唾液腺导管内癌27例临床病理学特征及分子遗传学分析

Intraductal carcinomas of the salivary glands:a clinicopathological and molecular genetic analysis of twenty-seven cases

目的探讨唾液腺导管内癌(intraductal carcinoma)的临床病理学特征、分子遗传学特点及鉴别诊断。方法收集2008年1月至2023年7月上海交通大学医学院附属第九人民医院口腔病理科25例、河南省人民医院病理科2例诊断为导管内癌的病例,回顾性分析其临床病理学特征,行荧光原位杂交及一代测序检测分子改变,随访患者并复习相关文献。结果27例导管内癌患者,男性15例,女性12例,年龄20.0~80.0岁(平均55.9岁)。临床上多表现为无痛性肿块,肿瘤最大径1.0~3.0 cm(平均2.0 cm)。所有患者均接受手术治疗,20例患者获得随访,其中1例因肺癌死亡,余均存活、无复发。组织学上,闰管型占63.0%(17/27),顶浆分泌型占25.9%(7/27),嗜酸细胞型占7.4%(2/27),混合型占3.7%(1/27)。闰管型S-100蛋白阳性,雄激素受体(AR)阴性,Ki-67阳性指数较低(1%~5%),9例检测到RET基因断裂,2例检测到BRAF V600E突变。顶浆分泌型S-100蛋白阴性,AR阳性,Ki-67阳性指数较高(10%~60%),1例检测到RET基因断裂。2例嗜酸细胞型与闰管型免疫表型相似,均检测到RET基因断裂。1例混合型表现为嗜酸细胞型与顶浆分泌型混合,检测到RET基因断裂阳性。结论导管内癌是一种少见的唾液腺低度恶性肿瘤,镜下形态结构多样,容易与形态相似的其他唾液腺肿瘤混淆,分子检测对鉴别诊断有帮助。

Objective To investigate the clinicopathological features,molecular genetic features,and differential diagnosis of intraductal carcinomas(IDC)of the salivary glands.Methods Twenty-five cases of salivary gland IDC diagnosed at the Department of Oral Pathology,Shanghai Ninth People′s Hospital and two cases from Department of Pathology,Henan Provincial People′s Hospital,Zhengzhou,China from January 2008 to July 2023 were collected.Their clinical and pathological features were analyzed retrospectively.Fluorescence in situ hybridization and Sanger sequencing were performed.The patients were followed up and related literatures were reviewed.Results There were 27 patients with IDC,including 15 males and 12 females,ranging in age from 20.0 to 80.0 years(mean 55.9 years).Clinically,the tumor often presented as a painless mass with a tumor diameter of 1.0-3.0 cm(mean 2.0 cm).All patients received surgical treatment.Twenty patients were followed up.One of them(1/20)died of lung cancer,while the rest survived without tumor recurrence.Histologically,IDC were classified as:intercalated(63.0%,17/27),apocrine(25.9%,7/27),oncocytic(7.4%,2/27)and mixed(3.7%,1/27)types.Intercalated tumors showed positive S-100 and negative androgen receptor(AR)immunoreactivity.Ki-67 proliferation index was low(about 1%-5%).Nine cases had the RET gene disruption,and 2 cases showed the BRAF V600E mutation.Apocrine tumors showed strong AR immunoreactivity but no S-100 immunoreactivity.Ki-67 proliferation index was high(about 10%-60%),and the RET gene rupture was detected in 1 case.Oncocytic tumors were similar to that of intercalated type in 2 cases,and RET gene disruption was detected in the both cases.Mixed tumors showed histologic features of oncocytic and apocrine patterns and harbored the RET gene disruption.Conclusions IDC is a rare low-grade malignant tumor of the salivary gland and easily confused with other salivary gland tumors with similar morphology.Molecular testing is helpful for its differential diagnosis.