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北京大学学报（医学版） ›› 2026, Vol. 58 ›› Issue (4): 700-706. doi: 10.19723/j.issn.1671-167X.2026.04.004

• 论著 • 上一篇    下一篇

获得性囊性肾病及相关肾细胞癌的临床病理和分子特征

刘海静1,2, 郭文阳2, 史姝男2, 贺慧颖1,2,*()   

  1. 1. 北京大学基础医学院病理学系，北京 100191
    2. 北京大学第三医院病理科，北京 100191
  • 收稿日期:2026-03-02 出版日期:2026-08-18 发布日期:2026-05-18
  • 通讯作者: 贺慧颖
  • 基金资助:
    国家重点研发计划(2024YFA1014101)

Clinicopathological and molecular features of acquired cystic kidney disease and associated renal cell carcinoma

Haijing LIU1,2, Wenyang GUO2, Shunan SHI2, Huiying HE1,2,*()   

  1. 1. Department of Pathology, Peking University School of Basic Medical Sciences, Beijing 100191, China
    2. Department of Pathology, Peking University Third Hospital, Beijing 100191, China
  • Received:2026-03-02 Online:2026-08-18 Published:2026-05-18
  • Contact: Huiying HE
  • Supported by:
    the National Key Research and Development Program of China(2024YFA1014101)

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摘要：

目的: 探讨长期接受透析治疗的终末期肾病(end-stage renal disease，ESRD)患者发生获得性囊性肾病(acquired cystic kidney disease，ACKD)及继发肾细胞癌(renal cell carcinoma，RCC)的临床病理和分子遗传学特征。方法: 回顾性分析北京大学第三医院病理科2020—2025年收集的9例ACKD患者的临床病理资料，其中7例伴RCC，用免疫组织化学和高通量测序(next-generation sequencing，NGS)方法分别检测RCC常见蛋白及已获批或临床研究阶段靶向药物的标志物相关基因的变异情况和微卫星不稳定性(microsatellite instability，MSI)，总结患者的临床病理和分子遗传学特征。结果: 9例患者均为男性，年龄29~64岁，发生ESRD的病因包括高血压、IgA肾病、慢性肾小球肾炎和糖尿病等，透析时间为1~30年(中位9.0年)，其中3例有肾移植病史。影像学检查均可见肾脏体积缩小伴多发囊肿，部分为复杂囊肿，7例RCC中的5例患者局部囊壁可见实性占位，1例肾移植后的患者超声检查发现原肾脏实性占位，结节最大径为1.3~7.0 cm(中位3.0 cm)。组织病理学检查可见ACKD的典型形态学改变，并可见非典型肾囊肿、乳头状腺瘤及出血，6例伴ACKD相关性RCC(ACKD-associated RCC，ACKD-RCC)，1例伴乳头状RCC(papillary RCC，pRCC)。ACKD-RCC肿瘤细胞的胞质多呈嗜酸性，5例以乳头状结构为主，1例以筛囊状结构为主伴有腺泡样/实性/微乳头结构，肿瘤内均可见草酸盐结晶，多数伴坏死及钙化。免疫组织化学检测P504S/CK7阳性，CD10小灶状阳性，CAⅨ阴性。ACKD-RCC肿瘤细胞的世界卫生组织/国际泌尿病理学会(World Health Organization/International Society of Urological Pathology, WHO/ISUP)核分级为2~3级；ACKD伴pRCC为小灶状呈肉瘤样分化，WHO/ISUP核分级为3~4级。5例RCC患者的病理分期为pT1，2例为pT3a。NGS检测发现，1例ACKD-RCC患者检出PIK3CA点突变，pRCC患者检出SETD2缺失突变，这两例患者均有显著凝固性坏死且分期为pT3a。7例伴RCC的患者术后规律随访1~32个月，未进行其他治疗，未见复发和转移。结论: ACKD是进行透析治疗的ESRD患者常见的并发症，本组病例中，ACKD-RCC的病理形态学以乳头状结构为主，均可见草酸盐结晶，P504S及CK7阳性。本组的ACKD不论是否继发肿瘤均可见非典型肾囊肿，2例RCC患者NGS分别检出PIK3CA和SETD2变异(Tier Ⅱ级变异)，伴凝固性坏死且病理分期晚，可能提示预后差。对于长期透析的中青年男性ESRD患者应加强肾癌的影像学筛查，应充分取材以发现非典型肾囊肿等可能潜在的癌前病变，ACKD-RCC的预后需要结合临床、病理和分子遗传学特征综合分析。

关键词: 终末期肾病, 肾疾病, 囊性, 肾细胞癌, 临床病理学

Abstract:

Objective: To investigate the clinicopathological and genetic features of acquired cystic kidney disease (ACKD) and secondary renal cell carcinoma (RCC) in end-stage renal disease (ESRD) patients undergoing dialysis. Methods: The clinicopathological data of 9 patients with ACKD, of whom, 7 had concurrent RCC, of the Department of Pathology, Peking University Third Hospital from 2020 to 2025 were retrospectively analyzed. Immunohistochemistry (IHC) and next-generation sequencing (NGS) were used to detect RCC-related proteins and targeted-drug associated gene variations/microsatellite instability (MSI) status. Results: The 9 patients were all male, aged 29-64 years. Causes of ESRD included hypertension, IgA nephropathy, chronic glomerulonephritis, and diabetes. Dialysis duration ranged from 1 to 30 years (median 9.0 years), and 3 patients had kidney transplantation history. Imaging showed reduced kidney size and multiple cysts, including complex cysts. Solid lesions were found in the cyst wall of 5 patients with secondary RCC. The maximum diameter of tumors was 1.3-7.0 cm (median 3.0 cm). Histologically, except for typical morphological changes of ACKD and atypical renal cysts, some cases had papillary adenoma and hemorrhage. Six ACKD-associated RCC (ACKD-RCC) patients and 1 papillary RCC (pRCC) patient were diagnosed. Most ACKD-RCC tumor cells had eosinophilic cytoplasm; 5 patients predominantly showed papillary structure, and 1 patient mainly presented sieve-cystic with acinar/solid/micropapillary structures. Oxalate crystals were found in all ACKD-RCC cases, and most patients were accompanied by necrosis and calcification. P504S and CK7 were diffusely or focally positive in all the cases, while CAⅨ was negative. The World Health Organization/International Society of Urological Pathology (WHO/ISUP) nuclear grading of ACKD-RCC and pRCC were 2-3 and 3-4, respectively. Pathological staging of 5 RCC patients was pT1 and of the other 2 patients was pT3a. NGS results identified one PIK3CA point mutation and SETD2 deletion in one ACKD-RCC patient and the pRCC patient, which were accompanied by marked necrosis and pT3a staging. The RCC patients were regularly followed up for 1-32 months postoperatively without additional treatment, and no recurrence or metastasis was observed. Conclusion: ACKD is a common complication in ESRD patients undergoing dialysis. In our cohort, ACKD-RCC was predominantly characterized by papillary architecture histologically with oxalate crystals in all cases. Immunohistochemically, P504S and CK7 were positive. Regardless of secondary occurrent tumor, atypical renal cysts were present in all ACKD cases in this study. NGS detected PIK3CA and SETD2 (Tier Ⅱ) variants in 2 RCC patients, respectively, accompanied by coagulative necrosis and advanced pathological stage, which may indicate a poor prognosis. This study suggests that imaging screening for RCC should be strengthened in young and middle-aged male ESRD patients with long-term dialysis, and adequate sample examination should be performed to detect potentially precancerous lesions, such as atypical renal cysts. The prognosis of ACKD-RCC requires comprehensive analysis combining clinicopathological and molecular genetic features.

Key words: End-stage renal disease, Kidney diseases, cystic, Renal cell carcinoma, Clinical pathology

中图分类号: 

  • R737.11

表1

9例获得性囊性肾病及相关RCC临床特征"

Case Gender Age/years Etiologies of CKD Dialysis time/years Location Imaging Treatment Follow-up/months
1 Male 29 Hypertension 4 Left Multiple bilateral renal cysts with calcification, complex cyst of left kidney LRN 33
2 Male 34 GN 10 Bilateral Multiple bilateral renal cysts with hemorrhage LRN 30
3 Male 64 Hypertension 30 Left Multiple bilateral renal cysts, complex cyst with solid nodule of left kidney LRN 24
4 Male 46 IgAN 7 Right Multiple bilateral renal cysts with solid nodule of right kidney LRN+RPLND 11
5 Male 39 DKD 5.5 Left Multiple bilateral renal cysts, complex cyst with solid nodule of left kidney LRN 7
6 Male 45 GN 10 Left Multiple bilateral renal cysts with hemorrhage and solid nodule of left kidney LRN 1
7 Male 60 Hypertension 9 Left Multiple bilateral renal cysts, complex cyst with solid nodule of left kidney LRN+RPLND 2
8 Male 51 IgAN 1 Bilateral Multiple bilateral renal cysts LRN 31
9 Male 54 NA 10 Left Multiple bilateral renal cysts with hematoma of left kidney LRN 36

图1

ACKD及相关RCC的组织病理学和IHC特点"

表2

9例获得性囊性肾病及相关RCC的病理特征"

Case Number of tumors Diameter/cm Histology WHO/ISUP grading Necrosis Oxalate crystals Calcification pT stage Concurrent lesions
1 1 3 ACKD-RCC 2-3 Yes Yes No T1 Atypical renal cysts
2 2 2.5, 1.3* ACKD-RCC 2-3 Yes Yes Yes, No T1 Atypical renal cysts and papillary adenoma
3 7 3.5# ACKD-RCC 3 Yes Yes Yes T1 Atypical renal cysts
4 1 2.4 ACKD-RCC 3 No Yes Yes T1 Atypical renal cysts
5 1 3.8 ACKD-RCC 3 Yes Yes Yes T1 Atypical renal cysts
6 1 7 ACKD-RCC Yes Yes Yes T3a Atypical renal cysts
7 1 3 ACKD, pRCC 3-4 Yes No Yes T3a Atypical renal cysts
8 ACKD No No Yes Atypical renal cysts and papillary adenoma
9 ACKD No No No Atypical renal cysts
1
Stewart JH , Buccianti G , Agodoa L , et al. Cancers of the kidney and urinary tract in patients on dialysis for end-stage renal disease: Analysis of data from the United States, Europe, and Australia and New Zealand[J]. J Am Soc Nephrol, 2003, 14 (1): 197- 207.

doi: 10.1097/01.ASN.0000039608.81046.81
2
Tickoo SK , de Peralta-Venturina MN , Harik LR , et al. Spectrum of epithelial neoplasms in end-stage renal disease: An experience from 66 tumor-bearing kidneys with emphasis on histologic patterns distinct from those in sporadic adult renal neoplasia[J]. Am J Surg Pathol, 2006, 30 (2): 141- 153.

doi: 10.1097/01.pas.0000185382.80844.b1
3
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.

doi: 10.1016/j.eururo.2016.02.029
4
Li MM , Datto M , Duncavage EJ , et al. Standards and guidelines for the interpretation and reporting of sequence variants in cancer a joint consensus recommendation of the association for molecular pathology, American society of clinical oncology, and college of American pathologists[J]. J Mol Diagn, 2017, 19 (1): 4- 23.

doi: 10.1016/j.jmoldx.2016.10.002
5
Pope JC , Koch MO , Bluth RE . Renal cell carcinoma in patients with end-stage renal disease: A comparison of clinical significance in patients receiving hemodialysis and those with renal transplants[J]. Urology, 1994, 44 (4): 497- 501.

doi: 10.1016/S0090-4295(94)80046-4
6
Duong NX , Le MK , Nguyen TT , et al. Acquired cystic disease-associated renal cell carcinoma: A systematic review and meta-analysis[J]. Clin Genitourin Cancer, 2024, 22 (3): 102050.

doi: 10.1016/j.clgc.2024.02.001
7
Kojima F , Gandhi JS , Matsuzaki I , et al. Comprehensive clinicopathologic analyses of acquired cystic disease-associated renal cell carcinoma with focus on adverse prognostic factors and metastatic lesions[J]. Am J Surg Pathol, 2020, 44 (8): 1031- 1039.

doi: 10.1097/PAS.0000000000001482
8
Palathingal Bava E , Sanfrancesco JM , Alkashash A , et al. Acquired cystic disease associated renal cell carcinoma: A clinicopathologic and molecular study of 31 tumors[J]. Hum Pathol, 2024, 149, 48- 54.

doi: 10.1016/j.humpath.2024.06.002
9
Shah A , Lal P , Toorens E , et al. Acquired cystic kidney disease-associated renal cell carcinoma (ACKD-RCC) harbor recurrent mutations in KMT2C and TSC2 genes[J]. Am J Surg Pathol, 2020, 44 (11): 1479- 1486.

doi: 10.1097/PAS.0000000000001530
10
Przybycin CG , Harper HL , Reynolds JP , et al. Acquired cystic disease-associated renal cell carcinoma (ACD-RCC): A multi-institutional study of 40 cases with clinical follow-up[J]. Am J Surg Pathol, 2018, 42 (9): 1156- 1165.

doi: 10.1097/PAS.0000000000001091
11
Chen YB , Tickoo SK . Spectrum of preneoplastic and neoplastic cystic lesions of the kidney[J]. Arch Pathol Lab Med, 2012, 136 (4): 400- 409.

doi: 10.5858/arpa.2011-0485-RA
12
Matoso A , Chen YB , Rao V , et al. Atypical renal cysts: A morphologic, immunohistochemical, and molecular study[J]. Am J Surg Pathol, 2016, 40 (2): 202- 211.

doi: 10.1097/PAS.0000000000000557
13
Sun Y , Argani P , Tickoo SK , et al. Acquired cystic disease-associated renal cell carcinoma (ACKD-RCC)-like cysts[J]. Am J Surg Pathol, 2018, 42 (10): 1396- 1401.

doi: 10.1097/PAS.0000000000001124
14
Zhou L , Xu H , Liu Y , et al. Acquired cystic disease-associated renal cell carcinoma with PTCH1 mutation: A case report[J]. Front Oncol, 2024, 14, 1349610.

doi: 10.3389/fonc.2024.1349610
15
Kim SH , Park WS , Chung J . SETD2, GIGYF2, FGFR3, BCR, KMT2C, and TSC2 as candidate genes for differentiating multilo-cular cystic renal neoplasm of low malignant potential from clear cell renal cell carcinoma with cystic change[J]. Investig Clin Urol, 2019, 60 (3): 148- 155.

doi: 10.4111/icu.2019.60.3.148
16
Ricketts CJ , De Cubas AA , Fan H , et al. The cancer genome atlas comprehensive molecular characterization of renal cell carcinoma[J]. Cell Rep, 2018, 23 (1): 313- 326. e5.

doi: 10.1016/j.celrep.2018.03.075
17
Vanhaesebroeck B , Stephens L , Hawkins P . PI3K signalling: The path to discovery and understanding[J]. Nat Rev Mol Cell Biol, 2012, 13 (3): 195- 203.

doi: 10.1038/nrm3290
18
Lin PH , Huang CY , Yu KJ , et al. Genomic characterization of clear cell renal cell carcinoma using targeted gene sequencing[J]. Oncol Lett, 2021, 21 (2): 169.

doi: 10.3892/ol.2021.12430
19
Wang XM , Lu Y , Song YM , et al. Integrative genomic study of Chinese clear cell renal cell carcinoma reveals features associated with thrombus[J]. Nat Commun, 2020, 11 (1): 739.

doi: 10.1038/s41467-020-14601-9
20
Amori M , Amori G , Takaoka EI , et al. Multiple distinct renal cell carcinomas in a patient with acquired cystic kidney disease: A case report and literature review[J]. Int J Surg Pathol, 2026, 34 (4): 962- 969.

doi: 10.1177/10668969251398811
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ISSN 1671-167X
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