Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Mod Pathol. 2020 Aug;33(8):1571-1580. doi: 10.1038/s41379-020-0517-0. Epub 2020 Mar 12.
INSM1 is a diagnostic marker for neuroendocrine tumors originating in multiple anatomic sites. In the lung, INSM1 shows 76-97% sensitivity for neuroendocrine tumors overall. Our aim was to characterize INSM1 as a diagnostic marker for small cell carcinoma in the context of its epithelial, lymphoid, and mesenchymal morphologic mimics. Immunohistochemistry was performed on 231 tumors, including lung neuroendocrine tumors, nonneuroendocrine carcinomas of the thoracic cavity, diffuse large B-cell lymphomas, and small round cell sarcomas, using an anti-INSM1 mouse monoclonal antibody. Extent (0-100%) and intensity (1-3+) of nuclear INSM1 staining was multiplied in each case to calculate an H-score. Demographic and clinical information was obtained from the medical record. INSM1 had an overall sensitivity and specificity of 81.5% and 82.7% for small cell carcinoma, respectively, using a threshold established with a receiver operating characteristic curve. 40/48 (82.7%) small cell carcinomas were positive for INSM1, including 19/24 (79%) small cell carcinomas that were negative for chromogranin and synaptophysin. 5/5 carcinoids and 21/28 (75%) large cell neuroendocrine carcinomas showed INSM1 expression. Among nonneuroendocrine tumors, 7/38 (18%) lung adenocarcinomas, 2/17 (12%) lung squamous cell carcinomas, 4/10 (40%) thymic carcinomas, 4/12 (33%) adenoid cystic carcinomas, 1/19 (5%) diffuse large B-cell lymphomas, 4/11 (36%) alveolar rhabdomyosarcomas, and 4/23 (17%) Ewing sarcomas were positive for INSM1. No synovial sarcomas or desmoplastic small round cell tumors were positive. Weak, focal INSM1 expression alone is insufficient as a diagnostic marker for small cell carcinoma, but is sensitive and specific, easy to interpret in small biopsies, and makes a valuable addition to a diagnostic panel.
INSM1 是一种起源于多个解剖部位的神经内分泌肿瘤的诊断标志物。在肺部，INSM1 对所有神经内分泌肿瘤的敏感性为 76-97%。我们的目的是在其上皮、淋巴和间充质形态模拟物的背景下，将 INSM1 作为小细胞癌的诊断标志物进行特征描述。使用抗 INSM1 小鼠单克隆抗体对 231 种肿瘤进行免疫组织化学染色，包括肺神经内分泌肿瘤、胸腔非神经内分泌癌、弥漫性大 B 细胞淋巴瘤和小圆细胞肉瘤。在每种情况下，将核 INSM1 染色的程度（0-100%）和强度（1-3+）相乘，以计算 H 评分。从病历中获取人口统计学和临床信息。使用受试者工作特征曲线确定的阈值，INSM1 对小细胞癌的总体敏感性和特异性分别为 81.5%和 82.7%。48 例小细胞癌中有 40 例（82.7%）INSM1 阳性，包括 24 例（79%）神经内分泌癌阴性的 chromogranin 和 synaptophysin。5 例类癌和 28 例（75%）大细胞神经内分泌癌显示 INSM1 表达。在非神经内分泌肿瘤中，38 例肺腺癌中有 7 例（18%）、17 例肺鳞癌中有 2 例（12%）、10 例胸腺癌中有 4 例（40%）、12 例腺样囊性癌中有 4 例（33%）、19 例弥漫性大 B 细胞淋巴瘤中有 1 例（5%）、11 例肺泡横纹肌肉瘤中有 4 例（36%）和 23 例尤文肉瘤中有 4 例（17%）INSM1 阳性。没有滑膜肉瘤或促结缔组织增生性小圆细胞肿瘤阳性。单独的弱阳性、局灶性 INSM1 表达不足以作为小细胞癌的诊断标志物，但具有敏感性和特异性，易于在小活检中解释，并为诊断面板增添了有价值的内容。
