Clear Cell Adenocarcinoma of the Urinary Tract Primary to the Renal Pelvis: A Multi-institutional Clinicopathologic and Molecular Study of Five Patients.
Journal
The American journal of surgical pathology
ISSN: 1532-0979
Titre abrégé: Am J Surg Pathol
Pays: United States
ID NLM: 7707904
Informations de publication
Date de publication:
10 Oct 2024
10 Oct 2024
Historique:
medline:
25
10
2024
pubmed:
25
10
2024
entrez:
25
10
2024
Statut:
aheadofprint
Résumé
Clear cell adenocarcinoma (CCA) of the urinary tract is a rare malignancy and tumors involving the renal pelvis are notably sparse in the literature, with only 5 other patients reported. We present 5 patients, 4 women, and 1 man, with CCA of the renal pelvis. The age at presentation ranged from 29 to 81 years. The tumor size ranged from 4.5 to 8.0 cm. Tumors exhibited shared morphologic and immunohistochemical features with CCA of the female genital tract and those originating in the bladder and urethra, including cells with large nuclei, prominent nucleoli, nuclear hobnailing, and scant clear cytoplasm. Common immunohistochemical findings included reactivity for PAX8, CK7, HNF1β, and Napsin-A. One of the tumors arose in the background of a mixed epithelial and stromal tumor. Another tumor occurred in a renal allograft and tumor cells were positive for the BK virus, demonstrated by SV40 immunohistochemistry. All tumors were negative for TFE3 and TFEB rearrangement and lacked TERT alterations. Follow-up was limited with no recurrence in 4 patients at a maximum of 20 months follow-up and 1 patient died of an unrelated cause at 25 months of follow-up. Next-generation sequencing analysis of all 5 CCAs revealed mutations within genes implicated in DNA damage repair and chromatin remodeling pathways, including ATM, BRCA1, BRCA2, ARID1A, DICER1, SMAD4, NOTCH1, and MYC amplification. These molecular findings underscore the dysregulation of fundamental cellular processes essential for genomic integrity maintenance.
Identifiants
pubmed: 39450999
doi: 10.1097/PAS.0000000000002320
pii: 00000478-990000000-00426
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.
Références
Oliva E, Amin MB, Jimenez R, et al. Clear cell carcinoma of the urinary bladder: a report and comparison of four tumors of Mullerian origin and nine of probable urothelial origin with discussion of histogenesis and diagnostic problems. Am J Surg Pathol. 2002;26:190–197.
Grosser D, Matoso A, Epstein JI. Clear cell adenocarcinoma in men: a series of 15 cases. Am J Surg Pathol. 2021;45:270–276.
Perez D, Naous R. A rare case of clear cell carcinoma, Mullerian type in the renal pelvis of a 21-year-old woman. Case Rep Pathol. 2018;2018:1521598.
Kongkarnka S, Kitirattakarn P, Katayama H, et al. Clear cell adenocarcinoma of the renal pelvis in a male patient. Case Rep Pathol. 2013;2013:494912.
Liu KW, Lin VC, Chang IW. Clear cell adenocarcinoma of the renal pelvis: an extremely rare neoplasm of the upper urinary tract. Pol J Pathol. 2013;64:308–311.
Kilic I, Acosta AM, Ulbright TM. Clear cell carcinomas of Mullerian type and rete testis origin presenting as scrotal masses: a study of seven cases. Am J Surg Pathol. 2024. Epub ahead of print.
Tong GX, Weeden EM, Hamele-Bena D, et al. Expression of PAX8 in nephrogenic adenoma and clear cell adenocarcinoma of the lower urinary tract: evidence of related histogenesis? Am J Surg Pathol. 2008;32:1380–1387.
Brimo F, Herawi M, Sharma R, et al. Hepatocyte nuclear factor-1beta expression in clear cell adenocarcinomas of the bladder and urethra: diagnostic utility and implications for histogenesis. Hum Pathol. 2011;42:1613–1619.
Lin CY, Saleem A, Stehr H, et al. Molecular profiling of clear cell adenocarcinoma of the urinary tract. Virchows Arch. 2019;475:727–734.
Ortiz-Bruchle N, Wucherpfennig S, Rose M, et al. Molecular characterization of Muellerian tumors of the urinary tract. Genes (Basel). 2021;12:880.
Argani P, Reuter VE, Zhang L, et al. TFEB-amplified renal cell carcinomas: an aggressive molecular subset demonstrating variable melanocytic marker expression and morphologic heterogeneity. Am J Surg Pathol. 2016;40:1484–1495.
Matoso A, Zhou Z, Hayama R, et al. Cell lineage-specific interactions between Men1 and Rb in neuroendocrine neoplasia. Carcinogenesis. 2008;29:620–628.
Humphrey PA, Moch H, Cubilla AL, et al. The 2016 WHO classification of tumours of the urinary system and male genital organs-part B: prostate and bladder tumours. Eur Urol. 2016;70:106–119.
Iorgulescu JB, Shaw LK, Rashid A, et al. Mullerian-type clear cell carcinoma of donor origin in a male patient with a kidney transplant: ascertained by molecular testing. Curr Oncol. 2023;30:9019–9027.
Shih CM, Huang CT, Chi CH, et al. CA125-producing clear cell adenocarcinoma arising from the upper ureter and renal pelvis. J Chin Med Assoc. 2010;73:40–43.
Bertz S, Ensser A, Stoehr R, et al. Variant morphology and random chromosomal integration of BK polyomavirus in posttransplant urothelial carcinomas. Mod Pathol. 2020;33:1433–1442.
Akgul M, MacLennan GT, Cheng L. The applicability and utility of immunohistochemical biomarkers in bladder pathology. Hum Pathol. 2020;98:32–55.
Kuroda N, Sakaida N, Kinoshita H, et al. Carcinosarcoma arising in mixed epithelial and stromal tumor of the kidney. APMIS. 2008;116:1013–1015.
Mudaliar KM, Mehta V, Gupta GN, et al. Expanding the morphologic spectrum of adult biphasic renal tumors—mixed epithelial and stromal tumor of the kidney with focal papillary renal cell carcinoma: case report and review of the literature. Int J Surg Pathol. 2014;22:266–271.
Jung SJ, Shen SS, Tran T, et al. Mixed epithelial and stromal tumor of kidney with malignant transformation: report of two cases and review of literature. Hum Pathol. 2008;39:463–468.
Arriola AGP, Taylor BL, Ma S, et al. Malignant mixed epithelial and stromal tumor of the kidney with 2 simultaneous renal carcinomas in a male patient: case report and review of the literature. Int J Surg Pathol. 2018;26:56–63.
Odetola OE, Isaila B, Pambuccian SE, et al. Unusual BK polyomavirus-associated urologic malignancies in renal transplant recipients: Report of two cases and review of the literature. Diagn Cytopathol. 2018;46:1050–1059.
Sirohi D, Vaske C, Sanborn Z, et al. Polyoma virus-associated carcinomas of the urologic tract: a clinicopathologic and molecular study. Mod Pathol. 2018;31:1429–1441.
Dao M, Pecriaux A, Bessede T, et al. BK virus-associated collecting duct carcinoma of the renal allograft in a kidney-pancreas allograft recipient. Oncotarget. 2018;9:15157–15163.
Alexiev BA, Randhawa P, Vazquez Martul E, et al. BK virus-associated urinary bladder carcinoma in transplant recipients: report of 2 cases, review of the literature, and proposed pathogenetic model. Hum Pathol. 2013;44:908–917.
Fernandez Rivera C, Alonso Hernandez A, Mosquera Reboredo J, et al. Association of bladder adenocarcinoma and BK virus infection in a pancreatico-renal transplant recipient. NDT Plus. 2010;3:300–302.
Mehra R, Vats P, Kalyana-Sundaram S, et al. Primary urethral clear-cell adenocarcinoma: comprehensive analysis by surgical pathology, cytopathology, and next-generation sequencing. Am J Pathol. 2014;184:584–591.
Choi M, Kipps T, Kurzrock R. ATM mutations in cancer: therapeutic implications. Mol Cancer Ther. 2016;15:1781–1791.
Van Raamsdonk CD, Bezrookove V, Green G, et al. Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi. Nature. 2009;457:599–602.
Dhanasekaran R, Deutzmann A, Mahauad-Fernandez WD, et al. The MYC oncogene - the grand orchestrator of cancer growth and immune evasion. Nat Rev Clin Oncol. 2022;19:23–36.
Carvalho MA, Marsillac SM, Karchin R, et al. Determination of cancer risk associated with germ line BRCA1 missense variants by functional analysis. Cancer Res. 2007;67:1494–1501.
Fleming NI, Jorissen RN, Mouradov D, et al. SMAD2, SMAD3 and SMAD4 mutations in colorectal cancer. Cancer Res. 2013;73:725–735.
Zhang Y, Musci T, Derynck R. The tumor suppressor Smad4/DPC 4 as a central mediator of Smad function. Curr Biol. 1997;7:270–276.
Wu JN, Roberts CW. ARID1A mutations in cancer: another epigenetic tumor suppressor? Cancer Discov. 2013;3:35–43.
Giannakis M, Mu XJ, Shukla SA, et al. Genomic correlates of immune-cell infiltrates in colorectal carcinoma. Cell Rep. 2016;15:857–865.
Joshi A, Mishra R, Desai S, et al. Molecular characterization of lung squamous cell carcinoma tumors reveals therapeutically relevant alterations. Oncotarget. 2021;12:578–588.