J Periodontol • May 2006

Case Report
Eosinophilic Granuloma Masquerading as
Aggressive Periodontitis
S.S. Silvestros,* A.A. Mamalis,† A.D. Sklavounou,‡ F.X. Tzerbos,§ and D.D. Rontogiannii

Background: Eosinophilic granuloma (EG) is the

E
osinophilic granuloma (EG) of bone, Hand-
mildest and mainly localized form of the clinicopatho- Schüller-Christian disease, and Letterer-Siwe
logic spectrum of Langerhans’ cell histiocytosis. It is a disease are included in the clinicopathologic
destructive osseous lesion characterized by a vast spectrum of a collective designation called histiocy-
number of eosinophils and histiocytes. The etiology tosis X, which was first introduced for this group of
remains unknown. In this paper, a case of EG is pres- disorders. It was suggested that they should be con-
ented that was initially diagnosed and treated as ag- sidered a single disease entity because of the over-
gressive periodontitis (AP). lapping clinical features and the similar histopathologic
Methods: Despite treatment procedures, the EG picture characterized by proliferation of histiocyte-
continued to expand very quickly, destroying the lin- like cells.1
gual cortical bone and the neighboring soft tissues More recently, an alternative terminology, Langer-
and exhibiting periosteal reaction. Diagnosis of EG hans’ cell histiocytosis, was proposed,2-4 based on the
was established on the basis of histopathologic and ultrastructural and immunohistochemical similarities
immunohistochemical evaluation. Moreover, certain between the distinctive histiocytic cells of this disorder
manifestations in the skeletal and respiratory system and Langerhans’ cells that normally reside in the ep-
were observed. idermis and mucosa.5-7 The localized form, EG of
Results: Surgical curettage of the lesions was effec- bone, is the most common and most benign variant
tive; however, corticosteroids and low-dose radiation of the triad and usually affects children and young
were used as adjunctive therapy. adults, with males having a significant preponderance
Conclusion: The rapid progress of eosinophilic over females. Although the skull, mandible, ribs, and
granuloma, the diagnostic problems, and the conse- long bones are more frequently involved, any bone,
quences of late diagnosis and treatment are dis- with the exception of hands and feet, can be af-
cussed. J Periodontol 2006;77:917-921. fected.8,9 The mandible is affected three times as of-
ten as the maxilla.8 Most of the lesions are located in
KEY WORDS
the posterior area of the mandible,10 causing sore
Corticosteroids; histiocytosis, Langerhans’ cell; mouth, halitosis, pain, swelling, loosening of the teeth,
periodontitis; radiation; respiratory; skeletal. retarded healing after extraction, and an unpleasant
taste. Oral lesions accompanied by symptoms such
as persistent headache and malaise may be initial
signs and may lead to diagnosis.11
Radiographs show solitary or multiple areas of round
or oval radiolucencies in the mandible, usually with
well-defined yet non-corticated margins (scooped-out
lesions).12 Destruction of the lamina dura results in the
radiographic appearance of ‘‘floating teeth.’’2,9 Clinical
and radiological features of EG may simulate severe
localized periodontitis or periapical infection.13-17
The purpose of this report is to present a case of EG
with multifocal involvement accompanied by sys-
* Department of Prosthodontics, Dental School, University of Athens,
temic manifestations that developed with irregular in-
Greece. tervals. The need for an interdisciplinary approach to
† Department of Experimental Physiology, Medical School, University of
Athens.
achieve an accurate diagnosis and the importance of
‡ Department of Oral Pathology, Dental School, University of Athens. clinical follow-up are emphasized. The protocol was
§ Department of Oral and Maxillofacial Surgery, Dental School, University of
Athens.
i Department of Pathology, Evangelismos General Hospital, Athens, Greece. doi: 10.1902/jop.2006.050236

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Systemic Langerhans’ Cell Histiocytosis Masquerading as Aggressive Periodontitis Volume 77 • Number 5

approved by the ethics committee of the Dental lingual cortical bone and, in some areas, the produc-
School, University of Athens (according to the Helsinki tion of newly formed bone (Fig. 3).
Declaration). The case subject signed an informed A complete skeletal survey and skull films revealed
consent form. skeletal bone lesions: lytic lesions of the right half of
the T8 vertebral body and the ipsilateral lower surface
CASE REPORT of T7. However, there was no involvement of the pos-
In December 2003, a 30-year-old female was exam- terior vertebral element or the spinal canal, and the in-
ined by one private practitioner for the presence of vertebral disks were preserved (Fig. 4).
deep periodontal pockets. The lesions were diag-
nosed as being of periodontal origin, and the patient
was treated accordingly with scaling, root planing,
and subgingival curettage.
In May 2004, the periodontal condition had con-
siderably worsened, and the patient was referred to
another private practitioner limited to periodontics.
Intraoral examination disclosed that the female had
a marked enlargement of the left side of the mandible.
Figure 2.
Panoramic radiography showed very large multiocu- Ulcerative lesions in the mandible-maxilla and sinus formation.
lated radiolucent lesions (Fig. 1) with well-delineated
margins, an erosion of the cortex (right side of the man-
dible), and an advanced destruction of the periodontal
tissues, with some teeth appearing to float in space (left
side of the molar region). Extensive bone loss in the peri-
apical region of teeth #2 to #4, #7 to #8, #13 to #14, #18
to #21, and #20 was also found. Periapical radiographs
showed bone loss corresponding to the distal surfaces of
teeth #3 and #14 and an extensive bone lesion of tooth
#18; the presence of radiolucent lesions at the periapical
regions of the left lower premolars was also confirmed.
Intraoral examination disclosed ulcerative lesions
with sinus formation (Fig. 2). Periodontal probing re-
vealed deep (7- to 8-mm) pockets symmetrically dis- Figure 3.
tributed in correspondence to the left mandibular Lytic lesions (arrows) of the mandible.
molars, whereas 5-mm pockets were found on the dis-
tal surfaces of the right and left maxillary first molars.
Also, pockets were present on the right upper incisors.
The patient was subsequently referred to a physi-
cian. Magnetic resonance imaging demonstrated that
the lytic lesions involved the left quadrant of the man-
dible with complete erosion and disappearance of the

Figure 1. Figure 4.
Panoramic radiograph showing multiple foci of extensive bone loss Lytic lesions (arrow) of the right half of the T8 vertebral body and the
with ‘‘floating teeth.’’ ipsilateral lower surface of T7.

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J Periodontol • May 2006 Silvestros, Mamalis, Sklavounou, Tzerbos, Rontogianni

pathologic mechanisms have

been proposed. The lesion is
viewed by many investigators
as a reactive process of a disor-
der rather than a neoplasm,18
whereas studies examining the
clonality of the lesional cells
of this condition have shown
this to be a monoclonal pro-
liferation, a finding that is more
consistent with a neoplasmic
process.17,18
Increasing evidence impli-
Figure 5. cates Langerhans’ cells, which
Parenchymal lung changes. share similar morphologic fea-
tures with histiocytes, including
Computed tomography of the chest cavity and ab- the presence of Langerhans’ cell granules,18 and,
domen revealed lesions of intrathoracic organs, such therefore, it has been proposed that all of the clinical
as parenchymal lung changes (Fig. 5). variants of Langerhans’ cell histiocytosis represent a
A mucoperiosteal flap was elevated in the left lower proliferation of abnormal Langerhans’ cells.19
quadrant, the bone was removed with a low-speed bur, An inflammatory etiology has also been proposed
and a biopsy of the lesion was taken at the Department based on the microscopic features, the clinical course,
of Oral and Maxillofacial Surgery, Dental School, Uni- and the response of the disease to conservative therapy
versity of Athens. The specimen consisted of several in most instances. A bacteriologic origin has also been
small fragments of a hemorrhagic grayish-yellow tis- suggested, but the specific causative microorganisms
sue. Microscopic examination was performed at the De- have not been identified.20 Lesions have appeared to
partment of Oral Pathology, Dental School, University be similar to those seen in periodontitis lesions.21,22
of Athens; it showed the presence of sheets of large cells Langerhans’ cell histiocytosis may present either
with abundant cytoplasm and reniform or coffee bean- as a unifocal lesion or as a multifocal process. Oral
shaped nuclei. Multinucleated cells, eosinophils ar- lesions may simulate periodontitis or periapical in-
ranged in a follicular pattern, and phagocytic cells were fections and may be early or, in many cases, the only
also present. Immunohistochemical evaluation indi- manifestation of the disease.10,13,23 Tooth mobility
cated intense positivity of putative Langerhans’ cells and poor healing after extraction are sequelae com-
for S-100 protein and CD-1A antigen (Figs. 6 and 7). monly observed. Swelling and ulceration of the gingiva
A diagnosis of Langerhans’ cell histiocytosis may develop if the disease breaks out of bone.24
(chronic localized form) was rendered. The patient The disease is more frequently seen in the late teens
was started on a chemotherapeutic regimen with or early adulthood and has a distinct predilection for
antibiotics (oral penicillin 2 mg/kg) and corticosteroids males.13,25,26 EG occurs as a solitary radiolucency, al-
(prednisone) for 5 weeks. Low-dose radiation (250 though a significant number of cases with bilateral or
cGy per day for 3 days) in both the mandible and multifocalinvolvement, mimicking advanced periodon-
the thoracic spine was carried out at the Department tal disease, have been described. Rapidly progressive
of Pathology, Evangelismos General Hospital. periodontitis27 (now usually classified as generalized
Due to severe bone loss, extraction of teeth #3, #4, aggressive periodontitis or chronic periodontitis) is
#5, #7, #15, #17, #18, and #20 was determined to be clinically characterized by episodic, generalized emer-
necessary. Additionally, root canal therapy was per- gence of severe and rapid bone destruction without any
formed in teeth #6, #8, #12, #21, and #22, which consistent pattern.27 Eosinophilic granuloma may oc-
did not respond to vitality tests. casionally be misdiagnosed and treated as a periodon-
A follow-up examination 4 months later showed a de- tal condition like the present case. Furthermore, when
crease in the enlargement of the right side of the mandi- microbiological tests are included in the diagnostic pro-
ble and healing of the oral soft tissue lesions. Moreover, cess, e.g., for the presence of black-pigmented Bacte-
significant bone remodeling was observed at the periapi- roides spp., rapidly progressive periodontitis may be
cal regions of teeth #20, #21, and #22 (Fig. 8). the tentative diagnosis. Interestingly, periodontitis-like
lesions in eosinophilic granuloma may indeed respond,
DISCUSSION at least partially, to scaling, root planing, and subgingi-
The etiology and pathogenesis of Langerhans’ cell his- val curettage, but this treatment approach is considered
tiocytosis remain largely unknown, and various etio- inappropriate.24,28

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Systemic Langerhans’ Cell Histiocytosis Masquerading as Aggressive Periodontitis Volume 77 • Number 5

Almost any bone can be involved, but the calvarium

is the single most common site. The femur, pelvis, ribs,
and mandible are other frequent sites of involvement.2
Only rarely is the mandibular condyle involved.8 The
size of the lesions varies from 1 to 15 cm (with an aver-
age of 4 to 6 cm).28 Oral mucosal ulcerations may be
present less frequently,29 whereas EG solitary lesions
of the oral mucosa are extremely rare.30
Gingival lesions are often associated with adjacent
bone involvement, as in our case, in which palatal and
lingual soft tissue lesions were associated with alveo-
lar bone loss. Loosening of neighboring teeth and
infection can occur,31,32 thus making root canal
therapy inevitable. The differential diagnosis must
include periapical or granuloma cysts, malignant
lesions, or inflammatory processes.33-35
Figure 6.
Positive immunoreactivity of Langerhans’ cells against CD-1A Loosening of the teeth was the first clinical manifes-
(hematoxylin and eosin; original magnification ·100). tation of the disease in our case, followed by failure of
an extraction socket to heal. Moreover, gingival reces-
sion intermixed with gingival hyperplasia occurred
and was related to the poor hygiene of our patient,
leading to false pocket formation. The oral manifesta-
tions were generally confined to the molar area and
the angle of the mandible. To evaluate in detail the ex-
tent of the granulomatous tissue to the neighboring
tissue’s bone involvement, a computed axial tomog-
raphy (CAT) scan was performed.4
In general, the radiographic features vary widely ac-
cording to the phase of the disease.28 The lesion usually
begins as a small, centrally located, lytic process with
shaggy, poorly delineated borders. In mid-phase, the
borders tend to become more sharply delineated,
whereas in the late phase there is resolution of periosteal
lamellations, sharper circumscription, and occasion-
ally a thick ring of sclerosis.34 Occasionally, there is
an expanded cortical shell that may be perforated
Figure 7. and accompanied in 5% to 10% of patients by a soft tis-
Positive S-100 immunoreactivity within the cytoplasm of Langerhans’ sue mass,16,28,33 which can be highly suggestive of a
cells (hematoxylin and eosin; original magnification ·100). malignant tumor.14 In some cases, the periosteal bone
formation may produce a typical onion-skin lamellated
appearance, and EG can be radiographically confused
with osteomyelitis, Ewing’s sarcoma, non-Hodgkin’s
lymphoma, and osteosarcoma.28 Microscopic exami-
nation of the lesions is essential for correct diagnosis.35
Because the true nature, etiology, and pathogenesis
of Langerhans’ cell histiocytosis have not been eluci-
dated, variable treatment modalities have been pro-
posed.24 Excellent response has been reported in 28
cases of eosinophilic granuloma of bone after surgery
and radiation.36 Also, it has been stated that curettage
should be the treatment of choice and that radiotherapy
or chemotherapy should be reserved for numerous or
surgically inaccessible regions.29 In monostotic and
Figure 8. polyostotic eosinophilic granuloma, the jaw lesions
Panoramic radiograph showing significant bone gain at the periapical are ordinarily accessible for surgical therapy, and sim-
regions of teeth #20, #21, and #22.
ple excision or curettage may be successful. Not all

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J Periodontol • May 2006 Silvestros, Mamalis, Sklavounou, Tzerbos, Rontogianni

teeth involved by the disease require removal, except 16. Fenches RE, Mills SE. Tumors of the Bone and Joints,
for those with marked mobility and lytic bone lesions 3rd series. Bethesda, MD: Armed Forces Institute of
Pathology; 1993:211-215.
around the root apices.10 Regardless of the type of ther-
17. de Graaf JH, Egeler RM. New insights into pathogen-
apy used, the prognosis for a true solitary eosinophilic esis of Langerhans cell histiocytosis. Curr Opin Pediatr
granuloma of bone, as in our case, seems to be good, 1997;9:46-50.
with remarkable bone gain noticed at the periapical re- 18. Granda FM, McDaniel RK. Multiple progressive eosin-
gion of the left side of the mandible.10,15,32,33 ophilic granuloma of the jaws. J Oral Maxillofac Surg
1982;40:174-178.
19. Krutchkoff DJ, Jones CR. Multifocal eosinophilic gran-
CONCLUSIONS
uloma: A clinical pathologic conference. J Oral Pathol
In patients with a periodontal condition suggestive 1984;13:472-488.
of a diagnosis of aggressive or rapidly progressive 20. Hartman KS. Histiocytosis X: A review of 114 cases
periodontitis, several diseases, including eosinophilic with oral involvement. Oral Surg Oral Med Oral Pathol
1980;49:38-54.
granuloma, need to be considered in the differential di-
21. Eckardt A, Schultze A. Maxillofacial manifestations of
agnosis. Until the etiology is known and definitive treat- Langerhans cell histiocytosis: Clinical and therapeutic
ment is developed, early diagnosis allowing treatment analysis of 10 patients. Oral Oncol 2003;39:687-694.
at an early stage seems to be of utmost importance. 22. Loesche WJ, Syed SA, Morrison EC. Bacterial profiles
of subgingival plaque in periodontitis. J Periodontol
1985;56:447-456.
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