Benign metastasizing fumarate hydratase (FH)-deficient uterine leiomyomas: clinicopathological and molecular study with first documentation of multi-organ metastases

Yin X, Wei X, Al Shamsi R, Ali FS, Al Kindi F, Zhang X, Liang J, Pan X, Al Masqari M, Zheng L, Zhou Q, Agaimy A, Chen N (2024)

Publication Language: English

Publication Type: Journal article

Publication year: 2024

Journal

Virchows Archiv Springer Verlag (Germany)

DOI: 10.1007/s00428-024-03806-8

Abstract

Leiomyoma is the most prevalent benign tumor of the female reproductive system. Benign metastasizing leiomyoma (BML) is a rare phenomenon that presents at distant sites, typically the lungs, exhibiting histopathological features similar to the primary uterine tumor in the absence of malignancy features in both. Fumarate hydratase-deficient uterine leiomyoma (FH-d UL) is an uncommon subtype among uterine smooth muscle tumors (0.5–2%), showing distinctive histomorphology and FH inactivation. The majority of FH-d ULs are sporadic, caused by somatic FH inactivation, while a minority of cases occur in the context of the hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome caused by germline FH inactivation. Metastasizing FH-d UL has not been well documented and might be under-reported. Here, we present two cases (21- and 34-year-old females) who presented with metastasizing FH-d UL after myomectomy/hysterectomy with histologically proven multiple lung metastases in both, in addition to multi-organ involvement in one case (cervical-thoracic lymph nodes, left kidney, perihepatic region, left zygomatic bone, and soft tissues). Pathological examination confirmed FH-d leiomyomas in the primary/recurrent uterine tumors, multiple lung lesions, and a renal mass. The minimal criteria for diagnosis of leiomyosarcoma were not fulfilled. Genetic testing revealed germline pathogenic FH variants in both cases (c.1256C > T; p.Ser419Leu in Case 1 and c.425A > G; p.Gln142Arg in Case 2). These novel cases highlight a rare but possibly under-recognized presentation of FH-d BML. Our study suggests that FH-d BML cases might be enriched for the HLRCC syndrome.

Authors with CRIS profile

Abbas Agaimy Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie

Involved external institutions

Royal Hospital Oman OM Oman (OM) West China Medical Center of Sichuan University / 四川大学华西医学中心 CN China (CN) West China Second University Hospital of Sichuan University (WCSUH-SCU) CN China (CN)

How to cite

APA:

Yin, X., Wei, X., Al Shamsi, R., Ali, F.S., Al Kindi, F., Zhang, X.,... Chen, N. (2024). Benign metastasizing fumarate hydratase (FH)-deficient uterine leiomyomas: clinicopathological and molecular study with first documentation of multi-organ metastases. Virchows Archiv. https://doi.org/10.1007/s00428-024-03806-8

MLA:

Yin, Xiaoxue, et al. "Benign metastasizing fumarate hydratase (FH)-deficient uterine leiomyomas: clinicopathological and molecular study with first documentation of multi-organ metastases." Virchows Archiv (2024).

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