Rosai-Dorfman Disease Initially Misdiagnosed as Sarcoidosis



Illustration 1.

The patient, a 24-year-old woman with longstanding nasal obstruction, presented with subcutaneous nodules of 1-year duration. She had been diagnosed as having sarcoidosis based on histopathologic analysis of salivary and sinus tissue and had received steroid therapy without effect. Positron emission tomography with 18F-labeled fluorodeoxyglucose and computed tomography scanning showed increased uptake in the left maxillary sinus. Increased uptake was also observed in lymph nodes and in innumerable subcutaneous nodules (A). Lymph node biopsy revealed histiocytes with pale abundant cytoplasm (B). Macrophages within the lymph node sinuses had so-called emperipolesis, prominent intracytoplasmic vacuoles containing viable lymphocytes (arrow in C), plasma cells, or neutrophils (arrows in D). Immunohistochemical analysis revealed high expression of S100 proteins on histiocytes, without expression of CD1a (E). Thus, the diagnosis of Rosai-Dorfman disease was established histologically and by immunohistochemical analyses of lymph node and skin biopsy samples. Rosai-Dorfman disease is a rare, non-neoplastic, idiopathic proliferative disorder also known as sinus histiocytosis with massive lymphadenopathy. Presenting signs typically include massive bilateral painless cervical lymphadenopathy with leukocytosis, hypergammaglobulinemia, and systemic symptoms (1). Extranodal involvement occurs in 43% of cases, affecting skin, upper airways, and bone (2, 3). Diagnosis is typically delayed due to misinterpretation of clinical and histologic data. Indeed, the diagnosis of Rosai-Dorfman disease is a real challenge as it can be misdiagnosed as sarcoidosis, spondyloarthritis (3), juvenile idiopathic arthritis, or metastatic subcutaneous nodules. Proliferation of histiocytes and S100 protein expression without CD1a expression are typical of Rosai-Dorfman disease, in contrast to Langerhans' cell histiocytosis in which both S100 and CD1a are detected (1–3). Spontaneous recovery is common, and treatment should be reserved for patients with severe and aggressive presentations. Fatal outcome occurs in <7% of cases (2).