title: An Unusual Case of YWHAE-NUTM2A/B Endometrial Stromal Sarcoma With Confinement to the Endometrium and Lack of High-Grade Morphology.
abstract: Endometrial stromal sarcoma (ESS) characterized by YWHAE-NUTM2A/B genetic fusion is a recently recognized entity that is classified as a high-grade (HG) ESS in the 2014 World Health Organization Classification. These are myoinvasive neoplasms and typically contain a monomorphous HG round-cell cyclinD1-positive component with or without an accompanying low-grade (LG) component that is only focally positive/negative for cyclinD1. We report a case of YWHAE-NUTM2A/B ESS in a 46-yr-old woman that showed a number of unusual histologic features, including being entirely confined to the endometrium with no myoinvasion or lymphovascular space invasion. The initial hysteroscopic biopsy showed a cyclinD1-positive classic LG ESS-like component which merged with a smaller cyclinD1 negative/focally positive fibroblastic component with no HG areas. YWHAE-NUTM2A/B genetic fusion was shown by real-time quantitative polymerase chain reaction and Sanger sequencing. In the subsequent hysterectomy specimen, the tumor was entirely confined to the endometrium and was largely composed of cellular and classic LG ESS-like areas (80%) which were strongly and diffusely positive for cyclinD1 and a focal fibroblastic component (20%) which was largely cyclinD1 negative. Despite the cellular areas showing mild nuclear enlargement, the entire tumor had a very low mitotic and proliferation index and showed strong and diffuse positivity for estrogen and progesterone receptors. The patient remains alive and well with no evidence of disease 14 mo following diagnosis. To our knowledge, this is the first reported case of YWHAE-NUTM2A/B ESS that is confined to the endometrium and which exhibits entirely LG morphology.
authors.affiliation: Departments of Histopathology (A.D.A, K.V., S.J.H.) Surgery (D.P.J.B.), Royal Marsden Hospital Institute of Cancer Research (K.K.), London Department of Pathology (W.G.M.), Belfast Health and Social Care Trust, Belfast Department of Molecular Diagnostics (D.W.), Royal Marsden Hospital, Sutton, Surrey, UK Department of Pathology (P.D.C.), Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Ayoma D
authors.initials: AD
authors.lastname: Attygalle
authors.forename: Katherine
authors.initials: K
authors.lastname: Vroobel
authors.forename: Dorte
authors.initials: D
authors.lastname: Wren
authors.forename: Desmond P J
authors.initials: DP
authors.lastname: Barton
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Hazell
authors.forename: Paola Dal
authors.initials: PD
authors.lastname: Cin
authors.forename: Konrad
authors.initials: K
authors.lastname: Koelble
authors.forename: W Glenn
authors.initials: WG
authors.lastname: McCluggage
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000032:analysis; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D050596:Oncogene Fusion / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D018203:Sarcoma, Endometrial Stromal / Q000235:genetics* / Q000473:pathology*
chemical_list: D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; C482983:YWHAE protein, human