原发性肾输尿管小细胞神经内分泌癌的诊断与治疗(附10例报告)

Diagnosis and treatment of primary small cell neuroendocrine carcinoma of kidney and ureter(Report of ten cases)

目的：探讨原发性肾输尿管小细胞神经内分泌癌（NEC）的临床病理特点,提高该类疾病的诊治水平。方法：回顾分析四川大学华西医院2003-2012年诊治的10例原发性肾输尿管小细胞NEC的临床病理资料,总结该类疾病临床特点、免疫组化特点、鉴别诊断要点及临床预后。结果：10例患者病理诊断为完全的NEC7例（完全低分化6例,低分化和中分化混合1例）,NEC混合高级别尿路上皮癌3例（肾盂2例,输尿管1例）。2例肿瘤局限在肾脏内,8例肿瘤侵犯肾周和输尿管外脂肪,6例淋巴结转移阳性,1例切缘阳性。免疫组化分析：CD56、嗜铬颗粒素A（CgA）、突触素、神经元烯醇化酶不同程度表达;10例患者上述4个指标中至少1个指标阳性。CD99（6/6）,RCC（5/5）,WT-1（5/5）等指标均为阴性。PCK和Ki-67指数不同程度表达。1例术后3个月失访;1例术后47个月无复发证据存活至今;1例术后8个月出现肝脏及肺转移;其余7例死亡,平均生存8个月（3~17个月）。结论：原发性肾输尿管NEC临床罕见,侵袭性强,确诊时多数伴有转移,同时合并尿路上皮癌常见。早期局限在肾内的肿瘤,根治性肾切除可取得较好效果;而合并转移的晚期肿瘤,尽管采取手术治疗和术后化疗,预后仍差。寻找包括分子靶向药物在内的新的治疗方法可能是今后治疗的方向。

Objective：To investigate the clinicopathological feature of primary small cell neuroendocrine carcinoma of kidney and ureter.Method：Clinicopathological data of ten patients with primary small cell neuroendocrine carcinoma of kidney and ureter were analyzed retrospectively,and clinical manifestations,characteristics of immunohistochemistry,clues for differential diagnosis and prognosis were summarized.Result：With histopathological examination,seven of ten cases were pure neuroendocrine carcinoma（poor differentiation in six cases,poor and intermediate differentiation in one case）,and another three patients were neuroendocrine carcinoma admixed with high grade upper urinary tract urothelial carcinoma.The tumor invaded the perinephric and periureteral adipose tissue in eight cases and was confined to the kidney in two cases.Lymph node metastases were identified in six patients who underwent lymph node dissection（6/6）.Marginal positive was identified in one case.With immunohistochemistry staining,CD56,chromogranin A,synaptophysin,neuron-specific enolase were positively expressed in different levels.There were at least one positive indicator in above four biomarkers in all ten cases.None of them were positive for CD99,RCC,WT-1.Pancytokeratin（PCK）and Ki-67 index were positively expressed in different levels.The data of follow-up were as follows：one case lost follow-up three months after surgery;one case is alive for 47 months without disease after surgery;one case is alive for eight months with multiple metastases in liver and lung;seven patients died at a mean of eight months（range,3-17months）after surgery.Conclusion：Primary small cell neuroendocrine carcinoma of kidney and ureter is a rare and highly aggressive disease that often presents at an advanced stage with metastases,and it is not uncommon to admix with high grade upper urinary tract urothelial carcinoma.Patients with organ-confined tumors may achieve curative outcome followed by radical nephrectomy.However,patients with nonorgan-confined disease usually have a poor clinical outcome despite of multimodal therapy.Searching for new treatments,including molecular targeted drugs,may be the future direction of treatment.