329 Unique Genomic Alterations in a Case of Splenic Angiosarcoma

Abstract

Angiosarcoma of the spleen is an uncommon condition, comprising only 2.7% of all angiosarcomas. It is common for splenic angiosarcoma to metastasize to other organs. The diagnosis of splenic angiosarcoma is made by either acute abdominal symptoms after splenic rupture or incidentally from radiologic surveillance. We report herein a case of splenic angiosarcoma with documented unique genomic mutations that have not been previously reported. An 81-year-old man presented with thrombocytopenia and progressive splenomegaly over several years; a diagnosis of immune thrombocytopenia purpura was initially made. The patient subsequently developed sclerotic-blastic bone lesions with worsened splenomegaly. Bone marrow and bone biopsies revealed angiosarcoma, which was considered to be metastatic from the spleen based on imaging. He received multiple cycles of chemotherapy with minimal improvement. Eventually, the patient underwent splenectomy and the diagnosis of primary splenic angiosarcoma was made. Tissue sections showed a mitotically active cellular spindle cell neoplasm with pleomorphic nuclei, diffusely configured in anastomosing vasoformative channels. Zones of fibrosis, infarction, or active tumor necrosis comprised less than 5% of the splenic volume. Metastases to lymph nodes, peripancreatic fat and bone marrow were documented. Immunostains showed diffuse and strong immunoreactivity for CD31 and CD34, supporting a vascular origin. Molecular testing showed mutations in the following genes: ATRX, CDKN2A/B, EPHA3, MLL2, NOTCH2, and TET2. Primary splenic angiosarcoma is a rare entity with limited published molecular data. To our knowledge, the composite of genomic mutations outlined herein have not been previously reported in splenic angiosarcomas. CDKN2A/B has been reported in hepatic angiosarcomas.