子宫颈浸润性复层产黏液的癌22例临床病理分析

Cervical invasive stratified mucin-producing carcinoma:a clinicopathological analysis of 22 cases

目的探讨子宫颈浸润性复层产黏液的癌(invasive stratified mucin-producing carcinoma,ISMC)的临床病理学特征、诊断、鉴别诊断及预后。方法回顾性分析22例子宫颈ISMC的临床资料,分别行免疫组化EnVision两步法染色、PAS染色,应用qRT-PCR法进行HPV检测,并进行电镜观察。结果22例子宫颈ISMC患者年龄32~68岁,中位年龄47岁,平均45.9岁。镜下见肿瘤细胞呈实性片状、巢团状或腺管状排列,瘤细胞呈圆形、卵圆形及柱状,细胞质丰富,部分胞质空亮,胞质内可见多少不等的黏液,周边细胞栅栏状排列,细胞均无角化或细胞间桥形态出现。所有病例均可见腔缘的核分裂象或凋亡小体(22/22),多数病例可见中性粒细胞浸润(17/22)。免疫表型:p16均弥漫强阳性,CK7、CAM5.2、CEA弥漫阳性或部分阳性,CK5/6、p40、p63散在阳性或阴性,PAX-8部分局灶阳性,ER、PR阴性。PAS染色均可见多少不等的细胞内黏液。qRT-PCR结果显示22例患者均与高危型HPV感染有关。电镜显示细胞表面有许多微绒毛,可见胞质内空腔及大小较一致的黏液空泡,核膜清晰。肿瘤细胞间以缝隙连接为主,未见桥粒结构,并且缺乏细胞张力丝。多数患者行广泛全子宫+双侧附件及双侧盆腔淋巴结清扫术,部分年轻患者及有特殊要求的患者保留双侧附件或双侧卵巢,术后辅助放、化疗或联合放化疗。22例患者中有21例存活,1例死亡(术后6个月)。结论ISMC是与HPV感染有关的、少见的子宫颈腺癌,具有HPV相关型腺癌的形态学特点,易与低分化鳞状细胞癌混淆,患者预后相对较差。

Purpose This study was to investigate the clinicopathological features,diagnosis,and prognosis of invasive mucin-producing carcinoma(ISMC)of the cervix.Methods The clinicopathological features of 22 patients of cervical cancer with ISMC components were retrospectively analyzed.Immunohistochemical EnVision two-step staining and PAS staining were performed respectively.The load of HPV was detected by qRT-PCR.Ultra-microscopic features were observed by electron microscope.Relevant literatures were reviewed.Results The 22 ISMC patients were between 32-68 years old,with a median age of 47 years and an average age of 45.9 years.Microscopically,the tumor cells were solid sheet,nest or glandular arrangement,and the tumor cells were round,oval and columnar.The cytoplasm of the cells was abundant,some was empty,and there were varying amounts of mucus in the cytoplasm.The surrounding cells were palisade arrangement with no keratinization or intercellular bridge.Mitosis or apoptotic bodies were observed at the luminal margin in all cases(22/22),and neutrophil infiltration was observed in most cases(17/22).Immunohistochemical results showed that all ISMC were diffusely and strongly positive for p16,CK7,CAM5.2 and CEA were diffusely or partially expressed,CK5/6,p40 and p63 were scattered or not expressed,PAX-8 was partially focal,whereas ER and PR were both negative.Intracellular mucus could be seen with PAS staining.The HPV expression level of all 22 patients were associated with high-risk human papillomavirus(HPV)infection.The electron microscopy images showed that there were many microvilli on the cell surface,cytoplasmic cavities,mucous vacuoles of uniform size and clear nuclear membrane.Intercellular gap junctions were mainly found between the tumor cells without desmosomes and cytotension filament.Most patients underwent extensive total hysterectomy plus bilateral adnexectomy and bilateral pelvic lymph node dissection,while some young patients and those with special requirements retained bilateral adnexectomy or bilateral ovaries,and then postoperative adjuvant radiotherapy,chemotherapy or combined chemoradiotherapy were applied.Twenty-one of the 22 patients survived and one died(6 months postoperatively).Conclusion ISMC is a rare cervical adenocarcinoma associated with HPV infection.There is a unique morphological characteristics of HPV-associated adenocarcinoma,and easily confused with poorly differentiated squamous cell carcinoma.The prognosis of ISMC is relatively poor.