尿路上皮癌的临床病理学特征

doi:10.16150/j.1671-2870.2023.03.13

摘要/Abstract

摘要：

目的：探讨膀胱尿路上皮癌（urinary bladder urothelial carcinoma, UBUC）及上尿路上皮癌（upper tract urothelial carcinoma, UTUC）患者的临床病理特征，并分析预后。方法：随机选取2017年5月至2020年2月东部战区总医院及南京大学医学院附属鼓楼医院收治的115例尿路上皮癌（urothelial carcinoma, UC）患者，其中UBUC 80例，UTUC 35例。回顾性分析其临床资料，利用χ²检验和Fisher精确检验分析两者的临床病理特征差异，利用Kaplan-Meier法及Log-rank检验进行生存分析，并采用Cox比例风险模型进行多因素分析。结果：与UBUC组比较，UTUC患者中，女性患者更常见（28.6%比10.0%, P=0.012），而UTUC患者则更少发生神经侵犯（5.7%比33.7%, P=0.002）及血管侵犯（20.0%比45.0%, P=0.011），UTUC患者伴发原位癌也更为少见（2.9%比23.7%, P=0.007）。UBUC的组织学变异型主体为微乳头分化（31.3%）、鳞状分化（25.0%）和腺样分化（12.6%）；而UTUC多见差分化癌（33.3%）、肉瘤样分化（22.2%）及神经内分泌分化（22.2%）。生存分析显示，UTUC患者的3年总生存率（overall survival, OS）略高于UBUC（81.8%比73.8%），但差异尚无统计学意义（P>0.05）。神经侵犯、血管侵犯、临床分期、淋巴结转移与UC患者的总生存期（overall survival，OS）相关，且血管侵犯和神经侵犯是UC患者总生存期的独立预测因子。结论：相较UBUC，UTUC女性构成比明显高于男性；UBUC则更易发生神经侵犯及血管侵犯、伴发原位癌。两者的预后并无明显差异。血管侵犯及神经侵犯是UC患者OS的独立预后因子。

关键词: 尿路上皮癌, 上尿路癌, 膀胱癌, 临床病理, 预后

Abstract:

Objective: This paper aims to investigate the clinicopathological features of bladder cancer (UBUC) and upper urinary tract cancer (UTUC). Methods: A total of 115 patients with urothelial carcinoma (UC) admitted to Jinling Hospital and Nanjing Drum Tower Hospital from May 2017 to February 2020 were randomly selected and retrospectively analyzed, including 80 cases of UBUC and 35 cases of UTUC. The differences in clinicopathological characteristics between the two groups were analyzed by chi-square test and Fisher’s exact test. Kaplan-Meier method and Log-rank test were used for survival analysis, and Cox proportional hazards model was used for multivariate analysis. Results: Female patients were more common in UTUC (28.6% vs. 10.0%, P=0.012). UBUC was more likely to have neural invasion (33.7% vs.5.7%, P=0.002), vascular invasion (45.0% vs. 20.0%, P=0.011), and carcinoma in situ (23.7% vs. 2.9%, P=0.007). The main histological variants of UBUC were micropapillary differentiation (31.3%), squamous differentiation (25.0%) and adenoid differentiation (12.6%), while poorly differentiated carcinoma (33.3%), sarcomatoid differentiation (22.2%) and neuroendocrine differentiation (22.2%) were more common in UTUC. Survival analysis showed that there was no significant difference in overall survival (OS) between UTUC and UBUC (P>0.05). Neural invasion, vascular invasion, clinical stage, and lymph node metastasis are associated with OS in UC, and vascular invasion and neural invasion are independent predictors of overall survival in UC. Conclusions: Compared with UBUC, the incidence of UTUC in women is significantly higher than that in men, while UBUC is more likely to have neural invasion, vascular invasion and carcinoma in situ. Histological variants of UBUC are micropapillary, squamous and adenoid, while UTUC is mostly poorly differentiated carcinoma, sarcomatoid and neuroendocrine differentiation. There is no significant difference in prognosis between the two groups. Vascular invasion and neural invasion are significant predictors of UC-OS.

Key words: Urothelial carcinoma, Upper urinary tract cancer, Bladder cancer, Clinical pathology, Prognosis

中图分类号:

R737.13

周晓蝶, 陈巍魏, 余波, 王璇, 王建军, 石群立, 饶秋, 鲍炜. 尿路上皮癌的临床病理学特征[J]. 诊断学理论与实践, 2023, 22(03): 292-299.

ZHOU Xiaodie, CHEN Weiwei, YU Bo, WANG Xuan, WANG Jianjun, SHI Qunli, RAO Qiu, BAO Wei. Clinicopathological features of urothelial carcinoma[J]. Journal of Diagnostics Concepts & Practice, 2023, 22(03): 292-299.

图/表 4

表1

UBUC和UTUC的临床病理特征

Patient characteristics	Total （n=115）	UBUC （n=80）	UTUC （n=35）	P value
Median age	69（36-88）	69（36-88）	68（45-84）
Gender				0.012
Male	97（84.4%）	72（90.0%）	25（71.4%）
Female	18（15.6%）	8（10.0%）	10（28.6%）
Age (years)				0.508
<60	16（13.9%）	10（12.5%）	6（17.1%）
≥60	99（86.1%）	70（87.5%）	29（82.9%）
Smoking history				0.099
No	95（82.6%）	63（78.8%）	32（91.4%）
Yes	20（17.4%）	17（21.2%）	3（8.6%）
Neural invasion				0.002
No	86（74.8%）	53（66.2%）	33（94.2%）
Yes	29（25.2%）	27（33.7%）	2（5.7%）
Vascular invasion				0.011
No	72（62.6%）	44（55.0%）	28（80.0%）
Yes	43（37.4%）	36（45.0%）	7（20.0%）
AJCC clinical staging				0.502
Ⅰ/Ⅱ	44（38.3%）	29（36.3%）	15（42.9%）
Ⅲ/Ⅳ	71（61.7%）	51（63.7%）	20（57.1%）
Single/multifocal				0.311
Single	92（80%）	62（77.5%）	30（85.7%）
Multifocal	23（20%）	18（22.5%）	5（14.2%）
With carcinoma in situ				0.007
Without	95（82.6%）	61（76.3%）	34（97.1%）
With	20（17.4%）	19（23.7%）	1（2.9%）
UC subtype, n (%)				0.139
Low-grade	5（4.3%）	2（2.5%）	3（8.6%）
High-grade	68（59.1%）	45（56.3%）	23（65.7%）
Histological type	42（36.5%）	33（41.3%）	9（25.7%）	<0.001
Micropapilly	11（26.2%）	11（33.3%）	0（0.0%）
Glandular	4（9.5%）	4（12.1%）	0（0.0%）
Squamous	9（21.4%）	8（24.2%）	1（11.1%）
Plasmacytoid	4（9.5%）	4（12.1%）	0（0.0%）
Sarcomatoid	5（11.9%）	3（9.1%）	2（22.2%）
Nested	2（4.8%）	2（6.1%）	0（0.0%）
Neuroendocrine	2（4.8%）	0（0.0%）	2（22.2%）
Lymphoepithelioma-like	2（4.8%）	1（3.0%）	1（11.1%）
Poorly differentiated	3（7.1%）	0（0.0%）	3（33.3%）
Surgical margin				0.071
Negative	108（93.9%）	73（91.3%）	35（100%）
Positive	7（6.1%）	7（8.7%）	0（0%）
Lymph node				<0.001
No	27（23.5%）	7（8.7%）	20（57.1%）
Yes	88（76.5%）	73（91.3%）	15（42.9%）
Median	12（1-34）	13（1-34）	4（1-16）
Lymph node metastasis				0.807
No	61（69.3%）	51（69.9%）	10（66.7%）
Yes	27（30.7%）	22（30.1%）	5（33.3%）
Tumor location
Renal pelvis	-	-	16（45.7%）
Ureter	-	-	17（48.5%）
Renal pelvis+Ureter	-	-	2（5.7%）
Urethral diversion
Ileal conduit	-	47（58.8%）	-
Cutaneous ureter- ostomy	-	25（31.2%）	-
Orthotopic bladder substitute	-	8（10.0%）	-
Surgical operation				0.568
Open	1（0.9%）	1（1.3%）	0（0）
Laparoscopic	22（19.1%）	14（17.5%）	8（22.9%）
Robot-assisted	92（80.0%）	65（81.2%）	27（77.1%）

表1

图1

图2

表2

参考文献 26

[1]	MARGULIS V, SHARIAT S F, MATIN S F, et al. Outcomes of radical nephroureterectomy: a series from the upper tract urothelial carcinoma collaboration[J]. Cancer, 2009, 115(6):1224-1233. doi: 10.1002/cncr.24135 pmid: 19156917
[2]	SHARIAT S F, FAVARETTO R L, GUPTA A, et al. Gender differences in radical nephroureterectomy for upper tract urothelial carcinoma[J]. World J Urol, 2011, 29(4):481-486. doi: 10.1007/s00345-010-0594-7 pmid: 20886219
[3]	GANDAGLIA G, BIANCHI M, TRINH Q D, et al. Survival after nephroureterectomy for upper tract urothelial carcinoma: a population-based competing-risks analysis[J]. Int J Urol, 2014, 21(3):249-256. doi: 10.1111/iju.12267 pmid: 24033809
[4]	BABJUK M, BURGER M, CAPOUN O, et al. European Association of Urology Guidelines on Non-muscle-invasive Bladder Cancer (Ta, T1, and Carcinoma in Situ)[J]. Eur Urol, 2022, 81(1):75-94. doi: 10.1016/j.eururo.2021.08.010 URL
[5]	LUGHEZZANI G, BURGER M, MARGULIS V, et al. Prognostic factors in upper urinary tract urothelial carcinomas: a comprehensive review of the current literature[J]. Eur Urol, 2012, 62(1):100-114. doi: 10.1016/j.eururo.2012.02.030 pmid: 22381168
[6]	RICHTERS A, ABEN K K H, KIEMENEY L A L M. The global burden of urinary bladder cancer: an update[J]. World J Urol, 2020, 38(8):1895-1904. doi: 10.1007/s00345-019-02984-4 pmid: 31676912
[7]	CUMBERBATCH M G, ROTA M, CATTO J W, et al. The role of tobacco smoke in bladder and kidney carcinogenesis: a comparison of exposures and meta-analysis of incidence and mortality risks[J]. Eur Urol, 2016, 70(3):458-466. doi: 10.1016/j.eururo.2015.06.042 pmid: 26149669
[8]	XYLINAS E, RINK M, ROBINSON B D, et al. Impact of histological variants on oncological outcomes of patients with urothelial carcinoma of the bladder treated with radical cystectomy[J]. Eur J Cancer, 2013, 49(8):1889-1897. doi: 10.1016/j.ejca.2013.02.001 pmid: 23466126
[9]	HUMPHREY P A, MOCH H, CUBILLA A L, et al. The 2016 WHO classification of tumours of the urinary system and male genital organs-part b: prostate and bladder tumours[J]. Eur Urol, 2016, 70(1):106-119. doi: S0302-2838(16)00205-0 pmid: 26996659
[10]	VESKIMÄE E, ESPINOS E L, BRUINS H M, et al. What is the prognostic and clinical importance of urothelial and nonurothelial histological variants of bladder cancer in predicting oncological outcomes in patients with muscle-invasive and metastatic bladder cancer? a european association of urology muscle invasive and metastatic bladder cancer guidelines panel systematic review[J]. Eur Urol Oncol, 2019, 2(6):625-642. doi: S2588-9311(19)30144-0 pmid: 31601522
[11]	GENITSCH V, KOLLÁR A, VANDEKERKHOVE G, et al. Morphologic and genomic characterization of urothelial to sarcomatoid transition in muscle-invasive bladder cancer[J]. Urol Oncol, 2019, 37(11):826-836. doi: S1078-1439(19)30376-X pmid: 31585777
[12]	MORI K, JANISCH F, PARIZI M K, et al. Prognostic value of variant histology in upper tract urothelial carcinoma treated with nephroureterectomy: a systematic review and meta-analysis[J]. J Urol, 2020, 203(6):1075-1084. doi: 10.1097/JU.0000000000000523 pmid: 31479406
[13]	KIM J K, MOON K C, JEONG C W, et al. Variant histo-logy as a significant predictor of survival after radical nephroureterectomy in patients with upper urinary tract urothelial carcinoma[J]. Urol Oncol, 2017, 35(7):458,e9-e15.
[14]	ZAMBONI S, FOERSTER B, ABUFARAJ M, et al. Incidence and survival outcomes in patients with upper urinary tract urothelial carcinoma diagnosed with variant histology and treated with nephroureterectomy[J]. BJU Int, 2019, 124(5):738-745. doi: 10.1111/bju.14751 pmid: 30908835
[15]	SHIBING Y, TURUN S, QIANG W, et al. Effect of concomitant variant histology on the prognosis of patients with upper urinary tract urothelial carcinoma after radical nephroureterectomy[J]. Urol Oncol, 2015, 33(5):204,e9-e16.
[16]	LOPEZ-BELTRAN A, HENRIQUES V, MONTIRONI R, et al. Variants and new entities of bladder cancer[J]. Histopathology, 2019, 74(1):77-96. doi: 10.1111/his.2019.74.issue-1 URL
[17]	崔庆敖, 覃茂, 张伟阳, 等. 机器人辅助腹腔镜根治性肾输尿管切除术治疗非转移性高危上尿路尿路上皮癌的疗效分析[J]. 重庆医科大学学报, 2022, 47(4):439-443.
	CUI Q A, QIN M, ZHANG W Y, et al. Efficacy analysis of robot-assisted radical nephroureterectomy and laparoscopic radical nephroureterectomy for non-metastatic high-risk upper tract urothelial carcinoma[J]. J Chongqing Med Univ, 2022, 47(4):439-443.
[18]	SCOSYREV E, NOYES K, FENG C, et al. Sex and racial differences in bladder cancer presentation and mortality in the US[J]. Cancer, 2009, 115(1):68-74. doi: 10.1002/cncr.23986 pmid: 19072984
[19]	ZHANG L, WU B, ZHA Z, et al. Concomitant carcinoma in situ may not be a prognostic factor for patients with bladder cancer following radical cystectomy: a PRISMA-compliant systematic review and meta-analysis[J]. World J Urol, 2020, 38(1):129-142. doi: 10.1007/s00345-019-02738-2 pmid: 30919100
[20]	REDROW G, GUO C C, BRAUSI M A, et al. Upper urinary tract carcinoma in situ: current knowledge, future direction[J]. J Urol, 2017, 197(2):287-295. doi: S0022-5347(16)31315-5 pmid: 27664578
[21]	SU X, TANG Q, FANG D, et al. Comparisons of prognosis between urothelial carcinoma of the upper urinary tract and bladder with pT3-4 cancer[J]. Int J Clin Exp Med, 2016, 9(9):18308-18315. pmid: 32351666
[22]	SATHIANATHEN N J, RISK M C, KONETY B R. Lymphadenectomy for muscle-invasive bladder cancer and upper tract urothelial cell carcinoma[J]. Urol Clin North Am, 2018, 45(2):215-228. doi: 10.1016/j.ucl.2017.12.006 URL
[23]	SHARIAT S F, KARAKIEWICZ P I, PALAPATTU G S, et al. Outcomes of radical cystectomy for transitional cell carcinoma of the bladder: a contemporary series from the bladder cancer research consortium[J]. J Urol, 2006, 176(6 Pt 1):2414-2422. doi: 10.1016/j.juro.2006.08.004 pmid: 17085118
[24]	ABDOLLAH F, SUN M, SCHMITGES J, DJAHANGIRIAN O, et al. Stage-specific impact of pelvic lymph node dissection on survival in patients with non-metastatic bladder cancer treated with radical cystectomy[J]. BJU Int, 2012, 109(8):1147-1154. doi: 10.1111/j.1464-410X.2011.10482.x pmid: 21883849
[25]	MASON R J, KASSOUF W, BELL D G, et al. The contemporary role of lymph node dissection during nephroureterectomy in the management of upper urinary tract urothelial carcinoma: the Canadian experience[J]. Urology, 2012, 79(4):840-845. doi: 10.1016/j.urology.2011.11.058 pmid: 22365453
[26]	CROZIER J, PAPA N, PERERA M, et al. Lymph node yield in node-negative patients predicts cancer specific survival following radical cystectomy for transitional cell carcinoma[J]. Investig Clin Urol, 2017, 58(6):416-422. doi: 10.4111/icu.2017.58.6.416 pmid: 29124240

Variables	Univariate analysis		Multivariate analysis
Variables	HR（95%CI）	P value	HR（95%CI）	P value
UBUC vs. UTUC	0.702（0.229-2.152）	0.536
Age (years)（<60 vs. ≥60）	0.040（0.000-15.987）	0.292
Smoking history	0.588（0.134-2.575）	0.481
Gender	2.971（0.394-22.409）	0.291
Neural invasion	2.688（1.021-7.079）	0.045	1.607（0.595-4.343）	0.035
Vascular invasion	4.327（1.597-11.723）	0.004	3.646（1.187-11.196）	0.024
AJCC clinical staging（Ⅲ-Ⅳ vs. Ⅰ-Ⅱ）	6.260（1.43-27.407）	0.015	4.799（0.988-23.304）	0.052
Single vs. Multifocal	2.101（0.707-5.710）	0.190
With carcinoma in situ	1.371（0.394-4.774）	0.620
Histological type	1.437（0.531-3.890）	0.475
Surgical margin	1.809（0.414-7.912）	0.431
Lymph node metastasis	3.019（1.145-7.961）	0.026	0.825（0.265-2.566）	0.739
Surgical operation (Open vs. Laparoscopic vs. Robot-assisted)	1.857（0.424-8.128）	0.411