CHAPTER 16

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HEAD AND NECK

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Reactive lesions:
• Irritation fibroma
• Pyogenic granuloma
• Peripheral ossifying fibroma
• Peripheral giant cell granuloma
• Aphthous ulcers – may be associated with IBD or Celiac
• Glossitis – iron or B12 deficiency

Oral Manifestations of Systemic Disease

• Scarlet fever – strawberry tongue
• Mono – Koplik spots around Stensons duct
• Diptheria – pseudomembrane over the tonsils
• HIV – hairy leukoplakia and oral infections
• Lichen planus, pemphigus, bullous pemphigoid, EM can all involve the oral cavity
• Pancytopenia – oral infections, cellulitis of the neck (Ludwigs angina)
• Melanotic pigmentation – Addisons disease, hemochromatosis, McCune-Albright syndrome (fibrous
dysplasia), Peutz-Jegher syndrome
• Phenytoin and pregnancy – gingival pyogenic granuloma
• Rendu-Osler-Weber syndrome – telangiectasias

Squamous Cell Carcinoma

• Patients have a 35% chance of developing a second primary within 5 years of first diagnosis of SCC
• Second primaries are the most common cause of death
• Pathogenesis:
• Smoking and alcohol
• HPV for oropharyngeal ca
• HPV-positive oropharyngeal carcinomas frequently occur in patients with no known risk
factors for HNSCC (ie, nonsmokers and nondrinkers), in younger aged patients, and are
associated with a better outcome (better overall and disease-specific survival). The
International Agency for Research of Cancer (IARC) recently concluded that there is
sufficient evidence that HPV16 is causal for a subset of oropharyngeal cancers. A similar
association has been suggested but not confirmed for oral cavity carcinoma.
• Family history
• Actinic change and pipe smoking for lower lip
• Betel nut chewing and paan
• Chronic irritation is thought to be a promoter
• Variants of Squamous Cell Carcinoma:
• Acantholytic squamous cell carcinoma
• Adenosquamous carcinoma
• Basaloid squamous cell carcinoma
• Carcinoma cuniculatum
• Papillary squamous cell carcinoma
• Spindle cell squamous carcinoma
• Verrucous carcinoma
• Lymphoepithelial ca
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 • 2 types of dysplasia in the oral cavity: keratinizing (most common) and non-keratinizing
• Grading is not reproducible as it is in the cervix:
• Invasive ca can develop from keratinizing dysphasia in the UADT that is limited in extent
and in absence of full thickness dysphasia (even if limited to lower third)
• Keratinizing severe dyspasia is often multifocal and often occurs near synchronous foci
of inv ca
• Keratinizing SE due dysplasia has a rate of progression to inv ca that is greater than that
of a "classic" CIS
• Dx if severe dysplasia requires therapeutic intervention, as well as clinical evaluation of
the upper aero digestive tract to exclude possible presence of additional foci of dysplasia
or carcinoma that may exist from field effect
• Margins – keratinizing dysplasia is different from non-keratinizing dysplasia in the oral cavity!
• The presence of keratinizing moderate or severe dysplasia at (or near) a surgical margin
should be viewed/reported as a positive margin
• Perineural invasion – poor prognosis and presence affects treatment decisions
• Lymph nodes – status is the most important prognostic indicator
• ENE is an indication for post-op RT
• Isolated tumor cells, single or cluster not more than 0.2 mm in greatest dimension (found on H
and E or by ancillary techniques) are counted as N0 at this time

Mucosal Melanoma
• Cancers limited to the mucosa are already T3 tumors (epithelium and LP)

Odontogenic Cysts and Tumors

• Classification of odontogenic cysts:
• Inflammatory versus developmental
• Inflammatory – periapical, residual, paradental
• Developmental – dentigerous, OKC, gingival cyst, eruption cyst, etc

Necrotizing lesions of the upper airway

• DDx: fungal infections, Wegeners, lethal midline granuloma (NK lymphoma)

Sequelae of strep pharyngitis

• Rheumatic fever (SPACE – Jone’s criteria), post infectious glomerulonephritis

Tumors of the Nose, Sinuses, and Nasopharynx

• Nasopharyngeal angiofibroma – almost exclusively in males in 20s, can be associated with APC

Xerostomia
• Autoimmune – Sjogren
• Iatrogenic – radiation therapy
• Medication related – anticholinergic, antidepressive, diuretic, antihypertensive, analgesic,
antihistamine
• Complications – increased dental caries, candidiasis, difficulty swallowing and speaking

Classify Sialadenitis
• Traumatic
• Infectious – viral (mumps), bacterial
• Autoimmune – Sjogren (Miculicz plus hypergammaglobulinemia and RA, anti-Ro and anti-La) and
Miculicz syndrome
• Biopsy the lower lip
• Focus score (the number of mononuclear cell infiltrates containing at least 50 inflammatory
cells in a 4 mm2 glandular section) of greater than 1 is probably the single most important test
result in the diagnosis of the oral component in SS
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Salivary Glands
• The likelihood of a salivary gland tumor becoming malignant is more or less inversely proportional to
the size of the gland
• Pleomorphic adenoma – thought to arise from myoepithelial cells, radiation exposure increases the
risk
• Malignant mixed tumors: Carcinosarcoma and Carcinoma ex pleomorphic adenoma – in situ,
minimally invasive (up to 1.5 mm), and invasive (> 1.5 mm)
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Comparison of common pattern grading schemes in Adenoid Cystic Carcinoma
Grade Perzin et al / Szanto et al Spiro et al
mostly tubular or cribriform (no stipulation
1 predominantly tubular, no solid on minor solid comp)
predominantly cribriform, <30% solid
2 50% solid
acceptable
3 solid >30% mostly solid

Brandwein-Gensler Grading System for Mucoepidermoid Carcinoma

Pararmeter Point Score
Cystic component <25% +2
Tumor front invades in small nests and islands +2
Pronoucned nuclear atypia +2
Lymphatic and/or vascular invasion +3
Neural invason +3
Necrosis +3
4+ more mitoses/10 hpf +3
Bony invasion +3
Grade Point Score
Low 0
Intermediate 2-3
High 4 or more

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Histologic Features Helpful in Dx of CaExPA
1. Diffuse and marked nuclear pleomorphism and hyperchromasia

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 2. Increased mitotic activity, especially atypical mitoses

3. Necrosis

4. Hyalinization of matrix (especially if calcified)

5. Capsular invasion

Perineural invasion

Lymphovascular invasion

Androgen receptor, p53 and Her2/neu immunoreactivity (if strong and diffuse)

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Sinonasal (Schneiderian) Papillomas
Inverted Type Exophytic Type Oncocytic Type
Incidence 47-73% 20-50% 3-8%
Gender M>F M>F M=F
Age 40-70 years 20-50 years > 50 years
Location Lateral nasal wall in region of middle Nasal septum Lateral nasal wall and sinuses
turbinates; may extend into sinuses (maxillary or ethmoid)
(maxillary or ethmoid)
Focality Typically unilateral; rarely bilateral Unilateral Unilateral
Histology Endophytic or "inverted" growth Exophytic to papillary proliferation Multilayered epithelial proliferation
composed predominantly of composed predominantly of composed of columnar cells with
squamous (epidermoid) cells with squamous (epidermoid) epithelium abundant eosinophilic and granular
scattered admixed mucocytes and with admixed mucocytes and cytoplasm; outer surface of epithelial
intraepithelial mucous cysts; mixed intraepithelial mucous cysts; delicate proliferation may demonstrate cilia;
chronic inflammatory cell infiltrate fibrovascular cores intraepithelial mucous cysts, often
characteristically seen within all containing polymorphonuclear
layers of surface epithelium leukocytes
Association ~ 38% positive; HPV 6 and 11; less ~ 50% positive; HPV 6 and 11; less Typically absent
with HPV frequently HPV 16, 18; rarely HPV frequently HPV 16, 18; rarely HPV
57 57
Malignant 2-27%; most common type is Rare 4-17%; most common type is
transform'n keratinizing SCC keratinizing SCC

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Olfactory Neuroblastoma Histologic Grading (Hyams's Criteria)
Microscopic
Grade 1 Grade 2 Grade 3 Grade 4
Features
Architecture Lobular Lobular ± lobular ± lobular
Pleomorphism Absent to slight Present Prominent Marked

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 Neurofibrillary Prominent Present May be present Limited
matrix
Rosettes Homer Wright Homer Wright Flexner-Wintersteiner Flexner-Wintersteiner
pseudorosettes pseudorosettes rosettes rosettes
Mitoses Absent Present Prominent Marked
Necrosis Absent Absent Present Prominent
Glands May be present May be present Usually limited Focally present
Calcifications Variable Variable Absent Absent

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Sinonasal Tract ITACs Classification
Barnes Kleinsasser & Schroeder Percentage of Cases 3-Year Cumulative Survival
Papillary type Papillary tubular cylinder cell I 18% 82%
Colonic type Papillary tubular cylinder cell II 40% 54%
Solid type Papillary tubular cylinder cell III 20% 36%
Mucinous type Alveolar goblet Uncommon 48%
Signet ring Uncommon 0%
Mixed type Transitional Rare 71%

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SNUC: Differential Diagnosis Based on Immunohistochemical Staining
IHC SNUC ONB SCUNC MMM NK/T RMS
CK ₊ ₋ ₊ ₋ ₋ ₋
p63 ± ₋ ± ₋ ± ₋
CK5/6 + - - - - -
CHR ± ₊ ₊ ₋ ₋ ₋
SYN ± ₊ ₊ ₋ ₋ ₋
CD57 ₋ ₊ ₊ ₋ ₋ ±
NSE - (may be focal +) + ₊ ± ₋ ₋
S100 protein + (peripheral + (lacks periph
- (may be focal +) + (diffuse) ₋ ₋
pattern) pattern)
VIM - ± ± + (diffuse) ± ₊
Melanocytic
markers ₋ ₋ ₋ ₊ ₋ ₋

CD45RB ₋ ₋ ₋ ₋ ₊ ₋
CD56 ± ₊ ₊ ₋ ₊ ±
Muscle
markers ₋ ₋ ₋ ₋ ₋ ₊

EBER ₋ ₋ ₋ ₋ ₊ ₋

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Clinicopathologic Comparison of Nasopharyngeal Carcinoma
Keratinizing NK, Differentiated NK, Undifferentiated
Incidence Approximately 25% Approximately 15% Approximately 60%
Gender/age M > F; 4th-6th decades; rare < 40 M > F; 4th-6th decades M > F; 4th-6th decades; may
years of age occur in children
Histology Keratinization, intercellular Little to absent keratinization, Absence of keratinization,
bridges; conventional squamous growth pattern interconnecting syncytial growth, cohesive or
carcinoma graded as well-, cords; typically, limited to absent noncohesive cells with round
moderately, or poorly desmoplastic response to invasion nuclei, prominent eosinophilic
differentiated; desmoplastic nucleoli, scant cytoplasm;
response to invasion prominent nonneoplastic
lymphoid component; typically,
absent desmoplastic response to
invasion
Association Weak association Strong association Strong association
with EBV
Treatment Supervoltage radiotherapy Supervoltage radiotherapy Supervoltage radiotherapy
(6,500–7,000+ rads) (6,500–7,000+ rads) (6,500–7,000+ rads)
Prognosis 5-year survival (20-40%) 5-year survival (~ 75%) 5-year survival (~ 75%)

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Differential Diagnosis of Basaloid Squamous Cell Carcinoma
BSCC AdCC SCUNC
Age/gender 6th-7th decades; M > F 5th-7th decades; equal gender 6th-7th decades; M > F
distribution except for
submandibular tumors, which
predilect to females
Location Predilects to hypopharynx Major and minor salivary glands Uncommon in head and neck;
(piriform sinus), larynx supraglottic larynx most common
(supraglottis), and oropharynx site
(palatine tonsil)
Surface Present in the form of Absent Absent
involvement intraepithelial dysplasia
Squamous Present but is the minor Absent May be present; limited in extent
component component and may only be when found
found focally
Neurotropism Present Present Present
IHC Immunoreactive for cytokeratins; Immunoreactivity for cytokeratins, Positive for cytokeratins;
neuroendocrine markers p63, S100 protein, calponin, immunoreactive for
(chromogranin, synaptophysin, actins, and vimentin; negative for neuroendocrine markers
others) usually negative but neuroendocrine markers (chromogranin, synaptophysin,
occasionally may be positive CD56, CD57, TTF-1); calcitonin
rarely is positive
HPV association No No No
Treatment Surgery, radiotherapy, Surgery, radiotherapy Systemic chemotherapy and
chemotherapy therapeutic irradiation

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 Prognosis Dependent on clinical stage but Short-term prognosis is good but Poor: 2-year survival (16%), 5-
overall considered to be poor; long-term prognosis is poor; year survival (5%)
nasopharyngeal-based BSCC survival rates include 5-year
appears to be less biologically (71-89%), 10-year (29-71%), 15-
aggressive than other head and year (29-55%)
neck BSCCs
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Clinical Features of Laryngeal Neuroendocrine Neoplasms (LNEC)
Small Cell
Laryngeal Paraganglioma Carcinoid Tumor Atypical Carcinoid Neuroendocrine
Carcinoma
Frequency Rare Least common LNEC Most common LNEC 2nd most common LNEC
Age/gender 5th decade; F > M 7th decade (on avg.); M 7th decade (on avg.); M 6th-7th decade; M > F
>F >F
Risk factor(s) None known None known Smoking Smoking
Site Supraglottis; aryepiglottic
fold and false vocal cord
Symptoms Hoarseness; dysphagia, Hoarseness Hoarseness Hoarseness
dyspnea, stridor
Paraneopl Exceptional; may be Rare Rare Occasional
syndrome multicentric occurring in
association with other
head & neck
paragangliomas
Treatment Surgery is curative Surgery Surgery; adjuvant Systemic chemotherapy
radiotherapy and and therapeutic
chemotherapy used but irradiation
of questionable utility
Metastasis None Approximately 33% have Metastasis common to Metastasis frequent (even
distant metastases (liver cervical lymph nodes, at presentation) to
and bone) lung, bone, liver, skin regional lymph nodes
and to liver, lung, bone,
and brain
Prognosis Excellent Indolent biology with Fully malignant Poor: 2-y survival (16%),
excellent behavior neoplasm; tumor 5-y survival (5%)
confined to larynx: 3.9-y
survival (62%), 5-y
survival (48%), 10–y
survival (30%)

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 Pathology of Laryngeal Neuroendocrine Neoplasms
Small Cell
Laryngeal Paraganglioma Carcinoid Tumor Atypical Carcinoid Neuroendocrine
Carcinoma
Histology Cell nest or "zellballen" Submucosal tumor with Submucosal tumor with Submucosal tumor with
pattern separated by organoid or trabecular organoid, trabecular, solid nests, sheets or
prominent fibrovascular growth pattern and cribriform or solid growth ribbons and absence of a
tissue fibrovascular stroma and fibrovascular stroma fibrovascular stroma
Chief cells are Neoplastic cells are Neoplastic cells retain Hypercellular tumor with
predominant cell type uniform with "salt and "salt and pepper" "salt and pepper" nuclear
pepper" nuclear chromatin chromatin; "crush"
chromatin artifact frequently present
Sustentacular cells lie at Absence of Mild to marked nuclear Confluent foci of necrosis
periphery of cells nests pleomorphism, mitoses, pleomorphism and and individual cell
but are difficult, if not necrosis increased mitotic activity necrosis seen; abundant
impossible, to identify by are present; necrosis mitoses, including
light microscopy uncommon atypical forms
? Invasive Absent Typically absent Present; may include Present; commonly
neurotropism and includes neurotropism
lymphovascular invasion and lymphovascular
invasion
Special Reticulin staining Presence of epithelial Presence of epithelial Epithelial mucin usually
Stains delineates cell nest mucin: Diastase-resistant, mucin: Diastase-resistant, absent but may be
growth pattern; tumor PAS(+); argyrophilic PAS(+) and occasionally present; argyrophilia
cells are argyrophilic mucicarmine(+); rarely present
(Churukian-Schenck[+]); argyrophilic; rarely,
argentaffin (Fontana), argentaffin(+)
mucicarmine and
periodic acid-Schiff stains
are negative
IHC Chief cells: CHR, SYN, Positive for CK, CHR, Positive for CK, CHR, Positive CK, CHR, SYN,
NSE, NFP positive; SYN, CD56, CD57, NSE, SYN, CD56, CD57, CD56, CD57; also
sustentacular cells: S100 EMA, CEA, TTF-1; may be calcitonin (> 80%); also positive for NSE, NFP,
protein(+); CK(-) positive for calcitonin, positive for NSE, NFP, EMA, CEA, TTF-1;
serotonin, somatostatin, EMA, CEA, TTF-1 calcitonin rarely is
bombesin positive

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