Department of Pathology and Laboratory Medicine, Division of Dermatopathology, Dartmouth-Hitchcock Medical Center, Lebanon.
Dartmouth Geisel School of Medicine.
Am J Surg Pathol. 2018 Nov;42(11):1541-1548. doi: 10.1097/PAS.0000000000001136.
Merkel cell carcinoma (MCC) is an extremely aggressive skin cancer that must be distinguished from other basaloid cutaneous neoplasms that have different treatments and prognoses. This is sometimes challenging in small shave specimens, crushed samples, lymph nodes, and core needle biopsies. Insulinoma-associated protein 1 (INSM1) immunohistochemistry is a sensitive nuclear marker of neuroendocrine differentiation. INSM1 staining was performed on 56 MCC (47 primary tumors, 9 nodal metastases), 50 skin control cases that included basal cell carcinomas, basaloid squamous cell carcinomas, Bowen disease, sebaceous neoplasms, melanoma, and B-cell lymphomas, and 28 lymph node control cases that included metastatic neuroendocrine neoplasms, melanomas, squamous cell carcinomas, lymphomas, and adenocarcinomas. Percent of staining nuclei (0, <25%, 25% to 50%, 50% to 75%, >75%) and intensity (weak, moderate, strong) were recorded for each sample. All 56 MCC expressed INSM1. By comparison, synaptophysin, CK20, and chromogranin were expressed in 96%, 92%, and 32% of MCC, respectively. While the 3 conventional markers showed significant variability in staining intensity and distribution, INSM1 stained >75% tumor nuclei in 89% of MCC and 50% to 75% of tumor nuclei in 11%. Staining intensity was strong in 85% and moderate in 15%. None of the 50 cutaneous basaloid non-MCC neoplasms in the control group stained with INSM1, and among the lymph node controls 5 of 5 neuroendocrine neoplasms expressed INSM1, confirming that INSM1 staining cannot distinguish MCC from metastatic extracutaneous neuroendocrine carcinoma. INSM1 holds promise as a neuroendocrine marker that can distinguish MCC from its mimickers in the skin and improve detection of sentinel lymph node metastases.
默克尔细胞癌（Merkel cell carcinoma，MCC）是一种极具侵袭性的皮肤癌，必须与具有不同治疗方法和预后的其他基底样皮肤肿瘤区分开来。在小的刮除标本、压碎样本、淋巴结和芯针活检中，这有时具有挑战性。胰岛素瘤相关蛋白 1（Insulinoma-associated protein 1，INSM1）免疫组化是神经内分泌分化的敏感核标志物。对 56 例 MCC（47 例原发肿瘤，9 例淋巴结转移）、50 例皮肤对照病例（包括基底细胞癌、基底样鳞状细胞癌、鲍文病、皮脂腺肿瘤、黑色素瘤和 B 细胞淋巴瘤）和 28 例淋巴结对照病例（包括转移性神经内分泌肿瘤、黑色素瘤、鳞状细胞癌、淋巴瘤和腺癌）进行了 INSM1 染色。记录了每个样本的染色核百分比（0、<25%、25%50%、50%75%、>75%）和强度（弱、中、强）。所有 56 例 MCC 均表达 INSM1。相比之下，突触素、CK20 和嗜铬粒蛋白分别在 96%、92%和 32%的 MCC 中表达。虽然这 3 种传统标志物的染色强度和分布存在显著差异，但 INSM1 在 89%的 MCC 中染色>75%的肿瘤核，在 11%的 MCC 中染色 50%~75%的肿瘤核。染色强度为强的占 85%，为中强度的占 15%。对照组 50 例皮肤基底样非 MCC 肿瘤均未染色 INSM1，淋巴结对照组 5 例神经内分泌肿瘤中均表达 INSM1，证实 INSM1 染色不能区分 MCC 与转移性皮肤外神经内分泌癌。INSM1 有望成为一种神经内分泌标志物，可将 MCC 与其在皮肤中的模拟物区分开来，并提高前哨淋巴结转移的检出率。
