Hemothorax

A 39-year-old man presented in the emergency room with complaints of movement-dependent, right-sided chest pain radiating to the right shoulder; shortness of breath; blood-tinged productive cough; and a single syncopal episode not associated with urinary or fecal incontinence. Physical examination revealed decreased breath sounds and increased vocal fremitus in the right lung. Chest radiograph on admission revealed a right pleural effusion and soft tissue densities on the right lung base. A subsequent contrast computed tomographic scan of the chest showed a complex right pleural effusion and diffuse right pleural thickening, which extended from the apex to the base (Figure 1). Computed tomography of chest, abdomen, and pelvis showed no sign of tumor metastases. His medical history was significant for panic disorder, lumbar radiculopathy (L5-S1) on maintenance steroid therapy, scoliosis, and alcohol abuse. He had no history of smoking, tuberculosis, or occupational exposure to asbestos. At thoracotomy, approximately 550 mL of bloody fluid was drained. The lesion identified on the chest computed tomographic scan was characterized by thick rinds of tissue growing along almost the entire parietal pleura and encasing the lung. A pleural decortication was performed. Grossly, the surface of the resected pleural tissue and underlying lung showed multiple polypoid projections.

On microscopic examination, the pleural tissue showed an infiltrating tumor in a desmoplastic fibrocollagenous background. The tumor cells formed zigzag interconnecting trabeculae that were solid or had slits to cystlike luminal spaces. Some cystic spaces were lined by tubulopapillary tumor projections (Figure 2). The tumor cells were elongated and had the appearance of plump endothelial cells in the outer portion of the nests, while they attained cuboidal to polygonal epithelioid contours near the center. They had a high nuclear-cytoplasmic ratio and pleomorphic vesicular nuclei with prominent purple nucleoli. Mitoses were readily found, approximately 6 per 10 high-power fields. Intracytoplasmic lumina occasionally containing erythrocytes were also identified (Figure 3). Immunohistochemical studies showed the tumor cells were positive for CD31 (Figure 4) and CD34, and negative for pan-keratin, calretinin, cytokeratin 5/6, CD15, carcinoembryonic antigen, and thyroid transcription factor 1.

What is your diagnosis?

Pathologic Diagnosis: Epithelioid Angiosarcoma of Pleura

Angiosarcoma is an uncommon tumor, accounting for approximately 1% of all soft tissue tumors, whereas soft tissue tumors constitute 0.7% of all malignant tumors. It can affect almost all organs and is commonly found in deep soft tissue, skin, liver, spleen, heart, and breast. Primary thoracic parietal angiosarcoma is rarely reported, and prognosis is very poor; most patients described to date succumbed to the tumor within a few months of the initial presentation.1,2 Our patient died 8 months after diagnosis, despite extensive chemotherapy. The etiology of angiosarcoma is not clear. Although tuberculous pyothorax was proposed as a causative factor for pleural angiosarcoma in Japan, no such strong causative relation has been extrapolated in the West.3 Previous radiation and asbestos exposure have been described in a few cases in Western countries.1,4,5 The age range of patients described in the literature is 22 to 79 years (mean, 57 years), and there is a male predominance (male-female ratio, 12:1).1,2

Most cases reported in the literature followed a typical clinical scenario: the patients presented with diffuse pleural thickening and effusion, radiologically and clinically prompting the diagnosis of mesothelioma in most cases.1-7 Definitive distinction between pleural angiosarcoma and mesothelioma has important medicolegal implications, as only mesothelioma is categorized as an asbestos-related malignancy for compensation purposes.5,6 Histologically, 70% of angiosarcoma cases exhibit epithelioid features, providing pathologists a morphologic challenge to differentiate angiosarcoma from mesothelioma and pseudomesotheliomatous carcinoma, a type of pulmonary adenocarcinoma emerging from an inconspicuous subpleural lung mass.6

Histologically, pleural epithelioid angiosarcoma consists of large polygonal epithelioid cells growing in anastomosed sheets or nests with occasional slitlike or cystlike spaces. Focally, the cystic spaces are lined by micropapillary tumor projections. Generally, the epithelioid tumor cells have large round to oval pleomorphic nuclei with vesicular chromatin, prominent nucleoli, and brisk mitotic figures. Extensive hemorrhage and necrosis are not common findings. A hyalinized or desmoplastic background is a prominent feature in some cases. Occasionally, spindled-shaped or clear tumor cells can also be noted. Sharply demarcated intracytoplasmic vacuoles containing entrapped intact or degenerating erythrocytes, unlike those observed in mesothelioma, are considered as hallmarks for malignant vascular tumors.1-7

Epithelioid hemangioendothelioma (EHE), a low-grade or borderline malignant vascular tumor resembling carcinoma or mesothelioma, has also been described in the pleura.2 Although the morphologic boundary between well-differentiated epithelioid angiosarcoma and EHE is not clearly defined, bland nuclei or a lower degree of nuclear atypia, limited polymorphism and necrosis, and scanty mitoses characterize EHE.2,5-7 Generally, the prognosis for EHE is much better than that for conventional angiosarcoma; however, clinical data from reported cases indicate that pleural EHE-like tumors are highly malignant, despite the lack of significant high-grade histology in some cases.2

Divergent differentiation of mesothelium has been described, and cases of malignant mesothelioma with leiomyoid, chondroid, osteoid, and liposarcomatous appearances have been reported.6 However, malignant mesothelioma showing angiosarcomatous differentiation has not been documented in the literature. Recent immunohistochemical analysis of 92 different subtypes of mesotheliomas using 3 of the most sensitive and specific vascular markers (CD31, CD34, and von Willebrand factor) showed no evidence of vascular differentiation in any of the mesotheliomas.6 Therefore, application of a combination of CD31 and CD34 allows effective differentiation of epithelioid angiosarcoma from mesothelioma.

All mesotheliomas and adenocarcinomas are strongly positive for cytokeratin, whereas epithelioid angiosarcomas are negative or weakly positive for cytokeratin and strongly positive for vimentin. In the cases that do not show morphologic features of angiosarcoma, immunohistochemical reactive patterns based on cytokeratin or vimentin may provide a clue to further pursue diagnosis of malignant vascular tumor by immunoreactivity of both CD31 and CD34.2,3

Ultrastructural findings, such as the presence of basal lamina material around the cell cords, abortive lumen formation by tumor cells, and especially the presence of Weibel-Palade bodies (an organelle used for storage of von Willebrand factor) can be used to validate the diagnosis of angiosarcoma.4,5

References

1. Lin BT, Colby T, Gown AM, et al. Malignant vascular tumors of the serous membranes mimicking mesothelioma: a report of 14 cases. Am J Surg Pathol. 1996;20:1431-1439.

2. Zhang PJ, LiVolsi VA, Brooks JJ. Malignant epithelioid vascular tumors of the pleura: report of a series and literature review. Hum Pathol. 2000;31:29-34.

3. Kimura M, Ito H, Furuta T, Tsumoto T, Hayashi S. Pyothorax-associated angiosarcoma of the pleura with metastasis to the brain. Pathol Int. 2003;53:547-551.

4. McCaughey WT, Dardick I, Barr JR. Angiosarcoma of serous membranes. Arch Pathol Lab Med. 1983;107:304-307.

5. Attanoos RL, Suyarna SK, Rhead E, et al. Malignant vascular tumours of the pleura in "asbestos" workers and endothelial differentiation in malignant mesothelioma. Thorax. 2000;55:860-863.

6. Falconieri G, Bussani R, Mirra M, Zanella M. Pseudomesotheliomatous angiosarcoma: a pleuropulmonary lesion simulating malignant pleural mesothelioma. Histopathology. 1997;30:419-424.

7. Alexiou C, Clelland CA, Robinson D, Morgan WE. Primary angiosarcomas of the chest wall and pleura. Eur J Cardiothorac Surg. 1998;14:523-526.

Lugen Chen, MD, PhD; Henry J. Shih, MD; Eliezer Seguerra, Jr, MD; Jen H. Lin, MD

Accepted for publication June 1, 2004.

From the Department of Pathology and Laboratory Medicine, Nassau University Medical Center, East Meadow, NY (Drs Chen, Shih, Seguerra, and Lin); and School of Medicine, State University of New York at Stony Brook, East Meadow, NY (Dr Lin).

The authors have no relevant financial interest in the products or companies described in this article.

Corresponding author: Henry J. Shih, MD, Department of Pathology and Laboratory Medicine, Nassau University Medical Center, 2201 Hempstead Turnpike, East Meadow, NY 11554 (e-mail: hshih@ numc.edu).

Reprints not available from the authors.

Copyright College of American Pathologists Nov 2004
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