The utility of MYC and FLT4 in the diagnosis and treatment of postradiation atypical vascular lesion and angiosarcoma of the breast

Hum Pathol. 2015 Jun;46(6):868-75. doi: 10.1016/j.humpath.2015.02.014. Epub 2015 Mar 10.


Atypical vascular lesions (AVLs) and angiosarcomas (ASs) are well-recognized complications of radiotherapy for breast cancer. Early diagnosis may be challenging, particularly on small biopsies, and the treatment options are limited. Recently, MYC and sometimes FLT4 gene amplification has been reported in AS, but not in AVL, and FLT4 may be a target for therapy. We evaluated the MYC/FLT4 status in AVL and AS by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), determined its utility in differentiating these 2 entities in small biopsies, and ascertained the value of FLT4 as a potential marker for targeted therapy. Thirty-five vascular neoplasms were reviewed from 21 breast cancer patients who received radiotherapy (AVL, n = 18; AS, n = 17). MYC expression by IHC and/or gene amplification by FISH were identified in 13 (77%) of 17 ASs, but none of the AVL cases. Four patients had biopsies with follow-up excisions, of which 1 showed the morphology of an AVL on biopsy and AS on excision, both positive for MYC. Of 17 ASs, 3 (18%) showed strong and diffuse 3+ cytoplasmic FLT4 staining by IHC and FLT4 gene amplification by FISH. All 3 cases were coamplified for the MYC gene. Focal and weak FLT4 cytoplasmic immunoreactivity was present in 2 (12%) of 17 AVL cases and 12 (70%) of 17 AS cases. Although MYC is a valuable ancillary tool in distinguishing AS from AVL, FLT4 IHC may be used to screen for patients with FLT4 gene amplification who might benefit from targeted therapy, as only diffuse strong FLT4 immunoreactivity correlated with FLT4 gene amplification.

Keywords: Angiosarcoma; Atypical vascular lesion; FISH; FLT4; Immunohistochemistry; MYC; Post-radiation.

MeSH terms

  • Adult
  • Aged
  • Breast / pathology
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / therapy*
  • Female
  • Hemangiosarcoma / diagnosis*
  • Hemangiosarcoma / therapy*
  • Humans
  • Immunohistochemistry / methods
  • Middle Aged
  • Neoplasms, Radiation-Induced / metabolism
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Vascular Diseases / diagnosis
  • Vascular Diseases / therapy
  • Vascular Endothelial Growth Factor Receptor-3 / metabolism*


  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • FLT4 protein, human
  • Vascular Endothelial Growth Factor Receptor-3

Supplementary concepts

  • Angiosarcoma of the breast