宫颈产生黏液的复层上皮肿瘤性病变临床病理学特征

目的对宫颈产生黏液的复层上皮内病变(SMILE)和浸润性复层产生黏液的癌(ISMC)的临床病理特征结合文献进行分析。方法收集空军军医大学西京医院病理科2007年1月至2019年3月16例具有SMILE/ISMC成分的宫颈肿瘤性病变,患者的临床病理资料包括发病年龄、临床表现、组织学类型、肿瘤浸润深度、脉管侵犯和淋巴结转移状态、国际妇产科联盟(FIGO)分期以及随访情况,同时行组织化学阿辛蓝和淀粉酶消化法过碘酸-雪夫(PAS-D)染色,免疫组织化学细胞角蛋白(CK)7、p16、p63、p40、PAX8、MUC6、p53染色,此外结合宫颈腺癌浸润模式分类系统对12例浸润性腺癌成分进行评估。结果患者平均发病年龄49.7岁(范围33~65岁),大多数患者(13/16)发生阴道出血。SMILE和ISMC形态学分别表现为非浸润性或浸润性复层上皮伴全层细胞,具有不等量的胞质内黏液。5例SMILE成分分别与原位腺癌(1例)、高级别鳞状上皮内病变(1例)或浸润性腺癌(3例)共存;13例ISMC成分分别为单一型ISMC(3例)、合并普通型宫颈腺癌(8例)、合并鳞状细胞癌(2例)。所有单一型ISMC均具有脉管侵犯且浸润深度超过10 mm。11例具有ISMC成分的浸润性腺癌均为Pattern C肿瘤,组织学呈弥漫破坏性间质浸润、实性结构或低分化肿瘤。组织化学阿辛蓝和PAS-D染色证实SMILE/ISMC成分(7/7)细胞质内富含酸性和中性黏液。免疫组织化学染色SMILE(4/4)和ISMC(8/8)成分CK7和p16均呈弥漫强阳性表达,p63和p40表达于SMILE(1/3)和ISMC(2/8)成分复层上皮细胞巢的周边细胞或仅少部分细胞,在ISMC成分中,部分瘤细胞MUC6(5/7)阳性表达、PAX8(2/8)局灶阳性表达、p53呈野生型表达模式(4/10)或完全阴性(6/10)。具有随访资料的13例患者目前均存活(平均随访时间50.5个月,范围4~140个月)。结论SMILE是一种少见、独特的宫颈上皮内病变,ISMC属于与其形态学相似的浸润性病变,具有ISMC成分的肿瘤可能具有较强的侵袭性,充分认识宫颈SMILE和ISMC对临床和病理医师尤为重要。

Clinicopathological features of stratified mucin-producing neoplastic lesions of the cervix

Objective To investigatethe clinicopathological features of stratified mucin-producing intraepithelial lesion(SMILE)and invasive stratified mucin-producing carcinoma(ISMC)of the cervix with review of the literature.Methods Sixteen patients with SMILE/ISMC components of the cervix were collected from files in the Department of Pathology at Xijing Hospital from January 2007 to March 2019.Clinicopathological data included age at diagnosis,clinical presentation,histological type,depth of invasion measurement,the status of lymphovascular space invasion(LVSI)and lymph node metastasis,FIGO staging and follow-up.Histochemistry AB and PAS-D staining and immunostaining for cytokeratin(CK)7,p16,p63,p40,PAX8,MUC6,p53 were performed simultaneously.In addition,twelve cases with invasive endocervical adenocarcinoma were evaluated using three-tiered pattern-based system(also called Pattern Classification).Results The average age at diagnosis for patients was 49.7 years(range,33 to 65 years),and vaginal bleeding occurred in the majority of cases(13/16).The characteristic morphology of SMILE and ISMC was present as non-invasive and invasive stratified epithelium that the full-thickness cells contained different amount of cytoplasmic mucin,respectively.Five cases of SMILE coexisted with adenocarcinoma in situ(1 case),high-grade squamous intraepithelial lesion(1 case),and invasive adenocarcinoma(3 cases).Thirteen cases with ISMC components included pure ISMC(3 cases),mixed with usual-type endocervical adenocarcinoma(8 cases)or squamous cell carcinoma(2 cases).All pure ISMC had lymph vascular space invasion and depth of invasion exceeded 10 mm.All eleven cases of invasive adenocarcinoma with ISMC components belonged to Pattern C tumors,which typically showed diffusely destructive stromal invasion,solid or poorly differentiated components.The results of histochemical staining confirmed that SMILE/ISMC cells were rich in acidic and neutral mucin.The immunohistochemical staining for CK7 and p16 was diffusely strong positive in SMILE(4/4)and ISMC(8/8)components.The positive expressions of p63 and p40 was located in peripheral cells of stratified epithelial nests or merely in a few cells of SMILE(1/3)and ISMC(2/8)components.In ISMC tissues,there were partial expression of MUC6(5/7),focal expression of PAX8(2/8),and wild-type expression pattern(4/10)or completely negative expression(6/10)of p53 protein.All thirteen patients with follow-up data were alive(mean 50.5 months,range 4 to 140).Conclusions As new tumor entities,SMILE is a rare and unique endocervical intraepithelial lesion,while ISMC belongs to an invasive leison.Given that the tumors with ISMC components may have aggressive behavior,it is important for clinicians and pathologists to fully understand the clinicopathological features of SMILE and ISMC.