Abstract：
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.
摘要：
涎腺分泌癌（SC），以前的乳腺模拟SC，是一种低度恶性肿瘤，其特征在于明确的形态学以及与乳腺SC相同的免疫组织化学和遗传谱。导致ETV6::NTRK3基因融合的t(12;15)(p13;q25)易位是SC与S100蛋白和乳腺球蛋白免疫阳性的特征。SC的遗传改变谱继续进化。这项回顾性研究的目的是收集唾液腺SCs的数据并将其组织学联系起来。免疫组织化学，和分子遗传学数据与临床行为和长期随访。在这项大型回顾性研究中，我们旨在建立组织学分级方案和评分系统。从作者的肿瘤登记处获得了在1994年至2021年之间诊断出的215例唾液腺SC。80例最初被诊断为SC以外的东西，最常见的是腺泡细胞癌。淋巴结转移占17.1%（20/117例可用数据），远处转移5.1%(6/117)。15％的患者出现疾病复发（n=17/113例，有可用数据）。分子遗传图谱显示ETV6::NTRK3基因融合率95.4%,其中ETV6::NTRK3和MYB::SMR3B双重融合1例。较低频率的融合转录物包括ETV6::RET(n=12)和VIM::RET(n=1)。使用6个病理参数的3层分级方案(主要结构，多态性，肿瘤坏死,神经周浸润（PNI），淋巴管浸润（LVI），应用有丝分裂计数和/或Ki-67标记指数）。44.7％（n=96）观察到1级组织学，二级在41.9%(n=90)，13.5%(n=29)的病例为3级。与低级和中级SC相比，高级别肿瘤与坚固的结构有关，更突出的透明化，浸润性肿瘤边界，核多态性，PNI和/或LVI的存在，Ki-67增殖指数>30%。高品位改造,2级或3级肿瘤的子集，8.8%(n=19)，被定义为将常规SC突然转变为高级形态，片状生长，和缺乏SC独特特征的肿瘤。总体生存率和无病生存率（5和10年）均受肿瘤分级的负面影响，舞台,和TNM状态（每个P<0.0001）。SC是一种低度恶性肿瘤，主要是实性-微囊性生长模式，由基因融合驱动，最常见的ETV6::NTRK3。局部复发的风险较低，总体长期生存率良好，远处转移的风险较低，但局部淋巴结转移的风险较高。肿瘤坏死的存在，透明质化,PNI和/或LVI，阳性切除边缘与较高的肿瘤分级相关，预后较差，和死亡率增加。统计结果使我们能够设计唾液SC的3层分级系统。
