title: BRAFV600Eexpression 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 BRAFV600Emutation have been reported, but this finding has not been confirmed in all studies.
  
  
  METHODS
  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 BRAFV600Eprotein 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 BRAFV600Emutation. Further research is needed to clarify the role of targeted therapies such as vemurafenib in the treatment of patients with this disorder.
authors.affiliation: Department of Internal Medicine, The Ohio State University, Columbus, OH, USA. John.Vaughn@osumc.edu.
authors.forename: John L
authors.initials: JL
authors.lastname: Vaughn
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH, USA.
authors.forename: C Eric
authors.initials: CE
authors.lastname: Freitag
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Hemminger
authors.affiliation: Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Jones
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D017809:Fatal Outcome; D005260:Female; D054747:Histiocytic Sarcoma / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy; D006801:Humans; D018442:Lymphoma, B-Cell, Marginal Zone / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy; D008875:Middle Aged; D000070659:Patient Comfort; D000090063:Proto-Oncogene Mas; D048493:Proto-Oncogene Proteins B-raf / Q000378:metabolism*; D019292:Skull Base Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy; D013160:Splenic Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy
chemical_list: D014408:Biomarkers, Tumor; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: Histiocytic sarcoma; Immunohistochemistry; Marginal zone B-cell lymphoma; Proto-oncogene proteins B-raf