Department of Pathology, University of Texas Southwestern Medical Center, Clements University Hospital UH04.250, 6201 Harry Hines Blvd., Dallas, TX, 75390, USA.
Department of Pathology & Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada.
Head Neck Pathol. 2021 Sep;15(3):723-726. doi: 10.1007/s12105-020-01280-7. Epub 2021 Jan 4.
Molecular analysis has allowed for refinement of salivary gland tumor classification and, in some cases, the recognition of entirely new tumor types. Microsecretory adenocarcinoma (MSA) is a salivary gland tumor described in 2019 characterized by microcystic growth, bland cytomorphology, luminal secretions, fibromyxoid stroma, and S100/p63 positivity with negative p40. Most important, MSA is defined by MEF2C-SS18 fusion. While this fusion has, to this point, been detected by next-generation sequencing, this is a technique that is currently inaccessible in most diagnostic laboratories. On the other hand, SS18 break-apart fluorescence in situ hybridization (FISH) is widely available and frequently used as an adjunct for diagnosing synovial sarcoma. It is not known if SS18 break-apart FISH is positive in tumors with MEF2C-SS18, or if it is entirely specific for MSA. Break apart FISH for SS18 was performed on 4 cases of MSA, as well as 8 tissue microarrays (TMAs) containing 423 various salivary gland carcinomas: 26 acinic cell carcinomas, 35 adenocarcinomas not otherwise specified, 96 adenoid cystic carcinomas, 3 basal cell adenocarcinomas, 20 epithelial-myoepithelial carcinomas, 15 hyalinizing clear cell carcinomas, 3 intraductal carcinomas, 12 myoepithelial carcinomas, 117 mucoepidermoid carcinomas, 30 polymorphous adenocarcinomas, 45 salivary duct carcinomas, 19 secretory carcinomas, and 2 undifferentiated carcinomas. SS18 break-apart FISH was also performed on whole slides of 2 tumors from the TMAs. All MSA cases demonstrated classic split patterns on SS18 break-apart FISH. On the TMAs, 374 cases were evaluable by FISH, and 372 cases were clearly negative for SS18 rearrangement. Two cases, both mucoepidermoid carcinomas, had rare split signals below the positivity threshold of 12% on their TMA cores, so FISH was performed on whole sections. On the whole sections both tumors were unequivocally negative for SS18 rearrangement. Taken together, SS18 break-apart FISH was 100% sensitive and 100% specific for a diagnosis of MSA. SS18 break-apart FISH, a diagnostic tool widely available in pathology laboratories, appears to be a highly accurate method for diagnosing MSA of salivary glands. Accordingly, this new tumor type may be molecularly confirmed without needing to resort to highly specialized techniques like next-generation sequencing.
分子分析使得唾液腺肿瘤的分类更加精细，并且在某些情况下还能识别出全新的肿瘤类型。微分泌性腺癌（MSA）是 2019 年描述的一种唾液腺肿瘤，其特征为微囊状生长、温和的细胞学形态、腔内分泌物、纤维粘液样基质和 S100/p63 阳性而 p40 阴性。最重要的是，MSA 由 MEF2C-SS18 融合定义。虽然到目前为止，这种融合已经通过下一代测序检测到，但这是一种目前在大多数诊断实验室都无法获得的技术。另一方面，SS18 分离荧光原位杂交（FISH）广泛可用，并且经常作为诊断滑膜肉瘤的辅助手段。目前尚不清楚 SS18 分离 FISH 在 MEF2C-SS18 肿瘤中是否为阳性，或者它是否完全特异于 MSA。我们对 4 例 MSA 以及包含 423 种不同唾液腺癌的 8 个组织微阵列（TMA）进行了 SS18 分离 FISH 检测：26 例腺泡细胞癌、35 例非特指性腺癌、96 例腺样囊性癌、3 例基底细胞癌、20 例上皮-肌上皮癌、15 例透明细胞癌、3 例导管内癌、12 例肌上皮癌、117 例黏液表皮样癌、30 例多形性腺癌、45 例唾液腺癌、19 例分泌癌和 2 例未分化癌。我们还对 TMA 中的 2 个肿瘤的全切片进行了 SS18 分离 FISH 检测。所有 MSA 病例的 SS18 分离 FISH 均显示典型的分离模式。在 TMA 中，有 374 例可进行 FISH 评估，并且 372 例均明显无 SS18 重排。2 例均为黏液表皮样癌，其 TMA 核心的阳性阈值为 12%，因此出现罕见的分离信号，因此对全切片进行了 FISH 检测。在全切片中，2 个肿瘤的 SS18 重排均为阴性。总之，SS18 分离 FISH 对 MSA 的诊断具有 100%的敏感性和特异性。SS18 分离 FISH 是一种在病理实验室广泛可用的诊断工具，似乎是一种高度准确的方法，可用于诊断唾液腺的 MSA。因此，这种新的肿瘤类型可以通过不需要使用下一代测序等高度专业化技术来进行分子确认。
