Leiomyoma with Bizarre Nuclei: a Study of 108 Cases Focusing on Clinicopathological Features, Morphology, and Fumarate Hydratase Alterations


Leiomyoma with bizarre nuclei (LBN) is an uncommon variant of uterine smooth muscle neoplasm. Involvement of fumarate hydratase (FH) has been suggested in the pathogenesis of a subset of LBN. The goal of our study is to assess the clinicopathological, morphological, immunohistochemical and molecular findings focusing on FH in LBNs (n = 108) and compare it with the findings in usual leiomyomas (UL; n = 50) and leiomyosarcomas (LMS; n = 42). Immunohistochemically, loss of FH expression was found in 67/108 of LBN, 1/50 of UL and in no LMS. Class 4/5 FH mutations were detected in 15/53 LBN with sufficient DNA quality for molecular analysis. Pathogenic variants of the FH gene were detected in neither UL nor LMS. Local recurrence after surgery was present in 18/92 of LBN patients, 7 of which were histologically verified and 2 of which were found to be LBN. Our results confirmed that LBN behave in a benign fashion, although they may relapse. FH gene mutations were a common finding only in LBN, but not in UL and LMS. Immunohistochemistry with an antibody against FH seems to have a good sensitivity (87%) and moderate specificity (58%) with regard to predicting FH gene mutations and could be used as a screening method in tumors with features suggestive of FH alterations to identify patients who are at risk for the FH aberrations.

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This work was supported by Ministry of Health, Czech Republic (Conceptual development of research organization 64165, General University Hospital in Prague), by Charles University (Project Progres Q28/LF1, UNCE 204065 and SVV 260367), by European Regional Development Fund, project EF16_013/0001674 and BBMRI_CZ LM2015089, and by OPPK (Research Laboratory of Tumor Diseases, CZ.2.16/3.1.00/24509).

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Correspondence to Ivana Tichá or Pavel Dundr.

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In compliance with the Helsinki Declaration, the project has been approved by Ethics Committee of the General University Hospital, Prague (reference number č.j. 98/16 Grant RVO-VFN 64165).

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Gregová, M., Hojný, J., Němejcová, K. et al. Leiomyoma with Bizarre Nuclei: a Study of 108 Cases Focusing on Clinicopathological Features, Morphology, and Fumarate Hydratase Alterations. Pathol. Oncol. Res. 26, 1527–1537 (2020). https://doi.org/10.1007/s12253-019-00739-5

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  • Leiomyoma with bizarre nuclei
  • Usual leiomyoma
  • Leiomyosarcoma
  • Fumarate hydratase