Low-grade Apocrine Intraductal Carcinoma: Expanding the Morphologic and Molecular Spectrum of an Enigmatic Salivary Gland Tumor.

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From: Head and Neck Pathology(Vol. 14, Issue 4)
Publisher: Springer
Document Type: Report
Length: 465 words

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Keywords: Salivary gland neoplasms; Intraductal carcinoma; Parotid gland; Phosphatidylinositol 3-Kinases (PI3K); HRAS; Oncogenes; Salivary duct carcinoma Abstract Intraductal carcinoma (IDC) is the current designation for a salivary gland neoplasm previously referred to as "low-grade salivary duct carcinoma" and "low-grade cribriform cystadenocarcinoma," among others. IDC is conceptually believed to be similar to ductal carcinoma in-situ of the breast. Although IDC is one entity in the current WHO Classification of Head and Neck Tumors, recent studies have suggested that at least three subtypes exist: a low-grade, intercalated duct-like variant with frequent RET rearrangements a high-grade apocrine variant with complex, salivary duct carcinoma-like genetics and a mixed variant. We sought to characterize an unusual form of low-grade, purely apocrine IDC. Three cases of apocrine-type IDC with low-grade histology were retrieved from the authors' consultation files. Immunohistochemistry for androgen receptor, GCDFP-15, S100, smooth muscle actin, and p40 was performed. A custom, targeted next generation sequencing (NGS) panel including 1425 cancerârelated genes was also done on all cases. All three cases developed in the parotid glands of men, aged 51, 63, and 73 years (mean, 62 years). All cases consisted of large, rounded macrocysts surrounded by smaller nests which were lined by cells with abundant granular eosinophilic cytoplasm and large round nuclei with prominent nucleoli. Pleomorphism was mild, the mitotic rate was low, and necrosis was absent. No cases had any invasive foci or areas of intercalated duct-like morphology. By immunohistochemistry, all cases were diffusely positive for androgen receptor and GCDFP-15, surrounded entirely by an intact layer of small myoepithelial cells positive for S100, smooth muscle actin, and p40. Targeted NGS results were obtained from two cases: both harbored HRAS mutations and copy number losses in TP53, while one case each harbored mutations in PIK3CA, SPEN, and ATM. Fusions were absent in both cases. All three patients were treated by surgery alone, and are currently free of disease (follow up 12--190 months). This study confirms the existence of a low-grade, purely apocrine form of IDC. In its pure form, i.e., without an intercalated duct-type component, low-grade apocrine IDC is genetically similar to high-grade salivary duct carcinoma, with frequent HRAS and PI3K pathway mutations. Despite its molecular similarities to the aggressive salivary duct carcinoma, low-grade apocrine IDC appears to behave in a very indolent manner, supporting is classification as a non-invasive neoplasm, and underscoring the need to distinguish these tumors from each other. Author Affiliation: (1) Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA (2) Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California At Los Angeles, Los Angeles, CA, USA (3) Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA (a) justin.bishop@utsouthwestern.edu Article History: Registration Date: 01/09/2020 Received Date: 12/05/2019 Accepted Date: 01/09/2020 Online Date: 01/27/2020 Byline:

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Gale Document Number: GALE|A642009031