title: Aggressive behavior and poor prognosis of endometrial stromal sarcomas with YWHAE-FAM22 rearrangement indicate the clinical importance to recognize this subset.
abstract: OBJECTIVE
  Although the World Health Organization (WHO) in 2003 defined endometrial stromal sarcomas (ESSs) in general have a good prognosis, considerable differences in clinical behavior and prognosis may exist between different patients with ESS. The ESSs of the type associated with YWHAE-NUTM2 (previously named YWHAE-FAM22) fusion have a more aggressive clinical behavior and poorer prognosis than conventional ESS. Recently, the WHO 2014 classification recognizes this subset of ESS as a separate entity and classifies these as high-grade ESSs. Recognition of this subset has therefore an important clinical impact. We performed a review of the literature to delineate the clinicopathologic features of ESS patients with an YWHAE-NUTM2 rearrangement, with the goal to recognize this subset of ESS.
  
  
  METHODS
  We report a case of a woman with WHO 2014-defined high-grade ESS. Furthermore, published English literature was reviewed for YWHAE-FAM22 ESS and uterus.
  
  
  RESULTS
  Twenty patients were identified, with a median age of 50 (range, 28-67) years. There were no clinical features able to recognize YWHAE-NUTM2 ESS. However, they characteristically contain specific histopathological features. Furthermore, YWHAE-NUTM2 ESSs are strongly cyclin D1 positive in contrast to conventional low-grade ESSs.
  
  
  CONCLUSIONS
  YWHAE-NUTM2 ESSs represent a subset of ESSs with an aggressive clinical behavior and poor prognosis. Specific histopathological features may indicate the presence of YWHAE-NUTM2 rearrangement, which subsequently can be confirmed by cyclin D1 immunostaining.
authors.affiliation: *GROW School for Oncology and Developmental Biology and †Department of Obstetrics and Gynaecology, Maastricht University Medical Center, Maastricht, The Netherlands; ‡Department of Pathology, Institut Bergonie, Bordeaux, France; §Department of Pathology, Maastricht University Medical Center, Maastricht, The Netherlands; and ∥Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Arnold-Jan
authors.initials: AJ
authors.lastname: Kruse
authors.forename: Sabrina
authors.initials: S
authors.lastname: Croce
authors.forename: Roy F P M
authors.initials: RF
authors.lastname: Kruitwagen
authors.forename: Robert G
authors.initials: RG
authors.lastname: Riedl
authors.forename: Brigitte F M
authors.initials: BF
authors.lastname: Slangen
authors.forename: Toon
authors.initials: T
authors.lastname: Van Gorp
authors.forename: Koen K
authors.initials: KK
authors.lastname: Van de Vijver
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011379:Prognosis; D012196:Review Literature as Topic; D018203:Sarcoma, Endometrial Stromal / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D015514:Oncogene Proteins, Fusion; C576541:YWHAE-FAM22 fusion protein, human