小肾细胞癌的临床与病理特征分析

doi:10.19723/j.issn.1671-167X.2019.04.004

摘要/Abstract

摘要：

目的:分析肿瘤最大径≤4 cm的小肾细胞癌患者的临床与病理特征,进一步了解其发生特点及影响术后复发、进展的因素。方法:采用分层抽样法选择肾细胞癌患者200例进行回顾性分析,收集患者的一般状况、肿瘤特征、肾细胞癌病灶的病理特征(含镜下特征)。按肾肿瘤病灶最大径将患者分组,使用单因素分析比较各组间患者肿瘤分期、分级与镜下病理特征间的差异,采用二元多因素Logistic回归方法分析小肾细胞癌患者肿瘤进展及与预后相关的因素。结果:200例肾细胞癌患者中127例患者的肿瘤最大径≤4 cm,病理亚型以肾透明细胞癌为主。随着肿瘤最大径增加,患者出现更高的T分期(P<0.01)、更高的WHO/国际泌尿病理学会(International Society of Urological Pathology,ISUP)分级(P<0.05), 淋巴结转移概率显著升高(P<0.01)。肿瘤最大径≤4 cm时,患者也可出现肿瘤侵犯肾周脂肪、肾窦,肿瘤分级升高(≥3级)及同时性肺转移。肿瘤最大径>4 cm且≤7 cm的肾细胞癌患者出现脉管内癌栓(9.3% vs. 0)、肿瘤坏死(27.8% vs. 5.5%)的比例显著高于肿瘤最大径≤4 cm的患者(P<0.01)。以肿瘤最大径2 cm作为分界点对小肾细胞癌患者行亚组分析,最大径>2 cm且≤4 cm的肿瘤与最大径≤2 cm的肿瘤相比,出现肿瘤内出血(44.7% vs. 23%,P<0.05)、坏死(8.2% vs. 0,P=0.095)的患者更多。Logistic回归分析提示,透明细胞癌出现肿瘤侵犯肾被膜的概率高于其他亚型小肾细胞癌(OR=5.15,95%CI:1.36~19.52), 肿瘤内部坏死的小肾细胞癌周围更有可能出现假包膜(OR=14.90,95%CI:1.41~157.50),肿瘤最大径增加会使出现高级别(≥3级)肾细胞癌的概率增加(OR=3.49,95%CI:1.11~10.93)。结论:小肾细胞癌(≤4 cm)整体病理分期、分级较低,但可能出现肾外侵犯及同时性远处转移(synchronous metastasis)现象。肿瘤内部出血、坏死,组织学亚型为透明细胞癌的肿瘤可能影响肿瘤侵犯肾被膜、肿瘤周围出现假包膜等病理特征的发生概率,可以作为进一步区分小肾细胞癌肿瘤学行为、评估预后的因素。

关键词: 肾细胞癌, 肿瘤分期与分级, 病理特征, 临床特征

Abstract:

Objective: To analyze the clinical and pathological features of small renal cell carcinoma (RCC), especially of those with diameter less than 4 cm and to understand the characteristics and factors related to recurrence and progression.Methods: A total of 200 patients with RCC were stratifiedly selected for retrospective analysis. Their baseline demographic features, tumor-specific clinical features, pathological features of renal lesions, especially microscopic features were collected. The patients were divided according to the largest diameter of renal tumor lesions. Univariate analysis was used to compare the differences between tumor staging and microscopic pathological features between the groups. Binary multivariate Logistic regression was used to investigate factors related to tumor progression and prognosis in the patients with small RCC.Results: The tumor diameters of 127 RCC patients were less than 4 cm and most of them had clear cell renal cell carcinoma (ccRCC). The increase in tumor diameter resulted in significantly higher T stage (P<0.01), higher WHO/International Society of Urological Pathology (ISUP) grade (P<0.05) and increasing chance of lymph node metastasis (P<0.01). Even when the tumor diameter was less than 4 cm, the patients might still have perirenal fat invasion, renal sinus invasion and greater elevated tumor grade (greater than grade 3) and synchronous lung metastasis. The incidences of intravascular thrombus (9.3% vs. 0) and tumor necrosis (27.8% vs. 5.5%) in the patients with RCC between 4-7 cm were significantly higher than those with RCC less than 4 cm (P<0.01). Sub-group analysis of small RCC (less than 4 cm) indicated that the patients with RCC between 2-4 cm were more likely to have intratumoral hemorrhage (44.7% vs. 23%, P<0.05) and necrosis than those with RCC less than 2 cm (8.2% vs. 0, P=0.095). Logistic regression analysis of small RCC showed that the incidence of tumor invasion to renal capsule was higher in ccRCC (OR=5.15, 95%CI: 1.36-19.52). Necrosis was closely related to the formation of peritumor pseudocapsule in small RCC (OR=14.90, 95%CI: 1.41-157.50). Increase in the tumor diameter was related to higher tumor grade (greater than grade 3) (OR=3.49, 95%CI: 1.11-10.93).Conclusion: The tumor stage and grade of small RCC (less than 4 cm) are low, but extra-renal invasion and synchronous distant metastasis may occur. Internal hemorrhage and necrosis in tumor, ccRCC subtype, along with microscopic features, such as the renal capsule invasion and perirenal pseudocapsule formation are relevant factors of malignant behavior of small RCC and could be considered in prognosis evaluation.

Key words: Renal cell carcinoma, Tumor stage and grade, Pathological characteristics, Clinical characteristics

中图分类号:

R737.11

张晓鹏,黄子雄,于路平,张晓威,李清,刘士军,徐涛. 小肾细胞癌的临床与病理特征分析[J]. 北京大学学报（医学版）, 2019, 51(4): 623-627.

Xiao-peng ZHANG,Zi-xiong HUANG,Lu-ping YU,Xiao-wei ZHANG,Qing LI,Shi-jun LIU,Tao XU. Clinical and pathological analysis of small renal cell carcinoma[J]. Journal of Peking University(Health Sciences), 2019, 51(4): 623-627.

图/表 4

表1

肾细胞癌患者的基线信息及临床特征"

Items	Total (n=200)	Group S1 (n=127)	Group S2 (n=54)	Group L (n=19)	P value
Male, n (%)	145 (72.5)	90 (70.9)	41 (75.9)	14 (73.7)	0.778
Age/years, $x ?$ ±s	57.91±12.09	58.52±12.03	56.61±12.71	57.53±10.81	0.338
BMI/(kg/m²), $x ?$ ±s	25.08±3.34	25.07±2.80	24.81±3.63	25.83±5.38	0.641
Operation (RN), n (%)	89 (44.5)	30 (23.6)	43 (79.6)	16 (84.2)	<0.01
Side (left), n (%)	102 (51.0)	62 (48.8)	26 (48.1)	14 (73.7)	0.038
T stage (T1+T2/T3+T4), n		124/3	45/9	8/11	<0.01
WHO/ISUP grade (G1+G2/G3+G4), n		102/7	34/14	5/9	<0.01
N1, n (%)		0 (0)	4 (7.4)	3 (15.8)	0.016
M1, n (%)		1 (0.8)	3 (5.6)	6 (31.6)	<0.01

表1

表2

表3

表4

参考文献 22

[1]	Kim SP, Thompson RH, Boorjian SA , et al. Comparative effectiveness for survival and renal function of partial and radical nephrectomy for localized renal tumors: A systematic review and meta-analysis[J]. J Urol, 2012,188(1):51-57.
[2]	Van Poppel H, Pozzo LF, Albrecht W , et al. A prospective, randomised EORTC intergroup phase 3 study comparing the oncologic outcome of elective nephron-sparing surgery and radical nephrectomy for low-stage renal cell carcinoma[J]. Eur Urol, 2007,59(4):543-552.
[3]	Long CJ, Canter D, Kutikov A , et al. Partial nephrectomy for renal masses ≥ 7 cm: technical, oncological and functional outcomes[J]. BJU Int, 2012,109(10):1450-1456.
[4]	Ljungberg B . Nephron-sparing surgery strategy: the current stan-dard for the treatment of localised renal cell carcinoma[J]. Eur Urol Suppl, 2011,10(3):e49-e51.
[5]	Thompson RH, Blute ML, Krambeck AE , et al. Patients with pT1 renal cell carcinoma who die from disease after nephrectomy may have unrecognized renal sinus fat invasion[J]. Am J Surg Pathol, 2007,31(7):1089-1093.
[6]	Feifer A, Savage C, Rayala H , et al. Prognostic impact of muscular venous branch invasion in localized renal cell carcinoma cases[J]. J Urol, 2011,185(1):37-42.
[7]	Huang Z, Du Y, Zhang X , et al. Clear cell renal cell carcinoma bone metastasis: What should be considered in prognostic evaluation[J]. Eur J Surg Oncol, 2019,45(7):1246-1252.
[8]	Forbes CM, Rendon RA, Finelli A , et al. Disease progression and kidney function after partial vs. radical nephrectomy for T1 renal cancer [J]. Urol Oncol, 2016, 34(11): 486. e17- 486. e23.
[9]	Moch H, Cubilla AL, Humphrey PA , et al. The 2016 WHO classification of tumours of the urinary system and male genital organs—Part A: renal, penile, and testicular tumours[J]. Eur Urol, 2016,70(1):93-105.
[10]	European Association of Urology. EAU guidelines [R]. EAU Annual Congress Copenhagen, 2018.
[11]	Dash A, Vickers AJ, Schachter LR , et al. Comparison of outcomes in elective partial vs radical nephrectomy for clear cell renal cell carcinoma of 4-7 cm[J]. BJU Int, 2006,97(5):939-945.
[12]	Crepel M, Jeldres C, Perrotte P , et al. Nephron-sparing surgery is equally effective to radical nephrectomy for T1BN0M0 renal cell carcinoma: A population-based assessment[J]. Urology, 2010,75(2):271-275.
[13]	Lughezzani G, Jeldres C, Isbarn H , et al. Tumor size is a determinant of the rate of stage T1 renal cell cancer synchronous metastasis[J]. J Urol, 2009,182(4):1287-1293.
[14]	Syed JS, Nawaf CB, Rosoff J , et al. Adverse pathologic characte-ristics in the small renal mass: implications for active surveillance[J]. Can J Urol, 2017,24(2):8759-8764.
[15]	Sun M, Shariat SF, Cheng C , et al. Prognostic factors and predictive models in renal cell carcinoma: A contemporary review[J]. Eur Urol, 2011,60(4):644-661.
[16]	Jeong IG, Jeong CW, Hong SK , et al. Prognostic implication of capsular invasion without perinephric fat infiltration in localized renal cell carcinoma[J]. Urology, 2006,67(4):709-712.
[17]	Pickhardt PJ, Lonergan GJ, Davis CJ Jr , et al. From the archives of the AFIP. Infiltrative renal lesions: radiologicpathologic correlation. Armed Forces Institute of Pathology[J]. Radiographics, 2000,20:215-243.
[18]	Cho S, Lee JH, Jeon SH , et al. A prospective, multicenter analysis of pseudocapsule characteristics: Do all stages of renal cell carcinoma have complete pseudocapsules?[J]. Urol Oncol, 2017,35(6):370-378.
[19]	Capitanio U, Cloutier V, Zini L , et al. A critical assessment of the prognostic value of clear cell, papillary and chromophobe histological subtypes in renal cell carcinoma: a population-based study[J]. BJU Int, 2009,103(11):1496-1500.
[20]	Keegan KA, Schupp CW, Chamie K , et al. Histopathology of surgically treated renal cell carcinoma: Survival differences by subtype and stage[J]. J Urol, 2012,188(2):391-397.
[21]	Kryvenko ON . Tumor necrosis adds prognostically significant information to grade in clear cell renal cell carcinoma: A study of 842 consecutive cases from a single institution[J]. Urol Oncol, 2017,35(6):454-455.
[22]	Collins J, Epstein JI . Prognostic significance of extensive necrosis in renal cell carcinoma[J]. Hum Pathol, 2017,66:108-114.

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Items			P value
Histology, n (%)			0.306
ccRCC	104 (81.89)	43 (79.63)
pRCC	5 (3.94)	2 (3.70)
chRCC	4 (3.15)	1 (1.85)
ccpRCC	2 (1.57)	0
Other	12 (9.45)	8 (14.81)
T stage (T1/T3+T4), n	124/3	45/9	<0.01
WHO/ISUP grade (G1+G2/G3+G4), n	102/7	34/14	<0.01
N1, n (%)	0	4 (7.4)	<0.01
M1, n (%)	1 (0.8)	3 (5.6)	0.08
Renal capsular invasion, n (%)	40 (31.5)	25 (46.3)	0.058
Peritumor pseudocapsule, n (%)	8 (5.5)	3 (5.6)	0.99
Sarcomatoid, n (%)	0	1 (1.9)	0.298
Intravascular thrombus, n (%)	0	5 (9.3)	<0.01
Hemorrhage, n (%)	48 (37.8)	18 (33.3)	0.568
Necrosis, n (%)	7 (5.5)	15 (27.8)	<0.01

Items	Total (n=127)	Tumor ≤ 2 cm (n=42)	Tumor > 2 cm (n=85)	P value
Operation (PN), n (%)		37 (88.1)	60 (70.6)	0.029
T stage (T1/T3+T4), n	124/3	41/1	83/2	>0.99
WHO/ISUP grade (G1+G2/G3+G4), n	102/7	33/1	69/6	0.431
Renal capsular invasion, n (%)	40 (31.5)	15 (35.7)	25 (29.4)	0.472
Peritumor pseudocapsule, n (%)	7 (5.5)	2 (4.8)	5 (5.9)	>0.99
Hemorrhage, n (%)	44 (34.6)	10 (23.8)	38 (44.7)	0.022
Necrosis, n (%)	7 (5.5)	0 (0)	7 (8.2)	0.095

Variable	Occurrence/Total, n (%)	OR	95%CI	P value
Renal capsular invasion
Histology (clear cell carcinoma)	37/104 (35.6)	5.15	1.36-19.52	0.02
Hemorrhage	12/48 (25.0)	0.55	0.23-1.32	0.18
Cystic degeneration	12/44 (27.3)	0.66	0.27-1.60	0.36
Necrosis	2/7 (28.6)	0.87	0.14-5.39	0.88
Size (per cm increased)		0.94	0.59-1.48	0.78
Peritumor pseudocapsule
Histology (clear cell carcinoma)	6/104 (5.8)	0.59	0.05-7.19	0.68
Hemorrhage	4/48 (8.3)	1.21	0.21-7.01	0.83
Necrosis	2/7 (28.6)	14.90	1.41-157.50	0.03
Cystic degeneration	4/44 (9.1)	0.96	0.53-29.64	0.18
Size (per cm increased)		1.08	0.14-20.90	0.88
WHO/ISUP grade 3 or 4
Hemorrhage	3/46 (6.5)	0.75	0.14-4.14	0.74
Cystic degeneration	2/44 (4.5)	0.41	0.63-2.71	0.36
Size (per cm increased)		3.49	1.11-10.93	0.03