Encyclopedia of Pathology

Living Edition
| Editors: J.H.J.M. van Krieken

Angiosarcoma of the Breast

  • Alberto PisacaneEmail author
Living reference work entry
DOI: https://doi.org/10.1007/978-3-319-28845-1_4699-1

Definition

A tumor composed of malignant cells with endothelial differentiation.

Clinical Features

Incidence

Angiosarcoma (AS) of the breast is a rare disease accounting for about 1% of all soft tissue breast tumors.

It may present as primary AS, without previous history of mammary carcinoma or any associated factor, or as secondary AS, most commonly associated with previous breast irradiation.

Primary AS represents <0.05% of all primary breast cancers.

Secondary AS presents a median of 10.5 years after radiotherapy for breast cancer. In those patients undergoing breast conserving surgery with adjuvant radiotherapy, the estimated incidence of radiation-induced AS is 0.05–0.3%.

AS rarely occurs after mastectomy with axillary dissection without irradiation and during pregnancy.

Age

Primary AS more frequently affects young and middle-aged women (median age 30–55 ys).

Secondary AS presents in older women (median age 67–71 ys) after radiotherapy for breast cancer.

Sex

Rare cases of AS have been described in male breast.

Site

Primary AS arises within the breast parenchyma and usually presents with fullness or swelling, which can rapidly grow forming palpable mass or masses, without skin changes.

Secondary AS arises in the cutaneous tissue and might secondarily invade breast parenchyma.

Treatment

Because of rarity of AS, few data are available to support treatment decisions. Surgical resection is key, with mastectomy preferred over breast-conserving therapy. Lymph node dissection is not routinely recommended.

The role of adjuvant radiotherapy and chemotherapy is poorly defined, with many agents showing activity and varying clinical benefit. It is generally agreed that multimodality therapy is the best for this aggressive tumor.

Outcome

The 5-year survival rate of secondary AS patients is in the range of 27%–48%. The 5-year disease-free survival rate is 35%. Tumor size, grade, and number of foci are important prognostic factors.

Low-grade tumors confer better outcomes in terms of disease-free survival interval. Conversely, no statistically significant correlation between tumor size and likelihood of local recurrence has been identified in primary AS, as far as no correlation seems to exist between tumor grade and the rate of local recurrence, distant metastases and death owing to disease.

Macroscopy

Single or multiple erythematous-violaceous nodules and/or papules may be present on the breast skin. On gross examination AS appear as poorly circumscribed, brown and hemorrhagic masses, friable, spongy or firm in breast parenchyma.

Microscopy

Microscopic spectrum ranges from tumors demonstrating well-formed vessels with mild cytologic atypia, to morphologically atypical and undifferentiated pleomorphic sarcoma (Nascimento et al. 2008).

Tumors are histologically graded using Rosen’s three-tier system into low (I), intermediate (II), or high (III) grade.

Low-grade AS (Fig. 1 H&E. Neoplastic vessels dissect mammary parenchyma) are composed of complex anastomosing vascular channels. The endothelium is flat with minimal nuclear atypia and no cellular stratification. Tumor dissects the stroma, causing distortion with little destruction of the preexisting lobules and ducts. The mitotic rate is low (median 2/10 HPF). Necrosis is generally absent.
Fig. 1

Low-grade AS: neoplastic vessels dissect mammary parenchyma

Intermediate-grade AS (Fig. 2 H&E. Cellular area of moderate nuclear atypia; an entrapped duct is in the center) are more cellular and are characterized by intermingled areas of low and moderate nuclear atypia. The endothelial cells lining neoplastic vessels are generally plump, multilayered, frequently arranged in papillary structures. Solid areas are not present. Mitotic rate is low (median 3/10 HPF). Necrosis may be present.
Fig. 2

Intermediate-grade AS: cellular area of moderate nuclear atypia

High-grade AS (Fig. 3) show a generally solid growth pattern with very poorly defined vascular channels, often with prominent areas of hemorrhage (so called “blood lakes”). Tumor cells are mostly spindled or epithelioid and show diffuse and prominent nuclear atypia. Mitotic figures are easily observed. Necrosis is frequent, and the tumor growth is infiltrating with dissection of adjacent breast parenchyma. High-grade AS may contain low- or intermediate-grade elements, especially at the periphery of the lesion.
Fig. 3

High-grade AS: cellular area of solid growth with very poorly defined vascular channels

Immunophenotype

Fli-1, FactorVIII, CD31, CD34, and ERG used in combination have the greatest sensitivity (94%) and specificity (up to 100%).

Molecular Features

MYC gene amplification and protein overexpression has been demonstrated in secondary AS, and more rarely in primary AS.

Differential Diagnosis

The most challenging differential diagnoses of breast AS are represented by low-grade pseudoangiomatous and angiomatous proliferations. Above all, hemangiomas, pseudoangiomatous stromal hyperplasia (PASH), and atypical vascular lesions (AVLs) must be kept in mind (Bowman et al. 2012; Rosen et al. 1988).

Hemangiomas and other benign vascular tumors are generally well-circumscribed lesions composed of well-formed vascular channels and lack a dissecting growth pattern within breast parenchyma (chapter “Hemangioma”).

PASH is a benign proliferation of stromal myofibroblasts, which express CD34 and focally smooth muscle actin or desmin, but not other more specific endothelial markers (CD31, Factor VIII, or ERG) (chapter “Pseudoangiomatous Stromal Hyperplasia”).

AVLs, typically develop 2–5 years after radiotherapy and is histologically characterized by a focal proliferation of dilated, sometimes anastomosing, vascular channels lined by a single layer of endothelial cells in the papillary and reticular dermis. Although AVLs lack cytologic atypia, their exact nature is not fully elucidated.

Immunohistochemical staining combined with fluorescence in situ hybridization for MYC are helpful in distinguishing post-radiation atypical vascular lesions from low-grade secondary AS. Amplification of MYC have been described in secondary AS and are absent in AVLs (Mentzel et al. 2012).

References and Further Reading

  1. Bowman, E., Oprea, G., Okoli, J., Gundry, K., et al. (2012). Pseudoangiomatous stromal hyperplasia (PASH) of the breast: A series of 24 patients. Breast Journal, 18(3), 242–247.CrossRefGoogle Scholar
  2. Lucas, D. R. (2009). Angiosarcoma, radiation-associated angiosarcoma, and atypical vascular lesion. Archives of Pathology & Laboratory Medicine, 133, 1804–1809.Google Scholar
  3. Mentzel, T., Schildhaus, H. U., Palmedo, G., Buttner, R., & Kutzner, H. (2012). Postradiation cutaneous angiosarcoma after treatment of breast carcinoma is characterized by MYC amplification in contrast to atypical vascular lesions after radiotherapy andcontrol cases: Clinicopathological, immunohistochemical and molecular analysis of 66 cases. Modern Pathology, 25, 75–85.CrossRefGoogle Scholar
  4. Nascimento, A. F., Raut, C. P., & Fletcher, C. (2008). Primary angiosarcoma of the breast, clinicopathologic analysis of 49 cases, suggesting that grade is not prognostic. The American Journal of Surgical Pathology, 32, 1896–1904.CrossRefGoogle Scholar
  5. Rosen, P. P., Kimmel, M., & Ernsberger, D. (1988). Mammary angiosarcoma, the prognostic significance of tumor differentiation. Cancer, 62, 2145–2151.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Candiolo Cancer Instutute – FPO IRCCsCandioloItaly