Breast malignant
Sarcoma
Angiosarcoma


Topic Completed: 1 June 2016

Revised: 17 October 2019

Copyright: 2002-2019, PathologyOutlines.com, Inc.

PubMed Search: Angiosarcoma [title] breast "loattrfree full text"[sb]

Emily S. Reisenbichler, M.D.
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Cite this page: Reisenbichler ES. Angiosarcoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/breastmalignantangiosarcoma.html. Accessed October 18th, 2019.
Definition / general
  • A tumor composed of malignant cells with endothelial differentiation
Essential features
  • Rare overall tumor of the breast (0.05% of all primary breast malignancies) but most common sarcoma of the breast
  • Occurs most frequently secondary to prior radiation therapy for breast carcinoma, typically in older patients
  • May arise as primary (de novo) sarcoma of the breast, typically in younger patients
  • Worst prognosis of all breast sarcomas
Etiology
  • Secondary to longstanding lymphedema, often after axillary lymph node dissection (Stewart-Treves syndrome)
  • Secondary to radiation, typically for breast carcinoma
  • Primary angiosarcoma of the breast may be idiopathic
Clinical features
  • Secondary angiosarcoma often presents with skin changes, typically in older patients (median age 70; median 10.5 years after radiation) due to prior breast cancer history
  • Primary angiosarcoma presents as a palpable mass in younger patients (median age 40)
  • Most frequently metastasize to lungs, skin (including contralateral breast), bone and liver
Radiology description
  • Mammographic and ultrasound findings of secondary angiosarcoma are nonspecific and may be indistinguishable from typical changes seen following breast conservation therapy, including skin thickening, retraction, edema and architectural distortion
  • MRI findings include skin thickening, skin enhancement, enhancing cutaneous nodules and enhancing intraparenchymal masses (J Magn Reson Imaging 2015;42:763)
  • MRI may allow more accurate assessment of extent of disease than other breast imaging modalities (J Magn Reson Imaging 2015;42:763)
Radiology images

Contributed by Mark R. Wick, M.D.

MRI

Prognostic factors
  • Angiosarcoma has the worst prognosis of all breast sarcoma, with median recurrence free survival < 3 years and medial overall survival < 6 years
  • Overall prognosis is poor with high rates of recurrence and metastasis
  • Better prognosis seen with non-menopausal status, complete surgical excision, absence of tumor necrosis, low or intermediate grade histology (Radiother Oncol 2007;85:355)
  • Tumor size has been shown by some to be prognostic (J Clin Oncol 2003;21:2583), while others have shown no correlation between size and survival (Radiother Oncol 2007;85:355)
Case reports
  • 38 year old woman with recurrent primary angiosarcoma of the breast presenting as Kasabach-Merritt Syndrome (J Clin Diagn Res 2016;10:XD04)
  • 55 year old woman with BRCA2 gene variation and angiosarcoma only 6 months after radiation for breast carcinoma (Clin Breast Cancer 2015;15:536)
  • 57 year old man with HIV and primary angiosarcoma of the breast (Breast J 2015;21:545)
  • 77 year old woman with bilateral angiosarcoma 12 years after radiation for breast carcinoma (Breast J 2013;19:547)
  • 77 year old woman with Stewart-Treves Syndrome following breast conservation therapy and axillary dissection for breast carcinoma 5 years prior (Breast J 2015;21:552)
Treatment
  • Complete surgical excision, typically mastectomy, is the gold standard for treatment
  • Since axillary metastasis are rare, axillary dissection is not indicated unless there is clinical evidence of nodal metastases (Ann Oncol 2014;25:iii102)
  • In cutaneous radiation-associated angiosarcomas, excision of all breast tissue, including all previously radiated skin, resulted in improved recurrence free and overall survival (Ann Surg Oncol 2012;19:3801)
  • Adjuvant chemotherapy use is varied, but has been shown to improve overall survival rates in those with localized (Cancer 2008;113:573) and metastatic angiosarcoma (Eur J Dermatol 2011;21:539)
  • Radiation therapy may be used for microscopically positive margins following surgical resection
Clinical images

Contributed by Mark R. Wick, M.D.

Breast

Postradiation

Gross description
  • Average tumor size is 5 cm
  • Purple to bluish nodules and patches of discoloration may be seen in the skin
  • Large, poorly circumscribed, hemorrhagic firm tumors
  • Borders / margins may be hard to assess grossly
Gross images

Contributed by Mark R. Wick, M.D.

Breast skin

Mastectomy
postradiation and
chemotherapy for
ductal carcinoma


 AFIP images

Well circumscribed mass

Microscopic (histologic) description
  • Microscopic spectrum ranging from morphologically low grade tumors demonstrating well formed vessels with mild cytologic atypia, to morphologically high grade tumors showing severe pleomorphism, mitotic activity and solid growth pattern resembling an undifferentiated pleomorphic sarcoma

  • Morphologically low grade (well differentiated):
    • Resemble benign vascular lesions
    • Anastomosing/branching, often dilated vascular channels lined by minimally atypical endothelial cells with plump, hyperchromatic nuclei
    • No/rare mitoses, no/rare tufting of endothelial cells
    • Key distinguishing feature from benign vascular lesions is an infiltrative growth pattern

  • Morphologically intermediate grade (moderately differentiated):
    • Similar to well differentiated/low grade tumors but with increased mitoses, endothelial tufting and foci of solid growth pattern

  • Morphologically high grade (poorly differentiated):
    • Marked pleomorphism, mitoses, necrosis and solid growth
    • Extravasation of blood from malignant vessels forming blood lakes
    • May show epithelioid and spindled cytology with no obvious vasoformative morphology
Microscopic (histologic) images

Contributed by Emily S. Reisenbichler, M.D.

Low grade angiosarcoma

Dilated cytologically bland vessels infiltrating breast lobules, H&E and ERG immunostain


 Intermediate grade angiosarcoma

Anastomosing
vascular channels
with endothelial
tufting



High grade angiosarcoma

Markedly atypical
cells with solid
growth pattern
and blood lakes

Solid growth pattern
with spindled
cytology and
increased mitoses

Vasoformative,
markedly pleomorphic
tumor with
epithelioid cytology


 Postradiotherapy

Anastomosing
vascular channels
infiltrating the
dermis

Cytology description
  • Variable nuclear atypia and mitoses depending on tumor grade
  • Individual cells can be spindled, epithelioid or plasmacytoid
  • In higher grade tumors, papillary structures may be present as vasoformative features, including hemophagocytosis (54%), cytoplasmic lumina/vacuoles (69%) containing red blood cells (54%) or neutrophils (31%), and endothelial wrapping (69%),
  • Vasoformative features such as hemophagocytosis, cytoplasmic lumina and endothelial wrapping are frequently seen but are not specific and can be seen in nonvascular neoplasms (Cancer Cytopathol 2016 Apr 12 [Epub ahead of print])
Positive stains
Molecular / cytogenetics description
  • MYC amplification is seen in secondary angiosarcoma, rarely in primary cutaneous (non-radiated) angiosarcoma, and not seen in atypical vascular lesions (Mod Pathol 2014;27:509, Mod Pathol 2012;25:75)
  • FLT4 co-amplification, possibly as a “second-hit” in tumor progression, is seen in a subset of secondary angiosarcomas but not in atypical vascular lesions or other radiation associated sarcomas (Genes Chromosomes Cancer 2011;50:25)
Additional references
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