ANGIOSARCOMA OF SOFT-TISSUE - A STUDY OF 80 CASES

The clinicopathologic, immunohistochemical, and ultrastructural featur es of soft tissue angiosarcomas are not well defined. Eighty cases of angiosarcoma that involved the deep subcutis, skeletal muscle, retrope ritoneum, mesentery, and mediastinum are reported. The lesions occurre d in 50 male and 30 female patients who were 5-97 years of age; the pe ak incidence was in the seventh decade of life. A variety of associate d conditions were documented in 20 of these cases, including a history of other neoplasms (some irradiated), synthetic vessel grafts, herita ble conditions, and prior trauma or surgery. The angiosarcomas occurre d in the extremities (n = 43 cases), trunk (n = 28), and the head and neck (n = 9) regions, with the thigh and the retroperitoneum being the most common sites. They often were characterized as enlarging, painfu l masses of several weeks' duration and were occasionally associated w ith acute hemorrhage, anemia, or a coagulopathy. The tumors measured 1 -15 cm in diameter (median 5 cm) and frequently were hemorrhagic and m ultinodular. There was a wide morphologic spectrum within and between cases, including areas similar to cavernous and capillary hemangioma, Dabska tumor, spindle cell and epithelioid hemangioendathelioma, vario us spindle cell sarcomas, or carcinoma. Histologically, epithelioid an giosarcoma was the most frequently observed pattern; 70% of cases had epithelioid cells that were arranged in nests, clusters, papillae, and gaping vascular channels. Hemorrhage tended to obscure the diagnosis in several cases and often was associated with papillary endothelial h yperplasia-like areas. All 42 cases studied immunohistochemically stai ned at least focally for Factor VIII-related antigen, and nearly all s tained strongly for vimentin, which accentuated the endothelial cells and vessel lumen formation. CD34 antigen was detected in 74% of cases, BNH9 in 72%, and cytokeratins in 35%. Epithelial membrane antigen, S- 100 protein, and HMB45 were not detected. Fifty-five percent of the tu mors had intracytoplasmic aggregates of laminin. Immunostains for alph a-smooth muscle actin demonstrated a prominent peticytic component in several tumors (24%). Ki67 immunostains with MIB1 indicated high proli ferative activity (greater-than-or-equal-to 10%) in 72% of cases. p53 immunoreactivity (>20% nuclear staining) was observed in 20% of cases. Ultrastructural studies performed on poorly differentiated areas of 1 2 cases showed groups of cells, which were frequently epithelioid, sur rounded by basal lamina, and closely associated with pericytes, along with intercellular and intracellular lumina with or without red blood cells. Whorls of abundant intermediate filaments, occasional tonofilam entlike structures, and pinocytotic vesicles also were noted. In contr ast to the findings of others, Weibel-Palade bodies were not seen. Fol low-up in 49 cases (61%) showed that 53% of patients were dead of dise ase at a median interval of 11 months, whereas 31% had no evidence of disease at a median interval of 46 months. The remaining patients were either alive with disease (14%) or alive but disease status was unkno wn (2%). There were local recurrences in 20% of cases and distant meta stases in 49%, most frequently to the lungs, followed by the lymph nod es, soft tissues, bone, liver, and other sites. These results indicate that angiosarcoma of soft tissue is a high-grade sarcoma. Older patie nt age, tumor location in the retroperitoneum, and larger tumor size a s well as detection of MIB1 in greater-than-or-equal-to 10% of the tum or cell population were all associated with a poorer prognosis.