结直肠具有腺癌和神经内分泌癌双向分化特征的癌临床病理学特征分析

Clinicopathological features of colorectal amphicrine carcinoma

目的:探讨结直肠具有腺癌和神经内分泌癌双向分化特征的癌(amphicrine carcinoma,AC)的临床病理学特征、免疫表型和分子遗传学特征。方法:收集南京大学医学院附属鼓楼医院及南京市第一医院2013—2020年诊断的8例结直肠AC的临床病理资料,分析其临床病理学特征、免疫表型、超微结构特点及分子病理学改变,并复习相关文献。结果:患者男性6例,女性2例。发病年龄28~80岁,平均为56岁。肿瘤发生的部位:乙状结肠4例、直肠3例、横结肠1例。组织学上肿瘤可见3种生长模式:第一种为巢团状生长伴间质胶原纤维增生;第二种为弥漫片状分布,间质较少;第三种为腺管状或筛状分布伴菊形团样结构。肿瘤细胞呈圆形或印戒样,细胞质丰富,可见较多黏液或嗜伊红粉染颗粒;细胞核呈卵圆形或不规则形,染色质较细腻,核仁不明显,核分裂象多见。电镜下肿瘤内可见神经内分泌颗粒和黏液颗粒。免疫组织化学及特殊染色:肿瘤细胞均呈现2种以上的神经内分泌标志物阳性,其中突触素和CD56表达较为广泛,均有7例阳性;嗜铬粒素A有5例阳性;所有病例均可见细胞质呈淀粉酶消化过碘酸雪夫特殊染色阳性的肿瘤细胞。分子病理学上,8例患者均为微卫星稳定型,其中有2例患者可见KRAS G12C点突变或NRAS Q61点突变。8例患者在诊断时均可见较多神经侵犯、脉管内癌栓和淋巴结转移,分期较晚。有6例患者获得随访资料,随访8~48个月,其中4例在诊断后3年内死亡,2例无病存活。结论:结直肠AC是一类罕见的伴有双向分化的肿瘤,主要发生在乙状结肠或直肠,该肿瘤具有独特的组织学特征和免疫表型,并且侵袭性强、预后较差,需要临床及病理医师多加重视。

Objective To investigate the clinicopathological,immunophenotypic and molecular features of colorectal amphicrine carcinoma(AC).Methods Eight cases of colorectal AC were collected at the Nanjing Drum Tower Hospital and Nanjing First Hospital,Nanjing,China from 2013 to 2020.The histopathological,immunohistochemical and molecular features were analyzed.The relevant literature was reviewed.Results There were 6 males and 2 females,with an average age of 56 years(range 28-80 years).The tumor sites were as follows:4 cases in sigmoid colon,3 cases in rectum,and 1 case in transverse colon.Microscopically,there were three different patterns in the tumors,including nests with collagen hyperplasia,sheets of cells with scant stroma,and glandular or cribriform growth of goblet-or signet ring-like cells.The tumor cells generally had abundant cytoplasm with abundant mucin or eosinophilic granules.The nuclei were oval or irregular with fine chromatin and inconspicuous nucleoli.Mitotic figures were common.Neuroendocrine granules and mucin granules could be identified clearly under electron microscope.All cases showed frequent perineural and lymphovascular invasions,lymphatic metastasis,and advanced stage.Regarding immunohistochemical and specific stains,the tumor cells expressed more than two neuroendocrine markers,particularly CD56 and synaptophysin which were diffusely positive in 7 of the 8 cases.They also showed intracellular mucin in the amphicrine components which was positive for D-PAS.KRAS G12C or NRAS Q61 gene mutations were found in 2 patients.Among the six cases with complete follow-up,four of them died of the disease within three years of the diagnoses,while two were alive without known disease progression.Conclusions Colorectal AC is a rare,distinct entity with both epithelial and neuroendocrine differentiation.It mainly occurs in the sigmoid colon and rectum.It typically has aggressive clinical courses,dismal prognosis and characteristic histological features and immunophenotype,which highlight the importance of recognizing this entity for clinicians and pathologists.