The fumarate hydratase-deficient uterine smooth muscle tumor:a clinicopatholog-ical and molecular genetic analysis of 17 cases
10.13315/j.cnki.cjcep.2025.11.011
- VernacularTitle:延胡索酸水合酶缺陷型子宫平滑肌肿瘤17例临床病理特征和分子遗传理学分析
- Author:
Lingling ZHONG
1
;
Haipeng ZHANG
1
;
Xuxiu TAO
1
;
Xingwei YANG
1
;
Gaoxiang HUANG
1
Author Information
1. 解放军联勤保障部队第九二四医院病理科,桂林 541002
- Publication Type:Journal Article
- Keywords:
uterine smooth muscle tumor;
fumarate hydratase;
S-(2-succino)-cysteine;
clinicopathological feature;
whole-exon sequencing
- From:
Chinese Journal of Clinical and Experimental Pathology
2025;41(11):1478-1484
- CountryChina
- Language:Chinese
-
Abstract:
Purpose To investigate the clinicopathological features and cytogenetic characteristics in the fumarate hydratase(FH)-deficient uterine smooth muscle tumors.Methods A total of 334 paraffin-embedded specimen of be-nign,borderline,and malignant uterine smooth muscle tumors were collected.FH-deficient uterine smooth muscle tumors were screened using the immunohistochemical detection with FH and S-(2-succino)-cysteine(2SC)antibodies.A retrospective analysis of the clinicopathological features and FH mutations was conducted.Results Compared with the 310 non-FH-deficient uterine leiomyomas(non-FH-dUL),14 cases(93.3％)out of the 15 FH-dUL presented with staghorn blood vessels(x2=52.86,P＜0.000 1),8 cases(53.3％)exhibited pulmonary edema-like stroma(x2=26.41,P＜0.000 1),8 cases(53.3％)had cytoplasmic eosinophilic globules(x2=41.85,P＜0.000 1),5 cases(33.3％)showed multifocal bizarre nuclei(x2=72.54,P＜0.000 1),5 cases(33.3％)had large eosino-philic nucleoli with viral inclusion-like halos(x2=38.85,P＜0.000 1),and 5 cases(33.3％)demonstrated a sig-nificant increase in cell density(x2=8.782,P=0.003).The above morphological features were also observed in a case of FH-d uSTUMP and FH-d uLMS.Among the 14 cases with follow-up,except for one death in the FH-d uLMS,none reported the renal cell carcinoma and cutaneous leiomyoma.FH mutations were identified in 11 cases and the hotspot mutations were found in exon 1,2,4,5,6 and 7.Among these variations,c.125C＞T,c.151C＞T and c.704A＞C were found to be the hotspot gene variations.Furthemore,7 gene variations(c.197A＞G,c.426G＞T,c.505C＞T,c.704A＞C,c.812A＞C,c.847T＞C,c.1006A＞G)were not included in COSMIC and ClinVar database and were supposed to be novel.Conclusion The combination of FH/2SC immunohistochemical detection and FH exon mutation analysis are reliable tools for the early identification of FH-deficient uterine smooth muscle tumors or hereditary leiomyomatosis and renal cell carcinoma(HLRCC)syndrome.
