University of Oulu

Uimari, O, Ahtikoski, A, Kämpjärvi, K, et al. Uterine leiomyomas in hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome can be identified through distinct clinical characteristics and typical morphology. Acta Obstet Gynecol Scand. 2021; 100: 2066– 2075. https://doi.org/10.1111/aogs.14248

Uterine leiomyomas in hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome can be identified through distinct clinical characteristics and typical morphology

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Author: Uimari, Outi1,2,3; Ahtikoski, Anne4,5; Kämpjärvi, Kati6,7;
Organizations: 1Department of Obstetrics and Gynecology, Oulu University Hospital, Oulu, Finland
2PEDEGO Research Unit, University of Oulu and Oulu University Hospital, Oulu, Finland
3Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland
4Department of Pathology, Oulu University Hospital and University of Oulu, Oulu, Finland
5Department of Pathology, Turku University Hospital and University of Turku, Turku, Finland
6Research Programs Unit, Applied Tumor Genomics, University of Helsinki, Helsinki, Finland
7Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland
8Department of Pathology, The Laboratory of Helsinki University Central Hospital (HUSLAB), Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland
9Department of Obstetrics and Gynecology, Kuopio University Hospital, Kuopio, Finland
10Department of Clinical Genetics, Oulu University Hospital, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.8 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2021110153216
Language: English
Published: John Wiley & Sons, 2021
Publish Date: 2021-11-01
Description:

Abstract

Introduction: Hereditary leiomyomatosis and renal cell cancer (HLRCC) constitute a tumor susceptibility syndrome caused by germline mutations in the fumarate hydratase (FH) gene. The most common features are leiomyomas of the uterus and the skin. The syndrome includes a predisposition to early-onset, aggressive renal cell cancer. It is important to identify women with HLRCC among other uterine leiomyoma patients in order to direct them to genetic counseling and to identify other affected family members.

Material and methods: We conducted a nationwide historical study to identify typical clinical characteristics, uterine leiomyoma morphology, and immunohistochemistry for diagnosing HLRCC. The study included 20 women with a known FH germline mutation and 77 women with sporadic uterine leiomyomas. The patient records of all women were reviewed to obtain clinical details regarding their leiomyomas. Uterine leiomyoma tissue specimens from 43 HLRCC-related leiomyomas and 42 sporadic leiomyomas were collected and prepared for histology analysis. A morphologic description was performed on hematoxylin & eosin-stained tissue slides, and immunohistochemical analysis was carried out for CD34, Bcl-2, and p53 stainings.

Results: The women with HLRCC were diagnosed with uterine leiomyomas at a young age compared with the sporadic leiomyoma group (mean 33.8 years vs. 45.4 years, P < 0.0001), and their leiomyomas occurred as multiples compared with the sporadic leiomyoma group (more than four tumors 88.9% vs. 30.8%, P < 0.0001). Congruently, these women underwent surgical treatment at younger age compared with the sporadic leiomyoma group (mean 37.3 years vs. 48.3 years, P < 0.0001). HLRCC leiomyomas had denser microvasculature highlighted by CD34 immunostaining when compared with the sporadic leiomyoma group (112.6 mean count/high-power field, SD 20.8 vs. 37.4 mean count/high-power field, SD 21.0 P < 0.0001) and stronger anti-apoptotic protein Bcl-2 immunostaining when compared with the sporadic leiomyoma group (weak 4.7%, moderate 44.2%, strong 51.2% vs. 26.2%, 52.4%, 21.4%, respectively, P = 0.003). No differences were observed in p53 staining.

Conclusions: Women with HLRCC may be identified through the distinct clinical characteristics: symptomatic and numerous leioymyomas at young age, and morphologic features of FH-mutant leiomyomas, aided by Bcl-2 and CD34 immunohistochemistry. Further, distinguishing individuals with a germline FH mutation enables proper genetic counseling and regular renal monitoring.

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Series: Acta obstetricia et gynecologica Scandinavica
ISSN: 0001-6349
ISSN-E: 1600-0412
ISSN-L: 0001-6349
Volume: 100
Issue: 11
Pages: 2066 - 2075
DOI: 10.1111/aogs.14248
OADOI: https://oadoi.org/10.1111/aogs.14248
Type of Publication: A1 Journal article – refereed
Field of Science: 3123 Gynaecology and paediatrics
Subjects:
Funding: Funding was received from the Academy of Finland (grant 307773 for PV), and the Sigrid Jusélius Foundation, Cancer Society of Finland, and Finnish Medical Foundation (for OU).
Copyright information: © 2021 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG). This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
  https://creativecommons.org/licenses/by-nc/4.0/