BRAF V600E expression in histiocytic sarcoma associated with splenic marginal zone lymphoma: a case report

Abstract

Background: Histiocytic sarcoma is a rare histiocytic neoplasm of unknown etiology that constitutes less than 1% of hematologic malignancies. A few cases of histiocytic sarcoma harboring the BRAF ^V600E mutation have been reported, but this finding has not been confirmed in all studies.

Case presentation: We report the case of a 63-year-old white woman with a history of splenic marginal zone lymphoma who presented with 2 weeks of right-sided neck swelling. Positron emission tomography revealed an intensely hypermetabolic and destructive soft tissue mass in her right skull base. A bone marrow biopsy was performed, which revealed an infiltrate of malignant cells characterized as large pleomorphic cells with frequent folded/irregular nuclei, variably prominent nucleoli, fine chromatin, and abundant amounts of eosinophilic cytoplasm. The malignant cells were positive for CD163, CD68 (granular), lysozyme (granular), CD4, and CD45 (partial). Based on the biopsy findings, she was diagnosed as having histiocytic sarcoma. The malignant cells tested positive for the BRAF^V600E protein using immunohistochemistry. Before treatment of her histiocytic sarcoma could be initiated, she developed disseminated intravascular coagulation and acute hypoxemic respiratory failure secondary to non-cardiogenic pulmonary edema. She decided to pursue comfort care and died in our hospital 2 weeks following admission.

Conclusions: Our case illustrates the aggressive nature of histiocytic sarcoma, and provides rare evidence that histiocytic sarcoma associated with indolent lymphomas may harbor the BRAF ^V600E mutation. Further research is needed to clarify the role of targeted therapies such as vemurafenib in the treatment of patients with this disorder.

Keywords: Histiocytic sarcoma; Immunohistochemistry; Marginal zone B-cell lymphoma; Proto-oncogene proteins B-raf.

Fig. 1

Positron emission tomography scan demonstrating hypermetabolic soft tissue fullness at the right tongue base with a maximum standardized uptake value of 4.5

Fig. 2

Positron emission tomography scan demonstrating an intensely hypermetabolic and destructive soft tissue mass in the right skull base with a maximum standardized uptake value of 31.6

Fig. 3

a Bone marrow biopsy with patchy involvement by histiocytic sarcoma (circles) as well as small paratrabecular lymphoid aggregates (arrows). Hematoxylin and eosin, ×40. b Histiocytic sarcoma comprised large pleomorphic cells with frequent folded/irregular nuclei and abundant amounts of eosinophilic cytoplasm. Hematoxylin and eosin, ×400. c Histiocytic sarcoma (arrowheads) and adjacent small paratrabecular lymphoid aggregate (arrows) composed of small lymphocytes. Hematoxylin and eosin, ×400. d The atypical paratrabecular B cell-rich lymphoid aggregates are highlighted by CD20 immunohistochemistry (×40). The histiocytic sarcoma is positive for e CD68 (×400), f CD163 (×200), g lysozyme (×400), and h BRAF^V600E (×200), as determined by immunohistochemistry. h An atypical paratrabecular lymphoid aggregate (asterisk) is negative for BRAF^V600E immunohistochemistry