodromal phase and
Figure 3.16: Rubeola. Histopathologic section of pharyngeal
disappear as antibody titers rise. These large cells have eosinophilic multinucleated
tonsil demonstrating lymphoid hyperplasia with scattered
giant cells.
cytoplasm and centrally placed clusters of darkly stained nuclei[11].
Treatment:-
? Measles is a self-limiting disease, duration of this disease is approximately 2 weeks. So the child
should be isolated because the disease is highly transmissible to those people who do not have either
natural or vaccine acquired immunity.
? Supportive care can be provided to the patient. It generally includes the rest, hydration, analgesics
as well as antipyretics, vitamin A therapy.
? Appropriate antibiotics can be prescribed to the patients with secondary bacterial infections.
? To prevent the spread of measles worldwide, individuals should receive timely recommended age-
appropriate dose of measles vaccine(MMR). The ? rst dose can be administered at 12 months or
older, with a second dose provided no sooner than 28 days later but more commonly administered at
ages 4 to 6 years.
? Appropriate protection can be attained by the administration of immunoglobulin through
intramuscular or intravenous route within 6 days of exposure to a patient with measles.
39
According to WHO, the children who are suffering from severe acute measles and require
?
hospitalization, should receive the 2 days course of vitamin A.
Rubella (German Measles)

It is a contagious viral infection, best known by its unique red rashes. Rubella virus is a single stranded
RNA virus, belongs to the Togaviridae family and is the sole member of the Rubivirus genus. It is the
causative agent of rubella disease or so-called “German measles.”
Etiopathogenesis:-
Humans are the only known reservoir of rubella virus. The disease can be transmitted via direct or
droplet contact with respiratory secretions, person to person transmission is very common. Rubella virus
usually multiply in the cells of respiratory epithelium and move to the ymph nodes this is followed by
viremic spread to target organs. Common target organs are spleen as well as lymph nodes, spread of the
virus to the target organs can cause the secondary viremia. Incubation period of the virus is 7 to 10 days, so
during this time virus can be discovered in the blood as well as in respiratory secretions of the patients.
Viremia vanishes shortly after the onset of rash; it is also linked to the emergence of circulating neutralizing
antibodies. However, virus shedding from the respiratory tract may continue for up to 28 days following the
onset of rash. Rubella infection during first 3 to 4 months of pregnancy can invade the placenta and cause
the infection in the fetus. Development of infection in the fetus generally depends on the gestational age of
the mother. There are approximately 40 to 60 percent chances of developing infection in patients if the
mother is infected during the first 2 months of pregnancy. This risk of the infection will reduce to
approximately 30 to 35 percent if the mother will be infected during the 3 months of pregnancy. The risk of
the infection in fetus is least or approximately 10 percent during the fourth month of gestation.
During fetal infection, the virus can proliferate in the body of the fetus and can damage any organ system. In
addition, rubella infection induces angiopathy of early placental and embryonic tissues, causing
obstruction with the fetal blood supply and successive compromised growth and/or deformities in the fetus.
In the congenitally infected fetus and infant, virus persistence occurs in the presence of neutralizing
antibodies; immunological tolerance does not occur.
Clinical Features:-
Ø Rubella or german measles is most commonly present in children and young adults.
Ø Initial clinical presentation of german measles generally show fever, mild malaise as well as
cervical lymphadenitis.
Ø Initially the fine reddish maculopapular rashes are present on the face, and extend to the trunk and
extremities in the later stage of the disease, erythema can be seen on the palate and throat.
Ø Rashes usually fades after 24 to 36 hours, disappear after 3 to 5 days of disease. No true koplik spots
are present in german measles as in the rubeola.
Ø The general intensity of symptoms in rubella is less than that in rubeola.
Ø Infection of german measles can involve the posterior lymphatic chains and give rise to
suboccipital lymphadenopathy.
The facial rash and palatal erythema will suggest rubeola(measles). The clinician must examine the
oral lesions carefully to assess the presence or absence of true koplik spots. In addition, scarlet fever,
infectious mononucleosis, and adenovirus pharyngitis will present with a similar general picture.
40
Diagnosis:-
? Adequate clinical history of the patient is the first step of the diagnosis. Virus can be detected in
respiratory secretions, urine, cerebrospinal fluid and blood.
? Laboratory diagnosis generally includes the serological testing or detection of IgM antibodies in
serum, which indicates recent rubella infection. Presence of IgG antibodies indicates the immunity
of healthy individuals to rubella.
? Antibodies can be detected by various methods such as neutralization test, hemagglutination
inhibition, ELISA, and indirect immunofluorescent immunoassay.
? Immunoperoxidase staining assays is an another useful method for the detection of viruses in an
inoculated cultures.
? Detection of congenital rubella in the neonates depends on the virus isolation or serological testing,
which is helpful for the detection of maternal IgG antibody as well as neonatal IgM antibodies in
affected neonates.
? Amplification of rubella virus RNA directly from a clinical specimen using RT-PCR is now
common. Assays that can reliably detect 3 to 10 copies of rubella virus RNA are necessary since
many specimens have small amounts of rubella RNA. Real-time and nested RT-PCR assays often
have this level of sensitivity.
Histopathology:-
Rubella is a mild, transient disease in which histology does not have a diagnostic role.
Treatment:-
The patient requires no specific therapy. Rubella is a short duration, self limiting viral disease.
Supportive care can be provided to the patient. Supportive care generally includes the rest, hydration,
analgesics as well as antipyretics. It is mandatory to isolate the infected individuals from nonimmunized
women of child bearing age. Apart from the supportive care, live attenuated rubella vaccines for the
prevention of rubella is also available. It is administered subcutaneously. Two doses are recommended. The
first may be given starting at 12 months. Most commonly, the initial dose is administered as a combined
vaccine containing attenuated mumps and measles viruses as well. The second dose is given either at school
entry or at entry to middle school or high school. Suggested additional strategies for rubella control include:
(1) Evidence of rubella immunity as a prerequisite for college entry.
(2) Requiring vaccination of susceptible health care and military personnel.
(3) Rubella prevention and control programs in correctional institutions.
(4) Motivating persons in religious groups who do not seek health care to accept vaccination.
(5) Vaccination of young adults visiting in or emigrating to the another countries in which rubella
vaccine is not used routinely.
(6) Vaccination of susceptible women after childbirth, miscarriage, or abortion.
Immunoglobulin is not very effective in the management of rubella, so it is not routinely
recommended for prophylaxis of rubella in early pregnancy[32].
Mumps
The mumps virus is a single-stranded, non-segmented, RNA virus belongs to Paramyxoviridae
family. Mumps is one of the older described infectious diseases, first documented by Hippocrates in the
fifth century BC. Before widespread use of mumps vaccines, mumps was a common disease of childhood,
with nearly everyone having serologic evidence of prior infection by age 15.
41
Etiopathogenesis:-
Mumps virus is transmitted via respiratory droplets, person to person transmission is also common.
MuV generally infect the upper respiratory tract and after the infection
of upper respiratory mucosa, infection extend to regional lymph nodes
and resulting in viremia during the early acute phase. Sub-maxillary,
sub-mandibular as well as sub-lingual glands can also be involved.
Virus usually replicates in salivary glands and local lymphoid tissue at
7-10 days of infection. On 15 day, virus spreads to spleen and
secondary lymphoid tissues. After 18 day, virus spreads throughout
the body to the brain, thyroid, respiratory tract, pancreas, testes,
ovaries and bladder.
Clinical Features:-
Ø Approximately, one third to one half of MuV infections are asymptomatic or result in only mild
respiratory symptoms.
Ø There is no specific sex predilection and is seen in children and elderly.
Ø Initial phase or prodromal phase of disease is characterized by fever, headache, malaise, myalgia.
Ø The most characteristic feature of mumps is salivary gland swelling, typically the parotid glands,
which forms the basis of a clinical diagnosis. A day after the initial symptoms appear, reports of
earache and tenderness of the parotid glands are common.
Ø An early acute phase of the disease is characterized by typical parotitis, which lasts from a few days
to 1 week. Parotitis is usually bilateral in this disease which leads to odema of parotid gland.
Ø During the established acute phase, orchitis, meningitis or encephalitis may appear.
Ø Oral Manifestations:
? Enlargement as well as redness of the opening of the stensen duct of the affected gland.
? Trismus generally leads to difficulty in eating and speaking.
? Involvement to submandibular and sublingual glands leads to the
swelling of the tongue.
Ø Other rare complications include- Cerebellar ataxia, transverse
myelitis, ascending polyradiculitis, a poliomyelitis-like disease,
arthropathy, autoimmune haemolytic anaemia, thyroiditis,
thrombocytopenia, hepatitis and retinitis and corneal endotheliitis. Figure 3.17: Mumps. Bilateral parotid enlargement
w The diseases that can cause swollen, tender parotid glands include bacterial parotitis, another viral
parotitis such as coxsackie A virus, cytomegalovirus, echovirus and parainfluenza viruses and
obstructive parotitis, usually from mucous plugs in stensen duct.
w Other conditions such as sialosis, sarcoidosis, sjogren syndrome, bulimia, lymphomas, among
others, produce parotid gland enlargement, but none of these will be associated with marked
tenderness and fever.
Diagnosis:-
The diagnosis of the mumps usually depends on the isolation of the paramyxovirus from saliva.
Serum analysis is also very useful for the demonstration of raised mumps antibody titers. Laboratory tests
usually help in the detection of lymphocytosis, serum amylase level.
42
Histopathology:-
Biopsy is not customarily used to diagnose mumps. However, the parotid gland will show swelling of
acinar cells with vacuolation of the cytoplasm and considerable interstitial edema with infiltration by
lymphocytes and plasma cells. Ductal dilation occurs, and desquamated epithelium may be found within
the lumen.
Treatment:-
Mumps, including complications involving other organs, is self-limiting. No specific therapy is
given other than supportive care, which usually consists of bed rest, antipyretics, analgesics and hydration.
Orchitis, if it develops, is treated with testicular elevation and ice. Meningitis, if it develops, may require
corticosteroids, elevation of the head, and induced hyperventilation to combat cerebral edema[33].
Heck's Disease
Multifocal epithelial hyperplasia is another name of heck's disease. It is rare, contagious,
asymptomatic and benign disease affecting the oral mucosa.
Pathogenesis:-
This disease is virally induced by human papillomavirus, HPV subtypes 13,32, 1, 6, 11 and 16 are
associated with this disease. Apart from HPV infection other etiological factors such as genetic
predisposition, nutritional deficiencies and environmental factors like poverty and lack of hygiene, role of
immunosuppression are also associated with this disease.
Clinical Features:-
Ø Heck's disease presents with white, sessile, raised mucosal patches and nodules which are
approximately 1.0 and 1.5 cm in diameter.
Ø It is more commonly seen in children and young adults, whereas elderly patients exhibit few or
even single lesions, which tend to be flat and popular and this disease is present in ethnic and racial
groups.
Ø Lesions are most commonly present on labial
mucosa, buccal mucosa and tongue, palate,
gingival. The lesions are usually painless and
do not blanch and surrounding mucosa is
normal in appearance and textures.
Figure 3.18: Heck's disease. Multiple, flattopped Figure 3.19: Heck's disease. The lesions may
Ø Intraoral lesions usually show multiple papules and nodules of normal coloration are demonstrate a papillary surface change and
seen on the lower lip of a child. paleness, as demonstrated on this child's tongue
coalescent papillary projections.
w The clinical appearance of focal epithelial hyperplasia resembles cluster of papillomas. Therefore,
it is often confused with multiple squamous papillomas or condyloma accuminatum.
w A confluence or tightly grouped cluster will resemble a verrucous carcinoma or even a squamous
cell carcinoma at times.
w Lesions that are more widespread and nodular may resemble that oral submucosal granulomas seen
in Crohn disease.
43
Diagnosis:-
Biopsy is a gold standard for the detection of focal epithelial hyperplasia. Edge of the surrounding
normal appearing should include in biopsy, which will best show the contrast in epithelial thickness and the
degree of hyperkeratosis.
Recent advancements in molecular biology techniques for HPV testing include light microscopy;
electron microscopy; nonamplified molecular techniques like in situ hybridization, southern blot, and dot
blot hybridization; target amplification using PCR; signal amplified techniques like hybrid capture
technology; and gene expression using DNA microarrays.
Histopathology:-
The epithelial hyperplasia consists of acanthosis with broadening and elongation of rete ridges, which
tend to anastomose and other rete ridges form clubbing called “bronze age battle axe” or “clubs. Virus
particles have been demonstrated within the nuclei and cytoplasm of the prickle cells, which can be
detected with the help of immunohistochemistry. Virally altered cells such as koilocytes with clear
perinuclear halos are present in the spinous layer. Atypical mitotic figures or mitosoid figures can also be
seen. The connective tissue is vascular and may contain a mild chronic inflammatory cell infiltrate.
Figure 3.20: Prominent acanthosis of the epithelium with broad and elongated rete ridges. Figure 3.21: Mitosoid cells (arrows) contain altered nuclei in this otherwise mature
The slightly papillary surface alteration noted here may or may not be present. and welldifferentiated stratified squamous epithelium.
Treatment:-
No treatment is indicated. Spontaneous involution over 3 years is the most common outcome,
especially in children. However, longer periods of time up to 30 years have also been reported. If the lesions
are a concern to the patient, accessible and few in number, excision is reasonable[34].
44
4 Fungal Infections
Candidiasis
?
Candidiasis
O
ral candidiasis is the most common opportunistic infection affecting the oral mucosa. Also
known as oral thrush. It is divided into primary and secondary infections. The primary
infections are restricted to the oral and perioral sites, whereas secondary infections are
accompanied by systemic mucocutaneous manifestations[35]. Species of oral Candida are: C. albicans, C.
glabrata, C. guillermondii, C. krusei, C. parapsilosis, C. pseudotropicalis, C. stellatoidea, C. tropicalis.
Classification of oral candidiasis:
Primary form includes:

? Acute forms
w Pseudomembranous
w Erythematous
? Chronic forms
w Hyperplastic
w Nodular
w Plaque like
w Erythematous
w Pseudomembranous
? Candida-associated lesions
w Denture stomatitis
w Angular cheilitis
w Median rhomboid glossitis
? Keratinized primary lesions superinfected with candida
w Leukoplakia
w Lichen planus
w Lupus erythematosus
Secondary form includes:

? Oral manifestations of systemic mucocutaneous candidiasis as a result of diseases such as thymic
aplasia and candidiasis endocrinopathy syndrome.
Etiopathogenesis:-
Lesions are caused by the yeast, Candida albicans. The yeast infects the epithelial cells through the
production of lipases, mannose, C3d receptors, mannoprotein and saccharins. Certain local and systemic
45
factors have the capacity to convert Candida from the normal commensal flora (saprophytic stage) to a
pathogenic organism (parasitic stage). Yeast cell adhere to host cell surfaces by the expression of adhesins,
this contact further triggers the yeast to hyphae transition and directed growth via thigmotropism. The
expression of invasins mediates uptake of the fungus by the host cell through induced endocytosis.
Adhesion, physical forces as well as secretion of fungal hydrolases has been proposed to assist the second
mechanism of invasion i.e. fungal-driven active penetration into host cells by breaking down barriers. The
attachment of yeast cells to abiotic (catheters) or biotic (host cells) surfaces can give rise to the formation of
biofilms with yeast cells in the lower part and hyphal cells in the upper part of the biofilm. Phenotypic
switching has been proposed to manipulate antigenicity and biofilm formation of Candida albicans. In
addition to these virulence factors, several fitness traits influence fungal pathogenicity. They include a
robust stress response mediated by heat shock proteins, auto-induction of hyphal formation through uptake
of amino acids, excretion of ammonia and concomitant extracellular alkalinization, metabolic flexibility
and uptake of different compounds as carbon and nitrogen sources, and uptake of essential trace metals.
Local predisposing factors for oral candidiasis and Candida-associated lesions:

? Denture wearing
? Smoking
? Atopic constitution
? Inhalation steroids
? Topical steroids
? Hyperkeratosis
? Imbalance of the oral microflora
? Quality and quantity of saliva
General predisposing factors for oral candidiasis:
? Immunosuppressive diseases
? Impaired health status
? Immunosuppressive drugs
? Chemotherapy
? Endocrine disorders
? Hematinic deficiencies
Clinical Features:-
Ø Pseudomembranous Candidiasis
This form of candidiasids is most commonly seen in infants and young adults, but it can also seen in
older individuals. It is most common form of Candidiasis that affect patients medicated with antibiotics for
long period of time, immunosuppressant drugs, or a disease that suppresses the immune system.
Infection presents as soft, white, slightly elevated plaques, which
resembles milk curd, consist chiefly of tangled masses of fungal hyphae with
intermingled desquamated epithelium, keratin, fibrin, necrotic debris,
leukocytes, and bacteria. Lesion most commonly occurs on the buccal
mucosa and tongue, but may also seen on the palate, gingiva, and floor of the
mouth. The white plaque can be scraped off, leaving either a relatively
normal appearing mucosa or an erythematous area. Figure 4.1: Pseudomembranous candidiasis
46
ØChronic Hyperplastic Candidiasis (candidal leukoplakia)
Lesion appears as firm, white persistent plaque which cannot be
scraped off. It usually occurs on lips, tongue, and cheeks and appear similar to
leukoplakia. These lesions may be homogeneous or speckled (nodular) and
persists for periods of years. These lesions resolve completely following
antifungal therapy. Figure 4.2: Chronic Hyperplastic Candidiasis
ØErythematous Candidiasis
It was earlier known as atrophic candidiasis. The lesion has a diffuse
border which helps to distinguish it from erythroplakia, which has a sharper
demarcation. The infection predominantly involves the palate and the
dorsum of the tongue. It may occur following the pseudomembranous
candidiasis but may also emerge de novo.
Figure 4.3: Erythematous Candidiasis.
Severe presentation of central papillary atrophy
Ø Chronic Plaque-Type and Nodular Candidiasis
The term chronic plaque type of oral candidiasis replaces the older term, candidal leukoplakia. Both the
chronic plaque-type and nodular candidiasis have been associated with malignant transformtion, but the
role of yeasts in oral carcinogenesis is unclear. It has been hypothesized that it acts through its capacity to
catalyze nitrosamine production.
Figure 4.4: Chronic plaque-type candidiasis Figure 4.5: Chronic nodular candidiasis in the left retrocommissural area
w Leukoplakia
w lichen planus
w lupus erythematosus.
They may appear similar to chronic hyperplastic candidiasis clinically but may not regress with
antifungal treatment as does the latter[36].
Diagnosis:-
? Staining Method-
Periodic acid-Schiff (PAS) or the Grocott-Gomori methenamine silver (GMS) stain, can be used to
identify candida hyphae and yeasts. Both techniques stain carbohydrates, present in large amount in fungal
cell walls; the organisms appear bright-magenta with the PAS stain (Fig 7.6) or black with the GMS stain.
47
Hyphae or pseudo-hyphae (which are essentially elongated yeast cells) of varying length may show
branching, can be observed.
A 10% to 20% potassium hydroxide
(KOH) preparation may also be used to rapidly
evaluate specimens for the presence of fungal
organisms. With this technique, the KOH lyses
the background of epithelial cells, allowing the
more resistant yeasts and hyphae to be
visualised. In addition, the organisms may be
cultured in a variety of media, including blood
agar, cornmeal agar and Sabouraud's broth,
Pagano-Levin agar, Imprint culture technique,
Salivary culture techniques helps in Figure 4.6: Cytologic preparation demonstrates tubular-appearing fungal hyphae and ovoid yeasts of Candida
establishing the diagnosis albicans. (Periodic acid-Schiff [PAS] stain.)
Serological tests
?
v
Serological tests for invasive candidiasis-
v
Detection of antibodies
v
Slide agglutination
v
Immunodiffusion
v
Phytohemagglutination
v
Coelectosynersis
v
Immunoprecipitation
v
A and B immunofluorescence
v
Nonspecific Candida Antigens
v
Latex agglutination
v
Immunobloting
v
Cell Wall Components
v
Cell Wall Mannoprotein (CWMP)
v
B- (1,3) - D- glucan
v
Candida Enolase Antigen testing.
Histopathological Feature:-
The histopathologic pattern of oral candidiasis may vary slightly, depending on which clinical form of
the infection has been submitted for biopsy. The common features include an increased thickness of
parakeratin on the surface of the lesion along with elongation of the epithelial rete ridges. Typically, a
chronic inflammatory cell infiltrate can be seen in the connective tissue immediately subjacent to the
infected epithelium, and small collections of neutrophils (microabscesses) are often identified in the
parakeratin layer and the superficial spinous cell layer near the organisms. The candidal hyphae are
embedded in the parakeratin layer and rarely penetrate into the viable cell layers of the epithelium unless the
patient is extremely immunocompromised.
48
Figure 4.7: Medium-power photomicrograph shows parakeratosis, neutrophilic microabscesses (arrow), Figure 4.8: High-power photomicrograph shows the tubular hyphae of Candida albicans embedded
a thickened spinous layer, and chronic inflammation of the underlying connective tissue associated in the parakeratin layer. (Periodic acid-Schiff [PAS] stain.
with long-standing candidal infection of the oral mucosa.
Treatment:-
In all forms of candidiasis, a significant requirement for treatment is reversal or withdrawal of the
associated underlying factor when possible. Specific therapy for mild oral disease include nystatin oral
suspension. Other antifungal agents such as clotrimazole, amphotericin B, and miconazole can also be used
in chronic well-established cases of candidiasis[11].
49
5 Genetic Diseases
Hereditary epidermolysis bullosa
?
Juvenile dermatitis herpetiform
?
Kawasaki disease
?
Familial acanthosis nigricans
?
Hereditary Epidermolysis Bullosa
I nherited epidermolysis bullosa (EB) is a heterogeneous group of genetic disorders characterized

by the inherited blistering mucocutaneous lesions.
Etiopathogenesis:-
There is a specific defect in the attachment mechanisms of the epithelial cells, either to each other or
to the underlying connective tissue. Depending upon the defective mechanism of the cellular cohesion,
there are four broad categories:
? Simplex- There is a specific mutations in the genes encoding keratin 5 and keratin 14, which is
responsible for the simplex type.
? Junctional- Mutations in the genetic codes for the alpha-3, beta-3 and gama-2 subunits of laminin
have been documented for the junctional type.
? Dystrophic- Mutation in the genes responsible for type VII collagen production generally leads to
the dystrophic type.
? Hemidesmosomal- Mutations of genes associated with various hemidesmosomal attachment
proteins, such as plectin, type XVII collagen and alpha6beta4 integrin, are responsible for
hemidesmosomal type.
Recent classification of inherited EB:-

? Epidermolysis bullosa simplex
? Junctional epidermolysis bullosa
? Dystrophic epidermolysis bullosa
? Kindler syndrome
Clinical Features:-
Ø Epidermolysis Bullosa Simplex
v It is associated with Autosomal dominant pattern of inheritance. It is most commonly seen in
neonates and infants.
v EBS is characterized by a disorder of keratinocytes, intraepidermal blistering and little systemic
involvement.
v Nail dystrophy, alopecia and mucosal lesions may occur in more severe forms of the disease.
v Skin lesions usually disappear without scarring, blistering decreases with age.
v EBS is further sub-divided into- localized EBS, Generalized EBS, EBS herpetiformis.
50
Localized EBS-
Ø This subtype is generally present with mild to severe blisters, hyperhidrosis in some patients.
Ø Severe forms of this subtype usually involve the hands, feet as well as limbs.
Generalized EBS-
Ø Palmoplantar hyperkeratosis as well as erosions can be seen in this sub-type.
EBS Herpetiformis-
Ø This sub-type usually involves the oral mucosa and leads to the
formation of herpetiform blisters in oral cavity.
Ø Other features of EBS includes the muscular dystrophy in
adulthood, which can be seen due to the defect in the expression of
the plectin. Plectin is a part of the cytoskeleton of skeletal muscles.
Pyloric atresia at birth is an another common feature of EBS.
Although the disease is described as precociously fatal, some
Figure 5.1: Epidermolysis bullosa simplex
individuals with milder symptoms can survive during childhood.
Junctional Epidermolysis Bullosa

v
Ø
This type also involve the oral mucosa, eyes, pharynx, GIT system. Most common features are
alopecia as well as anonychia, which are frequently present in this type.
Ø
Other features include- pyloric atresia, erosions around the lips, eyes and nose, Hoarseness of
voice, coughing as well as other respiratory symptoms are commonly present in this type.
Ø
Oral manifestations include the- erosions of mucous membrane of oral cavity, enamel hypoplasia
which results in the development of cavities.
Dystrophic Epidermolysis Bullosa

v
Ø
It is associated with autosomal recessive and dominant pattern of inheritance.
Ø
In autosomal dominant pattern of inheritance, clinical manifestations show generalized blistering
which are usually present at birth or during childhood but in adults blisters tend to be more
localized.
Ø
In autosomal recessive pattern of inheritance, mild to severe clinical manifestations can be seen.
This type generally involves the acral surface,
nail and oral mucosa.
Ø
Common clinical manifestations are-
esophageal obstruction, urethral and anal
stenosis, phimosis, corneal lesions, iron
deficiency anemia.
Figure 5.2: Epidermolysis Bullosa. Figure 5.3: Epidermolysis Bullosa.
Ø
Severe form of dystrophic epidermolysis dystrophic
A young girl, affected by the dominant
form of epidermolysis bullosa,
A teenaged boy, affected by dominant
dystrophic epidermolysis bullosa, shows
bullosa can also lead to the development of shows the characteristic hemorrhagic bullae,
scarring, and erosion associated with
a reduced depth of the labial vestibule
caused by repeated mucosal tearing
minimal trauma to the hands. and healing with scarring
aggressive squamous cell carcinoma in areas
of chronic lesions.
Epidermolysis bullosa is highly suggested by its familial inheritance, age of onset, and clinical
picture. Only a few serious considerations on a differential diagnosis are warranted, including bullous
51
impetigo, dermatitis herpetiformis, pemphigus vulgaris, and erythema multiforme. Any of these may form
significant bullae and cause scar formation and may occur in infants and young children.
Diagnosis:-
? Diagnosis of epidermolysis bullosa generally depends on the adequate history taking and clinical
presentation of the disease.
? Biopsy is a gold standard method to assess the ultrastructural changes associated with epidermolysis
bullosa. Principal diagnostic methods includes the- H & E sections, direct immunofluorescence and
electron microscopy.
? Use of immunofluorescence is helpful to map the basement membrane in frozen tissue sections with
a variety of antibodies, including laminin-1 and 5, collagen V, VII and XVII, bullous pemphigoid
antigen, integrin á6â4 and plectin. This is known as immunomapping[37].
Histopathology:-
The light microscopy of this disease is nonspecific. Accurate diagnosis generally requires the
electron microscopy and immunofluorescence mapping. From a histopathologic perspective, three types
are recognized and will relate to certain clinical types:
? Epidermal type- Separation occurs through the basal cell layer. There is intracellular edema below
the nuclei with subsequent vacuolation and disruption of the plasma membrane of the basal cell.
This is seen in the simplex types.
? Junctional Type- Separation occurs in the lamina lucida, secondary to decreased numbers of
hemidesmosomes and abnormal hemidesmosomes due to poorly developed attachment plaques and
sub-basal dense plates. Affected teeth show abnormal enamel formation. The initial layer of enamel
matrix is laminated, but the remainder is globular. The underlying problem is akin to that occuring in
the skin, as vesicles form between the ameloblasts and the odontoblasts with the basement
membrane remaining attached to the odontoblasts. It appears that ameloblasts develop normally or
until the time of dentin formation when the cells form a little enamel matrix and then undergo
squamous metaplasia. The dentin surface is irregular but not otherwise affected. This type is seen in
epidermolysis bullosa atrophicans generalisata graves and the dominant dystrophic/hypertrophic
types.
? Dermal Type- Separation occurs deep to the lamina densa where the
anchoring fibrils appear rudimentary and are decreased in number in
both lesional and non-lesional tissue. In addition, fibroblasts form
excessive amounts of collagenase, and a defect of a lamina densa
protein has been noted. Dental findings are similar to those in the
junctional form with enamel hypoplasia due to absence of the
enamel's normal prismatic structure. Overproduction of poorly the Figure 5.4: Epidermolysis Bullosa. Complete separation of
epithelium from the connective tissue is seen in this photo-
calcified cementum has also been described. This type is seen in the bymicrograph of a tissue section obtained from a patient affected
a junctional form of epidermolysis bullosa.
scarring types of epidermolysis bullosa.
Treatment:-
Treatment is annoying for the patient and clinician because at this time no treatment can alter the
defective basement membrane zone proteins, which are produced by mutations in specific genes. Because
these epidermolysis bullosa types are not autoimmune diseases so systemic corticosteroids are not
effective. Systemic corticosteroid regimens such as regimen I, IIIA, and IIIB are used, but they only
52
decrease secondary inflammation and scarring and do not modify the course of the disease. In addition,
dapsone, 50 to 100 mg per day; retinoic acid A, 30 to 60 mg per day; and beta carotene, 30 mg four times per
day, may also have some beneficial results.
Juvenile Dermatitis Herpetiform

It is an inflammatory disease of the skin, considered the specific cutaneous manifestation of celiac
disease. It is most commonly seen in the gluten-sensitive individuals.
Etiopathogenesis:-
Eighty five percent of affected individuals have a gluten- sensitive enteropathy associated with very
pruritic skin lesions. DH represents a classic model of autoimmune disease, owing that it can be switched on
or off by a known external trigger: the gluten. The pathogenesis of DH, which relies on a complex
inflammatory network along the gut-skin axis, remains at present only partly understood. Over the past 30
years, major efforts have led to the identification of eTG as the main autoantigen of DH and to well-
characterize the inflammatory microenviroment underlying skin lesions development.
Production of IgA autoantibodies against eTG occurs in the gut, probably as a result of an epitope
spreading phenomenon, due to the high sequence homology between tissue TG, which is a major
autoantigen in coeliac disease, and eTG. Activation of innate immunity in the gut leads to increased release
of IL-8, which is thought to be responsible for the initial priming of neutrophils. One theory suggests that, in
region of trauma, keratinocyte damage leads to shedding of eTG to the dermal-epidermal junction, where it
binds to anti-eTG IgA. An alternative hypothesis suggests that eTG/IgA complexes exists as circulating
immune complexes, which can deposit both at the dermal-epidermal junction and around dermal vessels. A
complex interplay between inflammatory cytokines and the activation of fibrinogen stimulate neutrophil
adherence to the activated endothelium and migration to the dermal papillae. Herein neutrophils, which
probably bind to IgA aggregates through the Fc IgA receptor, release proteases, which finally induce the
cleavage of the dermal-epidermal junction. In parallel, hyper-activation of Th2 cells activate eosinophils,
which also co-operate with neutrophils to the cleavage of the dermal-epidermal junction. Down-regulation
of Treg cells do also occur, favoring the maintenance of a pro-inflammatory microenvironment in DH skin.
Clinical Features:-
Ø It is a papulovascular disease usually presents with grouped erythematous papules and urticarial
plaques with profused vesicles.
Ø Vesicles may coalesce to form blister which usually contain the sero-hemorrhagic content, these
blister further grow centrifugally. When the blister rupture they further give rise to erosions and
excoriations. These lesions ultimately heal and leave the post inflammatory hypo and hyper
pigmentation.
Ø Commonly involved sites are- upper and lower limbs mostly elbows
as well as knees, shoulders, abdomen, buttocks and scalp but face as
well as groin are rarely involved.
Ø In many cases pruritus along with a stinging and burning sensation
of the skin are commonly seen.
Ø Oral Manifestations- Erosions as well as ulceration are commonly
present on the oral mucosa and tongue. Associated symptoms the Figure 5.5: Dermatitis herpetiformis rarely affects
mouth; when it does, lesion is generally purpuric
include pain and burning sensation.
53
v Psoriasis and lichen planus, because in both conditions broad crusty papules and pruritus are
common features.
v Sarcoidosis- because of the presence of the raised and distinctive rolled borders.
v Herpes zoster- because clinical lesion generally resembles a herpes skin eruptions.
Diagnosis:-
The most popular diagnostic aids are direct immunofluorescence and biopsy. A representative biopsy
specimen of the lesion's edge, along with clinically normal appearing skin, is diagnostic. Other diagnostic
methods are-
? Serologic analysis- It is useful for the detection of IgA anti-endomysium antibodies (EMAs), IgA
and IgG anti-deamidated synthetic gliadin-derived peptides (DGP), and IgA anti-epidermal
transglutaminase (eTG) antibodies.
? HLA haplotypes testing
? Small bowel biopsy[38].
Histopathology:-
? The most common histopathological findings in the lesional skin of the patients include the
subepidermal vesicles and blisters related to the increased amout of neutrophils at the papillary tips.
? In some cases, eosionphils can also be seen within the inflammatory infiltrate, making difficult the
differential diagnosis with bullous pemphigoid. The deeper tissue contains perivascular in filtrates
of mononuclear cells.
? Histopathology of the DH usually help in the detection of perivascular lymphocytic infiltrate as well
as minimal inflammation in dermal papillae.
? For the proper diagnosis of DH histopathologic examination should be always performed in
combination with DIF of perilesional skin, which represent the gold
standard for the diagnosis of DH. By means of direct
immunofluorescence, IgA may be demonstrated in the basement
membrane zone, usually in a granular pattern over the tips of the
papillae, although deposits may occur throughout the papilla. This
may be IgA antibodies may be present. The enteric component
involves the jejunum with atrophy of villi and lymphocytic Figure 5.6: Histology of dermatitis herpetiformis
infiltration of the epithelium.
Treatment:-
Gluten-free diet is the first choice treatment of the disease. Certain drugs such as dapsone, sulfones as
well as steroids are also sufficient to control the symptoms of the disease[38].
Kawasaki Disease
It is also known as the mucocutaneous lymph node syndrome. it is a complex of clinical signs and
symptoms in which mucocutaneous lesions and cervical lymphadenopathy are the two central findings.
Etiopathogenesis:-
The syndrome suggests a bacterial etiology. Its mechanism is thought to be associated with a subtle
staphylococcal infection or colonization. This produces an exotoxin, which in turn acts as a potent antigen.
54
This toxin antigen subsequently stimulates a profound T cell response that produces the observed signs and
symptoms of the syndrome.
Clinical Features:-
Ø KD is most commonly present in children younger than 10 years of age.
Ø Most common features are- fever,non suppurative conjunctivitis, edema, erythema as well as
desquamation of the skin. Cervical
lymphadenopathy can also be seen in some
patients, lymph nodes are generally mildly
tender and palpable.
Ø Oral manifestations generally include the
presence of inflamed tongue, which can be
refered as 'strawberry tongue', pharyngitis as
well as cracked and fissured lips.
Ø Complications- Coronary arteritis, coronary
artery aneurysm, myocardial infarction.
These complications generally make
Kawasaki syndrome one of the more common
causes of acquired pediatric heart disease. Figure 5.7: Kawasaki disease with lip involvement Figure 5.8: Kawasaki disease-The 'strawberry'
appearance of the tongue at presentation.
w The presentation of oral mucosal infections, fever, pharyngitis and cervical lymphadenitis is
suggestive of several specific diseases such as streptococcal pharyngitis, diphtheria, and infectious
mononucleosis.
w In addition, HIV-related lymphadenopathy and tuberculosis lymphadenitis in an HIV-positive child
are considerations in certain individuals.
w Once extremity signs or symptoms related to coronary arteritis such as chest pain and tachycardia
develop, a serious considerations for rheumatic fever is warranted.
w Mild cases will mimic nonspecific viral influenza, particularly when associated with other cases in
an epidemic pattern.
Diagnosis:-
Diagnosis of KD generally depends on the adequate clinical history taking as well as proper
evaluation of the sign and symptoms of the patients. Throat culture is useful for the demonstration of the
streptococcal pharyngitis. Other laboratory investigations include the complete blood count, c-reactive
protein. Kawasaki syndrome usually will be associated with leukocytosis and an elevated c-reactive
protein. In the absence of the oral lesions, CSF test can evaluate the leukocytosis.
Histology:-
Mucocutaneous lesions show only a nonspecific perivascular infiltration of lymphocytes and
histiocytes. The cutaneous lesions show changes similar to those found in polyarteritis nodosa, including a
panarteritis and perivascular infiltrates of neutrophils. The lymph nodes may show localized necrosis,
small thrombi, and inflammation of small vessels with a proliferation of immunoblast like cells around
postcapillary venules.
55
Treatment:-
The management of Kawasaki syndrome has focused on reducing the fever and the inflammation.
This is usually accomplished with aspirin, 80 to 100 mg/kg per day in divided doses, coupled with
intravenous immune globulin in high doses. In refractory cases, plasmapheresis is used. Corticosteroids are
not recommended to treat Kawasaki syndrome because of the fear of further weakening coronary artery
walls and thus increasing the likelihood for coronary artery aneurysms or worsening those already present.
In rare cases where coronary artery aneurysms obtain a size of 6.5 mm or larger, anticoagulation with
Coumadin (DuPont) is recommended[11].
Familial Acanthosis Nigricans

It is characterized by dark, rough, and thickened skin with a velvety feel, being symmetrically
distributed on the neck, axillae, antecubital and popliteal fossae, groin folds and face.
Classification of AN:-
The most commonly used classification was given by Schwartz, who categorized the entity into the
following eight types-
? Benign AN
? Malignant AN
? Obesity associated AN
? Syndromic AN
? Unilateral AN
? Drug-induced AN
? Mixed AN
? Acral AN
Etiopathogenesis:-
? Insulin has been established to cross dermoepidermal junction (DEJ) to accomplish keratinocytes.
When the serum insulin level is within normal limits, it crosses the dermoepidermal junction, binds
to the classical insulin receptors, and brings about a change in carbohydrate, lipid, and protein
metabolism, but it does not increase the proliferation of keratinocytes.
? However, at higher concentrations, it can bind to the insulin-like growth factor 1 receptors (IGF
1Rs) stimulate proliferation of keratinocytes and fibroblasts, leading to AN.
? IGF binding proteins (IGFBPs) bind to IGF 1 and thereby regulate the levels of metabolically active
“free” IGF 1. In obese patients with hyperinsulinemia, IGFBP 1 and IGFBP 2 are decreased which
increases the plasma concentrations of free IGF 1, promoting cell growth, and differentiation of
keratinocytes leading to AN.
? Cyclosporine has been successfully used in some cases of AN which has lead to the belief that there
could be some autoimmune factors responsible for the development of AN.
? Insulin and IGF levels are altered in hepatitis C infection which seems like a plausible explanation of
development of acrochordon and AN in some cases of hepatitis C.
? Malignancy associated AN might be explained by high levels of transforming growth factor á (TGF
á), exerting effects on epidermal tissue through epidermal growth factor (EGF) receptor. The
malignant cells produce TGF á which is structurally almost similar to EGF á and thus can bind to its
receptor on the basal keratinocytes and lead to increase proliferation of normal keratinocytes
causing AN.
56
Clinical Features:-
Ø AN is most commonly seen in children and adolescents.
Ø Most commonly involved sites are- axillae, posterior neck fold, flexor surfaces of the upper and
lower extremities, umbilicus, groin, inframammary folds, face, and perioral and perianal surfaces.
Ø It is generally presents as symmetric, velvety, brownish-black, hypertrophic, verrucous patches or
plaques.
Ø In children, AN generally starts from the axillae or back neck fold, hyperpigmentation can also be
seen during initial stage of the disease.
Ø Other clinical manifestations usually involve the mucosal surfaces of the conjunctiva, lips, oral
cavity as well as vulva and show the papillomatous like growth pattern on these sites.
Types:-
Benign Acanthosis Nigricans-

? This type of AN can be seen at birth or during childhood or adolescence.
? It is associated with autosomal dominant pattern of inheritance.
? Most commonly involved sites are palm and soles.
? Lesions usually show the unilateral as well as generalized involvement of the palms and soles.
Obesity Associated Acanthosis Nigricans- Figure 5.9 (a) Clinical photograph

showing classical features of
? This type is most commonly seen in children acanthosis nigricans involving
the neck in a 9-year-old obese girl
and young adults. (lateral view), family history of obesity
and acanthosis nigricans absent and
(b) Clinical photograph showing
? The most common manifestations of obesity classical features of acanthosis
nigricans involving the neck in a
associated AN are obesity as well as 9-year-old obese girl (posterior view),
family history of obesity and
hyperinsulinemia. acanthosis nigricans absent
Syndromic Acanthosis Nigricans-

? AN is associated with numerous syndromic conditions especially type A insulin resistance
syndrome.
? Young girls and middle aged women are more commonly affected.
? Other syndromes that are associated with AN are Berardinelli–Seip (congenital) and Lawrence
(acquired) syndromes of generalized lipodystrophy, Hirschowitz's syndrome, polycystic ovarian
syndrome, Donohue's syndrome (leprechaunism), Rabson–Mendenhall syndrome, Alstrom
syndrome, familial partial lipodystrophy (Dunnigan type), and Crouzon's, Bloom's, and
Prader–Willi syndrome.
Malignant Acanthosis Nigricans-

? This type is not common in pediatric patients.
Acral Acanthosis Nigricans-

? This type is more commonly seen in persons with dark complexion.
? Most commonly involved sites are knee, ankle, phalangeal joints, and
tarsophalangeal joints. Figure 5.10 (a) Typica l case of acra l acant hosi s
nigricans (over the dorsum of hands) in a 6-year-old boy &
(b) classical lesions of acra l acant hosi s nigr icans
over the dorsum of feet in the same patient
57
Unilateral Nevoid Acanthosis Nigricans-
? This type is more commonly seen in childhood.
? Clinical presentation of this type is unilateral and localized.
Drug-induced Acanthosis Nigricans-

? This type is most commonly seen in children.
? Most commonly involved sites are abdomen, flexor surface of skin.
? Patients with insulin-requiring diabetes may acquire AN as a result of repeated injection of the same
site.
? Other medications that are commonly involved in the development of drug-induced acanthosis
nigricans are oral contraceptives, diethylstilbestrol, heroin, corticosteroids, methyltestosterone,
fusidic acid, and hydantoin-like derivatives.
? Mixed type acanthosis nigricans-
? This type is most commonly seen when a patient with one type of AN develops another type of AN
lesion of a different type.
Diagnosis:-
Diagnosis of AN is generally depends on the histopathology. Other laboratory investigations include
the detection of fasting insulin level, fasting glucose and lipoprotein profile, hemoglobin A1c (HbA1c),
body weight, blood pressure, and an alanine transferase test for evaluation of fatty liver.
Histopathology:-
Biopsy characteristically demonstrates
epidermal hyperkeratosis and minimal to mild
acanthosis, and an upward projection of the dermal
papillae into a thinned overlying epidermis with
keratinaceous material filling up the regions between
the ridges. Hyperpigmentation is generally the result of
epidermal hyperkeratosis, but increased number of
melanosomes in the stratum corneum is also seen in
some patients. The dermis characteristically lacks an
inflammatory infiltrate.
Figure5.11: Acanthosis Nigricans. Medium-power photomicrograph of an oral lesion showing
papillomatosis, mild hyperkeratosisand acanthosis of the epithelium
Treatment:-
First step of the treatment is to eliminate the cause of AN. Obesity prevention or weight reduction is
very important in case of obesity-induced AN. The only Food and Drug Administration (FDA) approved
drug for use in adolescents aged 12–16 years is orlistat. A newer treatment modality that has shown promise
in treating idiopathic AN is long pulsed alexandrite laser treatment[39].
58
Dermatological
6 Diseases
Juvenile bullous pemphigoid
?
Childhood linear IgA disease
?
Vitiligo
?
Juvenile Bullous Pemphigoid
I t is an autoimmune disease, usually a chronic disorder of the skin and mucous membrane. JBP is
the rare form of the disease and is commonly seen in children and infants.
Etiopathogenesis:-
Pemphigoid is characterized by linear deposits of IgG and complement (in particular C3) and, less
frequently, other immunoglobulins. Complement activation plays an important role in this disease. There
seems to be no difference between the adult and juvenile forms. Binding of autoantibodies to BP180 and/or
BP230 of basal keratinocytes results in an inflammatory response with complement activation, mast cell
degranulation, recruitment and activation of neutrophils and eosinophils and release of different proteolytic
enzymes. Concerted, these enzymes induce the loss of cell-matrix adhesion and subepidermal blisters.
Autoantibodies might also interfere directly with the function of the target antigens or activate an
intracellular signal transduction leading to an induction of pro-inflammatory cytokines. The findings in
pemphigoid and BP, as io the juvenile forms, are almost identical and suggest that the pathogenetic
mechanism is the same[40].
Clinical Features:-
Ø JBP is characterized by large, tense as well as hemorrhagic bullae that are several centimeters in
diameter.
Ø Most commonly involved sites are face, neck, groin, palms, soles,
inner parts of thighs, genitals.
Ø The lesions commonly develop on normal looking, erythematous or
urticarial skin.
Ø Lesions of JBP usually develop in clusters or they may coalesce to
form large sized bullae. They may scattered over the body.
Figure 6.1: Bullous Pemphigoid. Cutaneous vesiculo
Ø Erythema may follow the bullous stage and is often accompanied by bullous lesions of the heel. The bullae eventually
rupture, leaving hemorrhagiccrusted areas.
pruritus. Degree of pruritis usually depends on the dissemination of
the disease.
Ø Almost all juvenile cases are disseminated.
Ø Involvement of the mucous membrane is common in cicatricial
pemphigoid. CP is another common form of the bullous
pemphigoid, which can also be seen in the children.
Ø There is a less involvement of the skin in case of CP, another Figure 6.2:Bullous Pemphigoid. These oral lesions appear
as large, shallowulcerations involving thesoft palate.
manifestations show the involvement of the larynx which further leads to the hoarseness of voice.
w Cutaneous pemphigoid must be distinguished from pemphigus vulgaris, which may also present
with skin vesicles or bullae and oral lesions. However, the bullae of pemphigus are smaller and not
as pruritic and will not have the marked erythema associated with cutaneous pemphigoid.
w The oral vesicles or ulcers of pemphigus vulgaris are also more painful. Although the mucosal
pemphigoids have a similar pathogenesis, their skin lesions are not as prominent and occur in only
20% of cases.
w Cutaneous/ erosive lichen planus remains a serious consideration because of its violaceous pruritic
skin lesions, which may have corresponding oral lesions.
Diagnosis:-
The diagnosis of JBP is generally depends on the light microscopy or histopathology because
pemphigus and pemphigoid can be distinguished by light microscopy. Other diagnostic methods include
the immunofluorescence, serum analysis for the demonstration of increased IgE levels and raised
eosinophil count in the serum of the patient.
Histopathology:-
Pemphigoid is characterized by formation of subepidermal bullae with scattered eosinophils within
the blister. The underlying dermis may contain a cellularly poor or rich infiltrate. In the poor form the
infiltrate is only moderately perivascular, and the number of eosinophils is prominent. ln the rich form the
perivascular infiltrate is dense and consists of neutrophils, many eosinophils, and lymphocytes, possibly
together with vascuitis in the superficial capillaries. ln general, the subepidermal blister in JBP is not
diagnostic, and the histology can be very similar to that of dermatitis herpetiformis, not distinguishable
from CBDC. It is extremely important to biopsy early blisters in pemphigoid because older ones show
epidermal regeneration and may then look intraepidermal.
Treatment:-
The mainstay of the treatment for pemphigoid is corticosteroids. If there is involvement of the oral
cavity especially in CP, then viscous lidocaine can be given to the patient before meals and it will be more
beneficial[41].
Childhood Linear Iga Disease

It is an autoimmune subepidermal vesiculobullous disease that could be idiopathic or drug-induced.
This disease is commonly seen in children and adults. In children, this disease is also known as “chronic
bullous disease of childhood”.
Etiopathogenesis:-
Drug induced LABD is commonly seen in adults. Most commonly vancomycin is responsible for
drug induced LABD, apart from this many antibiotics such as penicillin, cephalosporins, sulfonamides,
NSAIDs, Phenytoin, can also cause drug induced LABD. Drug induced LABD generally starts within the
first month of drug administration. The principal cause of LABD is circulating IgA anti-basement
membrane zone antibodies directed against the 97 kDa portion of BPAG2 (bullous pemphigoid antigen 2)
in the lamina lucida. The 97 kDa subunit is present within the well-known NC16A domain of the BPAG2
molecule. Additionally, some patients may exhibit autoantigens toward LAD-1. In bullous pemphigoid
(BP), circulating IgG antibodies bind to the MCW-1 area of the NC16A domain which is closer to the
amino-terminus, while the 97 kDa subunit lies at the carboxy terminus.
Production of offending IgA antibodies can also be seen in various infections, autoimmune diseases,
malignancies, gastrointestinal disease. Genetic tendency may also be responsible for the development of
chronic bullous disease of childhood or LABD, and several human leukocyte antigen (HLA) types have
been implicated as portending an increased risk of disease development. HLA-B8, HLA-DR3, HLA-DQ2,
and HLA-cw7 are well known for the association with both the childhood and adult variants of LABD.
Clinical Features:-
Ø This disease is more commonly seen in children between 6 months
and 10 years of age, LABD can also be seen in adults after the age of
60 years.
Ø More commonly involved sites in children are lower abdomen,
perineal area,oral cavity, eyes as well as inner thighs.
Ø Rarely involved sites in children are face, hands, feet.
Figure 6.3: (a) Widespread vesiculobullous
Ø More commonly involved sites in adults are extensor surfaces, trunk, eruption on the lower limbs with elements
in a “string of pearls” arrangement;
buttocks, face. (b) targetoid vesicular lesions on erythematous
skin involving the dorsa of the hands;
Ø The lesions are commonly appear as clear or hemorrhagic vesicles or (c) blisters with a “string of pearls”
configuration and crusts in the perioral area;
bullae with an erythematous or urticarial base. (d) erythematous, vesicular lesions partially
eroded on the posterior aspects of both thighs;
Ø Lesions are generally variable in size and form annular or circular (e) vesicles involving the vulvar area in a child
plaque
Diagnosis:-
A complete history as well as an accurate physical examination can guide the clinician towards a
diagnosis of LABD. A complete medical history can rule out the drug-induced LABD. Confirmation of the
diagnosis generally depends on biopsy or histopathological examination. The clinician should take two
samples of lesion, one for routine H & E staining and other for DIF. The sample for routine H & E should be
taken from the actual skin lesion and sample for DIF should be taken from perilesional area. Other
diagnostic aids include indirect immunofluorescence for the demonstration of circulating IgA anti-
basement membrane zone antibodies.
Histopathology:-
Routine H & E sections can show the subepidermal blistering with a predominately neutrophilic
infiltrate. In the early stage of disease, inflammatory cells are mainly localized to the dermal papillae.
In the advanced stage of the disease, subepidermal split becomes evident and
large number of eosinophils can also be seen with the neutrophils in the
dermis.
Immunopathology is the gold standard for the establishing a diagnosis
of LABD, which shows the linear deposition of IgA at the basement
membrane zone. There are two histopathologic subtypes of the disease
which depends on the location of IgA deposition. The most common variant
Figure 6.4: linear IgA bullous dermatosis. Epidermis with
is the lamina lucida subtype followed by the sub-lamina densa variant. subepidermal blister formation and neutrophils (arrow).
Linear IgA disease is sufficiently rare that is not likely to be the expected diagnosis. Because the
presentation is almost identical to that of cutaneous pemphigoid and mucosal pemphigoid, these diseases
are the two most important considerations. In addition, dermatitis herpetiformis and epidermolysis bullosa
acquisita as well as some clinical presentations of lichen planus and mild cases of pemphigus vulgaris may
also present with oral and skin vesicles.
Treatment:-
The treatment of LABD generally depends on the degree of involvement. The first line treatment
include the Dapsone, 100 mg daily for adults and 1 to 2 mg/kg daily for children. Another treatment options
include the use of another drugs mainly Sulfapyridine, various antibiotics such as tetracycline,
dicloxacillin, and trimethoprim-sulfamethoxazole[42].
Vitiligo
Vitiligo is an acquired pigmentary disorder and can occur at any age. The most significant feature of
vitiligo is the cosmetic concern it arouses in the mind of patients and their family members.
Classification:-
According to various studies, childhood vitiligo is classified into two types:
1. Segmental type- In this type, depigmented macules and patches occur along dermatomal and
quasi-dermatomal pattern without crossing the midline.
2. Non-segmental type- In this type, skin lesions could be generalized or localized. Generalized
form further divided into vitiligo vulgaris and universal vulgaris. Localized form divided into
focal, mucosal, acrofacial and acral type.
Etiopathogenesis:-
Genetic causes are predominant in the pathogenesis of vitiligo. Various susceptibility loci
(autoimmunity susceptibility gene) for vitiligo are AIS1 (chromosome 1), AIS2 (chromosome 7), AIS3
(chromosome 8) and SLEV1 (chromosome 17). Association of vitiligo with “transporter associated with
antigen processing protein-1 (TAP-1)” gene is suggestive of the possible role of MHC class I antigen in
antimelanocyte autoimmune response. Studies on HLA class I and class II genes in vitiligo have revealed
strong association and negative association with certain HLA types.
There is a strong association of NACHT-leucine-rich-repeat protein-1 (NALP1) gene (chromosome
17p13) in the occurrence of a group of multiorgan autoimmune and autoinflammatory disorders, including
vitiligo. Mutation in the autoimmune regulator (AIRE) gene (chromosome 21q22.3) results in a rare
recessive disorder. Link to NALP1 and AIRE gene may enlighten the relationship of vitiligo to other
autoimmune disorders and existence of circulating autoantibodies in these patients.
Clinical Features:-
Ø Vitiligo can occur anytime in life, including the neonatal period and childhood.
Ø It is characterized by asymptomatic, well-demarcated, ivory-white macules as well as patches that
may be localized or generalized.
Ø Vitiligo vulgaris is the most common type of the vitiligo, followed by focal vitiligo. Acralfacial,
universal vitiligo as well as mucosal vitiligo are very rare in children.
Most commonly involved sites of vitiligo in children are face and neck.
Ø
In NSV type, initially lesions are present on periocular, perinasal and perioral regions and further
Ø
spread to other parts of body.
In infants, the lesions are mostly present on perianal area.
Ø
In dark skinned children, typical multi-shaded trichome patches may be present.
Ø
Koebner phenomenon can be seen in both SV and NSV type, but most commonly seen in NSV type.
Ø
In SV, Koebnerization is limited to the
involved segment only.
Involvement of scalp can also be seen in some
Ø
cases of vitiligo. 'Scalp leukotrichia' is
referred as significant extent of graying of
scalp hair without underlying vitiliginous area
before 30 years of age, is a common finding in
Figure 6.5: Focal vitiligo with leukotrichia Figure 6.6: Acral vitiligo in a child
children with vitiligo.
Various nevoid and hereditary disorders with depigmentation may suggest vitiligo in children.
w Nevoid pigmentary disorders
w Oculo-cutaneous albinism
w Post inflammatory hypopigmenttaion
w Various infections such as Leprosy, Post-Kalaazar derma leishmaniasis, Pinta.
w Contact depigmentation
w Topical steroid abuse
Diagnosis:-
Diagnosis of vitiligo is generally clinical. Invasive techniques are not necessary to prove the
diagnosis of vitiligo. In children with fair skin, it is very hard to differentiate a lesion of vitiligo from the
surrounding normal skin. In these cases, wood's lamp can be used to examine the vitilgo.
Laboratory investigations include the complete blood count, fasting blood sugar. Other diagnostic aids
include the skin biopsy, demonstration for autoantibodies, Thyroid function status of the child can be
assessed by estimating T3, T4 and TSH levels.
Histopathology:-
Histopathological examination reveals total absence of melanocytes in established lesions of vitiligo.
In initial lesions, melanocytes are still retained but with various abnormalities such as vacuolization,
dilated endoplasmic reticulum and granular deposits. Mild inflammatory infiltration can also be seen,
which is the indicative of disease activity.
Treatment:-
v Medical
Topical
? Corticosteroids
? Tacrolimus/pimecrolimus
? Calcipotriol
? Pseudocatalase
? Combination
Systemic
v
Corticosteroids(OMP with betamethasone/ methylprednisolone)
?
vPhototherapy
Topical PUVA
?
NB-UVB
?
Systemic PUVA (>12years)
?
Phenylalanine+PUVA
?
Excimer laser (308nm)/targeted NB-UVB phototherapy
?
Surgical therapy
v
Conventional
Mini-punch graft
?
Suction blister epidermal graft
?
Thin Thiersch graft Newer cellular transplantation techniques
?
Epidermal cell suspension
?
Cultured melanocyte suspension
?
Cultured epidermis
?
Cosmetic camouflage
v
[43]
Total depigmentation using MBEH
v .
Traumatic Oral
7 Mucosal Lesions
Frictional keratosis
?
Linea alba
?
Riga- fede disease
?
Frictional Keratosis
Etiology
F rictional keratosis refers to a white lesion with a rough white keratotic patch caused by chronic
mechanical irritation.
Increased abrasion associated with constant rubbing of the mucosa, which may lead to white patches
that can be vanished if the causative agent or habit is discontinued. Causative habits include tooth brushing
and forcefully rubbing the tongue against the teeth.
Clinical Features:
Ø The Prevalence of frictional keratosis has been reported between
0.26% and 1.89% In children.
Ø Frictional hyperkeratosis is commonly seen along the occlusal line
in the buccal mucosa in children.
Ø It is characterized as a corrugated, gray or white lesion that could be
smooth or rough and occasionally irregular with small loose tags
of epithelium on the surface.
Ø The lesion is non-symptomatic and is reversible on elimination of
the irritant.
Figure 7.1: Frictional Keratosis. Frictional keratosis

on posterior mandibular alveolar ridge
(“alveolar ridge keratosis”).
Diagnosis:-
For most lesions, the diagnosis can be established based on clinical features. If the diagnosis is
doubtful, biopsy is mandatory to exclude premalignant lesions.
Histopathology:-
Microscopic feature characterized by hyperkeratosis.
65
Treatment:-
On removal of the irritant, the lesion usually resolve within 2 weeks. Biopsies should be performed on
lesions that do not heal to rule out a dysplastic lesion[8].
Linea Alba
This is mainly a benign finding, which is commonly present on the buccal mucosa along the
commissures and extending posteriorly towards the molars. The prevalence is 1.5% in children and upto
5.3% in adolescents.
Clinical Features:-
Ø It is characterized as a distinct white linear area on the buccal mucosa
opposing the plane of occlusion.
Ø It could also be seen on the lateral border of the tongue.
Figure 7.2: Linea Alba. White line of hyper keratosis

on the right buccal mucosa at the level of the
occlusal plane
Treatment:-
No treatment is needed, as this condition is benign[8].
Riga-Fede Disease
Riga-Fede disease or Riga-Fede granuloma is a benign, ulcerative, granulomatous condition which
generally occurs due to the repetitive trauma to the oral mucosa by teeth.
Clinical Features:-
Ø It Is commonly seen in infants, children younger than 2 years of age and may be an initial sign of a
developmental dysfunction or underlying neurologic disorder.
Ø Most commonly involved sites are ventral surface of the
tongue, lingual frenulum along the midline, corresponding
to the offending teeth.
Ø It is characterized by an exophytic, ulcerated, granulomatous
mass covered by a yellowish pseudomembrane.
Ø Appearance of the lesion coincides with the eruption of
primary teeth, especially the lower incisors.
Ø This disease is also associated with other conditions such as
7.3: Riga-Fede Disease. Newborn with traumatic ulceration
familial dysautonomia, Lesch-Nyhan disease, Gaucher's ofFigure anterior ventral surface of the tongue. Mucosal damage occurred
from contact of tongue with adjacent tooth during breastfeeding.
disease.
Treatment:-
Treatment of Riga-Fede generally depends on the prevention of trauma to the affected area.
Interventions include dental extraction, occlusal adjustment of sharp incisal edges, behavior modification,
surgical excision of the lesion as well as the use of intraoral appliances to cover the offending teeth[8].
66
Inflammatory/
8 Reactive Lesions
?Mucocele
?Irritation fibroma
?Peripheral ossifying fibroma
?Peripheral giant cell granuloma
?Pyogenic granuloma
Mucocele
It is also known as Mucous extravasation phenomenon, mucous escape reaction. It is considered

as the most common minor salivary gland disease and among the most common biopsied oral
lesions in pediatric patients.
Etiopathogenesis:-
It is caused by the traumatic severance of a salivary duct, that commonly produced by biting the lips or
cheek, pinching the lips by extraction forceps that leads to the spillage of mucin into the surrounding
tissues.
Based on the etiology, mucoceles are classified into two types- Retention, extravasation mucocele.
Extravasation mucocele- It is considered as pseudo-cyst with no epithelial lining and caused by trauma to
the excretory duct of minor salivary duct, followed by rupture of the duct causing extravasation and
accumulation of saliva in the surrounding connective tissue.
Retention mucocele- It is a true cyst with cubic or squamous cell epithelial linings. It is rare and caused by
ductal obstruction that interferes with the normal salivary flow causing mucosal swelling and ductal
dilatation.
Clinical Features:-
Ø Mucocele affects both genders equally, but more commonly seen in children and young adults.
Ø Most commonly involved sites are- buccal mcosa, anterior ventral tongue, floor of mouth.
Ø Mucocele is generally asymptomatic, but in some cases it can cause discomfort and can interfere
with speech, chewing and swallowing.
Ø It is characterized by a raised dome shaped vesicles, ranging in size from 1 or 2 mm to several
centimeters.
Ø Superficial mucocele, is a variant of mucocele,
which is commonly present on the soft palate,
retromolar area, posterior buccal mucosa,
presenting as single or multiple tense vesicles
measuring 1-4 mm in diameter.
Ø The vesicle can rupture and leave a shallow, Figure 8.1: Superficial Mucocele. Vesicle-like Figure 8.2: Mucocele. Exophytic lesion on the
lesion on the soft palate anterior ventral tongue.
painful, ulcer that can heal within few days.
67
w When the mucosal covering is thicker than usual or the lesion is not superficial, the appearance is
pink, not bluish. It is soft to rubbery in consistency and is fluctuant but not emptiable. In such
instances it must be differentiated from a superficial cyst, lipoma, plexiform neurofibroma,
relatively deep cavernous hemangioma, lymphangioma, and mucus producing salivary gland
tumor.
w If aspiration of the lesion produces a sticky, viscous, clear, mucus like fluid, all the preceding
lesions can be eliminated except the mucus-producing salivary gland tumours. These lesions are
uncommon.
w Mucoceles occur almost 80% of the time on the lower lip and rarely on the palate. Mucus-
producing malignant salivary gland tumors occur most often on the posterior hard palate,
retromolar area, and posterolateral aspect of the floor of the mouth. An induration at the base of a
retention phenomenon may be just fibrous tissue, but it should alert the clinician to the possibility of
a malignant tumor.
Diagnosis:-
Diagnosis of mucocele generally depends on adequate history taking, clinical evaluation of the
lesion. Biopsy is mandatory in case of superficial mucocele.
Histopathology:-
? Mucoceles consist of a confined cavity in the connective tissue and submucosa, producing an
obvious elevation of the mucosa with thinning of the epithelium as though it were stretched.
? The wall of the cavity is composed of a lining of compressed fibrous connective tissue and
fibroblasts. Sometimes these cells may be mistaken for flattened epithelial cells.
? The connective tissue wall is essentially granulation tissue, shows infiltration by abundant numbers
of polymorphonuclear leukocytes, lymphocytes, and plasma cells.
? The lumen of the cyst-like cavity is filled with the spilled mucin containing variable numbers of
cells, chiefly leukocytes and foamy histiocytes (macrophages). Occasional mucoceles reveal an
intact, flattened epithelial lining.
? It is probable that this simply represents the portion of the excretory duct bordering the line of
severance, if severance is actually the manner in which these lesions develop. The flattened
epithelial lining has been referred to as epithelium of the 'feeder duct'. In other instances, the
epithelium-lined mucocele represents a
mucous retention cyst.
? The salivary gland acini, which lie adjacent to
the area of the mucocele and are associated
with the involved duct, often show alterations.
These may consist of interstitial inflammation
or sialadenitis, dilatation of intralobular and
interlobular ducts with collection of mucus, Figure8.3: Mucocele. Mucin- Figure 8.4: Mucocele. High-power view showing spilled mucin
filled cystlike cavity beneath that is associated with granulation tissue containing
and breakdown of individual acinar mucous the mucosal surface. Minor foamy histiocytes.
salivary glands are present
cells resulting in the formation of tiny areas of below & lateral to the spilled
mucin.
pooled mucus.
68
Treatment:-
Mucocele rarely resolve on their own and surgical removal is mandatory. But surgical removal is a big
challenge in children with behavioral problems. Another treatment options include cryosurgery, intra-
lesional injection of corticosteroid, micro-marsupialization, conventional surgical removal, laser
ablation[44].
Irritation Fibroma
Fibroma or focal fibrous hyperplasia of the oral mucosa is the most common benign neoplasm of the
oral cavity. Fibromas are hyperplasias of fibrous connective tissue in response to local irritation or trauma.
Tissue enlargements attributable to injury represent a hyper-plastic reaction and are collectively grouped as
“reactive proliferations.” It is also known as irritational fibroma, traumatic fibroma, fibrous nodule, or
fibroepithelial polyp.
Etiopathogenesis:-
Fibroma is a reactive lesion of oral tissues, associated wih local factors such as trauma or presence of
dental biofilm. Mostly fibromas are present on buccal mucosa in the area adjacent to occlusal plane. It is
generally caused by tooth abrasion, cheek biting or sucking trauma.
Clinical Features:-
Ø It is the most common benign soft tissue lesion of adults, but can also seen in children.
Ø It is characterized as a nodule with a smooth surface or sometimes an ulcerated surface.
Ø It is generally rounded, does not blanch, not painful and is firm on palpation.
Ø The color of fibroma is similar to the
surrounding mucosa, and the overlying
mucosa is intact with mature epithelium
unless some form of trauma has caused
surface ulceration secondarily.
Ø Most commonly involved sites are buccal buccal Figure 8.5: Fibroma. Pink nodule of the posterior Figure 8.6: Fibroma. Lesion on the lateral
mucosa near the level of the occlusal plane. border of the tongue
mucosa, labial mucosa and lateral tongue.
Diagnosis:-
Accurate examination of fibroma generally depends on the clinical examination as well as the habit
history of the patient. Biopsy is a gold standard for the diagnosis of irritation fibroma.
Histopathology:-
A fibroma usually appears as a well-defined mass of hypocellular collagenized
tissue. Cellularity is variable, however, as is the degree of vascularity. If an
inflammatory component is present, it is usually found adjacent to the overlying
epithelium or perivascularly. The epithelium is often attenuated and may be
hyperkeratinized. Most of these lesions are reactive rather than neoplastic, and only
their circumscription separates them diagnostically from fibrous hyperplasia. Figure 8.7: Fibroma. Higher-power view
demonstrating dense collagen beneath
the epithelial surface.
Treatment:-
If the lesion interferes with normal oral function, then it is better to excise the lesion. If the source of
chronic trauma is not eliminated, the lesion may recur[8].
69
Peripheral Ossifying Fibroma
It is a benign neoplasm, thought to arise from cells of periodontal ligament or periosteum, so it is most
commonly found on gingiva.
Etiopathogenesis:-
These lesions may arise as a result of irritants such as trauma, microorganisms, plaque, calculus,
faulty restorations, and dental appliances.
Clinical Features:-
Ø It is commonly seen in children and young adults, females are more commonly affected than males.
Ø Most commonly involved site is anterior maxillary gingival, interdental
gingiva.
Ø It is characterized as a sessile nodule on the gingiva, soft to firm on
palpation, consistence of the lesion generally depends on the amount of
calcification.
Ø The color of lesion is generally similar to surrounding mucosa, but Figure 8.8: Peripheral Ossifying Fibroma.This
Red ulcerated mass of the maxillary gingival.
occasionally can appear red or with surface ulceration.
A peripheral ossifying fibroma must be distinguished histologically from a pyogenic granuloma or a
peripheral giant cell proliferation. In addition, gingival masses, particularly those arising from deeper
tissues, should suggest a possible primary malignant lesion or even a metastatic malignancy.
Diagnosis:-
The diagnosis of peripheral ossifying fibroma can be confirmed with biopsy. Other diagnostic aids
include the radiographic evaluation of the lesion.
Radiographic Features:-
A periapical radiographic evaluation may or may not detect the small foci of ossification in the lesion.
Radiographic flecks can be noted in lesions with large amount of ossification. In usual cases, only little
amount of ossification can be seen.
Histopathology:-
The lesion generally consists of very cellular fibrous tissue with areas of more delicate fibrovascular
tissue that often contain an inflammatory component
rich in plasma cells. Ossifications are present within
the cellular areas. Small, round calcific deposits can
also be seen in some areas, at the other extreme, broad
osseous trabeculae lined by active osteoblasts may be
formed. Multinucleated giant cells can also be seen in showing
Figure 8.9: Peripheral Ossifying Fibroma. A, Nonulcerated fibrous mass of the gingiva
central bone formation. B, Higherpower view showing trabeculae of bone
[11] with adjacent fibrous connective tissue.
some areas.
Peripheral Giant Cell Granuloma

Peripheral giant cell granuloma is a benign reactive lesion characterized by the presence of giant cells.
It is thought to arise from the cells in the periodontal ligament or periosteum.
70
Etiology:-
The exact etiology of PGCG is not known, but it may also be linked to local irritating factors such as
plaque, calculus, improper dental restorations, trauma, or tooth extractions.
Clinical Features:-
Ø It is present in patients of all ages, especially children and young adults. Females are more
commonly affected than males.
Ø It is characterized as a soft tissue nodule with a pedunclated or sessile base and either a smooth or
ulcerated lesion.
Ø Most commonly involved sites are interproximal dental papillae on
the buccal or lingual aspect, alveolar ridge.
Ø Lesion appear soft to firm on palpation, reddish purple in color.
Ø It can surround a tooth and produce displacement of adjacent tooth.
Ø PGCG may also be associated with primary hyperparathyroidism or
Figure 8.10: Peripheral Giant Cell Granuloma.
glycogen storage disease type Ib. Nodular blue purple mass of the mandibular gingiva
When lesion associated with teeth arise, the peripheral giant cell granuloma bears the closest
resemblance to the pyogenic granuloma followed by the peripheral ossifying fibroma. The clinician must
also differentiate such presentations from a primary or metastatic malignancy.
Diagnosis:-
Biopsy is a gold standard for the diagnosis of PGCG. Radiographic evaluation could also help in the
diagnosis of PGCG.
The lesion is generally asymptomatic with common radiographic characteristics. However, adjacent
tooth resorption may occasionally be seen radiographically.
Histopathology:-
PGCG is characterized by the presence of abundant multinucleated giant
cells as well as mononuclear stromal cells in the fibrous connective tissue.
Figure 8.11: Peripheral Giant Cell Granuloma. High-power

view showing scattered multinucleated giant cells within
a hemorrhagicbackground of ovoid and spindle-shaped
mesenchymal cells
Treatment:-
Complete surgical excision as well as the curettage of underlying bone is the preferred treatment. Early
diagnosis as well as appropriate treatment is important to minimize risk of bone or tooth loss.[45]
Pyogenic Granuloma
Pyogenic granuloma is a benign, acquired, vascular neoplasm of the skin and mucous membrane. It is
a vascular neoplasm, not a true granuloma.
71
Etiology:-
It is generally caused by chronic irritation, trauma and hormonal factors. Minimal trauma often
triggers profuse bleeding that is difficult to control, leading to a visit to the emergency room.
Clinical Features:-
Ø It is most commonly seen in children and young adults.
Ø It is characterized as sessile or pedunclated nodules, ranging in size from a few millimeters to 2 cm
and bright red in color.
Ø Most commonly involved sites are head, neck, extremities especially fingers and periungual area,
oral cavity.
Ø In oral cavity it is most commonly present on gingiva especially maxillary anterior labial gingiva,
lips, tongue, buccal mucosa and palate.
Ø It can rapidly increase in size and looks like a malignancy and can cause increased oconcern to the
patient and clinician.
Figure 8.12: Pyogenic Granuloma. Erythematous, hemorrhagic mass arising from the maxillary Figure 8.13: Pyogenic Granuloma. Ulcerated and lobulated mass on the dorsum of the tongue.
anterior gingiva.
A pyogenic granuloma is clinically indistinguishable from a peripheral giant cell granuloma. A
peripheral ossifying fibroma will also resemble a pyogenic granuloma, except that the former is usually
firmer and not as red. Of greatest importance, however, is its clinical resemblance to a primary or metastatic
malignancy. Squamous cell carcinoma, fibrosarcoma, leukemia, non-Hodgkin lymphoma, and metastatic
foci from the breast, lung, kidney have been known to seed bone and proliferate a soft tissue mass,
mimicking a pyogenic granuloma.
Diagnosis:-
Biopsy is a gold standard for the diagnosis of Pyogenic granuloma. Radiographic evaluation is not
satisfactory in case of pyogenic granuloma.
Histopathology:-
Pyogenic granuloma is partially or completely covered by parakeratotic or non-keratinized stratified
squamous epithelium. Major bulk of the lesion is formed by a lobulated or a non lobulated mass of
angiomatous tissue. Usually, lobulated lesions are composed of solid endothelial proliferation or
proliferation of capillary sized blood vessels. The amount of collagen in the connective tissue of pyogenic
granuloma is usually dense. Surface is usually ulcerated and shows edema, chronic inflammatory cell
infiltrates can also be seen.[46]
72
Figure 8.14: Pyogenic Granuloma. Low-powerview showing an exophytic mass of granulation -like Figure 8.15: Pyogenic Granuloma. Higher-power view showing capillary blood vessels and
tissue with an ulcerated surface. Note the lobular endothelial proliferation in the deeper connective tissue. scattered inflammation
Treatment:-
Surgical excision of the lesion is recommended. Another treatment modalities include cryosurgery,
electrosurgery, laser excision. Intralesional steroid therapy can also be used for recurrent lesions.
73
Benign Soft
9 Tissue Tumors
?Hemangioma
?Squamous papilloma
?Solitary neurofibroma of tongue
?Congenital granular cell tumor
?Lymphangioma of tongue
?Nasopharyngeal angiofibroma
?Melanotic neuroectodermal tumor of infancy
?Congenital epulis
Hemangioma
H emangiomas are benign proliferations of vessels closely resembling normal vessels. They
are also considered as a vascular malformations or congenital structural anomalies of blood
vessels that are non-neoplastic.
Hemangiomas may occur anywhere on the body. Some children may have more than one. There are
three main types:
1. Superficial type- Hemangiomas are present on the surface of the skin. These look flat at first,
and then become bright red with a raised, uneven surface.
2. Deep- Hemangiomas are present under the skin. These appear as a bluish-purple swelling with a
smooth surface.
3. Mixed- These hemangiomas have both superficial and deep components.
(a) Arteriovenous hemangioma
It is the most serious of all the hemangiomas and is life-threatening.
Etiopathogenesis:-
The pathogenesis of AVHs originates with fetal endothelial cell precursors. During development, one
or a few of these cells lose their capacity to form or secrete platelet-derived growth factor (PDGF) and
transforming growth factor beta-1(TGF-â1), which are essential to recruit adventitial cells around
developing vessels. Therefore, the daughter cells and finally the vessels that arise from these original cells
develop as single cell-lined vessels (arteries, arterioles, veins, and venules). During prepuberty there is
usually deficient pressure to cause these structurally unsupported vessels to expand and produce
symptoms. However, beginning at 10 years of age, the maturity of the cardiovascular system and the
increased systemic pressure causes these single cell-lined vessels to expand. As they expand, they create
turbulence and a negative pressure that reverses the local flow dynamics to feed blood into this expanded
lumen and even recruit new feeder vessels. This process is known as the black hole phenomenon.
Clinical Features:-
Ø It is most commonly seen in teenagers and young adults but this type is not present during infancy.
Ø
Most commonly involved sites are skin, lips, maxilla, mandible and tongue.
Ø
It is characterized as a solitary blue red nodule,
frequently occur in the skin of the midface and
around the lips.
Ø
AHV's can also give rise to paresthesias in the
lip, due to pulsatile pressure on the inferior
alveolar nerve.
Ø
The patient is often able to notice a “whirring
sound” or will claim to hear their heartbeat
within the lesion.
Ø
Hemangiomas are affecting maxilla and
mandible can give rise to mobility of teeth as
Figure 9.1: Arteriovenous hemangioma of lip
well as periodontal bone loss.
AVHs that occur in the jaws may be subclinical. They will resemble odontogenic tumors such as
ameloblastoma, odontogenic myxomas, and ameloblastic fibromas. Those with some fine bone
trabeculations may instead resemble fibro-osseous diseases such as fibrous dysplasia, ossifying fibroma,
central giant cell tumors, or even the infectious disease chronic sclerosing osteomyelitis.
Diagnosis:-
Diagnosis of AVHs generally depends on adequate clinical examination. Other diagnostic aids
include the Biopsy, Radiography, CT scan, MRI, angiogram which are helpful to determine the extent of the
disease.
Histopathology:-
Histologically, dilated vessels, comprising only a single row of endothelial cells, are
present. In close proximity, feeder arteries and veins may be seen. Often there is
thickening of the intima of the vein because of increased pressure, but no adventitial
cells are present.
Figure 9.2: Histopathology of arteriovenous

hemangioma
The radiographic picture will vary from distinctly radiolucent; to a well-defined multilocular
appearance, often described as a “soap bubble”; to a fine, mixed radiolucent-radiopaque appearance that
resembles fibrous dysplasia. It is also common to see periosteal new bone formation perpendicular to the
cortex, which on occlusal radiographs will have the so called sun-ray appearance more often associated
with osteosarcoma. A careful radiographic inspection frequently reveals periodontal bone loss around one
or more teeth, which will appear to be elevated in their sockets.
75
Treatment:-
The main aim of the treatment is to decrease the flow of the blood to the lesion, so it can be excised
with minimal blood loss. Ideal therapy for lesion includes the selective embolization followed by surgeries.
Some lesions in soft tissue may be unresectable. In particular, large lesions of the tongue may require total
glossectomy in young adults, creating obvious swallowing, speech, and aspiration difficulties. Such
“unresectable lesions” in soft tissue may be managed with serial embolizations, usually performed
annually. A few lesions resolve completely after several embolizations; most persist but no longer continue
to pose a bleeding threat; and a few others continue to develop new high pressure vessels, leading to a risky
resection or to eventual death.
(b) Juvenile Capillary Hemangioma
It is the most common vascular neoplasm in infants. The typical clinical course of juvenile capillary
hemangioma follows a pattern of growth (proliferation) followed by spontaneous involution. It is also
known as infantile hemangioma.
Etiopathogenesis:-
This hemangioma is a vascular malformation of a series of abnormal vessels fed by a single normal
arteriole and therefore is not under abnormally high pressure and does not pose a bleeding threat.
Pathogenesis of juvenile capillary hemangioma involves two phases such as-
v Proliferative phase
v Involuted phase
During the proliferative phase, the vessels are disorganized and composed of immature endothelial
cells but are not leaky, perhaps due to the abundance of á-smooth muscle actin (á-SMA)-positive
perivascular that circumscribe the vessels. When the tumor involutes, the vessels mature and enlarge but are
reduced in number. Fat, fibroblasts and connective tissue replace the vascular tissue, with few large feeding
and draining vessels evident. Both angiogenesis and vasculogenesis have been proposed as mechanisms
contributing to the neovascularization in hemangioma tumors. Angiogenesis is defined as the growth of
new vessels from pre-existing vessels, requiring degradation of the basement membrane, migration of
endothelial cells and tubulogenesis, followed by recruitment of perivascular cells. Vasculogenesis is the de
novo formation of blood vessels from stem or progenitor cells. In recent years, several of the “building
blocks”, the cells comprising the hemangioma, have been isolated. Among them are hemangioma
progenitor/stem cells (HemSC), endothelial cells (HemEC) and pericytes (HemPericytes)
Clinical Features:-
Ø It is most commonly seen in children and young adults. Girls are more commonly affected than
boys.
Ø Most commonly involved sites are superficial skin area of the chin, upper neck as well as parotid
area.
Ø It is characterized as a red-blue multinodular mass with a thin overlying skin.
Ø It is usually painless, it may ulcerate and can rupture the thin overlying skin.
Ø The lesion usually become apparent about 2 to 6 weeks after the birth and then rapidly enlarge to its
maximum size by 6 to 9 months of age.
Ø As the lesion regress, it loses its red to violaceous color and give pale appearance. As it involutes, it
give wrinkled appearance to the skin.
76
Ø
Port-wine stains are a common capillary malformation that occurs in 0.35% to 1.0% of newborns.
Ø
Syndrome associated with infantile hemangioma are PHACE
syndrome, LUMBAR syndrome, Sturge-Weber syndrome, Rendu-
Osler-Weber syndrome, Kasabach-Merritt syndrome, Maffuci
syndrome, von Hippel-Lindau syndrome, Klippel-Trenaunay-
Weber syndrome. Figure 9.3: Superficial capillary hemangioma
Diagnosis:-
Diagnosis of juvenile capillary hemangioma generally depends on the adequate clinical examination
and biopsy. Other diagnostic aids are not useful in the diagnosis of this disease.
Histopathology:-
Hemangiomas may be classified as either capillary or cavernous; however, both types consist of
proliferative vascular channels that are lined by endothelium and lack a muscular coat. Erythrocytes are in
the lumen. The arrangement is often lobular, since capillaries proliferate
around a feeder vessel. Capillary hemangiomas may initially be extremely
cellular lesions composed of endothelial cells and poorly canalized vessels.
Mitoses may be present. In early stages, these have been called juvenile
hemangiomas. Mast cells, which may be a source of angiogenic factors, can
be seen. As these lesions mature, the vessels are canalized, and the
endothelial cells flatten to form the typical capillary hemangioma. When Figure 9.4: Histopathology of juvenile capillary hemangioma
they undergo regression it is through interstitial fibrosis.
Treatment:-
The best therapy in most cases is time and the prevention of overaggressive therapy during the
hemangioma's active growth phase. Parental education and reassurance about involution are of great value.
Other treatment modalities include cosmetic/reconstructive surgery. Although cryosurgery, sclerosing
agents, and surgical excision have all been used, these methods often create more scarring and
disfigurement than the lesion itself or its involution.[47]
(c) Cavernous hemangioma
It is less common type than juvenile capillary hemangioma. Cavernous hemangiomas are more larger,
diffuse, deeper and partially involute. Therefore, they persist into adult life unchanged or somewhat
fibrosed.
Clinical Features:-
Ø Cavernous hemangioma is most commonly seen at or just after birth.
Ø It is characterized as a soft, diffuse, puffy mass in the parotid region
and in the posterior mandible.
Ø It can also be seen as a large, soft, blue-red, painless blanching mass
in the oral mucosa.
Ø Soft tissue cavernous hemangioma can also lead to the resorption of
bony cortex.
Figure 9.5: Cavernous hemangioma
77
These lesions generally do not undergo involution, they develop calcifications via phlebolith
Ø
formation.
ü Because of their deep location, the red-blue vascular nature of cavernous hemangioma is less
apparent and therefore initially may not be correctly recognized. Lymphangiomas can bear a
strong resemblance to cavernous hemangiomas because they too are soft and diffuse and can
impart a red-blue appearance by virtue of their hemangiomatous components, some blood in their
abnormal lymphatic spaces, and the bluish color of lymph when viewed through skin.
ü Neurofibromas and lipomas also clinically will have a soft, diffuse, and irregular quality to their
presentation, mimicking that of a soft tissue cavernous hemangioma.
ü Cavernous hemangiomas centrally located in bone will mostly resemble fibro-osseous diseases or
bone tumors. They will produce a radiographic appearance most similar to an ossifying fibroma or
an osteoblastoma. In the jaws, some may be confused with a developing odontoma, a calcifying
odontogenic cyst, or a calcifying epithelial odontogenic tumor.
Diagnosis:-
Diagnosis generally depends on the adequate clinical examination. Other diagnostic aids include
biopsy, radiography, angiogram.
Histopathology:-
Cavernous hemangiomas are less circumscribed than
capillary hemangiomas and have dilated vascular
channels with flattened endothelium. Calcifications
and formation of phleboliths occur through dystrophic
calcification of organizing thrombi, but regression
Figure 9.6: (A) Cavernous hemangioma at 10X (B) Cavernous hemangioma at 40X magnification does not occur.
magnification,
Radiographic Fatures:-
Radiography is helpful in the demonstration of dystrophic calcification in an organized thrombi.
Multiple small, round radiodensities superimposed over ramus and posterior body can also be seen.
Treatment:-
Surgical excision is recommended in soft tissue cavernous hemangioma. Other treatment modalities
include reconstructive surgery, ablation with cryosurgery, laser surgery. Sclerosing agents, such as sodium
morrhuate, sodium psyllate, or a slurry of 250 mg tetracycline in 5 mL of saline, are useful in inducing
fibrosis in most cavernous hemangiomas.[11]
Juvenile Nasopharyngeal Angiofibroma

It is a rare benign tumor arising predominantly in the nasopharynx of adolescents. It is a life-
threatening tumor because of its vascularity and location.
Etiopathogenesis:-
A hormonal theory has been suggested due to the lesion's occurrence in adolescents males. Other
theories include a desmoplastic response of the nasopharngeal periosteum or the embryonic fibrocartilage.
Efforts to determine the pathogenesis of the tumor have been done by studying the expression of various
78
growth factors and oncogenes such as C-KIT and C-MYC. Significantly higher immune staining with
CD34, vascular endothelial growth factor, flt-1 and flk-1 in JNF, when compared to orbital cavernous
hemangiomas, indicates its vasoproliferative nature. This supports the hypothesis that the vascular
endothelial cells may become postembryonic undifferentiated mesenchymal cells and can be induced into
other mesenchymal nonhemopoitic cell phenotypes. The GSTM 1 gene has been implicated in the
formation of JNA. Loss of expression of GSTM 1 (null genotype) is seen in this tumour.
Clinical Features:-
Ø This tumour is most commonly seen in children and young adults. Males are more commonly
affected than females.
Ø According to many reports, this tumour is more common in the Indian subcontinent than in the
west.
Ø Patient generally complaints of the nasal obstruction and episode of epistaxis.
Ø Juvenile nasopharyngeal angiofibroma is characterized as a red-blue polypoid mass, which may
protrude into the pharynx or into the anterior nasal cavity.
Ø The tumour is generally painless, but its size as well as its erosion into adjacent structures will
produce a variety of signs.
Ø Orbital invasion is also very common which leads to the visual changes such as diplopia.
Ø Obstruction of Eustachian tube further leads to the secondary otitis media as well as the obstruction
of sinus drainage can lead to the sinusitis in any of the paranasal sinuses.
Ø Based on the clinical as well as radiological features, JNA is classified into three types:-
v Type 1- includes lesions fundamentally localized to the nasal cavity, paranasal sinus,
nasopharynx, or pterygopalatine fossa.
v Type 2- JNA extending into the infratemporal fossa, buccal region, or orbital cavity with
anterior and/or minimal middle cranial fossa extension but intact dura mater.
v Type3- it is a calabash-like massive tumor lobe in the middle cranial fossa.
The clinical presentation of a nasopharyngeal angiofibroma is very distinctive. Occasionally, a
vascular nasal polyp will produce a mass-related epistaxis, or an allergic rhinitis will produce swollen
bleeding nasal membranes, which may be mistaken for a nasopharyngeal angiofibroma. Vascular
malformations and hemangiomas are other clinical possibilities.
Diagnosis:-
Accurate diagnosis generally depends on the CT scan, which is useful for assessing the extent as well
as location of the tumour. Another diagnostic aids include biopsy, angiogram. Incisional biopsy is not
indicated in all the cases because it can lead to the profuse bleeding.
Histopathology:-
JNV is firm, rubbery, lobulated mass which is fibrovascular. The
stromal collagen fibers are often in parallel arrangement, and there may be
areas of hyalinization and myxoid degeneration. The vessels may be slit-like,
but they are characteristically angulated or staghorn in shape. They have a
normal endothelial lining but lack elastic fibers, and smooth muscle is sparse
or absent. Mast cells are prominent. Figure 9.7: Nasopharyngeal Angiofibroma. Moderately
cellular fibrous connective tissue with prominent blood
vessels
79
Treatment:-
Recommended treatment for JNV is complete surgical excision with wide access and minimal blood
loss. The testosterone receptor blocker flutamide was reported to reduce the size of the tumour in early
stages. External beam irradiation is most often reserved for intracranial, unresectable or recurrent disease.
Postoperative radiographic surveillance is important due to high rates of recurrence.[48]
Squamous Papilloma
It is a benign proliferative lesion of the squamous epithelial origin. It is the most common lesion of the
oral cavity.
Etiopathogenesis:-
The squamous papilloma is also noteworthy for its uncertain pathogenesis. According to many oral
and maxillofacial specialist, human papilloma virus is the main causative agent of squamous papilloma.
HPV subtype 2, 6, 11, and 57 is most commonly involved.
Clinical Features:-
Ø Squamous papilloma is commonly seen in children and young adults. Children especially <10
years are more commonly affected.
Ø Most commonly involved sites are mucosa of hard and soft palate, uvula, vermilion of lips.
Ø It is characterized as a painless, slow growing, cauliflower like lesion, that is neither transmissible
nor threatening.
Ø Lesions are usually asymptomatic without
induration, they generally have a sessile base
but may sometimes have a stalk.
Ø Mode of transmission for children has been
reported as ingestion of viral particles of
Figure 9.8: Squamous Papilloma. A pedunculated Figure 9.9: Squamous Papilloma. A pedunculated
infected cells from the birth canal, whereas in lingual mass with numerous long, pointed and mass of the buccal commissure, exhibiting short
white surface projections. Note the smaller or blunted surface projections & minimal white
adults through sexual contact. projections around the base of the lesion coloration.
w Single squamous papillomas may resemble verrucous carcinomas or even exophytic squamous cell
carcinomas. If they have a sessile base. Certainly the finding of induration or ulceration would lead
the clinician to suspect these two concerning lesions more strongly than a squamous papilloma.
w In addition, clustered or multiple squamous papillomas would suggest focal epithelial hyperplasia.
w In addition, a verruciform xanthoma will clinically resemble squamous papilloma, but it is mostly
seen on the gingival or the edentulous alveolar ridge
Diagnosis:-
Diagnosis generally depends on clinical examination and adequate history taking. Other diagnostic
aids include cytology, biopsy, immunohistochemistry and molecular techniques such as PCR.
Histopathology:-
The papilloma is a benign proliferation of squamous epithelium. With the epithelium's dependence
for nutrition on the underlying fibrovascular tissue, the most efficient growth pattern is one of exophytic
papillary projections, each with a fibrovascular core. The epithelium may show orthokeratosis,
80
parakeratosis, and/or acanthosis. Mitoses may be numerous but are usually
confined to the basal area. The prickle cells may have a clear glycogen-filled
cytoplasm, particularly in lesions of the soft palate. Koilocytic cells
(epithelial cells with pyknotic nuclei surrounded by a clear halo), which are
often associated with viral disease, also may be present, but they can also be
found in nonvirally infected oral mucosa. Their presence is not sufficient to
9.10: Squamous Papilloma. Low-power view showing
confirm a viral etiology for any particular papilloma. The lamina propria aFigure pedunculated squamous epithelial proliferation. There are
multiple papillary projections with fibrovascular connective
frequently contains a chronic inflammatory infiltrate. tissue cores.
Treatment:-
Surgical excision is recommended for squamous papilloma. Recurrence or new lesions should raise
suspicions of a possible retransmission of a condyloma acuminatum or of carcinoma.[49]
Solitary Neurofibroma
Neurofibromas may present either as a solitary lesion or as a part of syndrome i.e. neurofibromatosis.
A solitary neurofibroma is generally a single neurofibroma that occurs in an individual who does not have
hereditary neurofibromatosis.
The condition may at first be difficult to identify because a single neurofibroma may be the first sign
of neurofibromatosis, and the hereditary history of neurofibromatosis may be lacking because of the high
incidence of new cases due to spontaneous mutations. Nevertheless, solitary neurofibromas account for
90% of cases of neurofibroma (the other 10% are associated with neurofibromatosis).
Clinical Features:-
Ø It is most commonly seen in teenagers, it is characterized as a an asymptomatic mass within the
subcutaneous or submucosal tissues.
Ø Neurofibromas can also be seen in infratemporal spaces, lateral pharyngeal spaces as well as in
pterygomandibular spaces.
Ø Clinicopathological subtypes of neurofibromas include- localized neurofibroma, diffuse
neurofibroma, plexiform neurofibroma, epithelioid neurofibroma.
Ø Localized as well as solitary neurofibroma develops along a peripheral nerve as a focal mass with
well-defined margins but is not encapsulated.
Ø Plexiform neurofibroma generally arise from multiple nerves, as a
solitary large pendulous mass with overlying pigmentation, lesion is
generally encapsulated.
Ø Neurofibroma of head and neck region can lead to upper airway
obstruction, difficulty in swallowing as well as mastication,
cosmetic distortion of face.
Ø Lesion can further infiltrate into the adjacent normal tissues such as nodular
Figure 9.11: Solita ry Neurofibroma. Smooth-surfaced,
mass of the maxillary gingival and alveolar mucosa.
muscles, glands and lymph nodes
The diffuse, soft nature of the neurofibroma will give the same tactile impression as that of a lipoma, a
vascular malformation, a lymphangioma, and a rhabdomyoma. Vascular malformations and
lymphangiomas especillay are seen more commonly in the same young age group as are neurofibromas.
81
Diagnosis:-
A neurofibroma is generally diagnosed by incisional biopsy. Other diagnostic aids include CT scan.
Radiotherapy is not an option because of the possibility of radiation sarcomas developing in future years.
Histopathology:-
The lesions are unencapsulated, consisting of interlacing bundles of spindle cells that typically have
wavy or “serpentine” nuclei. The stroma is often fibrillar and eosinophilic but may have mucoid areas. Mast
cells and scattered lymphocytes are usually present, and neurites may be found within the tumor. The
solitary neurofibroma and the usual neurofibroma of neurofibromatosis do not differ histologically.
Cellular atypia may be seen in benign neurofibromas, but mitotic activity indicates malignant change. This
phenomenon is more likely to be seen in neurofibromatosis. Although Schwann cells appear to be a major
component of neurofibromas, other cells, such as fibroblasts, are also present.
Treatment:-
The treatment modalities for solitary neurofibroma includes surgical excision, radical excision,
reconstructive surgery.
In rare cases of diffuse or plexiform neurofibromas where complete surgical excision is not possible,
lesions are often totally resected for cosmetic or
symptomatic relief. These patients require monitoring
to watch for rapid growth or recurrence at the discretion
of the clinical providers. Interferon-alpha has been
studied as an adjunct therapy for plexiform
neurofibromas, with variable results.[50] Figure 9.12: Low-power view showing a
cellular tumor mass below the epithelial surface.
Figure 9.13: High-power view showing
spindle shaped cells with wavy nuclei.
Congenital Granular Cell Tumour

The congenital granular cell tumor is a specific lesion representing a hamartomatous proliferation of
granular cells rather than a true neoplasm. It is also known as a Neuman tumor or congenital granular cell
epulis.
Most favored theories are odontogenic epithelial and gingival epithelial theories, which support its
origin from the mesenchyme.
Clinical Features:-
Ø It is most commonly present at birth, females are more commonly affected than males.
Ø Most commonly involved sites are anterior maxillary and mandibular gingiva, alveolar ridge and
tongue but maxillary gingiva is more commonly affected than mandibular gingiva.
Ø It is characterized as a painless mass, that arise from a narrow stalk, Some lesions are large in size
and can interfere with feeding.
w Congenital granular cell tumor is a clinically recognizable tumor if
the clinician identifies a stalk and an intact surface epithelium and
confirms that the tumor was present at birth. The melanotic
neuroectodermal tumor of infancy (MNETI) is the primary
differential that can easily be eliminated if the parents or obstetrician
can confirm the presence of the mass at birth. The MNETI is not a
congenital lesion; it will arise between 2 and 11 months of age. The Figure 9.14: Granular Cell Tumor. Nodular mass of the
buccal mucosa near the commissure
82
MNETI will also show clinically black to blue pigmentation and destruction of the anterior maxilla.
w
Malignancies such as a rhabdomyosarcoma or a neuroblastoma are also serious considerations, but
each will be a mass destructive of bone and will not have an associated stalk.
w
Benign lesions common to newborns, such as hemangiomas and lymphangiomas, are also
considerations, but these also will not emerge from a single stalk.
Diagnosis:-
The first step of diagnosis generally depends on adequate clinical examination as well as history
taking. Excisional biopsy is a gold standard for the diagnosis of congenital granular cell tumour.
Histopathology:-
The histologic appearance of the cells composing this tumor is
identical to that of the granular cell tumor because the cells have a granular
eosinophilic cytoplasm due to the presence of enlarged lysosomes. Certain
differences do exist, however. The congenital tumor does not show
pseudoepitheliomatous hyperplasia. It is also more vascular.
Ultrastructurally, it lacks angulate bodies but shows smooth muscle features
not present in the granular cell tumor. In addition, it is negative for S-100 showing
Figure 9.15: Granular Cell Tumor. Medium-high–power view
polygonal cells with abundant granular cytoplasm.
protein.
Treatment:-
Treatment generally depends on the surgical excision of the mass under either local anesthesia or
general anesthesia, as soon as possible after birth. Before the excision, it is well to educate the neonatal staff
and reassure parents that the tumor is not a dangerous one and that the child should not be permanently
affected in any way. It is also wise to inform the neonatal staff and parents that the baby will cry during the
procedure because of fear, not because of pain. Excision through the stalk may create a rapid blood loss in a
neonate such that transfusion is required. Such blood loss can easily be prevented. Before the lesion is
excised, the stalk should be stretched slightly and two hemostats placed on the stalk. The stalk should be cut
between the hemostats, the tumor mass delivered on one hemostat and the other hemostat used to gain a
tissue vascular tie. In this manner, the tumor can be removed with no blood loss.[51]
Lymphangioma
It is a benign tumour, resulting from a congenital malformation of the lymphatic system.
Lymphangiomas are generally categorized as deep or superficial based on the depth and size of the
abnormal lymphatic vessels or as congenital or acquired.
The deep forms of lymphangioma include two specific well defined congenital entities: cavernous
lymphangiomas and cystic hygromas. Superficial forms of lymphangioma include lymphangioma
circumscriptum and acquired lymphangioma, which can also be referred as lymphangiectasia.
Etiopathogenesis:-
Blockage of the lymphatic system during fetal development generally leads to the congenital
lymphangiomas, they generally develop before the age of 5 years. Cystic lymphangiomas are generally
associated with genetic disorders including trisomies 13, 18, and 21, Noonan syndrome, Turner syndrome,
and Down syndrome. Acquired lymphangioma circumscriptum occurs in association with chronic
lymphedema that leads to disruption of previously normal lymphatic channels.
83
Clinical Features:-
Ø It can be seen during infancy and early childhood. It is most commonly seen in head & neck region.
Ø Common intraoral sites are- dorsum of tongue, palate, buccal mucosa, gingiva and lips.
Ø Lymphangioma of the tongue is a common cause of macroglossia in children associated with
difficulty in swallowing and mastication, speech disturbances, airway obstruction, mandibular
prognathism, open bite and other possible deformities of maxillofacial structures.
Ø Clinically, lymphangiomas are characterized as multiple, grouped or scattered, translucent or
hemorrhagic vesicular papules.
Ø Mostly the purple area can be seen in the vesicular papule, because lesion is consist of a
combination of blood and lymph elements.
Ø Deep lesions are generally present as masses of diffuse growth, mostly depends on the anatomical
location.
Ø Acquired form of lymphangioma is most commonly found in the axilla, inguinal as well as in
genital areas. The symptoms associated with acquired form are- pruritus, pain, burning, lymphatic
drainage, infection, and aesthetic concerns.
Ø Cavernous lymphangioma is most commonly present during infancy, it is characterized as a
painless, ill-defined subcutaneous swelling, several
centimeter in diameter.
Ø Cystic hygromas are most commonly present in
infants, they are lymphatic malformations that are
clinically more circumscribed than cavernous
lymphangioma and typically occur on the neck, axilla,
or groin. These are generally soft lesions and are Figure 9.16: Lymphatic Malformation.
Figure 9.17: Lymphatic Malformation. Pebbly, vesicle-
present in various diameters. It is most commonly involving
Young boy with a cystic hygroma primarily like appearance of a tumor of the right lateral tongue
the right side of the face.
present on posterior neck.
Because of their soft quality, lymphangiomas will most closely resemble lipomas, salivary retention
phenomenon and hemangioma. Because many lymphangiomas actually have some blood in their
lymphatic channels, they are most often confused with hemangiomas; thus the term
hemangiolymphangioma has been applied to such lesions. However, these basically represent
lymphangiomas with communications to normal blood vessels.
Diagnosis:-
The first step of diagnosis generally depends on adequate clinical examination as well as history
taking. No definitive studies other than an exploration and biopsy will confirm the diagnosis of a
lymphangioma. MRI can be useful in determining the extent of anatomical involvement of cystic or
cavernous lymphangiomas. An angiography will rule out a vascular lesion such as an arteriovenous or
cavernous hemangioma. A CT scan will raise suspicions of a lymphangioma if it shows multiple areas or
large spaces that are homogeneous and do not enhance with contrast injections.
Histopathology:-
On histopathologic examination, lesions of superficial lymphangioma consist of a collection of large
lymphatic cisterns lying deep in the subcutaneous plane that communicate via dilated dermal lymphatic
channels lined with endothelial cells. The overlying epithelium is usually acanthotic or hyperkeratotic and
84
has an irregular elongation of rete pegs. No atypical
vascular features, nuclear atypia, mitotic activity, or
koilocytic changes typically exist. A mild to the
moderate inflammatory infiltrate may be present.
Cystic hygromas differ only in that they are usually
composed of very large, interconnecting, High-power Figure 9.18: Microcystic Lymphatic Malformation. Figure 9.19: Macrocystic Lymphatic Malformation.
photomicrograph showing dilated, Lesion from the neck showing markedly dilated
lymph-filled vessels immediately below the atrophic lymphatic vessels
endothelially lined, cyst-like spaces. surface epithelium
Treatment:-
Lymphangiomas are generally difficult to treat. Surgical excision is a treatment of choice for
lymphangiomas. Recurrence rates are generally high in case of lymphangiomas, so Wide local excision of
the affected lymphatic channels is necessary. Surgical success rates are higher for small, superficial
lymphangiomas.
Other treatment modalities include carbon dioxide (CO2) laser, long-pulsed Nd-YAG laser, and
electrosurgery. Compression may reduce swelling caused by lymphedema. If the cystic hygroma has
compromised the airway, a tracheostomy may be required before this time.[52]
Melanotic Neuroectodermal Tumor of Infancy

It is a rare and benign neoplasm of neuroectodermal origin.
Etiopathogenesis:-
The MNTI usually originates from neural crest cells, represents an overgrowth of these cells rather
than their usual involution. Normally, neural crest cells originate from a mantle around the developing
spinal cord and project out to the periphery along sympathetic nerves. In other parts of the body, they
populate the primordia of sympathetic ganglia and the adrenal medulla to become neurosecretory cells of
these respective structures. In the maxilla and most peripheral sympathetic neural pathways, they involute.
Those that develop into the MNTI are the rare failures of involution, which instead proliferate into a tumor.
Clinical Features:-
Ø It is most commonly seen in infants and children below 1 year of age without any predilection of
gender.
Ø Most commonly involved sites are- head and neck region especially
anterior region of the maxilla, mandible, skull, brain and
epididymis.
Ø It is characterized as a soft and rapidly growing, painless, pigmented
swelling, which can often lead to the destruction of underlying bone
and displacement of developing teeth.
Ø The mass generally appear as round with bluish black coloration and Infant
Figure 9.20: Melanotic Neuroectodermal Tumor of Infancy.
with an expansile mass of the anterior maxilla.
most commonly involve the primary central incisors.
85
w The rapid development and, at times, frightening growth of the MNTI suggest a malignancy. In
particular, the neuroblastoma is a distinct and serious consideration. The few cases of so-called
malignant MNTI that have recurred oe metastasized have probably represented neuroblastomas,
which are the most common early childhood malignancy and the fourth most common malignancy
in the head and neck area.
w Other infancy tumors with aggressive behavior and possible blue colorations are
rhabdomyosarcomas, which have a predilection for the head and neck area in children, and
hemangiomas or lymphangiomas, which indeed may present with a bluish color and often appear
within a few months after birth with rapid development.
w The congenital granular cell tumor, which also frequently arises from the anterior maxilla and is
seen in infants, is not a consideration because it is always congenital, whereas the MNTI is never
congenital. Questioning the parent or the birthing team about the presence of an oral mass at birth
will distinguish between the two.
Diagnosis:-
The most important diagnostic step is a confirmatory incisional biopsy. Conventional radiographs of
bony lesions usually show radiolucency with or without irregular margins. It is typical of CT scans to reveal
hyperdense masses, but hypodense variants have been reported as well. The CT can accurately define the
extent of the lesion and thus provides a good basis for surgical planning. Magnetic resonance imaging
shows a hypodense mass with focal areas of hyperdensity. IHC markers are helpful in differentiating MNTI
from embryonal rhabdomyosarcoma (desmin and myoglobin positive), Burkitt's lymphoma (common
leukocyte antigen positive) and malignant melanoma (HMB-45 and S-100 positive). A high level of
urinary VMA is useful for diagnosing tumors of neural crest origin.
Histopathology:-
These infiltrating, unencapsulated tumors have irregular alveolar spaces and a dense, fibrous stroma.
The spaces contain two types of cells. The larger cuboidal cell usually lines the space and has a pale nucleus
and abundant cytoplasm, which often contains melanin. These cells are S-100 negative, however. The more
centrally located cells are smaller and round with a deeply staining nucleus and scant cytoplasm,
resembling neuroblasts. Mitoses are not seen. These tumors appear to be of neural crest origin, and
neuroblastic and melanocytic cell lines have been identified ultrastructurally. Both cell types are positive
for neuron specific enolase and synaptophyisn and
negative for S 100. The larger cells are cytokeratin
positive and HMB (human melanoma block)-45
positive, features that are noted in pigmented retinal
epithelium. In the rare instances in which these tumors
have behaved in a malignant fashion, their histologic Figure 9.21: Melanotic Neuroectodermal Tumor Figure 9.22: Melanotic Neuroectodermal Tumor
of Infancy. Low-power view showing nests of of Infancy. High-power view of a tumor nest
appearance and clinical behavior have paralleled epithelioid cells within a fibrous stroma. demonstrating two cell types: 1) small, hyper-
chromatic round cells and 2) larger epithelioid
cells with vesicular nuclei. Some stippled
those of the neuroblastoma. melanin pigment is also present
86
Treatment:-
Complete surgical excision is a treatment of choice for MNTI. Other treatment modalities include
chemotherapy alone, chemotherapy with radiotherapy, chemotherapy before and after the surgical
treatment, radiotherapy and surgical treatment or a combination of all. Chemotherapy may serve as an
alternative or adjuvant option in the treatment of widely extended MNTIs.[53]
Congenital Epulis
It is a benign tumour of the oral cavity, is an extremely rare condition in newborn. It is also known as
'Neumann tumour', mostly occurs as a single tumour but rarely as multiple.
A number of researches have suggested that the congenital epulis is a malformation of the dental blastema
and should be regarded as a type of embroynal hamartoma and not a true neoplasm. The basis for such a
belief is the presence of numerous epithelial rests in some sections of the tumour. Such epithelial inclusions
are remnants of the dental lamina and may be found normally in most jaws of infants. Their occurrence in
the congenital epulis is more likely to be coincidental than associated with the development of the lesion.
Other theories of origin include the fibroblastic, histiocytic, myogenic and neurogenic.
Clinical Features:-
Ø This tumour is most commonly present at birth, females are more commonly affected than males.
Ø Most commonly involved sites are- alveolar ridges of maxilla and mandible as well as maxillary
and mandibular gingiva, but it is more frequently seen in maxilla than mandible.
Ø It is characterized as a large, sessile or pedunclated lesion, varying
in diameter, pink or red in color, nonpainful on palpation and
generally found in deciduous lateral incisor-canine region.
Ø The lesion can lead to various dental abnormalities such as missing
and hypoplastic teeth, mid face hypoplasia. The lesion can also
interfere with respiration as well as feeding in infants.
Ø Other defects in which congenital epulis may be associated are alveolarFigure 9.23: Polypoid mass of the anterior maxillary
ridge in a newborn
polydactyly, goiter, neurofibromatosis, triple X syndrome.
Diagnosis:-
The most important diagnostic step is a biopsy. Apart from this, Perinatal MRI of the oral cavity helps
in differentiating congenital epulis from other masses of oral cavity and in determining characteristics of
the mass.
Histopathology:-
The congenital epulis is histologically similar to the granular cell tumour, although
pseudoepitheliomatous hyperplasia does not occur in the former lesion. Thus sheets of large, closely
packed cells showing fine, granular, eosinophilic cytoplasm comprise the tumour mass. Neither mitoses
nor cross-striations are visible, but capillaries are numerous. In fact, the vascular component is much more
prominent than in the granular cell tumour.
Electron microscopic study revealed junctional complexes between some of the granular cells which
suggests an epithelial origin but is not conclusive. However, ultrastructural findings strongly support a
mesenchymal histogenesis. In addition, their tissue assay for estrogen receptors was negative, but
considering the marked predilection of the lesion for females, a hormonal factor could not be ruled out in its
development. Congenital epulis is negative for S100 and other markers found in the granular cell tumour.
87
Figure 9.24: Low-power photomicrograph showing a nodular tumor mass. Note the atrophy Figure 9.25: High-power view of rounded cells with abundant granular cytoplasm
of the rete ridges
Treatment:-
It can be managed by complete surgical excision under general and local anesthesia. Recurrence is
rare in case of congenital epulis. If congenital epulis is not interfering with feeding or respiration,
nonsurgical management can be considered. But if these issues arise, surgical intervention should be
strongly considered.[54]
88
Malignant Soft
10 Tissue Tumors
?Rhabdomyosarcoma
?Alveolar soft part sarcoma
?Osteosarcoma
?Ewing sarcoma
?Acute lymphoblastic leukemia
Rhabdomyosarcoma
I t is the most common soft tissue sarcoma of childhood and it is the third most common
extracranial solid tumour of childhood after neuroblastoma and Wilms tumour.
Rhabdomyosarcomas are malignant tumours of primitive mesenchymal cells that undergo partial
rhabdomyoblast differentiation. There are three basic histologic types of rhabdomyosarcoma-
a) Embryonal type
b) Alveolar type
c) Pleomorphic type
The embryonal rhabdomyosarcoma develops from undifferentiated mesenchymal stem cells, which
can resemble different stages in the development of skeletal muscle. In embryonal rhabdomyosarcoma, the
loss of heterozygosity of chromosome IIp15 was identified and in alveolar type unique translocation occurs
between the FKHR gene on chromosome 13 and either the PAX3 gene on chromosome 2 or the PAX7 gene
on chromosome I. Individuals with the PAX7 translocation are younger and may have longer event-free
survival than those with the PAX3 translocation.
Clinical Features:-
Ø It is most commonly seen in children and young adults.
Ø Most commonly involved sites are- nasal cavity, mouth, sinuses, cheek and neck.
Ø This tumor is characterized as a rapidly growing, fleshy mass, which readily invades and destroys
bone.
Ø Rhabdomyosarcoma can also involve the medial upper quadrant of the orbit, which leads to the
destruction of nasal and orbital bone as well as
invasion into the eyelids producing marked
eyelid edema.
Ø Clinical features of orbital tumours include
diplopia and epiphora, tumor of maxillary
sinus and cheeks usually invade into adjacent
bone and the orbit.
Ø Involvement of sensory nerve leads to sensory
nerve loss and involvement of motor nerve
leads to paresis or paralysis.
Figure 10.1: Embryonal Rhabdomyosarcoma. Young child with a mass of the right maxilla
89
A tumour with rapid growth and destructiveness in a child or young adult should suggest a
rhabdomyosarcoma. Other rapidly destructive lesions in this age group are Ewing sarcoma,
neuroblastoma, an acute langerhans cell histiocytosis, and less commonly, a malignant peripheral T-cell
lymphoma. All of these are also known to invade bone in a destructive manner.
Diagnosis:-
Incisonal biopsy is a gold standard for the diagnosis of rhabdomyosarcoma. Plain radiographs, a CT
scan, or an MRI scan is required to understand the tumor's size, spatial anatomic relationship, and extent of
bony destruction. A chest radiograph is taken to rule out lung metastasis, and because rhabdomyosarcomas
have a propensity to metastasize to bone marrow, a bone marrow aspiration is also a strong consideration.
Histopathology:-
Rhabdomyosarcomas are classified according to their histologic appearance into one of three
categories:-
Embryonal Rhabdomyosarcoma- In embryonal rhabdomyosarcoma, tumors may contain small

?
round cells, but they may also contain spindle cells. Depending on their differentiation, the
cytoplasm may be scant and indistinct or more abundant and strongly eosinophilic. The cytoplasm
may be vacuolated because of the deposition of glycogen. Tadpole-shaped cells may be present, and
cross-striations can sometimes be identified in more well-differentiated tumors. Nuclei are usually
hyperchromatic and on occasion may be eccentrically situated. Mitoses may be numerous. Stromal
collagen is scant. A characteristic pattern shows areas of hypercellularity with densely packed cells
alternating with less cellular myxoid areas. These tumors are infiltrative. They may be difficult to
distinguish from other round cell tumors of childhood, such as neuroblastoma, Ewing's sarcoma,
and malignant lymphoma. A variant of
embryonal rhabdomyosarcoma is the botryoid
type, which is usually seen within mucosa-
lined cavities such as the nasopharynx and
nasal and oral cavities. Because of their
unrestricted growth, these polypoid tumors
have a mucoid stroma and myxoid appearance
with relatively few cells. Below the covering
epithelium, a dense zone of undifferentiated
cells, which has been termed the cambium layer
of Nicholson, is often found. Figure 10.2: Embryonal Rhabdomyosarcoma. Medium-power view showing a sheet of small,
round cells with hyperchromatic nuclei.
Alveolar Rhabdomyosarcoma- The alveolar

?
rhabdomyosarcoma is characterized by the
presence of clefts or alveolar spaces, which are
formed through loss of cohesion within the
tumor cell aggregates. The spaces are lined by a
single layer of tumor cells, which are attached
to fibrous septae. Some of the cells may
protrude into the space in pseudopod-like Figure 10.3: Histopathology of alveolar rhabdomyosarcoma
90
fashion. Most of the tumor cells are rounded. Multinucleated giant cells and mitoses are common.
Cross striations may sometimes be identified.
Pleomorphic Rhabdomyosarcoma- Pleomorphic rhabdomyosarcoma may be difficult to separate

?
from other pleomorphic sarcomas such as
malignant fibrous histiocytoma. There is great
variation in the size and shape of the cells.
Racquet-shaped cells, tadpole - shaped cells,
strap cells, and giant cells may be present, and
bizarre mitoses are not uncommon. Cross
striations are not usually observed. Figure 10.4: Histopathology of pleomorphic rhabdomyosarcoma
The histologic diagnosis of rhabdomyosarcoma is often difficult and usually requires ultrastructural
examination and immunohistochemistry.
Treatment:-
Rhabdomyosarcoma is treated by radical surgical excision followed by multiagent chemotherapy.
Postoperative radiotherapy is used for those cases which cannot be completely resected. Metastasis is
present in 20% of cases.[11]
Alveolar Soft Part Sarcoma

It is a rare mesenchymal tumour characterized by ASPL-TFE3 translocation. In recent years,
pathologists have shown this tumour to be a variant of a rhabdomyosarcoma. Chromosome rearrangement
at 17q25 and Xp11.2 in alveolar soft-part sarcoma was demonstrated.
Clinical Features:-
Ø It is a rare tumour that account for only 0.5-1%
of all soft tissue sarcoma.
Ø It is commonly seen in children and young
adults, females are more commonly affected
than males.
Ø Most commonly affected sites are- thigh,
buttocks, tongue and orbit.
Ø The lesions are usually slow growing, well-
circumscribed masses with no distinguishing
gross features.
Ø An important characteristic is the marked
vascularity with the potential for severe Figure 10.5: Alveolar soft part sarcoma—tumor occupying whole of hard palate with extension of soft palate
hemorrhage at surgery.
91
Diagnosis:-
Biopsy is useful for the confirmation of alveolar soft-part sarcoma.
Histopathology:-
The alveolar soft part sarcoma is a poorly circumscribed, friable tumor, typically with a uniform
histology in which the tumor cells have a nest-like arrangement. The cell clusters are divided by thin-walled
blood vessels. The cells are large, usually polygonal, with single or multiple nuclei. The abundant
cytoplasm is eosinophilic and granular. Mitoses are rare. In the center of the
nests, there is frequently necrosis with loss of cell adhesion, giving a
pseudoalveolar pattern. A characteristic feature is the presence of PAS
positive, diastase resistant crystals that are rhomboid or rod-shaped and are
visible ultrastructurally. Dilated veins, often showing tumor invasion, are
seen at the periphery. Occasionally, but particularly in children, the tumors
have a more uniform appearance and lack the nesting arrangement. These Figure 10.6: Alveolar Soft-Part Sarcoma. Alveolar
collections of large, polygonal cells containing
often have a better prognosis. abundant granular cytoplasm.
Treatment:-
Radical surgical excision is the accepted treatment for this lesion because of the high frequency of
recurrence, metastases and death of patients. When compared to other soft tissue sarcoma, around 30%
metastasise to the brain. The recurrence or metastatic rate is 70%.[11]
Osteosarcoma
It is the most common type of primary malignant bone tumour, it is thought to arise from a primitive
mesenchymal bone-forming cell and is characterized by production of osteoid.
The exact cause of osteosarcoma is unknown, but a number of risk factors exist. Rapid bone growth
appears to predispose patients to osteosracoma, as suggested by the increased incidence, during the
adolescent growth spurt, and osteosarcoma's typical location near the metaphyseal growth plate of long
bones. Exposure to radiation is the only known environmental risk factor. A genetic predisposition may
exist, for example-
? Familial cases where the deletion of chromosome 13q14 thus inactivating the retinoblastoma gene
leading to development of retinoblastoma and is associated with a particularly high risk of
osteosarcoma to develop.
? Bone dysplasias, including Paget disease, fibrous dysplasia as well as hereditary multiple exostoses
increase the risk of osteosarcoma.
? Li-Fraumeni syndrome is a predisposing factor for osteosarcoma development.
? Rothmund-Thomson syndrome is also associated with increased risk of osteosarcoma.
Clinical Features:-
Ø It is commonly seen in children and young adults, males are more commonly affected than females.
Ø Most commonly affected sites are- femur, tibia, humerus, skull and jaw bones, pelvis.
Ø Most patients with OS present with pain and swelling in the involved site. The pain is constant and
tends to worsen over time, may result in limp.
Ø Systemic symptoms such as fever and night sweats are rare.
Ø Oral Manifestations- Most common presenting symptoms of the patients are swelling of the
involved area, often producing facial deformity and pain, followed by loose teeth, paraesthesia,
92
toothache, bleeding, nasal obstruction and a variety of other manifestations. Mandible is more
commonly affected than maxilla.
A number of variants of osteosarcoma are
Ø
conventional types (i.e. osteoblastic,
chondroblastic, fibroblastic) multifocal,
telangiectatic, small cell, intraosseous well-
differentiated, intracortical, periosteal,
paraosteal, high grade surface and Figure 10.7: Osteosarcoma. A, This massive tumor had been present for many months before
the patient sought treatment. B, Intraoral photograph of the tumor mass.
extraosseous.
w The radiographic and clinical picture of an osteosarcoma can be similar to that of infections such as
osteomyelitis with proliferative periostitis, chronic sclerosing osteomyelitis, and suppurative
osteomyelitis; to benign bone tumors or benign tumors within bone such as osteoblastoma,
ossifying fibromas, and cavernous hemangiomas within bone; to odontogenic tumors such as
calcifying epithelial odontogenic tumors and ameloblastic fibro-odontomas; and to fibro-osseous
diseases or systemic diseases of bone such as fibrous dysplasia and Paget disease.
w An important clinical differential feature is neurosensory loss. Other than a rare osteomyelitis or
neural loss from a previous biopsy or surgery, only malignancies can produce objective
paraesthesias. In addition, radiographs or CT scans at right angles to the cortex should show
extracortical bone and a destroyed cortex. Fibrous dysplasia and ossifying fibroma will not have
extracortical bone. The extracortical bone seen in osteomyelitis with proliferative periostitis will be
associated with an intact cortex. Even when other osteomyelitides produce extracortical bone, it is
parallel to the cortex rather than at right angles as is seen in an osteosarcoma.
Diagnosis:-
The evaluation of a patient with suspected OS begins with a full history, physical examination, and
plain radiographs. The history is usually remarkable for the presence of pain and swelling at the primary
tumor site.The diagnosis of osteosarcoma can be confirmed by biopsy. Other diagnostic modalities include
plain X rays, bone scans, MRI, CT scan.
· Osteosarcomas may indeed produce the often described “sun-ray” appearance. However, because of
calcified cartilage or distension of reactive periosteum, other malignancies will also produce the sun-ray
appearance. Even some benign tumors or infections causing reactive periosteal distension can produce this
appearance.
? A widening of the periodontal ligament space, also called Garrington sign, is seen in several
mesenchymal malignancies as an early finding
but is most commonly seen in osteosarcoma.
? Most radiographs and computed tomographic
(CT) scans show a mottled radiopaque or mixed
radiolucent radiopaque appearance in the
medullary space. Figure 10.8: The panoramic radiograph shows a “sunburst” Figure 10.9: Osteosarcoma. Computed
tomography (CT) scan showing a mottled
pattern of trabeculation.
? Extracortical bone formation is common and radiopacity of the mandible with cortical
destruction and a focal “sunburst”
periosteal reaction.
may or may not produce the sun-ray
93
appearance. However, cortical bone destruction is characteristic and should be evident.
Maxillary osteosarcomas produce a sun-ray appearance and extracortical bone formation less
?
frequently. Because they also grow into the air space of the maxillary sinus as a bulbous radiopaque
mass, they may suggest a benign tumor of bone or a fibro-osseous disease rather than an infiltrating
malignant bone tumor.
Radiograph shows widening of periodontal ligament space and absence of lamina dura of the distal
?
root of left 1st molar due to osteosarcoma A sign of radial spicules and Codman's triangle seen in
Osteosarcoma of mandible.
Histopathology:-
? The histologic appearance of osteosarcomas is highly variable. What all osteosarcomas have in
common is the direct formation of osteoid from a sarcomatous stroma. The quantity of osteoid and
bone that is formed varies considerably, ranging from a sclerotic osseous tumor to one in which
multiple sections may be necessary to identify some semblance of osteoid.
? The stromal cells may be osteoblastic, chondroblastic, and/or fibroblastic. However, distinguishing
osteoblastic, chondroblastic, and fibroblastic osteosarcomas based on the most prominent pattern
does not seem to have any prognostic significance.
? In general, osteoblastic tumors are most common, but in the jaws the chondroblastic pattern
prevails.
? A myxoid stroma is also frequently seen, and an atypical myxoid proliferation should alert one to the
possibility of osteosarcoma. The majority of tumors are not homogeneous, reflecting the
pluripotentiality of the proliferating mesenchymal cell.
? Some osteosarcomas are very heavily ossified, and in these cases there may be entrapment of tumor
cells within the sclerotic osteoid, such that the cells appear to represent osteocytes. This process is
known as normalization because the osteocytic cells are small and no longer retain their malignant
morphologic features.
? Mitoses may be present, but they are not usually numerous.
? Multinucleated giant cells may also be present, sometimes in large numbers, although they are
unusual in the jaws.
? Stromal cells may be predominantly rounded, spindled, angulated, or pleomorphic with marked
atypia. Other histologic variants include a telangiectatic type in which there are numerous widely
dilated vascular channels and prominent multinucleated giant cells. This type is uncommon in the
jaws.
? The small cell osteosarcoma may resemble Ewing's sarcoma histologically, but unlike Ewing's
sarcoma, it forms osteoid. Particularly in tumors with prominent chondroblastic or fibroblastic
features, or those in which identification of osteoid is difficult, the recognition of bone-specific
alkaline phosphatase in fresh tissue may be helpful diagnostically.
? It is important to emphasize that biopsy specimens from the superficial or peripheral aspects of the
tumor—that is, from the advancing edge—are least likely to be representative of the tumor and
frequently fail to demonstrate osteoid formation. Periosteal osteosarcomas are essentially
chondroblastic osteosarcomas that expand into the soft tissue from an intact cortex.
Treatment:-
The management of osteosarcoma include various modalities such as surgery, Radiotherapy,
Chemotherapy. Surgery involves resection of the entire tumor with wide margins. The postoperative
chemotherapy is intended to sterilize any tumor foci not excised during the surgical resection. If the
94
osteosarcoma is in the maxilla, the resection will take
the form of a hemimaxillectomy or a variation of it.
Because an oral-nasal-antral communication is certain,
the surgeon should have an obturator prosthesis ready
for placement at the time of surgery. This obturator
prosthesis will reduce hypernasal speech and nasal
Figure 10.10: Osteosarcoma. Anaplastic tumor Figure 10.11: Osteosarcoma. This tumor produced
regurgitation of fluids and foods in the early cells forming cellular disorganized bone. a combination of malignant cartilage and bone.
postoperative phase.[55]
Ewing Sarcoma
Ewing sarcoma is a sarcoma of the bone, classically described under small round cell tumours.
According to WHO Ewing sarcoma as well as PNET generally correspond to the same process because they
share common genetic alterations in most of the cases.
The origin of ES is not clear, tumour is supposed to arise from the neuroectodermal cells. According to
various studies, tumor can also arise from the immature reticular cells as well as primitive mesenchymal
cells of the bone marrow.
Clinical Features:-
Ø It is the second most common malignant bone tumour of infancy and childhood after osteosarcoma.
Ø Males are more commonly affected than females, more frequent in Caucasian children than in
black children.
Ø It is very aggressive malignant tumour, so metastasis usually occurs and can be seen at the time of
diagnosis in most of the cases.
Ø It can rarely occur in the jaws but most commonly seen in the long bones. Other affected sites are
posterior body of mandible, angle as well as ramus region of mandible, skull, clavicle, ribs,
shoulder, pelvic girdles.
Ø Involvement of the jaw generally leads to the facial neuralgia, lip paresthesia as well as loosening
of teeth.
Ø Pain as well as the swelling of the involved bone is the earliest
clinical sign and symptom of the ES. Jaw swelling is characterized
as an intraoral mass which may become ulcerated.
Ø Other common features of ES are- low grade fever, elevated white
blood cell count, weight loss as well as anemia.
Ø Extraskeleton form of the ES is known as Ewing sarcoma of soft
Figure 10.12: Ewing Sarcoma. A rapidly growing,
tissues, which is most commonly present in older patients and ulcerated tumor of the right posterior mandible
generally involves the trunk region.
w The presence of pain, fever, and at times leukocytosis will suggest a suppurative osteomyelitis. This
will be reinforced if the radiographs show a destructive bone pattern with bone foci resembling a
sequestrum. If it is an early Ewing sarcoma with minimal osteolysis and with a layered periosteal
onion-skin radiographic appearance, it may resemble osteomyelitis with proliferative periostitis.
w The usual more destructive and expansile tumors will point to an aggressive malignancy from the
outset.
95
wOther aggressive malignancies that occur in this young age group include rhabdomyosarcoma,
osteosarcoma, fibrosarcoma and neuroblastoma.
In the uncommon situation of an older individual developing Ewing sarcoma, one also would need
w
to consider a non-Hodgkin lymphoma and a carcinoma metastatic to the mandible.
In early presentations and in younger individuals, a seeding of leukemia cells, particularly acute
w
lymphocytic leukemia and acute myelogenous leukemia, is a possibility.
Diagnosis:-
Biopsy is a gold standard for the diagnosis of ES. Other diagnostic aids include CT scan as well as
chest radiography, CT scan is useful to determine the local extent of the tumor in bone and soft tissue, chest
radiography is required to assess for metastasis to the lung, which is the most common metastatic site.
Laboratory investigations such as CBC, WBC count, platelet count are necessary for the demonstration of
leukocytosis and anemia.
Panoramic radiographs and a CT scan will show an illdefined, irregular resorption of bone with focal
areas of residual bone resembling sequestra. Pathologic fractures are common, attesting to the degree of
bone destruction. Ewing's sarcoma has often been reported to produce a multilayered periosteal reaction
that has been described as an “onion skin” appearance, similar to that commonly observed in an
osteomyelitis with proliferative periostitis. However, such a radiographic appearance is almost never seen
when Ewing sarcoma arises in the jaws, although it is seen occasionally when Ewing sarcoma arises within
the diaphysis of long bones. Ewing's sarcoma in the jaws will produce a destructive radiolucency with
resorbed tooth roots and displaced teeth. On rare occasions, a Ewing's sarcoma may produce a periosteal
new bone formation perpendicular to the cortex and thereby create the “sunray” appearance more
frequently seen in osteosarcoma.
Histological Features:-
ES is an excessively cellular neoplasm composed of solid sheets or masses of small round cells with
very little stroma, although a few connective tissue septa may be present. The cells are usually smaller as
well as rounded in shape, with scanty cytoplasm and relatively large round or ovoid nuclei with dispersed
chromatin and hyperchromasia. The cell borders are indistinct. The sarcoma
cells are arranged
In filigree pattern. Mitotic figures can also be seen. Increased cellular
pleomorphism as well as increased numbers of bizarre giant cells can be seen
in patients with advanced disease. The periodic acid-Schiff technique (PAS),
which stains carbohydrates red, is usually positive in ES, revealing the
Figure 10.13: Ewing Sarcoma. Broad sheets of small
presence of intracellular glycogen granules, which help differentiate the round cells with well-defined nuclear outlines and ill-
defined cytoplasmic borders
disease from tumors of neural lineage.
Treatment:-
The neoplasm is radiosensitive, but unfortunately, in the past, has seldom been cured by X-ray
radiation. Radical surgical excision has been done, alone and coupled with X-ray radiation, but it has been
common for metastatic foci to appear in other bones and organs, such as lungs as well as lymph nodes,
within a matter of a few weeks or months.
It has a poor prognosis as metastasis through blood and to the lung occurs too early. Tumours of the
96
jaw have a better prognosis than the long bone.[56]
Acute Lymphoblastic Leukemia

Leukemia is a malignancy of the bone marrow and blood. It is the most common childhood cancer in
india.
Leukemia is associated with scattered proliferation of immature or blast cells of the bone marrow that
replace the normal marrow elements and tends to accumulate in various tissues of the body. Leukemia is of
two types-
? Lymphocytic leukemia- it is associated with increased number of lymphocytes.
? Myelogenous leukemia- it is associated with increased number of granulocytes.
It is further divided into acute as well as chronic form, Acute leukaemia is the result of excessive
production of the malignant cells that spill into the peripheral blood and crowd out the normal cells, the
course of the disease is acute. Chronic leukaemias on the hand, is generally caused by the accumulation of
abnormal white blood cells that fail to die and accumulate in the bone marrow, blood and other organs.
Among various leukemias, acute lymphoblastic leukemia (ALL) accounts for 60-85% of all cases in
children in India.
Classification of oral complications seen in leukemic children- There have been several approaches to
classify the oral complications in leukemic children; however, the most accepted and broad classification
can be described as:
? Primary Complications- These complications generally occurs because of disease itself, leukemic
infiltration in the oral cavity especially in gingival and bone. For example- Leukemic gingival
enlargement.
? Secondary Complications- These complications generally occurs due to the direct effect of
radiation as well as chemotherapy. In these cases, there is tendency to bleed and more susceptibility
to infections and ulcers.
? Tertiary Complications- These complications are usually due to a complex interplay of the therapy
itself, its side effect, and a systemic condition arising out of the therapy. Common features of these
complications are- ulcerations, mucositis, taste alteration, skin desquamation, candidiasis, gingival
bleeding, xerostomia, dysphasia, opportunistic infections, trismus, etc.
Some features are usually present in advanced cases and these are- vascular lesions, tissue atrophy,
permanent taste loss or change, fibrosis, edema, soft tissue necrosis, loss of teeth, salivary flow
decrease, carious lesions, osteoradionecrosis, and chondronecrosis.
Aetiology:-
A number of possible aetiological factors that may act singly or in combination have been identified in
relation to different types of leukaemia. These factors may be external such as exposure to high doses of
radiation, alkylating agents, benzene, formaldehyde or viruses such as the Human T-cell leukaemia virus
(HTLV). Genetic abnormalities linked with syndromes like Down syndrome, Fanconi anaemia, ataxia
telangiectasia and Bloom syndrome are the recognized internal risk factors for leukaemia.
Clinical Features:-
Ø Acute leukaemia most commonly occur in children and young adults while chronic leukaemias are
most frequently seen in adults of middle age or older.
Ø Males are more commonly affected than females.
97
Ø
No notable differences exist in the clinical manifestations of the morphologic forms of leukaemia
except that the acute forms progress rapidly through a short yet fatal
course without treatment.
General features are- weakness, fever, headache, acquired or
Ø
repeated infections, delayed healing, petechial or ecchymotic
haemorrhages in the skin and mucous membrane as well as evidence
of anaemia.
Other symptoms include- lymphadenopathy, bone pain, swollen and
Ø
Figure 10.14: Diffusely swollen gums and infiltration by
bleeding gingival, abdominal pain due to enlargement of liver or leukemic cell
spleen.
w Before the results of any laboratory studies are known, a child with headache, vomiting, and bone
pain may seem to have a common flu or meningitis. If laboratory studies identify an anemia and the
white blood cell count is not extremely high, the picture still may represent meningitis or some other
systemic infection.
w In addition, childhood anemia such as sickle cell anemia and thalassemia intermedia should be
considered,
Diagnosis:-
Peripheral WBCs count that may include varying numbers of the blast cells is usually
increased in leukaemia. Various laboratory investigations include CBC, needle biopsy
aspiration of bone marrow from a pelvic bone will need to be done to test for leukaemic
cells, DNA markers, and chromosome changes in the bone marrow.
Figure 10.15: Marked proliferation

of small lymphoblasts
Treatment:-
Treatment modalities include chemotherapy, radiation therapy, bone marrow transplantation. Apart
from this, targeted drug therapy is beneficial to attack specific abnormalities present in cancer cells that help
them grow and thrive. Targeted therapy may be used during or after chemotherapy. Drugs can be used in
targeted therapy are tyrosine kinase inhibitors such as imatinib and nilotinib. The biological treatment
interferon alfa, chemotherapy drugs such as busulphan, hydroxyurea.[36]
98
Salivary
11 Gland Tumors
?Pleomorphic adenoma
?Mucoepidermoid carcinoma
Pleomorphic Adenoma
I
Etiology:-
t is also known as enclavoma, branchioma, endothelioma, enchondroma. It is a benign
neoplasm of salivary glands, consisting of cells exhibiting the capacity to differentiate into
epithelial as well as mesenchymal cells.
The etiology of pleomorphic adenoma is unknown, but the incidence of this tumor has been
increasing in the last 15-20 years in relation to the exposure of radiation. One study suggests that oncogenic
simian virus (SV40) may play a role in the onset or progression of pleomorphic adenoma. Prior head and
neck irradiation is also a risk factor for the development of these tumors.
Clinical Features:-
Ø It is the most common tumour of salivary glands, especially the parotid gland.
Ø It is commonly present in fourth to sixth decade but can also be seen in young adults and children.
Females are more commonly affected than males.
Ø Most commonly involved sites are- mucosa over the posterior hard palate and anterior soft palate;
pleomorphic adenomas can occur in any location where minor salivary glands exist.
Ø Lesions are characterized as a a painless firm mass in the superficial lobe of the parotid gland and a
painless firm mass in the posterior palatal mucosa.
Ø It can also presents as a freely movable, firm mass. Peculiarly and rarely, these can fluctuate in size
or be painful.
Ø When a pleomorphic adenoma arises from the deep lobe of the parotid gland, it usually goes
unrecognized for a number of years until its size creates symptoms of dysphagia or gagging.
Ø Pleomorphic adenoma is present orally as a bulge arising from the tonsillar fossa area.
Pleomorphic adenoma of parotid shows irregular nodular lesion having firm consistency although
areas of cystic degeneration may be palpated if they
are superficial.
Ø In the palatal mucosa, the mass will seem to be fixed to
the palate. Since the pleomorphic adenoma cannot
invade bone, this is not caused by bony invasion but
rather by the inelasticity of the palatal mucosa, which
becomes distended by the tumor mass and may
eventuate in a cupped-out resorption of bone.
Ø Pleomorphic adenoma of intraoral accessory gland is
never more than 1-2 cm in diameter. It causes
difficulty in mastication, talking and breathing. Figure 11.1: Pleomorphic adenoma
w The differential diagnosis of a firm mass in the parotid gland must include a Warthin tumor, which is
particularly likely in men, and basal cell adenoma, which preferentially develops in the parotid
gland.
w In addition, malignant salivary gland tumors that must be considered include mucoepidermoid,
adenoid cystic, and acinic cell carcinomas. Non- salivary gland neoplasms that are known to occur
in the parotid gland-i.e. hemangiomas, lymphangiomas, lipomas, and lymphomas within parotid
lymph nodes-may also present in a similar fashion.
w The clinician also must be aware that skin nodules such as epidermoid cysts can form a
subcutaneous mass in the area that may give an impression of being located in the parotid gland.
w The differential diagnosis of a firm mass in the palatal mucosa with intact overlying epithelium is
primarily a subset of other salivary gland neoplasms. In order of statistical likelihood, they are
adenoid cystic carcinoma, mucoepidermoid carcinoma, and polymorphous low-grade
adenocarcinoma.
w Another benign tumor that requires some consideration is the canalicular adenoma. In addition,
several non-salivary gland tumors may present with a similar appearance, such as non-Hodgkin
lymphoma and neurofibroma.
w The differential diagnosis of a firm mass in the submandibular triangle should include other salivary
gland neoplasms except for the polymorphous low-grade adenocarcinoma, which is not generally
known to occur in major salivary glands, as well as sialadenitis, sialithiasis, and several diseases
known for lymph node enlargement such as Hodgkin and non-Hodgkin lymphoma, HIV,
lymphadenopathy, cat-scratch disease, and sarcoidosis.
Diagnosis:-
The diagnostic aids include CT scan, MRI are useful to confirm the location of tumour in the
parotid, specifically in the superficial lobe. This should be followed by a superficial parotidectomy, which
represents both the diagnostic biopsy and the definitive treatment. For pleomorphic adenomas in other
mucosal sites, a peripheral excision with 1 cm margins is recommended.
Histopathology:-
Histologically in following types:
? Principally myxoid.
? Myxoid and cellular components present in equal proportion.
? Predominantly cellular.
? Extremely cellular.
The mixed tumors will have a well-developed capsule, these are well-demarcated, masses.
v
Unfortunately, this characteristic, coupled with the fact that these tumors are clinically freely
moveable, particularly when palpated in such areas as the lip, believes the fact that tumor cells are
found within the capsule and as extensions through and beyond it. Thus a “conservative”
enucleation would almost ensure residual tumor cells and set the patient up for multifocal
recurrences. Grossly, these tumors have a smooth, sometimes bosselated surface. The cut surface is
typically white and resembles a cut potato. Bluish areas representing cartilage-like material may be
seen, and a gelatinous component may be present. Older tumors often show cyst formation.
v
Tumors in major glands may have incomplete fibrous capsule cut surface is rubbery, fleshy mucoid
and glistering. Foci of hyalinization, bone and fat is noted in connective tissue stroma. The
microscopic picture is typically diverse . Essentially, there is a proliferation of both ductal
epithelium and a myoepithelial component. This gives rise to cellular, epithelial areas as well as
mesenchymal-like tissue that usually has a myxochondroid appearance.
v
In general, the minor salivary gland tumors are more cellular than those of the major glands. The
cellular portion of the tumor may form a variety of patterns such as islands, sheets, ribbons, or
ductal configurations. Squamous cells and keratin pearls may be present. Occasionally, there may
be cribriform areas, suggesting the pattern of adenoid cystic carcinoma. However, such areas
usually compose only a small portion of the tumor, and the infiltrative nature of the carcinoma is
not evident. Aggregates of oncocytic cells may be seen, but this can occur in a variety of salivary
gland tumors. Plasmacytoid (hyaline) cells and spindle cells may also be seen. Both of these have
been identified as myoepithelial cells. In some tumors, one or both of these cell types constitute
practically the entire lesion. If the ductal and glandular component constitutes less than 5% of the
tumor, these would be classified as myoepitheliomas. Basal lamina produced by myoepithelial
cells appears to be responsible for the eosinophilic hyalinized material that can form a striking
component of many tumors. These were called 'hyaline cell.'
vThe myoepithelium also deposits the basophilic, mucoid material, which then separates the cells
so that the tissue appears myxoid. Degeneration of cells with vacuolation produces the chondroid
pattern. Crystalline material may sometimes
be seen. Glandular epithelium is mainly
found. A neoplastic altered cell with the
potential for multidirectional differentiation
is histogenetically responsible for
pleomorphic adenoma. It also shows
cytogenetic abnormalities involving
chromosome no12q13-15.
vMalignant degeneration is possible within
pleomorphic adenomas, and the incidence
increases with tumor duration and size.
Histologic features suggestive of malignant
transformation include extensive
hyalinization, cellular atypism, necrosis, Figure 11.2: Histopathology of pleomorphic adenoma
calcification, and invasion.
Treatment:-
The accepted treatment for this tumour is surgical excision. The intraoral lesions can be treated,
somewhat more conservatively by extracapsular excision. Since these tumours are radio-resistant, the use
of radiation therapy is of little benefit and is there for contraindicated.
Rarely, a malignant tumour may arise within this tumour, a phenomenon known as carcinoma ex
pleomorphic adenoma. There is a second class of tumours which are called metastasizing benign mixed
tumours. Metastisis occurs rarely, if persist can involve many structures such as lungs, regional lymph-
nodes, skin and bone.[57]
Mucoepidermoid Carcinoma
It is a most common malignant epithelial tumour of major and minor salivary glands. As the name
implies, the tumour is composed of both mucous secreting cells as well as epidermoid type cells in varying
proportions.
Pathogenesis:-
Mucoepidermoid carcinomas arise from reserve cells in the salivary duct system. Therefore, they
can partially differentiate into mucin producing cells or duct like epidermoid cells. Both cell types are
altered neoplastic cells. Because the reserve cell can become neoplastic at any stage of its maturation, the
resultant tumor may emerge with variable biologic behavior and histologic grading as is typical of the
mucoepidermoid carcinomas.
Clinical Features:-
Ø It is the most common malignant salivary gland tumour occurs in children, with a slight female
predilection.
Ø Parotid gland is the most common site of occurrence but tumour can also be seen in submandibular
gland.
Ø Intraorally, mucoepidermoid carcinoma shows a strong predilection for the palate.
Ø Other commonly involved sites are- buccal mucosa, tongue, retromolar areas.
Ø Low grade mucoepidermoid carcinomas will possess an infiltrative growth pattern and a very slow
growth rate similar to that of a pleomorphic adenoma. Mucoepdermoid carcinoma metastazise
rarely, only late in their courses.
Ø On the other side, high grade mucoepidermoid carcinomas behave like poorly differentiated
squamous cell carcinoma with rapid infiltrative growth as well as metastasis.
Ø Determination of the grade (low, intermediate, or high) is not limited to histopathologic criteria
alone. The clinical features of each differ and are important in the final determination of grade.
Ø Many tumors will appear bluish because their well-differentiated character creates mucin-filled
spaces that appear blue through the mucosal cover.
Ø Intermediate-and high-grade mucoepidermoid carcinomas are faster growing, more diffuse, and
ulcerate early, these carcinomas usually appear as a solid masses with a normal color of the
overlying epithelium or with an ulcerated surface.
Ø In case of high grade malignancy, patient
complains of trismus, drainage from ear,
dysphagia, numbness of adjacent areasand
ulceration.
Ø High grade carcinoma infiltrates surrounding
tissues and metastazise to regional lymph
nodes. Distant metastasis is seen in lung, bone,
brain and subcutaneous tissues.
Ø A parotid mucoepidermoid carcinoma is
characterized as a freely movable parotid
mass, may also be diffused and less Figure 11.3: Mucoepidermoid Carcinoma. Blue-pigmented mass of the posterior lateral hard palate.
circumscribed.
w A low grade mucoepidermoid carcinoma in the mucosa of the palate may or may not be ulcerated. If
it has an intact overlying mucosa, the most likely lesion would be a pleomorphic adenoma followed
by an adenoid cystic carcinoma and a polymorphous low-grade adenocarcinoma. If the surface is
ulcerated and unattributable to trauma, the likelihood of pleomorphic adenoma is remote.
Therefore, because of its slow growth rate and malignant nature, which can ulcerate the surface
mucosa, adenoid cystic carcinoma becomes the primary differential lesion, followed by
polymorphous low-grade adenocarcinoma and perhaps a carcinoma ex pleomorphic adenoma.
w A high-grade mucoepidermoid carcinoma of the palate will be infiltrative, ulcerated, and
destructive of bone. Therefore, squamous cell carcinoma is the most important differential lesion in
this location. Other considerations are sinus or nasal carcinomas that have extended down through
the palate and perhaps a carcinoma ex pleomorphic adenoma as well. An adenoid cystic carcinoma
would not appear clinically like a high-grade mucoepidermoid carcinoma despite its malignant
nature. Adenoid cystic carcinoma tend to be slower in growth and develop more of a mass than a
diffuse growth pattern. Although extranodal non-Hodgkin lymphomas occur in the palatal mucosa
as a preffered site, their presentation is more that of a nonulcerated, fleshy mass.
w A low-grade mucoepidermoid carcinoma in the parotid gland would present as the more common
benign parotid tumors as well as some malignant tumors, mainly adenoid cystic carcinoma and
acinic cell carcinoma.
w A high grade mucoepidermoid carcinoma in the parotid gland usually has a presentation suggestive
of an aggressive malignancy, including rapid growth, large size, possible facial muscle paresis, and
induration. Its differential would include adenoid cystic carcinoma, salivary duct carcinoma,
carcinoma ex pleomorphic adenoma, and possibly seeding of a regional metastasis from an oral or a
nasopharyngeal squamous cell carcinoma.
Diagnosis:-
Incisonal biopsy is required for appropriate diagnosis. Other diagnostic modalities include CT
scan, MRI scan. These diagnostic modalities are required to assess the location as well as the size of the
tumour.[58]
Histopathology:-
The biologic behavior of these tumors, which ranges from extremely low grade to highly
aggressive, depends primarily on the histology. In general, these masses are unencapsulated, although the
lowgrade tumors are usually well-circumscribed while the high grade tumors show considerable
infiltration.
Several cell types are seen, including:
Mucous-secreting cells which are usually large cells with pale foamy cytoplasm. They may occur in
clusters or single cells, or they may line cystic spaces. They elaborate epithelial mucin, which can be
identified by mucicarmine or PAS stain; the latter is resistant to diastase digestion. Particularly when the
mucous component is scant, special stains may be necessary for identification.
Epidermoid cells which lie in sheets or line cystic spaces. They may show interlacing patterns with
intercellular bridges. Occasionally, keratin pearls are seen. They have squamoid features and polygonal
shape, arranged in glandular pattern.
103
Intermediate cells which are basaloid cells that vary from small, dark-staining cells to larger, more
epidermoidlike cells. They may lie in sheets or line cystic spaces. They tend to blend into epidermoid cells.
These cells are believed to differentiate into epidermoid, mucous, and clear cells.
Clear cells that may form broad sheets or occur as single cells or clusters within epidermoid cells. Although
these cells are usually negative on mucin staining, some mucin may occasionally be identified. They are
glycogen free cells.
Figure 11.4: Mucoepidermoid Carcinoma. Figure 11.5: Mucoepidermoid Carcinoma. High-power Figure 11.6: Mucoepidermoid Carcinoma. Figure 11.7: Mucoepidermoid Carcinoma. High-
This low-grade tumor shows numerous large view showing a sheet of squamous cells with focal Clear cell mucoepidermoid carcinoma. power view showing a sheet of pleomorphic
mucous cells surrounding a cystic space. mucus-producing cells (left). squamous epithelial cells intermixed with mucous
and intermediate cells
The grading of mucoepidermoid carcinoma depends primarily on the relative mixture of cell types,
although growth pattern and cellular atypia also play significant roles.
Low grade tumours- These show well-formed glandular structures and prominent mucin filled cystic
spaces, minimal cellular atypia and a high proportion of mucous cells.
Intermediate-grade tumour- These tumours have solid areas of epidermoid or squamous cells with
intermediate basaloid cells. Cyst formation is seen but is less prominent than that observed in low-grdae
tumours. All cell types are present, but intermediate cells predominate.
High-grade tumours- These consist of cells present as solid nests and cords of intermediate basaloid and
epidermoid cells. Prominent nuclear pleomorphism and mitotic activity is noted. Cystic compoinent is
usually very less. Glandular component is rare, although it may predominate occasionally. Necrosis and
perineural invasion may be present.
Variants of Mucoepidermoid Carcinoma:-
Sclerosing Mucoepidermoid Carcinoma- Although mucoepidermoid carcinoma is the most

?
common primary malignancy of the salivary glands, the sclerosing morphologic variant of this
tumour is extremely rare. It is characterized by an intense central sclerosis that occupies the whole
tumour, frequently with an inflammatory infiltrate of plasma cells, eosinophils, lymphocytes.
The sclerosis associated with these tumours may obscure their typical morphologic features and
result in diagnostic difficulties. Tumour infarction and extravasation of mucin resulting in reactive
fibrosis are two mechanisms that have been suggested as the cause of this morphological variant.
Intraosseous mucoepidermoid carcinoma- Mucoepidermoid carcinoma may originate within the
?
jaws. This tumour type is known as central mucoepidermoid carcinoma. It is thought to form by the
malignant transformation of the epithelial linning of odontogenic cysts. The tumour presents as an
asymptomatic radiolucent lesion and is histologically of low-grade malignancy. The mandible is
more commonly affected than the maxilla.
Treatment:-
Conservative excision with preservation of the facial nerve, if possible, is recommended for low
as well as intermediate-grade mucoepidermoid carcinomas of the parotid gland. The affected
submandibular gland should be removed entirely. Radical neck dissection is performed in patients with
clinical evidence of cervical node metastasis. Treatment for the minor glands is also primarily surgical.
Some investigators have recommended postoperative irradiation only for high-grade malignancies.[11]
105
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Pediatric Soft Tissue Lesions

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Contents

Chapter Page No.

7. Trauma due to chronic frictional insult.....................................................................65

9. Benign soft tissue tumors.........................................................................................74

10. Malignant soft tissue tumors....................................................................................89

11. Salivary gland tumors..............................................................................................99

Necrotizing ulcerative gingivitis

N UG is a well-defined and particular form of periodontal diseases, more common in children

Oral Tuberculosis & Scrofula

Ziehl Neelsen staining-

Figure 2.14: Tuberculosis (TB). Acid-fast stain of

Tetanus (Lock Jaw)

Herpes simplex infections

Herpes Encephalitis and Meningitis:-

Herpes in immunocompromised host:-

HSV associated Erythema Multiforme:-

Herpangina and hand-foot-and-mouth disease (HFMD)

Acute lymphonodular pharyngitis

Sources of significant exposure to varicella or zoster-

cytoplasm and centrally placed clusters of darkly stained nuclei[11].

Rubella (German Measles)

Classification of oral candidiasis:

Primary form includes:

Secondary form includes:

Local predisposing factors for oral candidiasis and Candida-associated lesions:

Hereditary Epidermolysis Bullosa

I nherited epidermolysis bullosa (EB) is a heterogeneous group of genetic disorders characterized

Recent classification of inherited EB:-

Junctional Epidermolysis Bullosa

Dystrophic Epidermolysis Bullosa

Juvenile Dermatitis Herpetiform

Familial Acanthosis Nigricans

Benign Acanthosis Nigricans-

Obesity Associated Acanthosis Nigricans- Figure 5.9 (a) Clinical photograph

Syndromic Acanthosis Nigricans-

Malignant Acanthosis Nigricans-

Acral Acanthosis Nigricans-

Drug-induced Acanthosis Nigricans-

Juvenile Bullous Pemphigoid

Childhood Linear Iga Disease

Figure 7.1: Frictional Keratosis. Frictional keratosis

Figure 7.2: Linea Alba. White line of hyper keratosis

It is also known as Mucous extravasation phenomenon, mucous escape reaction. It is considered

Peripheral Giant Cell Granuloma

Figure 8.11: Peripheral Giant Cell Granuloma. High-power

(a) Arteriovenous hemangioma

It is the most serious of all the hemangiomas and is life-threatening.

Figure 9.2: Histopathology of arteriovenous

(b) Juvenile Capillary Hemangioma

(c) Cavernous hemangioma

Juvenile Nasopharyngeal Angiofibroma

Congenital Granular Cell Tumour

Melanotic Neuroectodermal Tumor of Infancy

most commonly involve the primary central incisors.

Embryonal Rhabdomyosarcoma- In embryonal rhabdomyosarcoma, tumors may contain small

Alveolar Rhabdomyosarcoma- The alveolar

Pleomorphic Rhabdomyosarcoma- Pleomorphic rhabdomyosarcoma may be difficult to separate

Alveolar Soft Part Sarcoma

generally involves the trunk region.

Acute Lymphoblastic Leukemia