膀胱副神经节瘤11例临床病理分析

Paraganglioma of urinary bladder: clinicopathologic analyses of 11 cases

目的探讨膀胱副神经节瘤（paraganglioma of urinary bladder, PUB）的临床病理特征、诊断及鉴别诊断。方法收集11例PUB，对其临床特征、病理学形态和免疫表型进行观察。结果本组11例PUB中男性6例，女性5例，发病年龄26～81岁，平均和中位年龄分别为50.8岁和52岁。肿瘤最大径0.8～6 cm，平均1.8 cm。10例会诊病例中3例误诊为“尿路上皮癌”，1例误诊为“类癌”，1例将“恶性副神经节瘤”误诊为“良性副神经节瘤”。11例中7例获得随访资料，随访时间22～60个月，平均40个月，其中1例于术后60个月发生腰椎转移，1例术后40个月死亡，其余5例无复发或转移。镜检：8例良性肿瘤细胞呈经典的巢状（Zellballen）排列，细胞巢之间有明显的血管网分隔。瘤细胞圆形、多边形，细胞质嗜酸、嗜碱性或透亮，细胞核卵圆形，核分裂象及坏死罕见或缺乏。2例恶性肿瘤细胞呈浸润性生长，境界不清，瘤细胞呈弥漫性和（或）大巢状分布，细胞异型明显，核分裂象易见，脉管内可见瘤栓，有肿瘤性坏死。余1例未能定性。免疫表型：肿瘤细胞弥漫阳性表达神经内分泌标志物Syn、CgA、NSE、CD56，不表达上皮性标志物CK和CK（AE1/AE3），部分肿瘤细胞和（或）肿瘤细胞巢周围支持细胞表达S-100蛋白。结论PUB罕见，可能过诊为尿路上皮癌或类癌，特征性巢状结构是副神经节瘤的诊断线索；免疫组化标记有助于诊断及鉴别诊断；肿瘤的浸润性生长、Zellballen巢扩大或瘤细胞弥漫分布、核分裂象增多及肿瘤性坏死是恶性PUB诊断的重要依据。

Purpose To investigate the clinicopathologic characteristics and differential diagnosis of paraganglioma of urinary bladder （PUB）, Methods The clinical and pathological characteristics of 11 cases of PUB were reviewed. Immunohistochemical study was performed. Results The eleven cases involved 6 males and 5 females with the age ranging from 26 - 81 years （ mean, 50. 8 years, median, 52 years）. Grossly, the tumors in size ranged from 0.8 cm to 6 cm in maximum diameter （mean 1.8 cm）. Of the ten consultation cases, three ones were misdiagnosed as ＂transitional cell carcinoma＂, one case as carcinoid, and one case, which was ＂malignant PUB＂, as ＂benign PUB＂. Follow-up data were obtained in 7/11 of the cases, from 22 to 60 months （ mean 40 months）. One of the seven patients had lumbar metastasis at 60 months after surgery, and one died at 40 months after surgery, and other five cases had no recurrence or metastasis. Microscopically, eight cases showed the typical ＂Zellballen＂ growth pattern separated by prominent vascular networks. The neoplastic cells were composed of round or polygonal cells with amphophilic or acidophilic or clear cytoplasm and o- void nuclei. Scattered larger or even bizarre nuclei were occasionally present. Mitoses and necrosis were rare, usually absent. The eight cases were diagnosed as benign ones. Two cases presented infiltrating and ill-defined borders, their neoplastic ceils were arranged in diffuse and/or large nests with somewhat atypia and brisk mitoses, tumor emboli were obvious, and coagulation necrosis was found. The two cases were diagnosed as malignant ones. One case was difficult to judge benign or malignant. Immunohistochemically, neo-plastic cells showed diffusely positive for Syn, CgA, NSE and CD56, whereas epithelial markers CK （AE1/AE3） and pan-cytokeratin were negative in all the cases. Some of neoplastic cells and/or sustentaeular ceils were positive for S-100 protein. Conclusion PUB is a rare tumor, easily overdiagnosed as urothelial carcinoma or carcinoid. The characteristic ＂Zellballen＂ pattern is a diagnostic clue to the PUB. Immunohistochemical markers can be helpful for diagnosis and differential diagnoses of the PUB. Invasive growth, expanded ＂Zellballen＂ and diffuse growth patterns, increased mitoses and tumor necrosis are important evidences for diagnosis of malignant PUB.