Document Detail

Morphologic and molecular characteristics of uterine leiomyomas in hereditary leiomyomatosis and renal cancer (HLRCC) syndrome.
MedLine Citation:
PMID:  23211287     Owner:  NLM     Status:  MEDLINE    
Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a hereditary cancer syndrome in which affected individuals are predisposed to the development of multiple leiomyomas of the skin and uterus and aggressive forms of kidney cancer. Affected individuals harbor a germline heterozygous loss-of-function mutation of the fumarate hydratase (FH) gene. Uterine leiomyomas are present in up to 77% of women with this syndrome. Previous studies have shown that inactivation of the FH gene is unusual for nonsyndromic leiomyomas. Therefore, it might be possible to distinguish 2 genetic groups of smooth muscle tumors: the most common group of sporadic uterine leiomyomas without FH gene inactivation and the more unusual group of HLRCC leiomyomas in patients who harbor a germline mutation of FH, although the exact prevalence of hereditary HLRCC is unknown. We reviewed the clinical, morphologic, and genotypic features of uterine leiomyomas in 19 HLRCC patients with FH germline mutations. Patients with HLRCC syndrome were younger in age compared with those with regular leiomyomata. DNA was extracted by microdissection, and analysis of loss of heterozygosity (LOH) at 1q43 was performed. Uterine leiomyomas in HLRCC have young age of onset and are multiple, with size ranging from 1 to 8 cm. Histopathologically, HLRCC leiomyomas frequently had increased cellularity, multinucleated cells, and atypia. All cases showed tumor nuclei with large orangeophilic nucleoli surrounded by a perinucleolar halo similar to the changes found in HLRCC. Occasional mitoses were found in 3 cases; however, the tumors did not fulfill the criteria for malignancy. Our study also showed that LOH at 1q43 was frequent in HLRCC leiomyomas (8/10 cases), similarly to what has been previously found in renal cell carcinomas from HLRCC patients. LOH is considered to be the second hit that inactivates the FH gene. We conclude that uterine leiomyomas associated with HLRCC syndrome have characteristic morphologic features. Both, uterine leiomyomas and renal cell carcinoma share some morphologic nuclear changes and genotypic features in HLRCC patients. The specific morphologic features of the uterine leiomyomas that we describe may help in the identification of patients who may be part of the hereditary syndrome.
Julian Sanz-Ortega; Cathy Vocke; Pamela Stratton; William Marston Linehan; Maria J Merino
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The American journal of surgical pathology     Volume:  37     ISSN:  1532-0979     ISO Abbreviation:  Am. J. Surg. Pathol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-12-17     Completed Date:  2013-02-12     Revised Date:  2014-01-10    
Medline Journal Info:
Nlm Unique ID:  7707904     Medline TA:  Am J Surg Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  74-80     Citation Subset:  IM    
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MeSH Terms
Carcinoma, Renal Cell / genetics,  pathology*
Cell Nucleus / pathology
DNA, Neoplasm / genetics
Fumarate Hydratase / genetics*
Germ-Line Mutation*
Kidney Neoplasms / genetics,  pathology*
Leiomyoma / genetics,  pathology*
Leiomyomatosis / genetics,  pathology*
Loss of Heterozygosity
Middle Aged
Neoplastic Syndromes, Hereditary / genetics,  pathology*
Skin Neoplasms
Tumor Markers, Biological / genetics
Uterine Neoplasms / genetics,  pathology*
Young Adult
Grant Support
Z01 BC010696-03/BC/NCI NIH HHS
Reg. No./Substance:
0/DNA, Neoplasm; 0/Tumor Markers, Biological; EC Hydratase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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