• Login
    View Item 
    •   Home
    • The Christie Research Publications Repository
    • All Christie Publications
    • View Item
    •   Home
    • The Christie Research Publications Repository
    • All Christie Publications
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of ChristieCommunitiesTitleAuthorsIssue DateSubmit DateSubjectsThis CollectionTitleAuthorsIssue DateSubmit DateSubjectsProfilesView

    My Account

    LoginRegister

    Local Links

    The Christie WebsiteChristie Library and Knowledge Service

    Statistics

    Display statistics

    Uterine smooth muscle tumors with features suggesting fumarate hydratase aberration: detailed morphologic analysis and correlation with S-(2-succino)-cysteine immunohistochemistry.

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Authors
    Reyes, C
    Karamurzin, Y
    Frizzell, N
    Garg, K
    Nonaka, Daisuke
    Chen, Y
    Soslow, R
    Affiliation
    Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
    Issue Date
    2014-07
    
    Metadata
    Show full item record
    Abstract
    Rare, sporadic uterine leiomyomas arise in the setting of severe metabolic aberration due to a somatic fumarate hydratase mutation. Germline mutations account for the hereditary leiomyomatosis and renal cell carcinoma syndrome, which predisposes for cutaneous and uterine leiomyomas and aggressive renal cell carcinomas. Altered fumarate hydratase leads to fumarate accumulation in affected cells with formation of S-(2-succino)-cysteine, which can be detected with the polyclonal antibody. High levels of these modified cysteine residues are found characteristically in fumarate hydratase-deficient cells but not in normal tissues or tumors unassociated with hereditary leiomyomatosis and renal cell carcinoma syndrome. We hypothesized that S-(2-succino)-cysteine-positive leiomyomas, indicating fumarate hydratase aberration, have morphologic features that differ from those without S-(2-succino)-cysteine positivity. Hematoxylin and eosin-stained slides of uterine smooth-muscle tumors were prospectively analyzed for features suggesting hereditary leiomyomatosis and renal cell carcinoma syndrome, such as prominent eosinophilic macronucleoli with perinucleolar halos, yielding nine cases. Germline genetic testing for fumarate hydratase mutations was performed in three cases. A detailed morphological analysis was undertaken, and S-(2-succino)-cysteine immunohistochemical analysis was performed with controls from a tissue microarray (leiomyomas (19), leiomyosarcomas (29), and endometrial stromal tumors (15)). Of the nine study cases, four had multiple uterine smooth muscle tumors. All cases had increased cellularity, staghorn vasculature, and fibrillary cytoplasm with pink globules. All cases had inclusion-like nucleoli with perinuclear halos (7 diffuse, 1 focal). All showed diffuse granular cytoplasmic labeling with the S-(2-succino)-cysteine antibody. Two of three tested patients had germline fumarate hydratase mutations. Only one leiomyoma from the tissue microarray controls was immunohistochemically positive, and it showed features similar to other immunohistochemically positive cases. Smooth-muscle tumors with fumarate hydratase aberration demonstrate morphological reproducibility across cases and S-(2-succino)-cysteine immuno-positivity. Although the features described are not specific for the germline fumarate hydratase mutation or the hereditary leiomyomatosis and renal cell carcinoma syndrome, their presence should suggest fumarate hydratase aberration. Identifying these cases is an important step in the diagnostic workup of patients with possible hereditary leiomyomatosis and renal cell carcinoma.
    Citation
    Uterine smooth muscle tumors with features suggesting fumarate hydratase aberration: detailed morphologic analysis and correlation with S-(2-succino)-cysteine immunohistochemistry. 2014, 27 (7):1020-7 Mod. Pathol.
    Journal
    Modern Pathology
    URI
    http://hdl.handle.net/10541/324255
    DOI
    10.1038/modpathol.2013.215
    PubMed ID
    24309325
    Type
    Article
    Language
    en
    ISSN
    1530-0285
    ae974a485f413a2113503eed53cd6c53
    10.1038/modpathol.2013.215
    Scopus Count
    Collections
    All Christie Publications

    entitlement

    Related articles

    • Fumarate Hydratase-Deficient Leiomyoma of the Uterine Corpus: Comparative Morphologic Analysis of Protein-Deficient Tumors With and Without Pathogenic Germline Fumarate Hydratase Gene Mutations.
    • Authors: Shi W, Liu Y, Aisagbonhi O, Roma AA, Hasteh F, Zare SY, Fadare O
    • Issue date: 2024 Apr
    • Leiomyoma with bizarre nuclei: a morphological, immunohistochemical and molecular analysis of 31 cases.
    • Authors: Bennett JA, Weigelt B, Chiang S, Selenica P, Chen YB, Bialik A, Bi R, Schultheis AM, Lim RS, Ng CKY, Morales-Oyarvide V, Young RH, Reuter VE, Soslow RA, Oliva E
    • Issue date: 2017 Oct
    • Pattern multiplicity and fumarate hydratase (FH)/S-(2-succino)-cysteine (2SC) staining but not eosinophilic nucleoli with perinucleolar halos differentiate hereditary leiomyomatosis and renal cell carcinoma-associated renal cell carcinomas from kidney tumors without FH gene alteration.
    • Authors: Muller M, Guillaud-Bataille M, Salleron J, Genestie C, Deveaux S, Slama A, de Paillerets BB, Richard S, Benusiglio PR, Ferlicot S
    • Issue date: 2018 Jun
    • Clinicopathological and molecular characteristics of fumarate hydratase-deficient uterine smooth muscle tumors: a single-center study of 52 cases.
    • Authors: Li H, Yang W, Tu X, Yu L, Huang D, Cheng Y, Chang B, Tang S, Ge H, Bao L, Zhou X, Bi R
    • Issue date: 2022 Aug
    • Morphologic and molecular characteristics of uterine leiomyomas in hereditary leiomyomatosis and renal cancer (HLRCC) syndrome.
    • Authors: Sanz-Ortega J, Vocke C, Stratton P, Linehan WM, Merino MJ
    • Issue date: 2013 Jan
    DSpace software (copyright © 2002 - 2025)  DuraSpace
    Quick Guide | Contact Us
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.