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Diagnosis and Discussion - Case 1122

Final Diagnosis

The findings were most compatible with “Extranodal Rosai Dorfman Disease”, which is an extranodal histiocytosis of uncertain etiology. A subset has been reported to be neoplastic while other studies have shown it to be polyclonal.

Discussion

Histiocytosis are rare disorders characterized by the accumulation of macrophage, dendritic cell, or monocyte-derived cells. More than 100 different subtypes have been described, with a wide range of clinical presentations and microscopic findings. They can arise in various organs and tissue types and are seen in both adults and children. The mean age of diagnosis is 50 years old. Rosai-Dorfman disease is one of 3 major types of histiocytosis which include Erdheim-Chester disease and Langerhans cell histiocytosis.  Rosai-Dorfman disease was initially considered a benign condition however it has been incorporated as a histiocytic neoplasm in the fifth edition of the World Health Organization classification of hematopoietic tumors and the International Consensus Classification [1].

The Histiocyte Society Classification has grouped systemic Rosai Dorfman Disease under the “R” group which includes both sporadic and familial cases. Rosai Dorfman Disease is also distinguished by whether it is nodal, known as the classic type or extranodal. Rosai Dorfman Disease can also have a cutaneous form which is classified under the “C” group [2]. Classical sporadic Rosai Dorfman Disease is more common in children and young adults, and more frequent in males of African descent. The most common presentation is bilateral painless massive cervical adenopathy. Men are more frequently affected than women with lymphadenopathy and constitutional symptoms including fever, night sweats, fatigue, and weight loss [3]. Rosai Dorfman Disease can also be associated with autoimmune conditions and neoplasia. [2].

Histologic diagnosis requires the presence of large histiocytic cells displaying hypochromatic nuclei and pale cytoplasm, often with emperipolesis. Immunohistochemistry shows positive staining for S100, fascin, CD68, CD14, HLA-DR, CD163. It has negative staining for CD1a and CD207 which is positive in Langerhans cell histiocytosis and is a helpful marker to distinguish both entities. Involved tissues usually contain an inflammatory infiltrate including plasma cells. In lymph nodes, histiocytes are mainly localized within the sinuses. The cortex usually contains abundant plasma cells and activated B cells. Lab testing can show nonspecific findings which include elevated erythrocyte sedimentation rate and leukocytosis, high ferritin, hypergammaglobulinemia, and autoimmune hemolytic anemia [4].

Rosai Dorfman Disease can present as extranodal disease which is seen in up to 40% of cases and may occasionally occur in the absence of nodal disease. Such cases are more often seen in older patients. Common extranodal sites of involvement include the skin, nasal cavity, bone, orbital tissue, and central nervous system. In the CNS the presentation is most often dural. When the bone is involved, the presentation is seen as lytic lesions. Central nervous system involvement may mimic meningioma clinically and is usually not associated with nodal disease. Extranodal disease can resemble nodal Rosai Dorfman Disease but may display more prominent lymphoid follicles with germinal centers, fibrosis, sclerosis and fewer histiocytes. Emperipolesis is not a requirement for the diagnosis and is often subtle at extranodal sites [5].

Rosai Dorfman Disease can also have a cutaneous form which is classified under the “C” group [2]. Cutaneous Rosai Dorfman Disease is typically a dermal-based lesion with a nodular poorly circumscribed growth pattern. Histiocytic cells with emperipolesis are a characteristic feature. The presence of storiform growth has been noted in patients with the cutaneous form. Plasma cells and neutrophils are often present with formation of microabscesses [6].

Rosai Dorfman Disease is associated with molecular pathway alterations. Mutations in MAPK signaling have been found in Rosai Dorfman Disease patients, including KRAS and NRAS mutations. Additionally, BRAF mutations have been reported in a subset of cases. This discovery can allow for the potential of targeted therapy in patients [7].

References

  1. Ravindran, A., & Rech, K. L. (2023). How I Diagnose Rosai-Dorfman Disease. Am J Clin Pathol,

     160(1), 1-10.

  2. Emile, J. F. et al. "Revised Classification of Histiocytoses and Neoplasms of the Macrophage

     Dendritic Cell Lineages." Blood, vol. 127, no. 22, 2016, pp. 2672-81.

  3. Rosai, J., & Dorfman, R. F. (1969). Sinus histiocytosis with massive lymphadenopathy. A newly recognized benign clinicopathological entity. Archives of pathology, 87(1), 63–70.

  4. Vaiselbuh, S.R., Bryceson, Y.T., Allen, C.E., Whitlock, J.A. and Abla, O. (2014), Updates on histiocytic disorders. Pediatr Blood Cancer, 61: 1329-1335.

  5. Bruce-Brand C, Schneider JW, Schubert P. Rosai-Dorfman disease: an overview

    Journal of Clinical Pathology 2020;73:697-705.

  6. Brenn, Thomas M.D., Ph.D.; Calonje, Eduardo M.D.; Granter, Scott R. M.D.; Leonard, Niamh M.B., M.R.C. Path.; Grayson, Wayne M.B.Ch.B., F.C.Path.(S.A.); Fletcher, Christopher D. M. M.D., F.R.C.Path.; McKee, Phillip H. M.D., F.R.C.Path. Cutaneous Rosai-Dorfman Disease Is a Distinct Clinical Entity. The American Journal of Dermatopathology 24(5):p 385-391, October 2002.

  7. Chang, L., Qiao, B., Cai, H. et al. Clinical phenotypes, molecular analysis, and outcomes of patients with Rosai-Dorfman disease. Leukemia 37, 2297–2300 (2023).