Abstract
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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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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DOI: https://doi.org/10.1007/s12253-019-00739-5