Renal tumors are one of the most diverse groups of tumors in pathology. Many emerging and important entities have been described recently. Here, we describe a series of renal tumors occurring in adult patients, with distinct histologic features, and with a striking resemblance to gonadal sex cord-stromal tumors. Patients were three males and three females aged 39-82 years; tumor size ranged from 0.9 to 3.6 cm. Five tumors were organ-confined, while one case had a focal perinephric invasion. No aggressive behavior was noted. Microscopically, all the tumors were composed of loose or compact tubular structures with elongated or angulated shapes. The tumor cells were cylindrical or cuboidal, with pale eosinophilic cytoplasm, irregular nuclear membranes, and ISUP/WHO grade 2-3 nuclei. The stroma showed focal or prominent collagen deposition with prominent basement membrane-like material. In all cases, the tumor cells were positive for PAX8, CD10, and vimentin and retained positivity for FH and SDHB. Cathepsin K and AMACR were variably positive. Tumors were negative for HMB45, Melan A, TFE3, SF1, inhibin, calretinin, ER, PR, CD117, OCT3/4, SALL4, ALK, and WT1. Molecular studies showed no abnormalities in TFEB, TFE3, or FH genes. In 3/4 tested cases, mutation of the NF2 gene was present. In all the tested male cases, loss of the Y chromosome was found. In the relatively short follow-up, these tumors appear to have indolent behavior. This study expands the clinicopathologic diversity of renal cell tumors by describing a series of potentially novel tumors morphologically resembling gonadal sex-stromal tumors, with negativity for sex cord-stromal markers. Potential relationship to recently described biphasic hyalinizing psammomatous renal cell carcinoma is discussed.

Department of Pathology BC Cancer Vancouver University of British Columbia Vancouver Canada

Department of Pathology Charles University Medical Faculty and Charles University Hospital Plzen Alej Svobody 80 304 60 Pilsen Czech Republic

Department of Pathology Cruces University Hospital Biocruces Bizkaia Institute University of the Basque Country Leioa Spain

Department of Pathology University of Erlangen Nürnberg Erlangen Germany

University of Tennessee Health Science Center Memphis TN USA

See more in PubMed

Moch H, Humphrey P, Ulbright T, et al (2016) editors WHO Classification Tumours of the Urinary System and Male Genital Organs. 4th ed

Trpkov K, Abou-Ouf H, Hes O et al (2017) Eosinophilic solid and cystic renal cell carcinoma (ESC RCC): further morphologic and molecular characterization of ESC RCC as a distinct entity. Am J Surg Pathol 41(10):1299–1308 DOI

Trpkov K, Athanazio D, Magi-Galluzzi C et al (2018) Biphasic papillary renal cell carcinoma is a rare morphological variant with frequent multifocality: a study of 28 cases. Histopathology 72(5):777–785 DOI

Trpkov K, Williamson SR, Gao Y et al (2019) Low-grade oncocytic tumour of kidney (CD117-negative, cytokeratin 7-positive): a distinct entity? Histopathology 75(2):174–184 DOI

He H, Trpkov K, Martinek P et al (2018) “High-grade oncocytic renal tumor”: morphologic, immunohistochemical, and molecular genetic study of 14 cases. Virchows Arch 473(6):725–738 DOI

Trpkov K, Williamson SR, Gill AJ et al (2021) Novel, emerging and provisional renal entities: the Genitourinary Pathology Society (GUPS) update on renal neoplasia. Mod Pathol 34(6):1167–1184 DOI

Chen YB, Mirsadraei L, Jayakumaran G et al (2019) Somatic mutations of TSC2 or MTOR characterize a morphologically distinct subset of sporadic renal cell carcinoma with eosinophilic and vacuolated cytoplasm. Am J Surg Pathol 43(1):121–131 DOI

Argani P, Reuter VE, Eble JN, et al (2020) Biphasic hyalinizing psammomatous renal cell carcinoma (BHP RCC): a distinctive neoplasm associated with somatic NF2 mutations. Am J Surg Pathol 44(7):901–916

Yakirevich E, Pavlick DC, Perrino CM et al (2021) NF2 tumor suppressor gene inactivation in advanced papillary renal cell carcinoma. Am J Surg Pathol 45(5):716–718 DOI

Rogala J, Kojima F, Alaghehbandan R et al (2020) Papillary renal cell carcinoma with prominent spindle cell stroma - tumor mimicking mixed epithelial and stromal tumor of the kidney: clinicopathologic, morphologic, immunohistochemical and molecular genetic analysis of 6 cases. Ann Diagn Pathol 44:151441 DOI

Chen YB, Xu J, Skanderup AJ et al (2016) Molecular analysis of aggressive renal cell carcinoma with unclassified histology reveals distinct subsets. Nat Commun 7:13131 DOI

Sourbier C, Liao PJ, Ricketts CJ et al (2018) Targeting loss of the Hippo signaling pathway in NF2-deficient papillary kidney cancers. Oncotarget 9(12):10723–10733 DOI

Mehra R, Vats P, Cieslik M et al (2016) Biallelic alteration and dysregulation of the Hippo pathway in mucinous tubular and spindle cell carcinoma of the kidney. Cancer Discov 6(11):1258–1266 DOI

Wang J, Papanicolau-Sengos A, Chintala S et al (2016) Collecting duct carcinoma of the kidney is associated with CDKN2A deletion and SLC family gene up-regulation. Oncotarget 7(21):29901–29915 DOI

Yoo NJ, Park SW, Lee SH (2012) Mutational analysis of tumour suppressor gene NF2 in common solid cancers and acute leukaemias. Pathology 44(1):29–32 DOI

Jiang F, Richter J, Schraml P et al (1998) Chromosomal imbalances in papillary renal cell carcinoma: genetic differences between histological subtypes. Am J Pathol 153(5):1467–1473 DOI

Kovacs G, Fuzesi L, Emanual A et al (1991) Cytogenetics of papillary renal cell tumors. Genes Chromosomes Cancer 3(4):249–255 DOI

Scarcella S, Dell’Atti L, Galosi AB (2018) Renal germ cell metastatic tumour with rupture, bleeding and syncope: an unusual clinical presentation in a young patient. BMJ Case Rep. 2018

Kinney SN, Eble JN, Hes O et al (2015) Metanephric adenoma: the utility of immunohistochemical and cytogenetic analyses in differential diagnosis, including solid variant papillary renal cell carcinoma and epithelial-predominant nephroblastoma. Mod Pathol 28(9):1236–1248 DOI

Md Zin R, Murch A, Charles A (2011) Pathology, genetics and cytogenetics of Wilms’ tumour. Pathology 43(4):302–312 DOI

Vujanic GM, Sandstedt B (2010) The pathology of Wilms’ tumour (nephroblastoma): the International Society of Paediatric Oncology approach. J Clin Pathol 63(2):102–109 DOI