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. 2026 Mar 11.
doi: 10.1097/PAS.0000000000002538. Online ahead of print.

Urinary Bladder Leiomyomas: A Clinicopathological Series With Hormone Receptor, HMGA2, 2SC, and Fumarate Hydratase Status Assessment

Raul E Perret  1   2 , Melissa Hruby  3 , Carina A Dehner  3 , Stephanie E Siegmund  4 , Valérie Velasco  1 , Mokrane Yacoub  2 , Gregoire Robert  5 , Jennifer B Gordetsky  6 , Adeboye O Osunkoya  7 , Muhammad T Idrees  3 , Andres M Acosta  3
Affiliations

Urinary Bladder Leiomyomas: A Clinicopathological Series With Hormone Receptor, HMGA2, 2SC, and Fumarate Hydratase Status Assessment

Raul E Perret et al. Am J Surg Pathol. .

Abstract

Leiomyomas (LMs) represent the most frequent mesenchymal tumors of the urinary bladder. Despite their relative frequency, large clinicopathological studies are scarce, and their pathogenesis remains poorly understood. In this study, we performed a clinicopathological analysis of 35 bladder LMs and explored whether they share pathogenic mechanisms previously documented in uterine LMs. The tumors occurred in 18 women and 17 men, with a median age of 55 years (range: 20 to 78 y). Clinical data were available for 30 cases (85%). Most tumors were incidentally discovered (16/30, 53%), while the remaining patients presented predominantly with lower urinary tract symptoms. Ten patients had a prior history of cancer, and 3 women had a history of uterine LM. Tumor size, available in 12 cases, ranged from 6 to 66 mm (mean, 31 mm). Histologically, most tumors showed a uniform morphology, consisting of well-circumscribed nodules composed of bland smooth muscle cells without mitotic activity. Rare findings included extensive necrosis (3/35, 8%) and a pseudohyperplastic appearance (1/20, 5%). On immunohistochemistry, a subset of tumors, predominantly in females, expressed estrogen receptors (7/28, 25%), progesterone receptors (5/24, 21%), and androgen receptors (10/23, 43%). HMGA2 expression was observed in one case (1/27, 4%). Fumarate hydratase (FH) expression was retained in all tested tumors (n=31); 2SC expression was detected in 4 tumors (4/32; 12%), all with preserved FH and lacking distinctive histomorphological features of FH-deficient LMs. DNA sequencing of 2SC-positive tumors identified a pathogenic FH variant in one of the 4 analyzed cases at a low variant allele frequency. No other known pathogenic variants, including MED12 commonly seen in uterine LMs, were detected. Altogether, this study characterizes the clinicopathological features of large cohort of bladder LMs, highlighting unrecognized morphologic features, including cases with massive necrosis. Our findings suggest that bladder LMs differ pathogenetically from their uterine counterparts, with a more limited role for hormone receptor signaling and distinct genetic alterations.

Keywords: 2SC; HMGA2; bladder; fumarate hydratase; hormone receptors; leiomyoma.

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Conflict of interest statement

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.

References

    1. Mäkinen N, Kämpjärvi K, Frizzell N, et al. Characterization of MED12, HMGA2, and FH alterations reveals molecular variability in uterine smooth muscle tumors. Mol Cancer. 2017;16:101.
    1. Munro MG, Tchaikovski SN, Murji A. The epidemiology and pathogenesis of uterine fibroids. Int J Gynaecol Obstet. 2025;171:1029–1045.
    1. Ploumaki I, Macri VI, Segars JH, et al. Progesterone signaling in uterine fibroids: molecular mechanisms and therapeutic opportunities. Life Sci. 2025;362:123345.
    1. McHenry A, Monsrud A, Pors J, et al. Prospective fumarate hydratase tumor predisposition syndrome screening in patients with uterine smooth muscle tumors: age, morphology, fumarate hydratase/S-(2-succino) cysteine immunohistochemistry, and germline testing. Am J Surg Pathol. 2025;49:315–327.
    1. Chen YB, Brannon AR, Toubaji A, et al. Hereditary leiomyomatosis and renal cell carcinoma syndrome–associated renal cancer: recognition of the syndrome by pathologic features and the utility of detecting aberrant succination by immunohistochemistry. Am J Surg Pathol. 2014;38:627–637.