Epithelioid Angiosarcoma of the Adrenal Gland (EAA) Rana Hoda New York Presbyterian Hospital Weill Cornell Medical College New York, NY

Clinical History CT-guided fine needle aspiration of right adrenal gland in a 68 year-old woman with a 12.5 cm mass. All images are from an alcohol-fixed Papanicolaou-stained direct smear. Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Figure 1 DiffQuik 10x Figure 2 Pap 20x Figure 3 Pap 40x Figure 4 Pap 40x Figure 5 Pap 40x Figure 6 Pap 60x Figure 7 Pap 60x Figure 8 Pap 60x Figure 9 Pap 60x Figure 10 Pap 60x Cytological Diagnosis: Malignant Neoplasm, Unclassified. Additional history was elicited. This 68 woman had a distant history of colon cancer status-post left hemicolectomy. Patient had no evidence of disease. In November 2008, the patient noted bilateral lower extremity swelling. The ventilation and quantification (V/Q) scan were negative for deep venous thrombosis and pulmonary embolism. She had been admitted for further work-up. Surgery: Right adrenalectomy and nephrectomy Histological Diagnosis: Epithelioid Angiosarcoma of the Adrenal Gland (EAA). Lymphovascular invasion and transcapsular extension of the tumor were present. Margins of resection were negative. Positive immunohistochemical staining of the tumor cells was obtained with CD31, CD34, Factor VIII and at least focally for Cam 5.2. Negative immunohistochemical staining of tumor cells was obtained with EMA, Pan-cytokeratin, CK7, CK20, chromogranin, monoclonal CEA, HCG, CKit, CDX-2, PLAP, CD56, HMB45, inhibin, S-100, synaptophysin, AFP, and CA19.9. Histochemical stains for cytoplasmic mucin (mucicarmine and PAS with and without diastase digestion) were negative. Discussion: Adrenal Angiosarcoma Important Features Angiosarcomas are responsible for 1-2% of all soft-tissue sarcomas. Incidence is 2-3 cases per 1,000,000 population annually. Primary mesenchymal neoplasms of the adrenal gland are extremely rare, and are predominantly comprised of angiosarcoma, leiomyosarcoma, and malignant peripheral nerve sheath tumors [1]. About 40 cases of primary adrenal angiosarcoma have been reported in the literature. Clinical features: EAA occur most frequently in 6th and 7th decades of life, age range 45-85 years (median, 60), no gender preference and can be uni- or bilateral. Usually there is no prior history of exposure to potential carcinogens and abdominal radiotherapy. Presenting symptoms vary; incidental, slight fever, fatigue, anorexia, pain [1]. Potential predisposing factors include radiation therapy, exposure to vinyl chloride, thorotrast and/or arsenic and prolonged use of anabolic steroids. Radiology: To evaluate the resectability of a suspicious adrenal tumor, pre-operative imaging of the tumor and screening for distant metastases is essential. In view of the rarity of primary adrenal angiosarcoma, the possibility of a clinically occult tumor elsewhere needs to be carefully ruled out before rendering this diagnosis. The combination of CT, MRI and angiography prove helpful. CT alone cannot determine if a large upper abdominal tumor is of adrenal origin. Angiography is of great value in the pre-operative work-up of such patients. Pathogenesis: There is little is known about pathogenesis of angiosarcomas arising in visceral organs including the adrenal gland. The liver is most commonly involved. Pathologic findings: including cytology, gross and histology show: Cytological findings: Fine needle aspiration (FNA) has been shown to be more accurate than needle core biopsy (NCB) for diagnosis of abdominal lesions. Sensitivity of FNA in one study was 86% sensitivity compared to 80.6% for NCB for malignant lesions. Combination of FNA and NCB increased the sensitivity to 90.7% [3]. Moreover, use of rapid cytology preparations at the time of the procedure ensures adequate sampling and allows for an accurate diagnosis. Cytology of epithelioid angiosarcomas reveals an architectural pattern of cells forming vaso-formative channels. The cells are medium to large, undifferentiated plasmacytoid malignant cells with moderate amount of pink and finely granular cytoplasm, round nuclei, and prominent nucleoli. The differential diagnosis based on the cytologic findings includes hepatocellular, adrenal, and renal carcinomas, melanoma, mesothelioma, and neuroendocrine tumors. Background shows abundant blood and closely associated with the tumor cells. Gross findings: Varies from well-circumscribed to invasive, solid to cystic and necrotic. Size ranges from 6-10cm. In general adrenal masses larger than 5 cm are suspicious of malignancy. Histologically, angiosarcomas are heterogeneous tumors, based on histology and anatomic location. A ngiosarcoma of adrenal tends to be epithelioid and need to be distinguished from adrenal epithelial neoplasms (primary or metastatic). Diagnostic problems may be further increased because some soft-tissue tumors including angiosarcomas may show cytokeratin immunoreactivity [1, 2]. Tumors show invasive cellular proliferation with extension beyond periadrenal soft tissue. Necrosis and hemorrhage can be extensive. Cells are usually arranged in solid sheets and nests. Irregular branching vascular channels are intermixed with solid areas. The vascular channels are lined by a single layer of pleomorphic endothelial cells which then transition to more solid nests that "tuft" into the lumen or are seen free-floating in the vascular spaces. Morphologically, cells lining the vascular spaces and those in the solid foci are identical. Cells are epithelioid with round to oval vesicular nuclei, prominent centrally placed eosinophilic nucleoli with a variable amount of eosinophilic cytoplasm. Mitotic rate is usually brisk. Additional features suggesting endothelial differentiation include presence of intracytoplasmic lumina, often containing identifiable red blood cells. The stroma can be delicate to dense fibroconnective tissue with associated inflammatory cells. Vascular lakes with papillae protruding inside are also seen. Residual adrenal cortex can be identified at the periphery, compressed by the tumor, and as small nests and single cells dispersed within the tumor proliferation [3]. Immunohistochemical stain for A-103 (Melan-A) can be utilized for detecting normal adrenal cortical cells [4]. Immunohistochemical stains include CD31, CD34, Factor VIII, Keratin, Vimentin and B72.3. Electron microscopy may show intracytoplasmic rod-shaped micotubulated bodies (Weibel-Palade bodies). Differential diagnosis includes adrenal cortical carcinoma, pheochromocytoma, metastatic carcinoma, malignant melanoma and epithelioid hemangioendothelioma. An accurate diagnosis can be rendered by careful light microscopic examination and immunohistochemistry. Treatment: Surgical resection (adrenalectomy) is the mainstay of treatment as it is the only known curative therapy. Prognosis: Typically very aggressive lesions, but long term survival after adrenalectomy has been observed. Median survival for nonmetastatic angiosarcomas arising in the trunk (thorax, abdomen, and pelvis) is 2.1±0.2 years. Overall survival is based on margin status on surgical pathology. Median time to recurrence is 7.7 months. Patients with visceral sites of origin demonstrate worse overall survival compared with head/neck sites (2). Our patient had a prior history of colon cancer. At the time of presentation she was largely asymptomatic except for bilateral lower extremity swelling. CT and MRI revealed a 12.5 cm tumor and no other evidence of disease. Cytologically, the tumor was considered to be a unclassified malignant tumor. Histologically, the tumor showed characteristic features of an epithelioid angiosarcoma. Results of immunohistochemistry supported the diagnosis. References: Wenig BM, Abbondanzo SL, Heffess CS. Epithelioid angiosarcoma of the adrenal glands. 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