July 2023 – Breast Pathology Case 2

The patient was a 73-year-old woman with a palpable lesion in the right breast. Mammography confirmed a 1.8 cm focal asymmetry at 3 o’clock, located 13-15 cm from the nipple in the posterior depth. The patient had a history of common variable immunodeficiency and chronic lymphocytic leukemia but no history of breast disease or radiation. Several immunohistochemical studies were performed and are provided below.

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

  • Angiosarcoma
  • Angiolipoma
  • Atypical vascular lesion (AVL)
  • Hemangioma

The correct answer is ...


The hematoxylin-eosin-stained slide sections from the right breast core biopsy confirm an architecturally complex vascular proliferation comprised of well-formed small- to medium-sized anastomosing vessels that surround adipocytes and islands of adipose tissue. The vascular channels have angulated luminal centers with varying degrees of endothelial lining atypia.

SMA IHC highlights smooth muscle in vascular wall spaces, and an HHV8 study is negative, helping to exclude Kaposi sarcoma (IHC not shown here). 

The combined morphology and ancillary testing findings are those a primary angiosarcoma of the breast. The majority of the disease in this small biopsy appears well differentiated. Importantly, grade has not been shown to correlate directly with outcomes/prognosis in primary angiosarcomas of the breast, and better differentiated tumors may metastasize. 

Angiosarcoma is a malignant tumor arising from the endothelial cells lining the blood vessels. It is characterized by the proliferation of haphazardly arranged vascular spaces lined by morphologically aberrant endothelial cells. The vessels within angiosarcomas often form complex anastomosing channels. Tumor borders are infiltrative, and involvement of lobules is common. The nuclei of the lesional endothelial cells often show enlargement, hyperchromasia, and pleomorphism. Tumor cells may proliferate to form papillary tufts within vessel lumina. Angiosarcoma can present as a mass in the breast or as diffuse involvement of the breast tissue. Immunohistochemical studies for endothelial markers such as CD31, CD34, and factor VIII can be used to confirm the diagnosis. 

Atypical vascular lesion is a benign lesion that can mimic angiosarcoma on histology. It is characterized by the presence of dilated lymphovascular channels in the dermis of the skin. These lesions lack significant atypia/pleomorphism and do not invade surrounding tissue or metastasize. 

Hemangioma is a benign tumor composed of blood vessels and can appear similar to angiosarcoma on histology, especially in small core biopsy samples. Hemangiomas are usually well-circumscribed and composed of thin-walled blood vessels lined by flattened endothelial cells without significant nuclear atypia.

Angiolipoma is a benign tumor composed of mature adipose tissue and small, round, capillary-sized blood vessels. Angiolipomas are most often identified in the subcutis and are less common in the substance of the breast proper. Histologically, angiolipoma is characterized by a mixture of mature adipose tissue and small, thin-walled blood vessels. Fibrin thrombi may be seen in the blood vessels. The endothelial cells in angiolipoma are not atypical and lack the proliferation and nuclear atypia seen in angiosarcoma. The distinction between angiosarcoma and other benign entities is important, as breast angiosarcomas can be aggressive malignancies with high potentials for recurrence and metastases. Treatment of angiosarcoma usually involves surgical resection of the tumor, often followed by radiation therapy and/or chemotherapy. The prognosis for breast angiosarcoma is generally poor. Relevant benign differential diagnoses, on the other hand, are conditions that may not require further treatment and may be cured by simple excision. 


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Tao Zhang, M.D.

Fellow, Surgical Pathology
Mayo Clinic

Charles Sturgis, M.D.

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.