Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, MN, 55905, USA.
Department of Radiology, Mayo Clinic Rochester, MN, 55905, USA.
Hum Pathol. 2023 Jan;131:79-86. doi: 10.1016/j.humpath.2022.11.003. Epub 2022 Nov 9.
The alternative lengthening of telomeres (ALT) phenotype is characterized by ultra-bright telomeres on fluorescence in situ hybridization (FISH) and is a marker of a unique mechanism of telomere maintenance in tumors. ALT does not occur in normal tissues. ALT has been described in hepatocellular carcinoma (5-10%) and in primary hepatic angiosarcomas (75%). To study the frequency of ALT in other primary hepatic tumors, a wide range of primary hepatic neoplasms were retrieved. The tumors included the following: intrahepatic and hilar cholangiocarcinomas (N = 110), hepatic adenomas (N = 35), hepatocellular carcinomas (N = 30), fibrolamellar carcinomas (n = 11), combined cholangiocarcinoma-hepatocellular carcinomas (N = 8), carcinosarcoma (N = 10), hepatoblastomas (N = 5), hemangiomas (N = 4), angiosarcomas (N = 8), epithelioid hemangioendotheliomas (N = 10), calcified nested stromal epithelial tumor (N = 2), embryonal sarcoma (N = 2), rhabdoid tumor (N = 1), bile duct adenoma (N = 1), and angiomyolipoma (N = 1). For epithelial tumors, ALT-FISH was positive in one carcinosarcoma (10% of cases), one cholangiocarcinoma (1% of cases), and one combined hepatocellular carcinoma-cholangiocarcinoma (13% of cases). In the hepatocellular carcinoma component of both the carcinosarcoma and the combined hepatocellular carcinoma-cholangiocarcinoma, the tumor cells showed patchy marked nuclear pleomorphism akin to that described previously for chromophobe hepatocellular carcinoma, which are typically ALT FISH positive. The ALT-positive cholangiocarcinoma also showed patchy, striking nuclear pleomorphism. For soft tissue tumors, ALT was positive in two angiosarcomas (N = 2; 25% of cases). In summary, this study shows that ALT-FISH is positive in rare carcinosarcomas, cholangiocarcinomas, and combined cholangiocarcinoma-hepatocellular carcinoma. ALT is not a significant mechanism of telomere maintenance in hepatocellular adenomas or fibrolamellar carcinomas and was negative in all other tested primary hepatic neoplasms. ALT-FISH is also positive in a subset of primary hepatic angiosarcomas.
端粒的替代性延长（ALT）表型的特点是荧光原位杂交（FISH）中端粒的超强亮度，是肿瘤中端粒维持的独特机制的标志物。ALT 不会发生在正常组织中。在肝细胞癌（5-10%）和原发性肝血管肉瘤（75%）中已描述 ALT。为了研究 ALT 在其他原发性肝肿瘤中的频率，我们检索了广泛的原发性肝肿瘤。这些肿瘤包括以下内容：肝内和肝门部胆管癌（N=110）、肝腺瘤（N=35）、肝细胞癌（N=30）、纤维板层样癌（n=11）、胆管细胞癌-肝细胞癌混合型（N=8）、癌肉瘤（N=10）、肝母细胞瘤（N=5）、血管瘤（N=4）、血管肉瘤（N=8）、上皮样血管内皮细胞瘤（N=10）、钙化巢状基质上皮瘤（N=2）、胚胎性肉瘤（N=2）、横纹肌肉瘤（N=1）、胆管腺瘤（N=1）和血管平滑肌脂肪瘤（N=1）。对于上皮性肿瘤，在 1 例癌肉瘤（10%的病例）、1 例胆管细胞癌（1%的病例）和 1 例混合型肝细胞癌-胆管细胞癌（13%的病例）中 ALT-FISH 阳性。在癌肉瘤和混合型肝细胞癌-胆管细胞癌的肝细胞癌成分中，肿瘤细胞显示出斑驳的明显核多形性，类似于先前描述的嗜铬细胞瘤，通常为 ALT-FISH 阳性。ALT 阳性的胆管细胞癌也显示出斑驳的明显核多形性。对于软组织肿瘤，在 2 例血管肉瘤（N=2；25%的病例）中，ALT 阳性。总之，本研究表明，在罕见的癌肉瘤、胆管细胞癌和混合型胆管细胞癌-肝细胞癌中，ALT-FISH 阳性。ALT 不是肝腺瘤或纤维板层样癌中端粒维持的重要机制，在所有其他测试的原发性肝肿瘤中均为阴性。ALT-FISH 也在一部分原发性肝血管肉瘤中阳性。
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