涎腺微分泌性腺癌的临床病理及分子特征分析

Clinicopathological and molecular characteristics of microsecretory adenocarcinoma in salivary gland

目的探讨涎腺微分泌性腺癌(microsecretory adenocarcinoma,MSA)的临床病理、免疫表型及分子遗传学特征,提高对该新型罕见肿瘤的认识。方法回顾性收集上海交通大学医学院附属第九人民医院口腔病理科确诊为MSA的病例,并通过病理复片2000年1月至2020年1月间的多形性腺癌和非特指腺癌病例筛选可能误诊的MSA病例。对所有确诊MSA病例行临床病理分析及随访,并复习相关文献。结果共收集到4例MSA,其中2例从多形性腺癌中筛选出来。男性3例,女性1例,平均年龄53岁(37~67岁)。3例发生于腭部,1例发生于颊部。临床表现为逐渐生长的无痛性肿物。肿瘤普遍较小,最大径为0.7~1.8 cm不等,平均1.2 cm。镜下见肿瘤无包膜,呈侵袭性生长。肿瘤细胞体积较小、形态温和,立方状、扁平状,排列呈微囊及腺管状。囊腔内见嗜碱性分泌物。肿瘤巢之间为黏液纤维间质。免疫组织化学示肿瘤细胞弥漫或部分表达细胞角蛋白7、S-100蛋白、SOX10、p63和波形蛋白;p40、Mammaglobin、Calponin均阴性;Ki-67阳性指数低(1%~3%)。4例MSA经荧光原位杂交检测证实存在SS18基因重排,其中2例经靶向RNA二代测序检测到MEF2C::SS18融合基因。4例患者均行单纯的手术切除,未行其他辅助治疗。随访3例,随访时间2~203个月,均未发现肿瘤复发、转移和造成患者死亡。结论涎腺MSA是一种新型且罕见的低级别肿瘤,具有独特且较一致的组织学形态、免疫表型和分子学改变。形态不典型或发生高级别转化时免疫组织化学染色及SS18基因检测可辅助诊断。

ObjectiveTo investigate the clinicopathological,immunohistochemical,and molecular genetic characteristics of microsecretory adenocarcinoma(MSA)of the salivary gland,and to improve the understanding of this rare tumor.MethodsCases originally diagnosed as MSA at the Department of Oral Pathology,the Ninth People′s Hospital of Shanghai Jiao Tong University School of Medicine were retrospectively collected.The cases of polymorphous adenocarcinoma and adenocarcinoma,not otherwise specified from January 2000 to January 2020 were reviewed to identify potential misdiagnosed MSA cases.Clinicopathological analysis and follow-up of all confirmed MSA cases were performed,and relevant literature was reviewed.ResultsA total of 4 MSA cases were identified,including 2 screened from the polymorphous adenocarcinoma cohort.Of the 4 MSA patients,3 were male and 1 was female,with an average age of 53 years(range,37-67 years).Three cases occurred in the palate,and one in the buccal region.The clinical manifestation was usually a slow-growing painless mass.Tumors were generally small,with a maximum diameter ranging from 0.7 to 1.8 cm(average,1.2 cm).Microscopically,the tumor was unencapsulated and showed an infiltrative growth pattern.The tumor cells appeared small in size and showed bland,cubic and flattened cytological features,forming microcystic lumens and glandular tubes.Significant basophilic secretions were seen in the lumens.Between the tumor nests there was fibro-myxoid stroma.Immunohistochemistry showed diffusely or partially positive staining for cytokeratin 7,S-100,SOX-10,p63 and vimentin and negative staining for p40,mammaglobin,and calponin.The proliferation index of Ki-67 was relatively low(1%-3%).Four MSA cases all harbored SS18 gene rearrangement as shown by fluorescence in situ hybridization(FISH),including 2 cases with MEF2C::SS18 fusion gene through RNA-targeted next generation sequencing.All 4 patients underwent surgical resection without any adjuvant treatments.Three patients were followed up for a period of 2 to 203 months.No tumor recurrence,metastasis,or disease-related death was found.ConclusionsSalivary gland MSA is a novel and rare low-grade carcinoma with unique and consistent histological morphology,immunophenotype,and molecular changes.Immunohistochemical staining and SS18 break apart FISH are useful for the diagnosis of the tumor with atypical morphology and high-grade transformation.