Primary Intranodal Epithelioid Hemangioendothelioma with Molecular Confirmation

Int J Surg Pathol. 2022 Aug;30(5):557-563. doi: 10.1177/10668969211070174. Epub 2022 Jan 31.


Epithelioid hemangioendothelioma (EHE) is a rare low-grade malignant vascular tumor with indolent biology, characterized by reciprocal t(1;3)(p36.6;q25) with resultant WWTR1::CAMTA1 gene fusion in the vast majority of cases, regardless of anatomic location. Only a small subset, exhibiting well formed vasoformative features will contain YAP1::TFE3 gene fusion. Primary intranodal EHE is exquisitely rare. We report a case in a 54-year-old male with persistent left groin mass with discomfort for nine months. A CT of the abdomen and pelvis showed a minimally enlarged left inguinal lymph node measuring 2.8 cm with no other masses or lymphadenopathy. PET/CT and MRI imaging of the abdomen showed no evidence of disease elsewhere. Sections showed an epithelioid vasoformative neoplasm, centrally necrotic and involving a lymph node. The cells were arranged in anastomosing cords with intracytoplasmic lumens, resembling "signet ring cells". By immunohistochemistry, the tumor cells were positive for vimentin, CD31, CD34, ERG and CAMTA1; and negative for AE1/3, CAM 5.2, KRT7, KRT20, desmin, actin, HMB-45 and S-100. Ki-67 proliferation index was estimated at <1%. Molecular studies including next generation sequencing (NGS) revealed the presence of WWTR1::CAMTA1 gene fusion, and fluorescence in situ hybridization for CAMTA1 (1p36.23) and WWTR1 (3p25.1) showed fusion signals, diagnostic of EHE. We highlight a rare occurrence of EHE in a lymph node exhibiting morphologic mimicry with metastatic carcinoma.

Keywords: Epithelioid hemangioendothelioma; WWTR1::CAMTA1 gene fusion; intranodal; molecular genetics; primary.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Calcium-Binding Proteins / genetics
  • Child
  • Hemangioendothelioma, Epithelioid* / diagnosis
  • Hemangioendothelioma, Epithelioid* / genetics
  • Hemangioendothelioma, Epithelioid* / pathology
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • Middle Aged
  • Positron Emission Tomography Computed Tomography
  • Sarcoma*
  • Trans-Activators / genetics
  • Transcription Factors / genetics


  • Calcium-Binding Proteins
  • Trans-Activators
  • Transcription Factors