Nimesh R Patel1,2, Alaa A Salim3, Hadi Sayeed1,2, Stephen F Sarabia1,2, Faith Hollingsworth1,2, Mikako Warren4, Jared Jakacky1,2, Munir Tanas5, Andre M Oliveira6, Brian P Rubin7, Alexander J Lazar3, Dolores López-Terrada1,2, Wei-Lien Wang3. 1. Department of Pathology, Texas Children's Hospital, Houston, TX, USA. 2. Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA. 3. Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 4. Department of Pathology and Laboratory Medicine, Cincinnati Children's Hospital, Cincinnati, OH, USA. 5. Department of Pathology, University of Iowa, Iowa City, IA, USA. 6. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. 7. Pathology and Laboratory Medicine Institute, Cleveland Clinic and the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA.
Abstract
AIMS: Epithelioid haemangioendothelioma (EHE) is a malignant vascular neoplasm. Subsets have been characterized previously by translocations resulting in either WWTR1-CAMTA1 or YAP1-TFE3 fusion. We sought to develop molecular and immunohistochemical (IHC) assays to aid in the diagnosis and characterization of EHE. METHODS AND RESULTS: Fifty-two formalin-fixed, paraffin-embedded (FFPE) cases diagnosed between 2002 and 2014 were retrieved from the pathology files of our institutions. Reverse transcription-polymerase chain reaction (RT-PCR) assays were optimized to detect WWTR1-CAMTA1 and YAP1-TFE3 fusion transcripts in FFPE tissue and transcription factor E3 (TFE3) protein accumulation was examined by immunohistochemistry (IHC). RNA was extracted from 33 adequate samples, with more recent cases providing a greater yield of high quality RNA. Fourteen of 18 informative cases were positive for WWTR1-CAMTA1 fusion transcripts, four of which showed higher-grade cytological features termed by some as 'malignant EHE'. Novel in-frame fusion transcripts were identified in four cases by direct sequencing. IHC revealed variable nuclear TFE3 staining in six of 17 cases; three with patchy staining showed WWTR1-CAMTA1 fusion. One of 18 informative cases was positive for YAP1-TFE3 fusion and showed strong nuclear TFE3 staining by IHC. CONCLUSIONS: This study confirms the high incidence of WWTR1-CAMTA1 and YAP1-TFE3 rearrangements in EHE and indicates that the staining pattern for TFE3 IHC is critical for specificity.
AIMS: Epithelioid haemangioendothelioma (EHE) is a malignant vascular neoplasm. Subsets have been characterized previously by translocations resulting in either WWTR1-CAMTA1 or YAP1-TFE3 fusion. We sought to develop molecular and immunohistochemical (IHC) assays to aid in the diagnosis and characterization of EHE. METHODS AND RESULTS: Fifty-two formalin-fixed, paraffin-embedded (FFPE) cases diagnosed between 2002 and 2014 were retrieved from the pathology files of our institutions. Reverse transcription-polymerase chain reaction (RT-PCR) assays were optimized to detect WWTR1-CAMTA1 and YAP1-TFE3 fusion transcripts in FFPE tissue and transcription factor E3 (TFE3) protein accumulation was examined by immunohistochemistry (IHC). RNA was extracted from 33 adequate samples, with more recent cases providing a greater yield of high quality RNA. Fourteen of 18 informative cases were positive for WWTR1-CAMTA1 fusion transcripts, four of which showed higher-grade cytological features termed by some as 'malignant EHE'. Novel in-frame fusion transcripts were identified in four cases by direct sequencing. IHC revealed variable nuclear TFE3 staining in six of 17 cases; three with patchy staining showed WWTR1-CAMTA1 fusion. One of 18 informative cases was positive for YAP1-TFE3 fusion and showed strong nuclear TFE3 staining by IHC. CONCLUSIONS: This study confirms the high incidence of WWTR1-CAMTA1 and YAP1-TFE3 rearrangements in EHE and indicates that the staining pattern for TFE3 IHC is critical for specificity.
Authors: Nimesh R Patel; John S A Chrisinger; Elizabeth G Demicco; Stephen F Sarabia; Jacquelyn Reuther; Erica Kumar; Andre M Oliveira; Steven D Billings; Judith V M G Bovée; Angshumoy Roy; Alexander J Lazar; Dolores H Lopez-Terrada; Wei-Lien Wang Journal: Mod Pathol Date: 2017-07-28 Impact factor: 7.842
Authors: Akeesha A Shah; N Paul Ohori; Linwah Yip; Christopher Coyne; Cristina R Antonescu; Raja R Seethala Journal: Endocr Pathol Date: 2016-06 Impact factor: 3.943
Authors: Arianeb Mehrabi; Katrin Hoffmann; Karl Heinz Weiss; Carolin Mogler; Peter Schemmer; Markus W Büchler; Ingo Alldinger Journal: Ann Med Surg (Lond) Date: 2016-03-10