FINAL DIAGNOSIS Cutaneous Rosai-Dorfman Disease
Rosai-Dorfman Disease was first described in 1965 and acknowledged as a clinical-pathological entity in 1969 (1). The disease may affect any age, but is more common in the first and second decades of life with a slight preference for males (1.4:1). The most frequently affected ethnical groups are black and white individuals, being rarely reported in Asians (2). Clinically, Rosai-Dorfman Disease is characterized as extensive, bilateral and painless lymphadenopathy, frequently associated with fever, anemia, leucocytosis with neutrophilia, high erythrocyte sedimentation rate, and polyclonal hypergammaglobulinemia (3). The disease has a clinically benign progression with typical regression, although recurrence can occur and no treatment is currently known.
Extra-nodal involvement is commonly observed and has a histopathologic pattern similar to what is observed in nodal involvement. Skin is the most common extra-nodal site. However, purely cutaneous involvement, as observed in this patient, is quite rare with only about 3% of patients having disease limited to the skin (4). Unlike the systemic syndrome, cutaneous Rosai-Dorfman can also affect any age but most commonly presents in the fourth decade with a female predominance (2:1) (3). The disease is seen in all ethnic populations including Asians. The systemic signs of pyrexia and night sweats and the laboratory changes of an elevated ESR, leukocytosis, and polyclonal hypergammaglobulinemia are usually absent.
Histologically, the lesions generally show varied growth patterns with a background of a mixed inflammatory infiltrate including plasma cells, lymphocytes, and neutrophils (3). The histiocytic cells are polygonal cells with abundant granular and palely eosinophilic cytoplasm as well as open vesicular nuclei with prominent nucleoli. These cells frequently contain intracytoplasmic inflammatory cells, including lymphocytes, plasma cells, and neutrophils. This process has been referred to as emperipolesis which, like the systemic counterpart, is a constant feature in cutaneous Rosai-Dorfman disease. The inflammatory response can be prominent with neutrophil microabscess formation. The finding of characteristic histiocytes within dilated lymphatic spaces has been previously reported to be a helpful clue in the diagnosis of cutaneous Rosai-Dorfman disease (5) while others have not found this finding helpful (3). Immunohistochemistry generally demonstrates that the polygonal cells are CD1a negative and strong S-100 positive. Proliferations of smaller histiocytes that are negative for S-100 in association with Rosai-Dorfman cells have been described (6). Emperipolesis can also be highlighted in the S-100 positive cells. The cells are variably CD68 positive with some lesions demonstrating weak staining or absent staining (3 and 5). The background plasma cells are polyclonal.
The etiology of cutaneous Rosai-Dorfman disease is unknown. Classical Rosai-Dorfman disease has been associated with human herpesvirus 6 (HHV-6) and some have postulated that the cause of the lesions is an exaggerated response to infection (7). Additionally, the virus has been found in the cutaneous lesions of classical Rosai-Dorfman disease. However, HHV-6 expression is usually not found in purely cutaneous Rosai-Dorfman disease (8). Because cutaneous Rosai-Dorfman Disease is benign and normally regresses with time with low risk of systemic involvement, treatment is usually not necessary. However, if surgery is deemed necessary due to patient wishes or locally aggressive lesions, surgical excision of the skin lesion is the exclusive effective treatment for disease limited to the skin (9). Other documented treatment options include radiation therapy, corticosteroids, cryotherapy, chemotherapy and isotretinoin (2, 6).
Contributed by Rebecca Ocque, MD and Fiona Craig, MD