Brain Pathology Case of the Month - May 2002

DIAGNOSIS:   Destombes-Rosai-Dorfman Disease (DRDD)


Histological diagnosis is based on presence of distinct histiocytic cells in the mixed inflammatory background. The histiocytic cells exhibit emperipolesis (which is critical for the diagnosis of DRDD), and characteristic immunohistochemical profile, with positivity for various monocyte/macrophage markers and for S100 protein, while CD1a is negative. Differential diagnosis includes several neoplastic and nonneoplastic entities, only some of which had to be seriously considered in the present cases. Among the neoplastic conditions, meningioma has to be excluded, as rare variants of this common tumor contain very prominent inflammatory infiltrates. In extreme cases, the inflammation may almost entirely obscure the minor meningothelial component. There appears to be a spectrum of lesions, from unequivocal meningiomas with prominent lymphoplasmacytic infiltrates to dura based inflammatory masses with either no distinguishable meningothelial component, or with a minor component which may represent entrapped arachnoid cells, rather than a neoplastic proliferation. Patients with inflammatory meningiomas and purely inflammatory dural lesions share certain clinical characteristics, including often young age and accompanying systemic manifestations. Occasionally, lesions representing various parts of this spectrum were encountered in the same patient. In the present cases, microscopic examination of multiple sections and immunostaining for the EMA did not disclose any meningothelial cells.

Because of very prominent plasmacytic component, plasmacytoma also has to be considered. The plasma cells in our cases were present in a mixed inflammatory background with fibrosis, and showed no atypia or mitotic activity. Lambda and kappa stains confirmed the polyclonal nature of plasma cell infiltrates. Although theoretically Hodgkin's disease and true histiocytic lymphoma should be included in differential diagnosis, lack of anaplasia helped to exclude these entities.

Various inflammatory processes may present as an isolated dural mass. Among these, plasma cell granuloma (inflammatory pseudotumor) of the CNS has been reported in about twenty cases, most commonly as an isolated intracranial mass. Like DRDD, it shows a mixed inflammatory infiltrate with various proportions of lymphocytes, plasma cells, and histiocytes, often associated with fibrosis. Myofibroblastic proliferation is present, and may be very prominent in some cases. Unlike in DRDD, there is no emperipolesis, and the histiocytes show no immunoreactivity for S100 protein.

Angiofollicular hyperplasia (Castleman's disease) has been rarely described in the intracranial location, and shares with DRDD predilection for dural involvement, and mixed inflammatory proliferation. Presence of active germinal centers and vascular changes would be expected in Castleman's disease. Clinically, fever, weight loss, anemia, leukocytosis, thrombocytosis, bone marrow plasmacytosis, splenomegaly, and lymphadenopathy are often seen in patients with intracranial Castleman's disease.

CNS involvement by Langerhans cell histiocytosis is usually contiguous with bone lesions, but rare cases of apparently isolated CNS lesions have been reported. Histologically there are mixed inflammatory infiltrates including Langerhans cells. These cells have characteristic folded or grooved nuclei. They are positive for S100 protein, like the histiocytic cells of DRDD, but are also positive for CD1a, and show diagnostic Birbeck granules on ultrastructural examination.


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Acknowledgments   We thank Dr. Susan Morgello for performing the immunostains for Epstein-Barr virus.

Contributed by Monika A Wrzolek, MD and David Zagzag, MD

International Society of Neuropathology