2例膀胱纯上皮性神经内分泌肿瘤临床病理特征差异及文献复习

doi:10.16150/j.1671-2870.2024.06.007

摘要/Abstract

摘要：

目的： 探讨膀胱纯上皮性神经内分泌肿瘤（neuroendocrine neoplasms, NEN）的临床病理学特征和预后。方法： 回顾性分析2018年至2024年间收治的2例膀胱纯上皮性NEN患者的临床资料、组织病理学形态以及免疫组织化学，并进行鉴别诊断和详细地文献复习。结果： 本组2例均为女性，年龄分别为85岁（例1）和84岁（例2），分别因下肢水肿和血尿就诊。B超及MRI检查示，例1膀胱三角区见一息肉状低回声，MRI增强无强化，考虑良性病变可能；例2膀胱前壁内见一结节状低回声，MRI增强呈明显强化，考虑恶性肿瘤可能，副神经节瘤不除外。巨检，2例分别为息肉状组织及结节状组织各一枚，最大径0.6~3.0 cm，例1表面光滑，例2切面呈灰黄色、质中。镜下，2例肿瘤均呈典型NEN的组织病理学形态，表面均被覆膀胱黏膜。例1肿瘤完全位于黏膜固有层内，例2肿瘤位于固有肌层内呈浸润性生长。例1诊断为分化好的神经内分泌肿瘤（well-differentiated neuroendocrine tumors，WD-NET），例2为大细胞神经内分泌癌（large cell neuroendocrine carcinoma，LCNEC）。2例肿瘤细胞均弥漫阳性表达广谱细胞角蛋白及神经内分泌标志物（2/2），P53均呈野生型表达（2/2），例1肿瘤Ki-67增殖指数为3%~5%，局部表达PSAP，例2肿瘤Ki-67增殖指数达60%~70%，少量表达GATA-3。2例均未行特殊治疗，例1随访76个月，无瘤生存；例2术后3个月复发伴肺转移死亡。文献复习提示，膀胱纯上皮性NEN均具有典型NEN肿瘤的病理组织学形态及免疫表型，WD-NET多呈惰性经过，而LCNEC多具有高度侵袭性，易复发转移，与本文报道的2例病例一致。结论： 膀胱纯上皮性NEN非常少见，明确诊断主要依据组织病理学检查和免疫组织化学染色，WD-NET完整切除后预后良好，而LCNEC具有高度侵袭性，预后不良。

关键词: 膀胱, 纯的神经内分泌肿瘤, 分化好的神经内分泌肿瘤, 大细胞神经内分泌癌

Abstract:

Objective To investigate the clinicopathological features and prognosis of pure epithelial neuroendocrine neoplasms (NEN) of the bladder. Methods A retrospective analysis was conducted on the clinical data, histopathological morphology, and immunohistochemistry of 2 patients with pure epithelial NEN of the bladder admitted between 2018 and 2024. A differential diagnosis was performed, and a detailed literature review was conducted. Results Both patients were females, aged 85 (Case 1) and 84 (Case 2), presenting with lower limb edema and hematuria, respectively. B-scan ultrasound and MRI examinations showed a polypoid hypoechoic lesion in the trigone of the bladder in Case 1, with no enhancement on MRI, suggesting a benign lesion. Case 2 showed a nodular hypoechoic lesion in the anterior bladder wall with significant enhancement on MRI, suggesting a malignant tumor, with paraganglioma not excluded. Gross examination revealed that the two cases had one polypoid tissue and one nodular tissue, respectively, with maximum diameters ranging from 0.6 cm to 3.0 cm. Case 1 had a smooth surface, while Case 2 had a grayish-yellow cross section with medium hardness. Microscopically, both tumors showed typical NEN histopathological features, with the surface covered by bladder mucosa. Case 1 was confined to the lamina propria, while Case 2 showed invasive growth into the muscularis propria. Case 1 was diagnosed as well-differentiated neuroendocrine tumor (WD-NET) and Case 2 as large cell neuroendocrine carcinoma (LCNEC). Immunohistochemically, both tumor cells diffusely expressed broad-spectrum cytokeratin and neuroendocrine markers (2/2), with wild-type expression of P53 (2/2). The Ki67 proliferation index was 3%-5% in Case 1, with focal PSAP expression, and 60%-70% in Case 2, with minimal GATA-3 expression. Neither patient received special treatment. Case 1 was followed up for 76 months with no recurrence, while Case 2 died of recurrence and lung metastasis 3 months after surgery. Literature review suggested that pure epithelial NEN of the bladder exhibited typical histopathological morphology and immunophenotype of NEN. WD-NET typically followed an indolent course, while LCNEC was highly invasive and prone to recurrence and metastasis, consistent with the two cases reported in this study. Conclusions Pure epithelial NEN of the bladder is extremely rare. The definitive diagnosis mainly relies on histopathological examination and immunohistochemical staining. WD-NET has a good prognosis after complete tumor resection while LCNEC is highly invasive and has a poor prognosis.

Key words: Bladder, Pure neuroendocrine neoplasm, Well-differentiated neuroendocrine tumors, Large cell neuroendocrine carcinoma

中图分类号:

R737.14
R445

周恒花, 林斓, 朱桂香, 刘敏, 黄文涛. 2例膀胱纯上皮性神经内分泌肿瘤临床病理特征差异及文献复习[J]. 诊断学理论与实践, 2024, 23(06): 602-611.

ZHOU Henghua, LIN Lan, ZHU Guixiang, LIU Min, HUANG Wentao. Pure epithelial neuroendocrine neoplasms of the bladder: clinicopathological characteristics of 2 cases and literature review[J]. Journal of Diagnostics Concepts & Practice, 2024, 23(06): 602-611.

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表1

表2

32例膀胱LCNEC临床病理特征和预后

Reference	Number	Age	Gender	Site	Size (cm)	Clinical feature	Staging	Treatment	Follow up and prognosis (mo)
[5]	1	73	M	Posterior wall	4.0	Hematuria	pT_3b	RC+LND	2,died of RE/ME
[23]	1	32	M	Anterior superior wall	3.0	Hematuria	pT₃	PC+CT	12,alive with RE/ME
[24]	2	40/43	M/F=1:1	NA	NA	NA	pT₂，pT₄	RC+CT，RC+RT	13,NED；12,died of ME
[25]	1	37	M	Posterior wall	2.5	Hematuria	pT_3b	RC+LND+CT	22,NED
[26]	1	19	M	NA	NA	NA	NA	PC+CT	14,died of ME
[27]	1	74	M	Left wall	NA	Brain metastases	NA	PC+CT+RT	5,died of pulmonary embolism
[28]	1	67	M	Left posterior lateral wall	5.0	Hematuria	pT₂	TURBT	0.5,died of heart failure
[29]	1	59	M	Bottom	Huge	Dysuria and hematuria	pT_4a	TURBT	NA
[30]	1	68	M	Top wall	2.8	Hematuria	pT_2b	RC+LND+CT	30,died of RE/ME
[31]	1	84	M	Posterior wall	NA	Hematuria	NA	TURBT+CT	NA
[32]	1	68	M	Top wall	2.8	Hematuria	pT_2b	RC+LND	NA
[33]	1	70	M	Left wall	3.5	Hematuria	pT_2b	TURBT	7,died of ME
[34]	1	58	M	Left and anterior walls	6.5	Hematuria	pT_3b	RC	5,died of ME
[35]	5	Mean71.8	M/F=4/1	NA	NA	NA	3,pT_3a/2,pT_4a	RC(5/5);1 NACT	2.4-116.4(Mean14.4), 3 died of RE/2 died from other
[36]	1	72	M	Bottom	NA	Back pain and acute renal failure	pT_4a	RC+CT	36,RE with regression
[37]	1	72	M	Diffuse	NA	Hematuria	pT₂	RC+CT+IT	11,died of ME
[38]	1	45	M	Left wall	4.0	Acute renal failure	NA	TURBT+CT+RT	NA
[39]	1	39	M	Right wall	4.1	Hematuria	pT_2b	RC+LND+CT	59,NED
[40]	1	30	M	Anterior wall	3.4	Hematuria	pT_3b	PC+CT	24,NED
[41]	1	49	M	Left wall	7.0	Vertebral metastasis	pT₂	TURBT+CT+RT	12,Pain improvemen
[42]	1	66	M	Left posterior wall	4.3	Hematuria	pT_3b	NA	10,NED
[43]	1	67	M	Right posterior wall and right ureteral orifice	4.4	Hematuria	pT_3a	RC+LND+CT	39,NED
[44]	1	56	F	Anterior wall, posterior wall, and trigone	3.8	Hematuria	pT₂	RC+CT	6,Lost follow-up
[45]	1	79	M	Left wall	5.0	Hematuria	pT₃	RC+IT	24,RE
[46]	1	72	M	Anterior wall	2.0	Hematuria	pT_2b	PC	10,NED
[47]	1	65	M	Right anterior wall	3.0	Hematuria	pT_2a	PC+CT	7,NED
Present case	1	84	F	Anterior wall	3.0	Urinary frequency, urgency, and hematuria	pT_3a	PC	3, died of RE/ME

表2

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