Original ArticlesMacrocystic (Mammary Analogue) Secretory Carcinoma An Unusual Variant and a Pitfall in the Differential Diagnosis of Cystic Lesions in the Head and NeckHernandez-Prera, Juan C. MD*; Holmes, Brittany J. MD†; Valentino, Alessandro MD‡; Harshan, Manju MD§; Bacchi, Carlos E. MD, PhD∥; Petersson, Fredrik MD, PhD¶; Liu, Kenian K. PhD*; Najfeld, Vesna PhD#; Wenig, Bruce M. MD* Author Information *Department of Pathology, Moffitt Cancer Center, Tampa, FL †Department of Pathology, Stanford University, Palo Alto, CA ‡Department of Pathology, Ospedale S. Andrea, La Spezia, Italy §Department of Pathology, Lenox Hill Hospital #Department of Pathology and Medicine, Tisch Cancer Institute, Mount Sinai Health System, New York, NY ∥Bacchi Laboratory, Pathology Reference Laboratory, Botucatu, Brazil ¶Department of Pathology, National University Health System, Singapore, Singapore Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Juan C. Hernandez-Prera, MD, Department of Pathology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612 (e-mail: [email protected]). The American Journal of Surgical Pathology 43(11):p 1483-1492, November 2019. | DOI: 10.1097/PAS.0000000000001309 Buy Metrics Abstract Mammary analogue secretory carcinoma (MASC) is a relatively recently described salivary gland adenocarcinoma characterized by ETV6-NTRK3 gene fusion and in most cases indolent clinical behavior. The majority of tumors show an admixture of microcystic, solid, and tubular growth patterns but only a few cases with dominant macrocystic growth have been reported. We report 15 cases of macrocystic MASC. There were 11 men and 4 women (17 to 88 y age range, average 47 y). The patients presented with a painless cystic mass, the majority in the region of the parotid gland (n=13), as well as in submandibular gland (n=1) and the neck (n=1). All tumors were circumscribed measuring 1.0 to 4.0 cm in greatest diameter (mean: 1.75 cm). Twelve tumors were unilocular, while 3 were multilocular. The cystic spaces were predominantly lined by a single epithelial cell layer with focal areas in which the epithelium was multilayered with papillary and hobnail features. In 3 of the cases there were more solid foci of intracystic tumor characterized by papillary and/or microcystic growth. The neoplastic cells were round to oval with hyperchromatic to vesicular nuclei with centrally located nucleoli and eosinophilic or vacuolated cytoplasm. Tumor cells showed strong positivity for S100 protein and mammaglobin, while DOG1 was uniformly negative. A minority of cases showed focal p63 reactivity predominantly limited to the periphery of the cystic lining. ETV6 gene rearrangement was identified in 9 cases. Macrocystic MASC can simulate benign and malignant salivary gland lesions and needs to be included in the differential diagnosis of cystic lesions in the head and neck. To the best of our knowledge, our report represents the first series of macrocystic MASCs wholly focusing on this unusual variant. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.