Expression of fumarate hydratase in multiple leiomyoma of the uterus_West China Medical Journal

Authors：

WEI Xiaoxia ¹ , LI Lei ¹ , LIU Tianming ¹ , WANG Mei ¹ , YU Na ¹ , HUANG Qin ¹ , LIU Qianqi ¹ ,  CHEN Ni ²

1. Department of Pathology, West China Second University Hospital, Sichuan University / Key Laboratory of Birth Defects and Related Diseases ofWomen and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan 610041, P. R. China;
2. Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

CHEN Ni, Email: chenni1@163.com

Keywords：

Leiomyoma; fumarate hydratase; bizarre nuclei; hereditary leiomyomatosis renal cell cancer syndrome

DOI：

10.7507/1002-0179.202201011

Video：

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Objective To investigate the expression and clinicopathological features of fumarate hydratase (FH) in multiple leiomyoma of the uterus. Methods Relevant clinicopathological data of patients with multiple leiomyoma of the uterus diagnosed pathologically between September 1, 2018 and August 31, 2019 were collected from the Department of Pathology of West China Second University Hospital. The morphology, FH protein expression and prognosis of FH negative patients were observed. Results A total of 900 patients were included. Among them, there were 825 cases of nonatypical leiomyomas, 36 cases of leiomyoma with bizarre nuclei, 34 cases of cellular leiomyoma and 5 cases of mitotically active leiomyoma. A total of 69 patients with negative FH expression were included, with an average age of (37.28±8.22) years. Among them, there were 43 cases of nonatypical leiomyomas, 19 cases of leiomyoma with bizarre nuclei, 6 cases of cellular leiomyoma, and 1 cases of mitotically active leiomyoma. At low magnification, staghorn shaped blood vessels, alveolar pattern edema, palisade distribution of smooth muscle cells and bizarre nuclei smooth muscle cells could be seen in patients with negative FH expression. At high magnification, cytoplasmic eosinophilicglobules andeosinophilic nucleolus surrounded by a halo could be seen in patients with negative FH expression. Among the 69 cases with negative FH expression, 60 cases (86.96%, 60/69) were followed up. All patients survived, of which 24 cases (40%, 24/60) recurred. Conclusion Immunohistochemically, the marker FH for multiple leiomyoma of the uterus is helpful to improve the identification of FH deficient leiomyoma in clinical work as well as early diagnosis in hereditary leiomyomatosis renal cell cancer syndrome.

Citation： WEI Xiaoxia, LI Lei, LIU Tianming, WANG Mei, YU Na, HUANG Qin, LIU Qianqi, CHEN Ni. Expression of fumarate hydratase in multiple leiomyoma of the uterus. West China Medical Journal, 2022, 37(8): 1197-1202. doi: 10.7507/1002-0179.202201011 Copy

1.	Launonen V, Vierimaa O, Kiuru M, et al. Inherited susceptibility to uterine leiomyomas and renal cell cancer. Proc Natl Acad Sci USA, 2001, 98(6): 3387-3392.
2.	Moch H, Cubilla AL, Humphrey PA, et al. The 2016 WHO classification of tumours of the urinary system and male genital organs-part A: renal, penile, and testicular tumours. Eur Urol, 2016, 70(1): 93-105.
3.	Harrison WJ, Andrici J, Maclean F, et al. Fumarate hydratase-deficient uterine leiomyomas occur in both the syndromic and sporadic settings. Am J Surg Pathol, 2016, 40(5): 599-607.
4.	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. Am J Surg Pathol, 2015, 39(11): 1529-1539.
5.	Miettinen M, Felisiak-Golabek A, Wasag B, et al. Fumarase-deficient uterine leiomyomas: an immunohistochemical, molecular genetic, and clinicopathologic study of 86 cases. Am J Surg Pathol, 2016, 40(12): 1661-1669.
6.	Siegler L, Erber R, Burghaus S, et al. Fumarate hydratase (FH) deficiency in uterine leiomyomas: recognition by histological features versus blind immunoscreening. Virchows Arch, 2018, 472(5): 789-796.
7.	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, 2020, 26(3): 1527-1537.
8.	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 leiomyomatosis renal cell carcinoma syndrome: a 5-year single institutional experience. Am J Surg Pathol, 2019, 43(5): 639-655.
9.	Kurman RJ, Carcangiu ML, Herrington CS, et al. WHO classification of tumours of female reproductive organs. 4th ed. Lyon: IARC Press, 2014.
10.	Patel VM, Handler MZ, Schwartz RA, et al. Hereditary leiomyomatosis and renal cell cancer syndrome: an update and review. J Am Acad Dermatol, 2017, 77(1): 149-158.
11.	Liu C, Dillon J, Beavis AL, et al. Prevalence of somatic and germline mutations of Fumarate hydratase in uterine leiomyomas from young patients. Histopathology, 2020, 76(3): 354-365.
12.	施凤, 钱宁, 吴王飞, 等. 子宫奇异核平滑肌瘤中延胡索酸水合酶的表达及意义. 临床与实验病理学杂志, 2020, 36(12): 1455-1457.
13.	Bennett JA, Weigelt B, Chiang S, et al. Leiomyoma with bizarre nuclei: a morphological, immunohistochemical and molecular analysis of 31 cases. Mod Pathol, 2017, 30(10): 1476-1488.
14.	Sanz-Ortega J, Vocke C, Stratton P, et al. Morphologic and molecular characteristics of uterine leiomyomas in hereditary leiomyomatosis and renal cancer (HLRCC) syndrome. Am J Surg Pathol, 2013, 37(1): 74-80.
15.	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. Mod Pathol, 2014, 27(7): 1020-1027.
16.	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. Am J Surg Pathol, 2011, 35(8): 1235-1237.
17.	Bayley JP, Launonen V, Tomlinson IP. The FH mutation database: an online database of fumarate hydratase mutations involved in the MCUL (HLRCC) tumor syndrome and congenital fumarase deficiency. BMC Med Genet, 2008, 9: 20.
18.	Stewart EA, Cookson CL, Gandolfo RA, et al. Epidemiology of uterine fibroids: a systematic review. BJOG, 2017, 124(10): 1501-1512.

1. Launonen V, Vierimaa O, Kiuru M, et al. Inherited susceptibility to uterine leiomyomas and renal cell cancer. Proc Natl Acad Sci USA, 2001, 98(6): 3387-3392.
2. Moch H, Cubilla AL, Humphrey PA, et al. The 2016 WHO classification of tumours of the urinary system and male genital organs-part A: renal, penile, and testicular tumours. Eur Urol, 2016, 70(1): 93-105.
3. Harrison WJ, Andrici J, Maclean F, et al. Fumarate hydratase-deficient uterine leiomyomas occur in both the syndromic and sporadic settings. Am J Surg Pathol, 2016, 40(5): 599-607.
4. 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. Am J Surg Pathol, 2015, 39(11): 1529-1539.
5. Miettinen M, Felisiak-Golabek A, Wasag B, et al. Fumarase-deficient uterine leiomyomas: an immunohistochemical, molecular genetic, and clinicopathologic study of 86 cases. Am J Surg Pathol, 2016, 40(12): 1661-1669.
6. Siegler L, Erber R, Burghaus S, et al. Fumarate hydratase (FH) deficiency in uterine leiomyomas: recognition by histological features versus blind immunoscreening. Virchows Arch, 2018, 472(5): 789-796.
7. 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, 2020, 26(3): 1527-1537.
8. 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 leiomyomatosis renal cell carcinoma syndrome: a 5-year single institutional experience. Am J Surg Pathol, 2019, 43(5): 639-655.
9. Kurman RJ, Carcangiu ML, Herrington CS, et al. WHO classification of tumours of female reproductive organs. 4th ed. Lyon: IARC Press, 2014.
10. Patel VM, Handler MZ, Schwartz RA, et al. Hereditary leiomyomatosis and renal cell cancer syndrome: an update and review. J Am Acad Dermatol, 2017, 77(1): 149-158.
11. Liu C, Dillon J, Beavis AL, et al. Prevalence of somatic and germline mutations of Fumarate hydratase in uterine leiomyomas from young patients. Histopathology, 2020, 76(3): 354-365.
12. 施凤, 钱宁, 吴王飞, 等. 子宫奇异核平滑肌瘤中延胡索酸水合酶的表达及意义. 临床与实验病理学杂志, 2020, 36(12): 1455-1457.
13. Bennett JA, Weigelt B, Chiang S, et al. Leiomyoma with bizarre nuclei: a morphological, immunohistochemical and molecular analysis of 31 cases. Mod Pathol, 2017, 30(10): 1476-1488.
14. Sanz-Ortega J, Vocke C, Stratton P, et al. Morphologic and molecular characteristics of uterine leiomyomas in hereditary leiomyomatosis and renal cancer (HLRCC) syndrome. Am J Surg Pathol, 2013, 37(1): 74-80.
15. 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. Mod Pathol, 2014, 27(7): 1020-1027.
16. 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. Am J Surg Pathol, 2011, 35(8): 1235-1237.
17. Bayley JP, Launonen V, Tomlinson IP. The FH mutation database: an online database of fumarate hydratase mutations involved in the MCUL (HLRCC) tumor syndrome and congenital fumarase deficiency. BMC Med Genet, 2008, 9: 20.
18. Stewart EA, Cookson CL, Gandolfo RA, et al. Epidemiology of uterine fibroids: a systematic review. BJOG, 2017, 124(10): 1501-1512.

West China Medical Journal

Expression of fumarate hydratase in multiple leiomyoma of the uterus

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