March 2022 – Breast Pathology

A 20-year-old woman presented with right breast palpable mass. No prior history of any malignancy, surgery, trauma, or radiation is noted. Ultrasound-guided right breast mass biopsy was performed, and the hematoxylin and eosin-stained slides were reviewed. Several immunohistochemical studies were also performed and the pictures are shown below.

Figure 1: H&E 20x
Figure 2: H&E 40x
Figure 3: H&E 60x
Figure 4: CD31-40X
Figure 5: ERG-40X
Figure 6: MYC-40X

Based on the histomorphology and immunohistochemical studies, what is the correct diagnosis?

  • Papillary endothelial hyperplasia
  • Atypical vascular lesion
  • Primary angiosarcoma of the breast
  • Pseudoangiomatous stromal hyperplasia

The correct answer is ...

Primary angiosarcoma of the breast.

The hematoxylin-eosin stained slide section shows the malignant vasoformative neoplasm. Small- to medium-sized anastomosing neoplastic vessels dissect through the background fibroadipose tissue. Sheet-like solid area with malignant spindled cells and a few admixed epithelioid cells are present. Geographic necrosis is present, and mitotic figures are identified.

The immunohistochemical (IHC) study slides show the neoplastic cells to be immunoreactive with ERG and CD31. In addition, MYC is overexpressed by IHC in the neoplastic cells. The combined histology and clinical data are most consistent with a high-grade primary (non-radiotherapy related) mammary angiosarcoma. MYC overexpression has been reported in a few primary angiosarcomas but is more commonly associated with post-radiation angiosarcomas in the breast. The prognostic significance of the MYC positivity is uncertain.

These tumors are typically located in deep breast parenchyma with infiltrative or poorly circumscribed border. The neoplastic vascular channels in angiosarcoma have dilated, compressed, or angulated lumina. The lining endothelial cells range from bland to variably atypical, usually spindled, hyperchromatic nuclei that may be plump or flattened. Poorly differentiated angiosarcomas have solid, cellular foci comprising of spindled to epithelioid cells intermingled with variably formed anastomosing vascular channels, associated with prominent blood-lakes, mitotic figures and areas of necrosis. 

Angiosarcomas express endothelial markers with strong, membranous CD31 staining and nuclear ERG immunoexpression noted. Variable CD34, FLI1, and D2-40 possibly can be seen. Most tumors lack MYC protein overexpression; however, some primary angiosarcoma can show MYC protein overexpression.


  1. Stephan A Vorburger et al: Angiosarcoma of the breast. Cancer 2005 Dec 15;104(12):2682-8. PMID: 16288486; DOI: 10.1002/cncr.21531.
  2. PP Rosen et al: Mammary angiosarcoma. The prognostic significance of tumor differentiation. Cancer. 1988 Nov 15;62(10):2145-51. doi: 10.1002/1097-0142(19881115)62:10< 2145:aid-cncr2820621014>;2-o.
  3. Ming Yin et al: Prognosis and treatment of non-metastatic primary and secondary breast angiosarcoma: a comparative study. 
    BMC Cancer. 2017 Apr 27;17(1):295. doi: 10.1186/s12885-017-3292-7.

Fnu Sakshi, M.B.B.S.

Fellow, Surgical Pathology
Mayo Clinic

Charles Sturgis, M.D.

Senior Associate Consultant, Anatomic Pathology
Mayo Clinic
Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science

MCL Education

This post was developed by our Education and Technical Publications Team.