An unusual presentation of Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a relatively rare and unique disease. An incidence of 7.9% in the jaws is reported. We report a case of 9-year-old male child referred to us from dental outpatient department, who presented with a firm swelling in right lower jaw along with bilateral submandibular lymphadenopathy for 1-month. Fine-needle aspiration was done from lytic lesion in the body of mandible and multiple smears were prepared. On the basis of the clinical and cytomorphological findings, a diagnosis of LCH was suggested. The diagnosis was confirmed on histology. Thus, a high possibility of LCH should be considered in children presenting with lytic lesions in head and neck region.

Introduction

Langerhans cell histiocytosis (LCH) is a relatively rare and unique disease characterized by an abnormal proliferation of immature dendritic cells.[1] The nomenclature — histiocytosis X was coined by Lichenstein in 1953 to account for 3 clinical varieties which showed similar histological characteristics, eosinophilic granuloma, Letterer-Siwe disease and Hand–Schuller-Christian syndrome. The term “histiocytosis” denotes proliferation of histiocytes and other inflammatory cells, whereas the letter “X” denotes unknown etiology of the disease. In 1973, LCH term was adopted because histiocytes involved in the disease present a phenotype that is similar to Langerhans cell found in normal mucosa and skin.[2] The annual incidence of LCH in children is reported to be 0.5-5.4 million/year. It is predominantly a childhood disease, and >50% of affected individuals are <15 years of age.[3] The clinical presentation is highly variable. The severity and prognosis depend on the type and extent of organ involvement.

Case Report

The 9-year-old male child came to the dental outpatient department with the complaints of pain and swelling in the right mandibular region since 1-month. There was a soft and tender swelling in the body of right mandible with bilateral submandibular lymphadenopathy. On oral examination, mild bulge was noted in the right lower premolar region. On percussion; right lower premolars were tender and mobile. All other teeth appeared unremarkable. Orthopantomograph showed single radiolucent lesion in the body of right mandible, which involved the premolar region and showed the radiographic appearance of premolar as “floating teeth” [Figure 1a].

Figure 1

(a) The arrow shows the lytic lesion in the body of right mandible with floating teeth (orthopantomograph). (b) The arrow shows the lytic lesion in right mandible (contrast enhanced computed tomography mandible)

Clinically, the dental surgeon suggested the following possibilities:

Dentigerous cyst.

Tuberculous osteomyelitis.

Odontogenic keratocyst.

Unicystic ameloblastoma.

Fine-needle aspiration (FNA) was performed, and blood mixed cellular aspirate was obtained. Cytological smears stained with Giemsa and Papanicolaou stains showed high cellularity comprising polymorphous cell population. Majority of cells were singly scattered and consisted predominantly of large cells with round to oval, pale staining nuclei. Nuclei showed nuclear folding, grooving and sieve-like chromatin with moderate and pale blue cytoplasm. Background showed plenty of eosinophils, few mature lymphocytes, multinucleated giant cells, and macrophages showed phagocytosis [Figure 2a and b]. There was no mitosis or necrosis. A cytological diagnosis of LCH was given. FNA from bilateral submandibular lymph node showed features of reactive lymphoid hyperplasia.

Figure 2

Cytology smears: (a) Histiocytes with nuclear groove, eosinophils (arrows), lymphocytes, multinucleated giant cell (inset) (Giemsa, ×400). (b) The arrow shows histiocytes with nuclear groove (Pap, ×1000)

Hemogram and routine biochemical investigations were normal except alkaline phosphatase, which was raised. Mantoux test was negative. Skeletal radiograph survey showed no other lytic lesion in the body and ultrasonography abdomen showed no hepatosplenomegaly or lymphadenopathy.

Contrast-enhanced computed tomography of the mandible showed a well-defined lytic lesion measuring approximately 1.8 cm × 2.1 cm × 2.2 cm in the body of mandible and symphysis menti on right side with destruction of both outer and inner cortical margins. The lesion was extending into the soft tissue with minimal surrounding enhancement [Figure 1b].

Above investigations ruled out multisystem involvement.

The patient underwent curettage of the lesion under local anesthesia. Multiple grey white firm to hard tissue fragments ranging from 0.3 cm × 0.2 cm × 0.1 cm to 1 cm × 0.5 cm × 0.3 cm were received in the histopathology laboratory. Sections stained with hematoxylin and eosin showed polymorphous cells arranged in diffuse sheets. Most of the cells were large, had an oval to elongated nuclei with nuclear grooves, indentation and inconspicuous nucleoli. Cytoplasm was moderate and eosinophilic. Interspersed amongst them were inflammatory cells comprising of lymphocytes, plasma cells and plenty of eosinophils [Figure 3a]. No necrosis or mitosis was seen.

Figure 3

Tissue section: (a) Histiocytes with nuclear groove (H and E, ×400). (b) S-100 positive (IHC, ×400). (c) CD1a-positive (IHC, ×400)

On immunohistochemistry, large cells showed positivity for S-100, CD1a [Figure 3b and c] and CD68.

Based on the clinical, histological and the immunohistochemical features, a diagnosis of LCH (unifocal eosinophilic granuloma) was made.

Patient showed improvement after receiving six intralesional corticosteroid injections.

Discussion

The etiology and pathogenesis of LCH are still unclear. Different hypothesis have been proposed, which include a disorder of immune regulation with deficiency of T suppressor lymphocytes, a neoplastic proliferation of Langerhans cells.[4] or other etiological factors like viruses, bacteria and genetic components.[5]

Incidence of LCH in jaws is 7.9% with angle and body of the mandible being the most common site.[6]

Manifestations of LCH may take various forms:[7]

Acute disseminated form or Letterer-Siwe disease. It has rapidly progressive clinical course, involves multiple organs and is fatal.

Chronic disseminated form or Hand-Schuller-Christian syndrome present as a triad of diabetes insipidus, exophthalmos and bony lytic lesions.

Chronic localized form or eosinophilic granuloma with only unifocal or multifocal bone lesions. It is the most common form of LCH forming approximately 60-70% of LCH cases. Eosinophilic granuloma has an incidence of one new case per 350,000-2 million/year.[8] It is the mildest form and appears to be less aggressive than the other varieties. The destruction of the alveolar bone is thought to be one of the characteristic signs of eosinophilic granuloma.[9]

Our case belongs to the third category as it presented with unifocal lytic lesion and was not associated with any systemic manifestation.

Tuberculous osteomyelitis, one of the differential diagnosis in our case, was ruled out as there was no epithelioid cell granuloma or necrosis. Clinically suspected ameloblastoma was excluded due to the absence of basaloid cells with peripheral palisading of nuclei. Absence of anucleated squames and keratinous debris ruled out odontogenic keratocyst and dentigerous cyst were excluded as cystic content was not aspirated.

The diagnosis of LCH is based on morphological, immunohistochemical and ultrastructural features. Morphologically, presence of classical nuclear grooves with associated eosinophilia and immunohistochemically S-100 and CD1a positivity are characteristics of LCH. Electron microscopy of LCH shows the presence of cytoplasmic granules, called Birbeck granules, which possess a tennis-racket morphology with transverse striations and are pathognomonic of Langerhans cells.[10]

To conclude, a careful clinical examination, good diagnostic skill and awareness of characteristic cytological features of LCH leads to earlier diagnosis and treatment with minimal deformity. Although unifocal lesions of LCH successfully respond to curettage, the possibility of recurrences or new lesions still remains which makes a long term follow-up necessary.