MYC Analysis by Fluorescent In Situ Hybridization and Immunohistochemistry in Primary Adrenal Angiosarcoma (PAA): a Series of Four Cases

Abstract

Primary adrenal angiosarcomas (PAA) are rare with 36 cases reported in the English literature. MYC protein expression and gene amplification have been detected in secondary angiosarcoma (AS), and a subset of primary AS. The aim of this study was to report the clinicopathologic features of PAA and examine these tumors for MYC amplification and protein expression in a small series of four cases (resection, n = 4). Three had available material for ancillary studies and were investigated for MYC gene abnormalities and protein expression using fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC), respectively. Tumors occurred in three females and one male with a mean age of 69 (53-75) years. The sizes ranged from 8.5 to 15 (mean 11.5) cm and were epithelioid in morphology. All tumors had prominent necrosis, and the mitotic count ranged from 4 to 41/10 high-power fields (HPFs) (mean 20/10 HPFs, ×400). Immunohistochemically, the tumor cells were positive for CD31 in 4/4 cases, CD34 in 1/4 cases, and cytokeratin in 4/4 cases. The mean follow-up period was 10.8 (3-19) months, of which three patients died of disease with distant metastases, and one patient was alive with disease. MYC nuclear staining was identified in the three cases tested. Two cases showed polysomy of chromosome 8 without MYC amplification or rearrangement. Two MYC-positive cases by IHC demonstrated copy number gain in chromosome 8, and one MYC-positive case was not associated with a chromosome 8/MYC gene abnormality. In the context of new targeted therapies, MYC positivity in PAA may be clinically valuable in treating patients with these aggressive neoplasms.

A Rare Case of Primary Adrenal Epithelioid Angiosarcoma

“…The patient responded well to treatment and exhibited no recurrence. In a study by Cornejo et al [34], 4 patients underwent surgery for tumor removal but did not receive chemotherapy. Two of them died from recurrence at 5 and 16 months after surgery, one showed recurrence of the disease but was still alive 19 months after surgery, and one was cured of the disease.…”

Primary Adrenal Epithelioid Angiosarcoma: A Case Report

“…16 Two groups have identified an association between alterations to chromosome 8 and MYC gene amplification or rearrangement in adrenal angiosarcoma, none of which were present in our patient's history. 17,18 The genomic findings showed significant amplification of CD274 (PD-L1) and PDCD1LG2 (PD-L2) and a CTNNB1 S45F mutation associated with apoptosis resistance. 19 We conducted a search on cBioPortal for CTNNB1 gene alterations in published studies.…”

Primary Angiosarcoma of the Adrenal Gland: Report of 2 Cases and Review of the Literature

“…Genetic alterations specific to primary adrenal angiosarcoma are poorly understood; in 1 case series, 3 out of 4 tumors had evidence of MYC amplification, although in 1 of these cases, MYC amplification by IHC was discordant with a normal FISH study. 27 Due to funding limitations, no molecular studies were performed on the 2 cases reported here to explore whether adrenocortical adenomas have any molecular signatures in common with adrenal angiosarcoma. Further investigation may reveal molecular markers useful in diagnosis, prognosis, and potentially targeted therapies.…”