Extranodal manifestation of Rosai-Dorfman disease with bilateral ocular involvement.

Rosai-Dorfman disease, that is, sinus histiocytosis with massive lymphadenopathy is a benign systemic proliferative disorder of histiocytes. The typical clinical presentation of the disease includes bilateral painless massive lymphadenopathy, fever and polyclonal hypergammaglobulinemia. Extranodal involvement is present in only a few cases and skin lesions are the most common form of extranodal disease. However, purely cutaneous Rosai-Dorfman disease is uncommon. In this study, we describe a 10-year-old child presenting with bilateral ocular involvement.

Introduction

Rosai-Dorfman disease is a benign systemic histioproliferative disease characterised clinically by massive bilateral cervical lymphadenopathy, fever, leukocytosis, raised erythrocyte sedimentation rate and pathologically by hyperplastic lymph node sinuses containing large histiocytosis with intact phagocytosed lymphocytes (emperipolesis).[1]

Sinus histiocytosis with massive lymphadenopathy (SHML) is generally a benign disorder in spite of its propensity to form large masses and to involve both nodal and extranodal site in 10% of the cases; skin and subcutaneous tissue being most common followed by soft tissue, upper respiratory tract, salivary gland oral cavity and genitourinary system.[1-3]

Case Report

An otherwise healthy 10-year-old boy sought treatment for bilateral diffuse eyelid swelling of a few months duration. Clinical examination reveals no lymphadenopathy or other detectable abnormalities. Other laboratory tests were within normal limits. Fine needle aspiration cytology (FNAC) revealed diffusely distributed histiocytes and a few histiocytes showing emperipolesis [Figure 1]. Histiocytes had single, with occasionally multiple, nuclei, fine evenly distributed chromatin and abundant pale eosionophilic cytoplasm. Background had mature lymphocytes, plasma cells and occasional neutrophils; hence, diagnosis of extranodal Rosai-Dorfman disease was made. Biopsy was sent for histopathological examination.

Figure 1

FNA smears showing lymphocytes and histiocyte showing emperipolesis (H and E, ×400)

Microscopic examination revealed sheets of polymorphous infiltrate in which lymphocytes and histiocytes with voluminous pale eosinophilic cytoplasm with indistinct cytoplasmic borders were the most prominent [Figure 2]. Several histiocytes contained lymphocytes in the cytoplasm, that is, showed emperipolesis [Figure 3]. A few multinucleated histiocytes, occasional plasma cells, neutrophils and rare eosinophils were also seen. Vascular channels surrounded by lymphocytes were also observed. Immunohistochemistry showed positivity to S-100 protein [Figure 4].

Figure 2

Histology showing dark-staining lymphocyte admixed with pale sinusoidal histiocytes (H and E, ×100)

Figure 3

Lymphocytes and sinusoidal histiocytes showing emperipolesis at higher magnification (H and E, ×400)

Figure 4

Histiocytes showing cytoplasmic positivity for S-100 (Peroxidase-antiperoxidase stain, × 100)

Discussion

Since the original description, the Rosai-Dorfman disease has become a rare but distinct clinico-pathological entity of idiopathic proliferation of histiocytes. It is currently defined as a unique histiocyte, which are large cell containing vesicular nucleus and voluminous cytoplasm, exhibiting lymphophagocytosis (emperipolesis).[12] It may affect any age group or any gender, without racial predilection, but 80% of the patients are aged 20 years or younger at onset. Most patients are characterized by bilateral painless massive lymphadenopathy with or without constitutional manifestation. Because of gradual awareness, more and more extranodal cases have been documented which manifested at least one extranodal site of involvement. Moresoever, extranodal disease may be the initial and sole manifestation of the disorder, making the eponym Rosai-Dorfman disease more appropriate than the original term SHML.[4]

Foucar et al.[2] considered the presence of emperipolesis and S-100 protein expression by the histiocytes with feathery borders to be diagnostic of Rosai-Dorfman disease. These histiocytes also showed positive immunostaining for CD11c, CD14, CD33 and CD68 antigens.[5]

Cytological features of Rosai-Dorfman disease revealed large voluminous histiocytes showing evidence of emperipolesis and lying against a mixed inflammatory background of lymphocyte, plasma cells and occasional neutrophils. Only a few well documented cases diagnosed by FNAC have been reported.[6]

To date, most authors have speculated that the histiocytes of Rosai-Dorfman disease probably derived from circulating monocytes and a sort of distinctive activated histiocytes with coexpression of partial immunophenotypic character of both monocyte/macrophage system and dendritic/Langerhans cell family.[7]

Cutaneous Rosai-Dorfman disease differs histologically from nodal disease in that there is a greater degree of fibrosis, fewer histiocytes and diminished emperipolesis. Hence, cutaneous Rosai-Dorfman disease can be overlooked if the index of suspicion for the disease is low. On morphological ground, the recognition of cutaneous form of Rosai-Dorfman disease should consider a variety of disease in the differential diagnosis including eruptive xanthoma, Langerhans cell histiocytosis, reticulohistiocytoma, juvenile xanthogranuloma, Hodgkin's lymphoma, malignant histiocytosis as well as inflammatory pseudotumor.[2]

The exact etiology of Rosai-Dorfman disease is not known. An underlying immune dysfunction has been postulated. Possibility of viruses like Human Herpes Virus 6, Klebsiella, Epstein-Barr virus, Cytomegalovirus or Brucella as a causative agent have been postulated.[58]

Rosai-Dorfman disease usually follows a course of spontaneous regression and recovery; however, in a small percentage of cases, the disease may be persistent and progressive, associated with widespread dissemination and involvement of the kidney, lower respiratory tract or liver. When Rosai-Dorfman disease is limited to the skin, most reports[2] indicate a favorable long-term prognosis with spontaneous regression.

Most of the cutaneous lesions generally do not require any further treatment, although roentgen therapy has been described as a useful therapeutic modality when the cutaneous disease runs a prolong course or when the lesions are aesthetically unacceptable to the patient.[9]