title: Immunophenotypic differences between neoplastic and non-neoplastic androgen-producing cells containing and lacking Reinke crystals.
abstract: We performed a detailed morphologic, immunophenotypic, and endocrine characterization of neoplastic and non-neoplastic lesions of androgen-producing cells known to harbor or lack Reinke crystals (RCs) with an aim to provide further insight into the nature of these cells and crystals. Study cases were selected from the files of participating hospitals and subclassified according to current classifications: 20 with Leydig cell tumors (LCTs), 2 with testicular adrenal rest tumors (TARTs), 2 with testicular tumors of adrenogenital syndrome (TTAGS), and 2 with androgen insensitivity syndrome (AIS). An extensive immunophenotypic panel including markers used in sex cord-stromal cell tumors, androgen hormones, enzymes, and receptors was applied to the cases and 10 non-tumoral adrenal glands. Non-tumoral tissues were scored separately. RCs were present in 90 % of LCT cases and all cases with normal Leydig cells; RCs stained specifically with calretinin and 3β-hydroxysteroid dehydrogenase (3BHSD) and were present only in cells with high concomitant expression of both proteins, a phenotype unique to Leydig cells and LCTs. Leydig cells from AIS cases lack RCs due to decreased expression of 3BHSD. Calretinin is decreased in testicular adrenal-like tumors and absent in normal adrenocortical cells, which explain why they lack RCs. Calretinin expression in androgen-producing cells is independent from androgen receptors and androgen synthesis. RCs represent for the most part, if not exclusively, crystallized forms of a 3BHSD/calretinin complex. Androgen-producing cells containing and lacking RCs differ mainly in the level of expression of these proteins and androgen receptors.
authors.affiliation: Department of Pathology and Laboratory Medicine, Veterans Administration Health Care System, One Veterans Drive, Minneapolis, MN, 55417, USA. Hector.Mesa@va.gov.|Minneapolis VA Health Care System, Office BB-104, One Veterans Drive, Minneapolis, MN, 55417, USA. Hector.Mesa@va.gov.
authors.forename: Hector
authors.identifier: http://orcid.org/0000-0003-1833-4642
authors.initials: H
authors.lastname: Mesa
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Minnesota School of Medicine, 420 Delaware Street S.E., Minneapolis, MN, 55455, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Gilles
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Minnesota School of Medicine, 420 Delaware Street S.E., Minneapolis, MN, 55455, USA.|Department of Pathology and Laboratory Medicine, Hospital Pathology Associates, 2800 10th Avenue South, Suite 2200, Minneapolis, MN, 55407, USA.
authors.forename: Milton W
authors.initials: MW
authors.lastname: Datta
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Minnesota School of Medicine, 420 Delaware Street S.E., Minneapolis, MN, 55455, USA.
authors.forename: Paari
authors.initials: P
authors.lastname: Murugan
authors.affiliation: Department of Pathology and Laboratory Medicine, Veterans Administration Health Care System, One Veterans Drive, Minneapolis, MN, 55417, USA.
authors.forename: Wendy
authors.initials: W
authors.lastname: Larson
authors.affiliation: Department of Pathology and Laboratory Medicine, Veterans Administration Health Care System, One Veterans Drive, Minneapolis, MN, 55417, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Dachel
authors.affiliation: Department of Pathology and Laboratory Medicine, Veterans Administration Health Care System, One Veterans Drive, Minneapolis, MN, 55417, USA.|Department of Pathology and Laboratory Medicine, University of Minnesota School of Medicine, 420 Delaware Street S.E., Minneapolis, MN, 55455, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Manivel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000728:Androgens / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000378:metabolism; D064032:Calbindin 2 / Q000378:metabolism*; D002648:Child; D005260:Female; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D007985:Leydig Cells / Q000166:cytology*; D008297:Male; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D011944:Receptors, Androgen / Q000378:metabolism; D018312:Sex Cord-Gonadal Stromal Tumors / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D013736:Testicular Neoplasms / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000728:Androgens; D014408:Biomarkers, Tumor; D064032:Calbindin 2; D011944:Receptors, Androgen
keywords: Adrenal rest tumor; Gonadal steroid hormones; Immunohistochemistry; Leydig cell; Reinke crystals