Final Diagnosis -- Rosai Dorfman disease and multiple sclerosis


  1. CNS Rosai Dorfman disease.
  2. Multiple sclerosis.


Rosai-Dorfman disease (sinus histiocytosis with massive cervical lymphadenopathy) was first described in 1969 (6); it is an immune disorder characterised by proliferation of B and T lymphocytes, and foamy histiocytes. The pathologic hallmark is emperipolesis, wherein histiocytes engulf lymphocytes and plasma cells within their cytoplasm. Rosai-Dorfman disease is typically confined to the lymph nodes, and the largest case series to date (423 cases) reports central nervous system (CNS) involvement in only 4% (2). A review of the CNS manifestations of Rosai-Dorfman disease reveals that the vast majority of patients present with focal dural-based hemispheric brain lesions mimicking meningioma (3),(1). Other reported sites of CNS involvement have included anterior optic pathway, cerebellopontine angle, spinal cord, or hemispheric white matter (3), (1). The present case expands the neurologic manifestations of Rosai-Dorfman disease to include intracranial arterial dissection (due to infiltration by inflammatory cells); and lends support to a prior report of diffuse dural inflammation in CNS Rosai-Dorfman disease, mimicking idiopathic hypertrophic pachymeningitis (7).

Multiple sclerosis (MS) is a chronic demyelinating neurological disorder, with a presumed autoimmune mechanism. The classical neuropathological findings in a chronic inactive MS plaque include a region of oligodendrocyte (myelin) loss, with relative preservation of axons, and minimal active inflammation or myelin breakdown products (4). These classical pathological findings were all observed in our patient.

Our case was quite atypical due to the co-existence of MS, Rosai-Dorfman disease, and polycythemia vera (all rare diseases) in a single patient. While the overlap may have been coincidental, one could raise the question of a common pathogenic mechanism, due to an underlying dysimmune state. In fact, some links between polycythemia vera and multiple sclerosis have already been established. Polycythemia vera is commonly caused by a somatic V617F mutation of the JAK2 tyrosine kinase, which is involved in signal transduction in both hematopoietic cells, and in cytokine receptors. IL-12 signalling through the JAK-STAT pathway plays a critical role in the pathogenesis of experimental autoimmune encephalitis (EAE), a Th1 cell-mediated disease model of multiple sclerosis (5). One could speculate whether JAK2 mutations may provide a link in the understanding of multiple sclerosis, Rosai-Dorfman disease, and polycythemia vera.


  1. Andriko JA, Morrison A, Colegial CH, Davis BJ, Jones RV (2001) Rosai-Dorfman disease isolated to the central nervous system: a report of 11 cases. Mod Pathol.14(3):172-8.
  2. Foucar E, Rosai J, Dorfman R (1990) Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): review of the entity. Semin Diagn Pathol.7(1):19-73.
  3. Kidd DP, Revesz T, Miller NR (2006) Rosai-Dorfman disease presenting with widespread intracranial and spinal cord involvement. Neurology.67(9):1551-5.
  4. Lucchinetti CF, Parisi J, Bruck W (2005) The pathology of multiple sclerosis. Neurol Clin.23(1):77-105, vi.
  5. Muthian G, Raikwar HP, Johnson C, Rajasingh J, Kalgutkar A, Marnett LJ, Bright JJ (2006) COX-2 inhibitors modulate IL-12 signaling through JAK-STAT pathway leading to Th1 response in experimental allergic encephalomyelitis. J Clin Immunol.26(1):73-85.
  6. Rosai J, Dorfman RF (1969) Sinus histiocytosis with massive lymphadenopathy. A newly recognized benign clinicopathological entity. Arch Pathol.87(1):63-70.
  7. Tanabe Y, Tagawa K, Komatsu T, Tai S, Mikami K, Shoshi S, Onda M (2002) [Rosai-Dorfman disease accompanying hypertrophic cranial pachymeningitis with an early symptom of right peripheral facial palsy]. Masui.51(10):1129-31.

Contributed by Ari Breiner, MD, William Dubinski, MD, Bruce Gray, MD, David G. Munoz, MD, FRCPC

Case IndexCME Case StudiesFeedbackHome