8例结直肠混合性腺神经内分泌癌临床病理分析

doi:10.3969/j.issn.1004-583X.2022.10.007

摘要/Abstract

摘要：

目的探讨结直肠混合性腺神经内分泌癌 (mixed adeno-neuroendocrine carcinoma,MANEC)的临床病理特征。方法回顾性分析2016年8月-2020年12月于天津市中西医结合医院(南开医院)经手术切除的结直肠MANEC 8例患者的临床资料。结果 8例患者中女性3例,男性5例,平均年龄63岁。临床表现无特异性。影像学表现为占位和淋巴结转移。肿瘤标记物检测示部分病例铁蛋白(2例)和癌胚抗原(2例)升高,所有病例甲胎蛋白和糖蛋白199均未见明显升高。6例行术前肠镜活检,诊断为腺癌5例,腺癌或MANEC 1例。肿瘤发生部位以结肠为主(6例)。溃疡型5例,隆起型3例,肿瘤最大径3~9 cm。光镜下:腺癌肿瘤细胞呈腺管样排列,2例伴有黏液腺癌;神经内分泌肿瘤细胞呈弥漫、巢团或器官样分布,小细胞型1例,大细胞型7例。淋巴结转移7例,肝转移1例。免疫组织化学示腺癌CK8/18、CK19和CEA不同程度阳性,神经内分泌肿瘤CgA、Syn和CD56不同程度阳性,Ki-67热点区40%~80%阳性。随访5例存活,中位生存时间17个月,2例死亡,平均生存时间8个月。结论结直肠MANEC发病率较低,缺乏临床特异性,易发生淋巴结转移,属于高度恶性肿瘤,诊断主要依赖免疫组织化学辅助的病理检查。

关键词: 结直肠肿瘤, 混合性腺神经内分泌癌, 组织细胞学制备技术, 免疫组织化学

Abstract:

Objective To explore the clinicopathological features of colorectal mixed adeno-neuroendocrine carcinoma (MANEC). Methods A retrospective analysis were porformed in 8 patients underwent MANEC eradication in Tianjin Hospital of ITCWM (Nankai Hospital) from August 2016 to December 2020. Results There were 3 female and 5 male, age averaged 63 years among these patients. Their clinical manifestations obviously had no-specificity, with the imaging showing space occupying and lymph node metastasis.The tumor marker detection verified 2 cases of significantly elevated ferritin, 2 cases of significantly elevated carcinoembryonic antigen (CEA), and all cases of insignificantly elevated alpha-fetoprotein and carbohydrate antigen 199 (CA199). The preoperative biopsy were conducted in 6 cases, 5 cases of adenocarcinoma and 1 case of adenocarcinoma or MANEC, with main space occupying in colon. There were 5 cases for ulcer type, 3 cases for protuberant type, with the maximum diameter of tumor for 3-9 cm. Under light microscope, the tumor cells of adenocarcinoma were arranged like glandular tubes, and 2 cases were accompanied with mucinous adenocarcinoma; neuroendocrine tumor cells showed diffuse, nest like or organ like distribution, including 1 case of small cell type and 7 cases of large cell type. Lymph node metastasis was found in 7 cases and liver metastasis in 1 case. Immunohistochemistry indicated that cytokeratin8/18 (CK8/18), cytokeratin19 (CK19) and CEA were positive to varying degrees in adenocarcinoma, chromogranin A (CgA), synaptophysin (Syn) and cluster of differentiation 56 (CD56) were positive to varying degrees in neuroendocrine tumors, and 40%-80% of Ki-67 hot spots were positive. Five patients survived, the median survival time was 17 months, and two patients died, the average survival time was 8 months. Conclusion Colorectal MANEC is a highly malignant tumor characterized by lower morbidity, no-specificity, and incident lymph node metastasis, its diagnosis mainly depends on pathology with immunohistochemistry.

Key words: colorectal neoplasms, mixed adeno-neuroendocrine carcinoma, histocytological preparation techniques, immunohistochemistry

中图分类号:

R735.3

张一鸣, 李明昭, 顾欣. 8例结直肠混合性腺神经内分泌癌临床病理分析[J]. 临床荟萃, 2022, 37(10): 921-926.

Zhang Yiming, Li Mingzhao, Gu Xin. Clinicopathological analysis of colorectal mixed adeno-neuroendocrine carcinoma: 8 cases report[J]. Clinical Focus, 2022, 37(10): 921-926.

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链接本文: https://huicui.hebmu.edu.cn/CN/10.3969/j.issn.1004-583X.2022.10.007

https://huicui.hebmu.edu.cn/CN/Y2022/V37/I10/921

图/表 10

表1 纳入患者的一般资料

病例	性别	年龄(岁)	临床表现
1	男	59	腹痛腹泻伴排气排便不畅
2	女	62	腹痛
3	男	53	腹痛
4	女	54	腹部不适伴便血
5	女	70	腹痛
6	男	51	腹痛伴血便
7	男	67	腹泻伴黏液脓血便
8	男	87	腹痛

表2 纳入患者的手术病理资料

编号	部位	大体类型	最大径(cm)	病理分级	分期	腺癌比例及分化	NEC比例及类型	淋巴结转移(腺癌/NEC/腺癌+NEC*)	Syn	CgA	CD56	Ki-67指数(腺癌百分比/NEC百分比)
1	乙状结肠	溃疡	5	T3N2bM0	ⅢC	50%,中分化	50%,大细胞	5/3/3	+	-	-	60/80
2	乙状结肠	溃疡	6	T3N1aM1a	ⅣA	30%,中-低分化	70%,大细胞	0/2/0	+	+	-	60/80
3	升结肠	隆起	5	T3N2bM0	ⅢC	70%,中-低分化(伴黏液腺癌)	30%,大细胞	10/2/0	+	-	+	80/60
4	横结肠	溃疡	9	T3N0M0	ⅡA	70%,中-低分化(伴黏液腺癌)	30%,大细胞	0/0/0	部分+	-	+	50/70
5	升结肠	溃疡	4	T3N2bM0	ⅢC	30%,高-中分化	70%,大细胞	8/0/0	+	弱+	弱+	50/60
6	直肠	隆起	3	T3N2bM0	ⅢC	30%,高-中分化	70%,大细胞	0/7/0	部分+	部分+	局灶+	40/60
7	直肠	溃疡	6	T3N2bM0	ⅢC	30%,高-中分化	70%,大细胞	1/1/0	部分+	部分+	-	50/70
8	乙状结肠	隆起	5	T3N2bM0	ⅢC	30%,高-中分化	70%,小细胞	3/13/3	+	-	零星+	50/60

图1 肿瘤HE染色 a.肿瘤由腺癌和NEC两种成分组成,相互混杂,40×;b.NEC成分,肿瘤细胞呈实性片状分布,细胞较大,可见核仁,100×;c.腺癌成分,肿瘤细胞呈腺管状排列,细胞异型性明显,周围间质纤维化,100×

图2 黏液腺癌HE染色 a.肿瘤由腺癌和NEC两种成分组成,腺癌部分呈黏液腺癌,NEC可见坏死,20×;b.NEC成分,肿瘤细胞呈小巢状分布,细胞较大,100×;c 黏液腺癌成分(图2a中右侧方框),细胞外可见淡蓝色黏液,100×

图3 腺癌成分CK8/18免疫组织化学染色 a.NEC(细胞质+),腺癌(细胞质+),40×;b. NEC(细胞质+),100×;c. 腺癌(细胞质+),100×

图4 腺癌成分CEA免疫组织化学染色 a.NEC(-),腺癌(细胞质+) 40×;b. NEC(-),100×;c. 腺癌(细胞质+),100×

图5 NEC成分CgA免疫组织化学染色 a.NEC(细胞质+),腺癌(-),40×;b. NEC(细胞质+),100×;c. 腺癌(-),100×

图6 NEC成分Syn免疫组织化学染色 a.NEC(细胞质+),腺癌(-),40×;b.NEC(细胞质+),100×;c. 腺癌(-),100×

图7 NEC成分CD56免疫组织化学染色 a.NEC局灶(细胞膜+),腺癌(-),40×;b.NEC局灶(细胞膜+),100×;c. 腺癌(-),100×

图8 肿瘤Ki-67免疫组织化学染色 a.NEC和腺癌不同程度(+),20×;b. NEC阳性指数高,局灶约70%,100×;c. 腺癌阳性指数约40%,100×

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