Primary Multicentric Angiosarcoma of Bone: True Entity or Metastases from an Unknown Primary? Value of Comparative Genomic Hybridization on Paraffin Embedded Tissues
A 69-year-old man with previous myeloid splenomegaly presented secondary acute myeloid leukemia (AML)(CD33+, 47XY, +9 and 49XY, +8, 10) in 2008. He underwent induction chemotherapy (aracytin/idarubicin), consolidation following remission, and allograft without total body irradiation. He underwent cyclosporin and steroid therapy for cutaneous graft versus host disease for six months. In April 2009, the patient, on remission from his AML, presented with painful swelling of the inferior extremity of his ulna. X-rays showed a destructive lytic mass with irregular borders and cortical erosion, complicated with spontaneous fracture. He underwent surgical biopsy, gross resection (curettage) and cementoplasty. Whole-body diagnostic work-up included X-rays of painful areas, blood tests, chest-abdomino-pelvic CT and bone scan. He had two other soap-bubble lytic lesions of his wrists () on X-rays, inT1-weighted hyposignal on MRI (, right insert). Pathological specimen showed a high-grade tumor. On microscopy, round epithelioïd tumor cells were separated by collagenous tissue, forming dense vascular channels and solid nests without necrosis (). Cells harbored enlarged nuclei of irregular shape and size with numerous mitoses and scant basophilic cytoplasm. Immunohistochemistry showed strong diffuse anti-CD31 (), CD34, FLI1 expression in tumor cells with Ki67 60%. Tumor cells were negative for anti-pancytokeratin antibodies AE1, AE3, EMA, desmin, protein S100, CD20, CD3, HHV8, LMP and D2.40. Centrally-reviewed diagnosis, within the French Sarcoma Group (FSG), was epithelioïd high-grade angiosarcoma of bone. The patient, WHO performance status 1, underwent hypofractionated radiation therapy with concomitant low-dose weekly paclitaxel (25 mg/m2) on bone tumors. The patient experienced symptomatic relief and grade 2 radiodermatitis. One month later, the patient had a round centimetric lymphadenopathy in the submandibular area, metastatic on biopsy from his angiosarcoma. The patient had worsening limited mouth opening. CT and MRI revealed unresectable contrast-enhanced masses of the right parapharyngeal space. Histology showed poorly-differentiated angiosarcoma () phenotypically comparable with his bone angiosarcoma (). Comparative Genomic Hybridization (CGH) performed on paraffin-embedded tissues, as previously described, upon patient consent and FSG approval, revealed gain of chromosomes 8 and 9, consistent with angiosarcoma. Genomic profiles were similar in bone and head and neck soft-tissue lesions (, ) suggesting tumor clonality. The bone fragment however presented additional 12p and 18p losses (, arrow) (). There was neither cMyc (8q24) amplification nor additional genomic instability. Profiles showed full chromosomes or chromosome arm alterations, rather indicated mitotic segregation instability.\nThe patient underwent conformal irradiation on gross head and neck disease with a complete response. He subsequently underwent 12 courses of radiation therapy on long bones, always with durable pain relief and consolidative effect. He had monthly zoledronate therapy for eight months. He then developed multifocal destructive lesions of the extremities and skin nodules in October 2011. He underwent 3 cycles of doxorubicin with progressive disease. AML relapsed in June 2012. He died of AML in July 2012, 36 months after the diagnosis of angiosarcoma, which was progressive at last follow-up.