title: Epithelioid Hemangioendothelioma: clinicopathologic, immunhistochemical, and molecular genetic analysis of 39 cases.
abstract: BACKGROUND
  Epithelioid hemangioendothelioma is a malignant, often indolent vascular tumor which occurs at various anatomic sites. Based on a reciprocal translocation t (1;3)(p36;q25), a consistent WWTR1-CAMTA1 fusion gene has been found. An alternate YAP1-TFE3 fusion has been detected in a small and distinct subset of cases.
  
  
  METHODS
  Thirty-nine tumors, from 24 females and 15 males with an age range 9-85 years, were located in soft tissue (head and neck [8], trunk [5], upper extremities [3], lower extremities [2], mediastinal [1], and paratesticular [1]), lymph node (1), breast (1), skin (2), bone (6), lung (7), and liver (2). The cases were investigated using a panel of immunohistochemical markers. The aforementioned fusion-genes were examined using RT-PCR and/or FISH in order to validate their diagnostic value.
  
  
  RESULTS
  Follow-up available for 17 patients ranged from 3 months to 7 years (median interval 1.5 years). Eleven patients were alive without disease, 2 patients were alive with disease after 1.5 and 2 years, respectively. Four patients died of disease after 4 months (n = 1), 5 months (n = 2), and 1.5 years (n = 1).The size, known for 30 lesions, was >3 cm in 9 of them. Histologically, all lesions had classical features, at least focally. Four tumors counted >3 mitoses/50 HPF. Immunohistochemically, all cases tested stained positive for ERG (21), FLI1 (5) and CD31 (39). CD34 and D2-40 positivity was seen in 81% and 71% of the examined cases, respectively. 11/35 cases expressed pan-keratin and 6/20 cases CK8.18. TFE3 showed a nuclear reaction in 21/24 cases, irrespective of TFE3 rearrangement.Molecular genetically, 35/35 cases revealed one of the fusion genes by FISH and/or RT-PCR with WWTR1-CAMTA1 in 33 cases and YAP1-TFE3 in 2 cases.
  
  
  CONCLUSIONS
  These results demonstrate the high diagnostic value of FISH and RT-PCR in detecting the fusion genes of EHE. The immunohistochemical utility of TFE3 appears questionable in this study.
  The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4010279141259481.
authors.affiliation: Department of Pathology, Radboud University Medical Center, P,O, Box 9101, 6500 HB Nijmegen, The Netherlands. uta.flucke@radboudumc.nl.
authors.forename: Uta
authors.initials: U
authors.lastname: Flucke
authors.forename: Rob J C
authors.initials: RJ
authors.lastname: Vogels
authors.forename: Nicolas
authors.initials: N
authors.lastname: de Saint Aubain Somerhausen
authors.forename: David H
authors.initials: DH
authors.lastname: Creytens
authors.forename: Robert G
authors.initials: RG
authors.lastname: Riedl
authors.forename: Joost M
authors.initials: JM
authors.lastname: van Gorp
authors.forename: Anya N
authors.initials: AN
authors.lastname: Milne
authors.forename: Clement J
authors.initials: CJ
authors.lastname: Huysentruyt
authors.forename: Marian A J
authors.initials: MA
authors.lastname: Verdijk
authors.forename: Monique M
authors.initials: MM
authors.lastname: van Asseldonk
authors.forename: Albert J H
authors.initials: AJ
authors.lastname: Suurmeijer
authors.forename: Johannes
authors.initials: J
authors.lastname: Bras
authors.forename: Gabriele
authors.initials: G
authors.lastname: Palmedo
authors.forename: Patricia J T A
authors.initials: PJ
authors.lastname: Groenen
authors.forename: Thomas
authors.initials: T
authors.lastname: Mentzel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D002648:Child; D005260:Female; D018323:Hemangioendothelioma, Epithelioid / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor