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A 33-year-old man presented with asymptomatic, gradually progressing, reddish nodules on the

thigh of 1 year’s duration. Six months later, nodules were noticed on the buttock of the same side.

At the same time, the inguinal and femoral lymph nodes increased in size and could be seen

as an elevated mass in the groin which, although painless, made the patient limp when walking.

On examination, a cluster of pink nodules on an erythematous, oval, indurated area,

measuring 10 cm × 5 cm, was seen on the lower medial aspect of the right thigh (Fig. 1). A

small, almost circular, cluster of papules was present on the lower part of the right buttock. Some

of these lesions, according to the patient, were reducing in size. The right inguinal and femoral

lymph nodes were markedly enlarged and firm. The overlying skin was normal. Clinical

differential diagnoses of dermatofibrosarcoma and localized, cutaneous T-cell lymphoma were

considered in this patient. Systemic examination revealed no abnormality.

Routine investigations showed a normal hemogram with an erythrocyte sedimentation rate

(ESR) of 25 mm/h. Urinanalysis, serum proteins, liver and renal function, chest X-ray, and

paranasal sinuses were within normal limits. Peripheral blood smear examination did not show

any abnormal cells. Immunoglobulin (Ig) levels showed: IgG, 12.9 g/L (reference range,

5.6–14.5 g/L); IgA, 4.6 g/L (reference range, 0.45–3.64 g/L); IgM, 0.7 g/L (reference range,

0.03–2.09 g/L).

An incisional biopsy was taken from the skin lesion and fine needle aspiration (FNA) of the

inguinal nodes was performed. FNA smears were moderately cellular. The cell population,

predominantly polymorphic, comprised mature lymphocytes, plasma cells, neutrophils, and

histiocytes. The histiocytes were large, having abundant cytoplasm, and the most prominent

feature was the presence of lymphocytes and plasma cells engulfed within the histiocyte

cytoplasm (emperipolesis) (Fig. 2). Skin biopsy from the lesion showed an essentially

unremarkable epidermis. The entire dermis was densely infiltrated by a polymorphic

inflammatory cell population. The predominant cell population was made up of large

histiocytes having abundant pale cytoplasm. Plenty of lymphocytes arranged in a nodular

pattern were also seen between the histiocytes. Plasma cells, neutrophils, and a few

eosinophils were also interspersed. The striking feature was, however, engulfed neutrophils and

lymphocytes within the histiocyte cytoplasm (emperipolesis) (Fig. 3). Immunohistochemical

stains revealed S-100 positivity in the histiocytes (Fig. 4). The cytologic, histologic, and

immunohistochemical findings were correlated and a diagnosis of Rosai–Dorfman disease

was made.

Blackwell Science, LtdOxford, UKIJDInternational Journal of Dermatology0011-9059Blackwell Science, 2002?CameoCutaneous Rosai–Dorfman diseaseUniyal et al.CameoCutaneous Rosai–Dorfman disease preceding inguinal lymphadenopathy

Shailesh K. Uniyal, MD, K. R. Beena, MD, V. Ramesh, MD, and Ashok Mukherjee, MD

From the Department of Dermatology and Institute of Pathology (ICMR), Safdarjang Hospital Campus, New Delhi, India

Correspondence Shailesh K. Uniyal, MD Department of DermatologySafdarjang HospitalNew Delhi – 110 029IndiaE-mail: drshaileshuniyal@rediffmail.com

Discussion

Rosai–Dorfman disease is a histiocytic disorder with anunknown etiopathogenesis. The disease affects all age groups,but is most common during the first and second decades oflife. The disorder does not show predilection for any ethnic groupor gender. It is a benign, self-limiting disease, often involvingthe lymph nodes, especially the cervical nodes. Extranodalinvolvement occurs in 30–40% of cases.1 Any organ in the

body can be involved, especially the skin, upper respiratorytract, salivary glands, bone, central nervous system, andsoft tissues.2 Extranodal localization may be the predominantor exclusive disease manifestation, as exemplified in this case.

Rosai–Dorfman disease, or sinus histiocytosis with massivelymphadenopathy, was first described by Rosai and Dorfmanin 1969.3 A registry of this entity contains records and patho-logic samples from over 600 cases.4 Pure cutaneous lesionswere reported for the first time in 1978.5

© 2002

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, 404–406

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et al. Cutaneous Rosai–Dorfman disease

Cameo

The etiology of the disease is unknown. It is a disorder ofthe mononuclear phagocyte and immunoregulator effectorsystem.

2

An abnormal response of histiocytes to an infectivestimulus is hypothesized. Human herpes virus 6 (HHV 6) hasbeen detected in involved tissues.

6

Elevated Epstein–Barr virusand herpes simplex virus antibody titers have been reported.

7,8

Clonal analysis performed in cases of Rosai–Dorfman diseaseshow that the cell infiltrate is polyclonal in nature, thussupporting a reactive rather than a neoplastic process.

9

Cutaneous lesions present as solitary or multiple papules,nodules, or plaques. Lesions may occasionally appear pso-riasiform or acneiform. The cervical lymph nodes are usuallythe most common node involved, followed by the axillary,inguinal or para-aortic, and mediastinal nodes. The patientmay also show features of anemia, an elevated erythrocyte

sedimentation rate (ESR), leukocytosis, and hypergamma-globulinemia. The disease is often associated with immunedisorders, preceding or occurring at the same time. Commonabnormalities are the presence of autoantibodies (againstred cell antigens), joint diseases (polyarthralgia to severearthritis), severe infections (pneumonia), glomerulonephritis,asthma, and juvenile-onset diabetes mellitus.

10

The diagnosis of Rosai–Dorfman disease in a nodal/extra-nodal site is indicated by the classic histologic/cytologicpattern: a polymorphous infiltrate together with histiocytesexhibiting features of emperipolesis. The latter feature,although not totally specific, provides an important clue tothe diagnosis.

Immunohistochemical stains provide a good aid to diag-nosis. The histiocytes show strong and consistent positivity to

Figure 1 Cluster of reddish nodules over the thigh

Figure 2 Photomicrograph of fine needle aspiration smears showing large histiocytes with engulfed lymphocytes and plasma cells (emperipolesis) (Giemsa, × 400)

Figure 3 Photomicrograph from the cutaneous nodule showing a dermal infiltrate of histiocytes, lymphocytes, neutrophils, and plasma cells. The large histiocytes reveal emperipolesis (hematoxylin and eosin, × 400)

Figure 4 Photomicrograph from the skin lesion showing a positive staining reaction with S-100 antibody within the histiocyte cytoplasm (avidin–biotin peroxidase, × 400)

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S-100 protein. Positive staining reactions are also observedwith CD14, CD68, CD30, CD25,

α

1-antitrypsin, and cathe-psin D and E.

Clinically and histologically, it may be important to differ-entiate Rosai–Dorfman disease from benign and malignantfibrous histiocytoma, large cell lymphoma, Hodgkin’slymphoma, Langerhans’ cell histiocytosis, melanoma, andmetastatic carcinoma. Emperipolesis is observed in many ofthese conditions.

Pure cutaneous lesions of Rosai–Dorfman disease are rare.It is not clear whether these cases actually remain limited tothe skin or whether they are associated with an undetectednodal or systemic lesion which may manifest later. This wasobserved in the present case.

The disease usually undergoes spontaneous regression, asobserved in our patient. There may occasionally be a chroniccourse or disseminated nodal or systemic involvement,however. Treatment is usually not required. Superficial X-rayor cryotherapy are viable therapeutic options. A combinationof vinca alkaloids and corticosteroids may be of value. Ourpatient was informed about the possibility of spontaneousremission, but desired active intervention. Cryotherapyfollowed by intralesional triamcinolone was started and wasgiven at intervals of 3 weeks. Skin lesions showed markedregression.

Poor prognostic signs include widespread dissemination,organ involvement, immunologic abnormalities, anemia,lymphocytopenia, and elevated ESR. A diagnostic work-upfor immunologic abnormalities, computed tomography,magnetic resonance imaging, and radionuclide bone scanningmay be helpful for follow-up and evaluation.

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