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Indiana Association 
of Pathologists, Inc.
Histology Laboratory, Indiana Medical History Museum 

Final Diagnosis:

Angiosarcoma

Discussion:

Angiosarcoma is a rare malignant vascular tumor that arises from cells of endothelial differentiation. These high-grade tumors are uncommon, comprising less than 1% of all sarcomas. They can occur in any anatomical location with a recognized predilection for skin and superficial soft tissues. An estimated 10% of cases arise in deep soft tissues, and the remainder has been identified in parenchymal organs such as breast, bone, heart, and spleen.

Unlike the cutaneous counterpart, pleural angiosarcoma is most commonly a secondary metastasis from another site. Primary pleural angiosarcoma is extremely rare, and it is an aggressive and rapidly fatal disease. It presents in adults with an average age of 57-59 (age range 33-79) and a male predominance (male to female ratio of 9:1). Etiology is unclear at this time. There has been an association with chronic tuberculous pyothorax in Japanese patients, but this has not been observed in other populations. Other suggested predisposing factors include chronic lymphedema, viral infections, radiation therapy, asbestos, and thorium.

Clinical signs and symptoms are nonspecific. Patients can frequently present with chest pain, shortness of breath, cough, hemoptysis, anemia, and weight loss. Radiologic findings are also variable, making it difficult to distinguish pleural angiosarcoma from other primary or secondary neoplastic processes. They can show diffuse pleural thickening, unilateral or bilateral effusions, or heterogeneous lobulated masses.

The diagnostic workup often includes a thoracentesisis, which will reveal a bloody effusion. However, cytologic examination is seldom helpful and exhibits no evidence of atypical or malignant cells. Most cases are diagnosed with surgical excision or at the time of autopsy with the use of immunohistochemical stains.

Primary pleural angiosarcoma can exhibit features of two histologic types, comprising classical and epithelioid variants. Microscopically, classical angiosarcoma is characterized by irregularly and variably sized vascular spaces lined by atypical endothelial cells. In contrast, epithelioid angiosarcoma may show little evidence of this vasoformative pattern. The epithelioid variant demonstrates solid sheets and nodules of large, round to polygonal epithelioid cells. The neoplastic cells have abundant eosinophilic cytoplasm, pleomorphic nuclei, and prominent nucleoli. Mitotic figures are readily apparent, and there are varying proportions of necrosis and hemorrhage. Extravasated red blood cells can also be seen within intracytoplasmic lumina.

With the biphasic appearance of the malignant cells, pleural angiosarcoma can easily be misdiagnosed. Differential diagnosis includes mesothelioma, adenocarcinoma, and sarcomatoid carcinoma. Immunohistochemistry plays an important role in the diagnosis. The neoplastic tumor cells are negative for mesothelial markers such as calretinin, cytokeratin 5/6, HMBE-1, and WT-1. These stains are utilized to exclude malignant mesothelioma.

Epithelial markers occasionally can be expressed in angiosarcoma, particularly in the epithelioid histologic variant. This can be misleading, but the positive staining is generally not as strong as that seen in carcinoma or mesothelioma. Expression of at least one endothelial marker (CD31, CD34, factor VIII, or FLI-1) is needed to confirm the diagnosis of angiosarcoma. CD31 is the most sensitive and specific marker for vascular neoplasms.

Treatment modalities include surgery, radiotherapy, and chemotherapy. Nevertheless, angiosarcoma is a highly aggressive neoplasm, and the clinical course is rapidly fatal. Prognosis is poor, and patients often die within 7 months of diagnosis.

References:

Abu-Zaid A, Mohammed S. “Primary pleural angiosarcoma in a 63-year-old gentleman.” Case Reports in Pulmonology. 2013.

Goldblum JR, Folpe AL, Weiss SW. “Chapter 23: Malignant Vascular Tumors.” Enzinger & Weiss’s Soft Tissue Tumors. Philadelphia: Saunders, an imprint of Elsevier, 2014.

Granville L, et al. “Review and update of uncommon primary pleural tumors: a practical approach to diagnosis.” Arch Pathol Lab Med. 2005; 129: 1428-1443.

Kao et al. “Primary pleural angiosarcoma as a mimicker of mesothelioma: a case report.” Diagnostic Pathology. 2011; 6: 130.

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