Case 8 -
Epithelioid Angiosarcoma of the Adrenal Gland (EAA)
New York Presbyterian Hospital
Weill Cornell Medical College
New York, NY
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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.
Case 8 - Slide 1
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.
Right adrenalectomy and nephrectomy
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 . About 40 cases of primary adrenal angiosarcoma have been reported in the
- 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 .
- 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.
There is little is known about pathogenesis of angiosarcomas arising in visceral organs including the
adrenal gland. The liver is most commonly involved.
findings: including cytology, gross and histology show:
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% .
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
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 .
Immunohistochemical stain for A-103 (Melan-A) can be
utilized for detecting normal adrenal cortical cells .
- 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
- 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
- Wenig BM, Abbondanzo SL, Heffess CS. Epithelioid angiosarcoma of the adrenal glands. A clinicopathologic study of nine cases with a discussion of the implications of finding "epithelial-specific" markers. Am J Surg Pathol. 1994 Jan;18(1):62-73.
- Fury MG, Antonescu CR, Van Zee KJ, Brennan MF, Maki RG. A 14-year retrospective review of angiosarcoma: clinical characteristics, prognostic factors, and treatment outcomes with surgery and chemotherapy. Cancer J. 2005 May-Jun;11(3):241-7.
- Stewart CJ, Coldewey J, Stewart IS. Comparison of fine needle aspiration cytology and needle core biopsy in the diagnosis of radiologically detected abdominal lesions. J Clin Pathol. 2002 Feb;55(2):93-7. Review.
- Shin SJ, Hoda RS, Ying L, DeLellis RA. Diagnostic utility of the monoclonal antibody A103 in fine-needle aspiration biopsies of the adrenal. Am J Clin Pathol. 2000 Feb;113(2):295-302.