Microscopic description:

IHC: Stained positive for vimentin, CAIX, CK7 (focal), CD10, desman (highlights muscle in stroma). Negative AMACR

Molecular testing:
  • FISH study performed, showed no loss of Chr 3p which confirms that this is not clear cell subtype.

Based on histopathological features, IHC stains, and molecular genetics results, this tumor shows features consistent with renal cell carcinoma with leiomyomatous stroma.

Discussion:

Renal cell carcinoma accounts for appx 3% of cancer cases in adults, and 90-95% of kidney neoplasms. It is also more common in males than females (2:1), and rare in children.

Clear cell renal cell carcinomas accounts for 65-75% of all malignant renal tumors.

Renal cell carcinoma with leiomyomatous stroma is a rare entity that is thought to be distinct from clear cell renal carcinoma, though research is still ongoing. So far, no gender predominance has been found, and the right kidney is affected as commonly as left.

Renal cell carcinomas with leiomyomatous stroma are well circumscribed tumors. The cut surface is typically gray-white fibrotic tissues, composed of small nests and nodules of renal epithelial cells with clear cytoplasms. Carcinoma cells are embedded in a cellular stroma composed of intertwining bundles of smooth muscle.

Leiomyomatous stromal component is proposed to be polyclonal and therefore reactive, rather than neoplastic. It is hypothesized to be derived from smooth muscle cells of large caliber veins located at the peripheral capsular region or within the collagenous septae of the tumors.

IHC typically positive for CK7 and CD10, as well as CAIX, pankeratin, vimentin, and HIF1-alpha

Prognosis is generally good, with low rate of tumor recurrence

Differential diagnostic from renal clear cell carcinoma include FISH , gene sequencing and methylation-specific multiplex ligation-dependent probe amplification analysis; where renal clear cell carcinoma will show deletion of chromosome 3p, VHL mutation, and VHL methylation abnormalities

Additional differential diagnostic methods may include genetic testing, as renal cell carcinomas with leiomyomatous stroma have shown recurrent mutations of TSC1/TSC2, MTOR, and/or ELOC, consistent with hyperactive MTOR complex.

References:

Yeh YA, Constantinescu M, Chaudoir C, Tanner A, Serkin F, Yu X, Fazili T, Lurie AA. Renal cell carcinoma with leiomyomatous stroma: a review of an emerging entity distinct from clear cell conventional renal cell carcinoma. Am J Clin Exp Urol. 2019 Oct 15;7(5):321-326. PMID: 31763363; PMCID: PMC6872474.

Kiremit MC, Acar Ö, Sağlıcan Y, Esen T. Bilateral renal cell carcinoma with leiomyomatous stroma: A rare entity diagnosed synchronously and treated surgically in a staged fashion. Turk J Urol. 2017 Dec;43(4):566-570. doi: 10.5152/tud.2017.68639. Epub 2017 Dec 1. PMID: 29201528; PMCID: PMC5687228.

Shah RB, Stohr BA, Tu ZJ, Gao Y, Przybycin CG, Nguyen J, Cox RM, Rashid-Kolvear F, Weindel MD, Farkas DH, Trpkov K, McKenney JK. "Renal Cell Carcinoma With Leiomyomatous Stroma" Harbor Somatic Mutations of TSC1, TSC2, MTOR, and/or ELOC (TCEB1): Clinicopathologic and Molecular Characterization of 18 Sporadic Tumors Supports a Distinct Entity. Am J Surg Pathol. 2020 May;44(5):571-581. doi: 10.1097/PAS.0000000000001422. PMID: 31850909.

Petersson, F., Branzovsky, J., Martinek, P. et al. The leiomyomatous stroma in renal cell carcinomas is polyclonal and not part of the neoplastic process. Virchows Arch 465, 89–96 (2014). https://doi.org/10.1007/s00428-014-1591-9

Martignoni, G., Brunelli, M., Segala, D. et al. Renal cell carcinoma with smooth muscle stroma lacks chromosome 3p and VHL alterations. Mod Pathol 27, 765–774 (2014). https://doi.org/10.1038/modpathol.2013.180

Michalova, Kvetoslava & Grossmann, Petr & Bulimbasic, Stela & Maris, Sperga & Montiel, Delia & Daum, Ondrej & Rotterova, Pavla & Kokoskova, Bohuslava & Vesela, Pavla & Pivovarcikova, Kristyna & Bauleth, Kevin & Branzovsky, Jindrich & Dubova, Magdalena & Hora, Milan & Hes, Ondrej. (2014). Renal cell carcinoma with leiomyomatous stroma - Further immunohistochemical and molecular genetic characteristics of unusual entity. Annals of diagnostic pathology. 18. 10.1016/j.anndiagpath.2014.08.004.

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