|Table of Contents|

Clinicopathological features and differential diagnosis of fumarate hydratase-deficient uterine leiomyoma

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2024 22
Page:
4358-4362
Research Field:
Publishing date:

Info

Title:
Clinicopathological features and differential diagnosis of fumarate hydratase-deficient uterine leiomyoma
Author(s):
LI Jing1; LUO Tian2; LI Juan2; YU Jing3; GAI Zhibo4
1.Department of Pathology,Changqing District People's Hospital of Jinan,Shandong Jinan 250300,China;2.Department of Pathology,Jinan Maternal and Child Health Care Hospital,Shandong Jinan 250000,China;3.Department of Pathology,Shandong Third Hospital,Shandong Jinan 250000,China;4.Experimental Center of Shandong University of Traditional Chinese Medicine,Shandong Jinan 250300,China.
Keywords:
smooth muscle tumor; fumarate hydratase-deficient uterine leiomyoma; smooth muscle tumor of uncertain malignant potential; differential diagnosis; immunohistochemistry
PACS:
R737.33
DOI:
10.3969/j.issn.1672-4992.2024.22.024
Abstract:
Objective:To investigate the clinicopathological features and differential diagnosis of fumarate hydratase-deficient uterine leiomyoma (FH-DUL).Methods:The clinicopathological data of 9 cases with confirmed FH-DUL were retrospectively analyzed to characterize their morphological features,and perform immunohistochemical analysis and differential diagnosis,and the relevant literatures were reviewed.Results:The 9 cases of FH-DUL were clinically similar to the normal uterine leiomyoma.Histologically,the tissue was composed of scattered hemangiopericytoma-like vessels,alveolar pattern edema,focal or diffuse distribution of bizarre cells,cytoplasmic eosinophilic globules,eosinophilic nucleoli and perinuclear halos.Immunohistochemical staining showed that FH expression was absent,2SC was positive and Ki-67 positive index was 1%~3%.All cases were followed up and the patients survived without evidence of disease progression.Conclusion:The pathological morphology and immunophenotype of FH-DUL overlap with smooth muscle tumor of uncertain malignant potential (STUMP),and are easily confused with each other.Antler vessels,loose edema area,cytoplasmic eosinophilic globules are important histological features of this tumor,which play an important role in the diagnosis of FH-DUL.Immunohistochemical FH negative and 2SC positive are helpful for the diagnosis and differential diagnosis of this tumor.If necessary,FH gene detection should be performed to assist the diagnosis.

References:

［1］ SIEGLER L,ERBER R,BURGHAUS S,et al.Fumarate hydratase (FH) deficiency in uterine leiomyomas:recognition by histological features versus blind immunoscreening［J］.Virchows Arch,2018,472(5):789-796.
［2］ MIETTINEN M,FELISIAK-GOLABEK A,WASAG B,et al.Fumarase-deficient uterine leiomyomas:an immunohistochemical,molecular genetic,and clinicopathologic study of 86 cases［J］.Am J Surg Pathol,2016,40(12):1661-1669.
［3］ KIM KR,LAX SF,LAZAR AJ,et al.WHO classification of tumours editorial board.WHO classification of tumours of female genital tumours［M］.Lyon:IARC Press,2020,272-276.
［4］ BENNETT JA,WEIGELT B,CHIANG S,et al.Leiomyoma with bizarre nuclei:a morphological,immunohistochemical and molecular analysis of 31 cases［J］.Mod Pathol,2017,30(10):1476-1488.
［5］ 许倩雯，黄海建，李柏成，等.延胡索酸水合酶缺陷型子宫平滑肌瘤29例临床病理特征［J］.临床与实验病理学杂志,2022,38（3）:299-302. XU QW，HUANG HJ,LI BC,et al.Fumarate hydratase deficiency in uterine leiomyomas:clinicopathological characteristics study of 29 cases［J］.Journal of Clinical and Experimental Pathology,2022,38(3):299-302.
［6］POPP B,ERBER R,KRAUS C,et al.Targeted sequencing of FH-deficient uterine leiomyomas reveals biallelic inactivating somatic fumarase variants and allows characterization of missense variants［J］.Mod Pathol,2020,33(11):2341-2353.
［7］ MEHINE M,MAKINEN N,HEINONEN HR,et al.Genomics of uterine leiomyomas:insights from high-through put sequencing［J］.Fertil Steril,2014,102（3）:621-629.
［8］ SANCHEZ-HERAS AB,CASTILLEJO A,GARCIA-DIAZ JD,et al.Hereditary leiomyomatosis and renal cell cancer syndrome in Spain:clinical and genetic characterization［J］.Cancers,2020,12(11):3277.
［9］ REYES C,KARAMURZIN Y,FRIZZELL N,et al.Uterine smooth muscle tumors with features suggesting fumarate hydratase aberration:detailed morphologic analysis and correlation with S-(2-succino)-cysteine immunohistochemistry［J］.Mod Pathol,2014,27(7):1020-1027.
［10］ RABBAN JT,CHAN E,MAK J,et al.Prospective detection of germline mutation of fumarate hydratase in women with uterine smooth muscle tumors using pathology-based screening to trigger genetic counseling for hereditary leioyomatosis renal cell carcinoma syndrome:a 5-year single institutional experience［J］.Am J Surg Pathol,2019,43(5):639-655.
［11］ CHAYED Z,KRISTENSEN LK,OUSAGER LB,et al.Hereditary leiomyomatosis and renal cell carcinoma:a case series and literature review［J］.Orphanet J Rare Dis,2021,16(1):34.
［12］ LIU C,DILLON J,BEAVIS AL,et al.Prevalence of somatic and germline mutations of fumarate hydratase in uterine leiomyomas from young patients［J］.Histopathology,2020,76(3):354-365．
［13］ YU Y,ZHENG M,ZHU W,et al.Hereditary leiomyomatosis and renal cell cancer (HLRCC):Case series and review of the literature［J］.Ural Oncol,2021,39(11):791.e9-791.e16.
［14］GARG K,RABBAN J.Hereditary leiomyomatosis and renal cell carcinoma syndrome associated uterine smooth muscle tumors:bridging morphology and clinical screening［J］.Genes Chromosomes Cancer,2021,60(3):210-216.
［15］王陈，沈丹华.延胡索酸水合酶缺陷型子宫平滑肌瘤临床病理特征与分子遗传学研究进展［J］.中国妇产科临床杂志，2022,23(1)：103-105. WANG C，SHEN DH.Advances in clinicopathological features and molecular genetics of fumarate hydratase-deficient uterine leiomyoma［J］.Chin J Clin Obstet Gynecol,2022,23(1)：103-105.
［16］ BASARAN D，USUBUTUN A，SALMAN MC,et al.The clinicopathological study of 21 cases with uterine smooth muscle tumors of uncertain malignant potential:Centralized review can purify the diagnosis［J］.Int J Gynecol Cancer，2018,28(2):233-240.
［17］闫熙瑶，林建龙，田瑞华，等.延胡索酸水合酶缺失型子宫平滑肌瘤38例患者的多中心回顾性研究［J］.中华妇产科杂志,2022,57(6):435-441. YAN XY,LIN JL,TIAN RH,et al.Multicenter retrospective study of 38 cases with fumarate hydratase deficiency uterine leiomyoma［J］.Chinese Journal of Obstetrics and Gynecology,2022,57(6):435-441.
［18］何妍谊，谢翠云，韩焕梅，等.经腹子宫肌瘤切除术和腹腔镜子宫肌瘤切除术术后复发率的比较［J］.现代肿瘤医学,2021,29（12):2117-2119. HE YY，XIE CY，HAN HM,et al.Comparative study of recurrence rate after open myomectomy and laparoscopic myomectomy［J］.Modern Oncology,2021,29(12):2117-2119.
［19］ HARRISON WJ,ANDRICI J,MACLEAN F,et al.Fumarate hydratase deficient uterine leiomyomas occur in both the syndromic and sporadic settings［J］.Am J Surg Pathol,2016,40(5):599-607.
［20］ GARG K,TICKOO SK,SOSLOW RA,et al.Morphologic features of uterine leiomyomas associated with hereditary leiomyomatosis and renal cell carcinoma syndrome:a case report［J］.Am J Surg Pathol,2011,35（8）:1235-1237.
［21］ JENNIFER P,JULIANNA J,KELLY A,et al.Fumarate hydratase deficiency should be considered in the differential diagnosis of uterine and extrauterine smooth muscle tumors of uncertain malignant potential (STUMP)［J］.Int J Gynecol Pathol,2021,41(3):268-275.
［22］ LI H,YANG W,TU X,et al.Clinicopathological and molecular characteristics of fumarate hydratase deficient uterine smooth muscle tumors:a single-center study of 52 cases［J］.Hum Pathol,2022,126:136-145.
［23］ AHVENAINEN T,KAUKOMAA J,KAMPJARVI K,et al.Comparison of 2SC,AKR1B10,and FH antibodies as potential biomarkers for FH deficient uterine leiomyomas［J］.Am J Surg Pathol,2022,45(4):537-546.
［24］ JOSEPH NM,SOLOMON DA,FRIZZELL N,et al.Morphology and immunohistochemistry for 2SC and FH aid in detection of fumarate hydratase gene aberrations in uterine leiomyomas from young patients［J］.Am J Surg Pathol,2015,39(11):1529-1539.
［25］ DAVID BC,AARTI S,LIVIA M,et al.Fumarate hydratase and S-(2-succinyl)-cysteine immunohistochemistry shows evidence of fumarate hydratase deficiency in 2% of uterine leiomyosarcomas:A cohort study of 348 tumors［J］.Int J Gynecol Pathol,2023,42(2):120-135.
［26］ YANG W,AISHENG D,MEILING C,et al.Intense FDG uptake in leiomyomatosis peritonealis disseminata with fumarate hydratase deficiency［J］.Clin Nucl Med,2024,49(2):e93-e95.

Memo

Memo:
-
Last Update: 1900-01-01