涎腺分泌性癌12例临床病理学分析

Salivary secretory carcinoma:a clinicopathological analysis of twelve cases

目的探讨涎腺分泌性癌(salivary secretory carcinoma,SSC)的临床病理学特征、免疫表型、治疗及预后。方法收集12例SSC的临床病理学资料,行免疫组化EnVision两步法染色和FISH法检测,并复习相关文献。结果12例SSC均发生于涎腺,包括腮腺9例、颌下腺2例和气管小涎腺1例。患者年龄15~78岁,中位年龄48岁;肿瘤平均最大径2.4 cm(0.5~5 cm)。SSC镜下形态结构多样,包括巢状、微囊、乳头状、实性和小管状结构。微囊和小管的腔内常充满黏液及嗜酸性胶样分泌物。瘤细胞核多为卵圆形,小核仁、核分裂象罕见,胞质丰富嗜酸性。免疫表型:9例CK7呈弥漫胞膜阳性,9例S-100呈弥漫阳性,2例S-100呈部分阳性,8例Mammaglobin呈弥漫胞质阳性,1例Mammaglobin呈部分阳性,2例Mammaglobin呈局灶阳性,5例GATA3呈弥漫胞核阳性。9例行DOG1检测,其中4例呈局灶阳性,1例呈部分阳性,4例呈阴性。6例行pan-TRK检测,其中3例呈弥漫核阳性,1例约10%肿瘤细胞核阳性及核仁阳性,另2例为单纯核仁阳性。5例采用融合探针FISH检测显示有特征性ETV6-NTRK3基因融合。12例患者临床均表现为相应部位的无痛性肿块,8例获得随访,中位随访时间24.5个月(8~28.5个月),均无复发或转移。结论SSC属于罕见的头颈部肿瘤,临床生物学行为多为惰性,pan-TRK免疫组化检测可用于初筛,确诊需经FISH或二代测序检测。

Purpose To investigate the clinicopathologic features,immunophenotype,therapy and prognosis of salivary secretory carcinoma(SSC).Methods The clinical and pathological data of 12 cases of SSC were collected.Immunohistochemical EnVision two-step analysis and FISH were performed.The literatures were reviewed.Results All tumors developed in salivary glands,including parotid gland(n=9),submandibular gland(n=2)and small salivary gland of trachea(n=1).There were seven males and five females with a median age of 48 years(age ranging from 15 to 78 years).The average size(maximum diameter)was 2.4 cm(ranging from 0.5 to 5 cm).Microscopically,all cases were composed of round or oval cells,showing nodular,microcystic,papillary,solid or tubular architecture.The microcystic and tubular growth pattern often contained luminal,mucus and eosinophilic colloid-like secretions.Some cells showed small nucleoli,mitotic figures were rare and the cytoplasm was abundant and eosinophilic.Immunophenotypically,the tumor cells in all examined cases were positive for CK7(9/9,all diffuse membrane positive),S-100(9 diffuse,2 partial),Mammaglobin(8 diffuse,1 partial,2 focal)and GATA3(5 diffuse nucleus positive).9 cases were tested for DOG1,of which 4 cases were focally positive,1 partially positive,and 4 negative.6 cases were tested for pan-TRK.A diffuse nuclear pattern was preserved in 3 cases,both nucleus and nucleolus positive was found in 1 case,and the other 2 cases were only nucleolus pattern.FISH detection using fusion probes showed that 5 cases had characteristic ETV6-NTRK3 gene fusion.The clinical manifestations of 12 cases were painless masses in the corresponding parts.Following-up information was available in 8 patients,and none of them had recurrence or metastasis(ranging from 8 to 28.5 months,median 24.5 months).Conclusion SSC is a rare head and neck tumor.It is easy to be misdiagnosed or missed due to its diverse structure.Immunohistochemical pan-TRK detection can be used for preliminary screening,and FISH or NGS detection is required for the diagnosis.The clinical behavior of SSC is mostly indolent,and correct diagnosis and molecular testing are helpful for its targeted therapy.