唾液腺分泌癌（SC），以前称为类乳腺SC，是一种低度恶性肿瘤，其形态定义明确，免疫组化和遗传学特征与乳腺SC相同。移位t(12;15)(p13;q25)导致的ETV6::NTRK3基因融合是SC的特征性特征，同时具有S100蛋白和乳球蛋白免疫阳性。SC的遗传变异谱仍在不断发展。这项回顾性研究的目的是收集唾液腺SC的数据，并将其组织学、免疫组织化学和分子遗传学数据与临床行为和长期随访相关。在这项大型回顾性研究中，我们旨在建立一个组织学分级方案和评分系统。从作者的肿瘤登记中获取了1994年至2021年诊断的215例唾液腺SC病例。80例最初被诊断为SC以外的疾病，最常见的是腺泡细胞癌。在117例有可用数据的病例中，17.1%发现有淋巴结转移，5.1%有远处转移。疾病复发在15%(n=113有可用数据的病例)中被观察到。分子遗传学文件显示，在95.4%中出现了ETV6::NTRK3的基因融合，其中一例同时出现ETV6::NTRK3和MYB::SMR3B的双重融合。较少的融合转录本包括ETV6::RET(n=12)和VIM::RET(n=1)。应用6种病理参数（优势构架、异形态、肿瘤坏死、周围神经侵犯(PNI)、淋巴血管侵犯(LVI)和有丝分裂计数和/或Ki-67标记指数）进行了3级分级方案。在病例中，44.7%(n=96)表现为1级组织学，41.9%(n=90)表现为2级组织学，13.5%(n=29)表现为3级组织学。与低级别和中级别SC相比，高级别肿瘤与实质性构架、更为显著的软骨化、渗透性肿瘤边界、核异形、PNI和/或LVI的存在以及Ki-67增殖指数>30%有关。高级别转化，是家2或3病例的一部分，在8.8%(n=19)中，定义为常规SC突然转化为高级别形态、片状生长、缺乏SC特征的肿瘤。无论是总生存还是无疾病生存（5年和10年），都与肿瘤级别、阶段和TNM状态相关（每个P<0.0001）。SC是一种低度恶性肿瘤，主要是实质性-小囊性生长模式，由基因融合驱动，最常见的是ETV6::NTRK3。局部复发的风险低，总体长期生存良好，远处转移的风险低，但局部区域淋巴结转移的风险较高。肿瘤坏死、软骨化、PNI和/或LVI的存在以及阳性切除边缘与更高的肿瘤级别、不利的预后和增加的死亡率相关。统计结果使我们能够设计一种三级分级系统用于唾液腺SC。Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.

Salivary gland secretory carcinoma (SC), previously mammary analog SC, is a low-grade malignancy characterized by well-defined morphology and an immunohistochemical and genetic profile identical to SC of the breast. Translocation t(12;15)(p13;q25) resulting in the ETV6::NTRK3 gene fusion is a characteristic feature of SC along with S100 protein and mammaglobin immunopositivity. The spectrum of genetic alterations for SC continues to evolve. The aim of this retrospective study was to collect data of salivary gland SCs and to correlate their histologic, immunohistochemical, and molecular genetic data with clinical behavior and long-term follow-up. In this large retrospective study, we aimed to establish a histologic grading scheme and scoring system. A total of 215 cases of salivary gland SCs diagnosed between 1994 and 2021 were obtained from the tumor registries of the authors. Eighty cases were originally diagnosed as something other than SC, most frequently acinic cell carcinoma. Lymph node metastases were identified in 17.1% (20/117 cases with available data), with distant metastasis in 5.1% (6/117). Disease recurrence was seen in 15% (n=17/113 cases with available data). The molecular genetic profile showed ETV6::NTRK3 gene fusion in 95.4%, including 1 case with a dual fusion of ETV6::NTRK3 and MYB::SMR3B. Less frequent fusion transcripts included ETV6::RET (n=12) and VIM::RET (n=1). A 3-tiered grading scheme using 6 pathologic parameters (prevailing architecture, pleomorphism, tumor necrosis, perineural invasion (PNI), lymphovascular invasion (LVI), and mitotic count and/or Ki-67 labeling index) was applied. Grade 1 histology was observed in 44.7% (n=96), grade 2 in 41.9% (n=90), and grade 3 in 13.5% (n=29) of cases. Compared with low-grade and intermediate-grade SC, high-grade tumors were associated with a solid architecture, more prominent hyalinization, infiltrative tumor borders, nuclear pleomorphism, presence of PNI and/or LVI, and Ki-67 proliferative index >30%. High-grade transformation, a subset of grade 2 or 3 tumors, seen in 8.8% (n=19), was defined as an abrupt transformation of conventional SC into high-grade morphology, sheet-like growth, and a tumor lacking distinctive features of SC. Both overall survival and disease-free survival (5 and 10 y) were negatively affected by tumor grade, stage, and TNM status (each P<0.0001). SC is a low-grade malignancy with predominantly solid-microcystic growth patterns, driven by a gene fusion, most commonly ETV6::NTRK3. There is a low risk for local recurrence and a good overall long-term survival, with a low risk for distant metastasis but a higher risk for locoregional lymph node metastasis. The presence of tumor necrosis, hyalinization, PNI and/or LVI, and positive resection margins correlate with higher tumor grade, less favorable prognosis, and increased mortality. The statistical results allowed us to design a 3-tiered grading system for salivary SC.Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.