Endometrial stromal tumors are rare lesions with a diverse morphology, which may make achieving the correct diagnosis challenging in some cases. We report a case of a uterine mesenchymal tumor diagnosed as endometrial stromal nodule with a peculiar whorled morphology and GREB1::CTNNB1 fusion confirmed by transcriptome RNA sequencing. The tumor was sharply demarcated, lacked invasive growth, and had benign behavior, as the patient remained without disease recurrence 15 years later. Immunohistochemically, the tumor cells showed diffuse nuclear expression of beta-catenin, confirming the activation of the beta-catenin pathway. Our case represents only the 4th reported case of CTNNB1-rearranged endometrial stromal tumor with extensive whorling. The biological nature of uterine tumors characterized by whorled morphology and rearrangement of CTNNB1 is not yet clear, which underscores the importance of genetic profiling for accurate diagnosis and potential targeted therapies in malignant cases.

Department of Pathology 1st Faculty of Medicine Charles University and General University Hospital Prague 12800 Prague Czech Republic

Department of Pathology Charles University Faculty of Medicine in Plzeň Bioptical Laboratory Ltd Pilsen Czech Republic

Virchows Arch. 2024 Dec 10. doi: 10.1007/s00428-024-03990-7. PubMed

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Tavassoli FA, Norris HJ (1981) Mesenchymal tumours of the uterus. VII. A clinicopathological study of 60 endometrial stromal nodules. Histopathology 5:1–10. https://doi.org/10.1111/j.1365-2559.1981.tb01761.x PubMed DOI

Ferreira J, Felix A, Lennerz JK, Oliva E (2018) Recent advances in the histological and molecular classification of endometrial stromal neoplasms. Virchows Arch 473:665–678. https://doi.org/10.1007/s00428-018-2470-6 PubMed DOI

Hoang L, Chiang S, Lee CH (2018) Endometrial stromal sarcomas and related neoplasms: new developments and diagnostic considerations. Pathology 50:162–177. https://doi.org/10.1016/j.pathol.2017.11.086 PubMed DOI

Dundr P, Machado-Lopez A, Mas A, Veckova Z, Mara M, Richtarova A, Matej R, Struzinska I, Kendall Bartu M, Nemejcova K, Dvorak J, Hojny J (2023) Uterine leiomyoma with RAD51B::NUDT3 fusion: a report of 2 cases. Virchows Arch. https://doi.org/10.1007/s00428-023-03603-9

Struzinska I, Hajkova N, Hojny J, Krkavcova E, Michalkova R, Bui QH, Matej R, Laco J, Drozenova J, Fabian P, Skapa P, Spurkova Z, Cibula D, Fruhauf F, Jirasek T, Zima T, Mehes G, Kendall Bartu M, Nemejcova K, Dundr P (2024) Somatic genomic and transcriptomic characterization of primary ovarian serous borderline tumors and low-grade serous carcinomas. J Mol Diagn 26:257–266. https://doi.org/10.1016/j.jmoldx.2023.12.004 PubMed DOI

Dundr P, Matej R, Hojny J, Hajkova N, Nemejcova K, Kendall Bartu M (2024) The spectrum of fusions occurring in non-smooth muscle mesenchymal uterine tumors: a review of the current knowledge. Arch Pathol Lab Med. https://doi.org/10.5858/arpa.2023-0324-RA

Davidson B, Matias-Guiu X, Lax SF (2020) The clinical, morphological, and genetic heterogeneity of endometrial stromal sarcoma. Virchows Arch 476:489–490. https://doi.org/10.1007/s00428-020-02762-3 PubMed DOI

Boyraz B, da Cruz Paula A, Deveraux KA, Tran I, da Silva EM, Young RH, Snuderl M, Weigelt B, Oliva E (2023) Endometrial/endometrioid stromal tumors with extensive whorling and CTNNB1 translocation: a report of 3 cases. Am J Surg Pathol 47:1285–1290. https://doi.org/10.1097/PAS.0000000000002094 PubMed DOI PMC

Croce S, Lesluyes T, Delespaul L, Bonhomme B, Perot G, Velasco V, Mayeur L, Rebier F, Ben Rejeb H, Guyon F, McCluggage WG, Floquet A, Querleu D, Chakiba C, Devouassoux-Shisheboran M, Mery E, Arnould L, Averous G, Soubeyran I, Le Guellec S, Chibon F (2019) GREB1-CTNNB1 fusion transcript detected by RNA-sequencing in a uterine tumor resembling ovarian sex cord tumor (UTROSCT): a novel CTNNB1 rearrangement. Genes Chromosom Cancer 58:155–163. https://doi.org/10.1002/gcc.22694 PubMed DOI

Logan CY, Nusse R (2004) The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol 20:781–810. https://doi.org/10.1146/annurev.cellbio.20.010403.113126 PubMed DOI

Camden AJ, Szwarc MM, Chadchan SB, DeMayo FJ, O’Malley BW, Lydon JP, Kommagani R (2017) Growth regulation by estrogen in breast cancer 1 (GREB1) is a novel progesterone-responsive gene required for human endometrial stromal decidualization. Mol Hum Reprod 23:646–653. https://doi.org/10.1093/molehr/gax045 PubMed DOI PMC

Brunetti M, Panagopoulos I, Gorunova L, Davidson B, Heim S, Micci F (2018) RNA-sequencing identifies novel GREB1-NCOA2 fusion gene in a uterine sarcoma with the chromosomal translocation t(2;8)(p25;q13). Genes Chromosom Cancer 57:176–181. https://doi.org/10.1002/gcc.22518 PubMed DOI

Bi R, Yao Q, Ji G, Bai Q, Li A, Liu Z, Cheng Y, Tu X, Yu L, Chang B, Huang D, Ge H, Zuo K, Li H, Chang H, Cai X, Jiang W, Zhou X, Yang W (2023) Uterine tumor resembling ovarian sex cord tumors: 23 cases indicating molecular heterogeneity with variable biological behavior. Am J Surg Pathol 47:739–755. https://doi.org/10.1097/PAS.0000000000002046 PubMed DOI

Qijun C, Wei W, Cheng W, Dongni L (2024) Clinicopathological features and molecular genetic changes in 17 cases of uterine tumor resembling ovarian sex cord tumor. Hum Pathol 143:33–41. https://doi.org/10.1016/j.humpath.2023.11.007 PubMed DOI

Lee CH, Kao YC, Lee WR, Hsiao YW, Lu TP, Chu CY, Lin YJ, Huang HY, Hsieh TH, Liu YR, Liang CW, Chen TW, Yip S, Lum A, Kuo KT, Jeng YM, Yu SC, Chung YC, Lee JC (2019) Clinicopathologic characterization of GREB1-rearranged uterine sarcomas with variable sex-cord differentiation. Am J Surg Pathol 43(7):928–942. https://doi.org/10.1097/PAS.0000000000001265 PubMed DOI

A molecular and immunohistochemical study of 37 cases of ovarian Sertoli-Leydig cell tumor