Mesa Hector, Gilles Scott, Datta Milton W, Murugan Paari, Larson Wendy, Dachel Susan, Manivel Carlos
Department of Pathology and Laboratory Medicine, Veterans Administration Health Care System, One Veterans Drive, Minneapolis, MN, 55417, USA.
Minneapolis VA Health Care System, Office BB-104, One Veterans Drive, Minneapolis, MN, 55417, USA.
Virchows Arch. 2016 Dec;469(6):679-686. doi: 10.1007/s00428-016-2028-4. Epub 2016 Oct 1.
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.
我们对已知含有或缺乏雷氏结晶（RCs）的雄激素产生细胞的肿瘤性和非肿瘤性病变进行了详细的形态学、免疫表型和内分泌特征分析，旨在进一步深入了解这些细胞和结晶的本质。研究病例从参与研究的医院档案中选取，并根据当前分类进行亚分类：20例为睾丸间质细胞瘤（LCTs），2例为睾丸肾上腺残余肿瘤（TARTs），2例为肾上腺生殖器综合征睾丸肿瘤（TTAGS），2例为雄激素不敏感综合征（AIS）。将包括性索间质细胞瘤、雄激素激素、酶和受体相关标志物的广泛免疫表型检测 panel 应用于这些病例以及10个非肿瘤性肾上腺。非肿瘤组织单独评分。RCs 存在于90%的 LCT 病例以及所有正常睾丸间质细胞病例中；RCs 特异性地被钙视网膜蛋白和3β - 羟基类固醇脱氢酶（3BHSD）染色，并且仅存在于同时高表达这两种蛋白的细胞中，这是睾丸间质细胞和 LCTs 特有的表型。AIS 病例中的睾丸间质细胞由于3BHSD 表达降低而缺乏 RCs。钙视网膜蛋白在睾丸肾上腺样肿瘤中减少，在正常肾上腺皮质细胞中不存在，这解释了它们为何缺乏 RCs。雄激素产生细胞中钙视网膜蛋白的表达独立于雄激素受体和雄激素合成。RCs 在很大程度上（如果不是完全的话）代表了3BHSD/钙视网膜蛋白复合物的结晶形式。含有和缺乏 RCs 的雄激素产生细胞主要在这些蛋白和雄激素受体的表达水平上有所不同。
