Breast – Malignant, Males, Children

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Breast-malignant, males, children

Angiosarcoma

Author: Nat Pernick, M.D, PathologyOutlines.com, Inc.

Reviewer: Daniel Visscher, M.D., University of Michigan Hospitals, February 2009 (see Reviewers page)

Revised: 14 April 2010

Last major update: October 2009

Definition

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● Tumor composed of malignant cells with endothelial features

Terminology

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● Also called lymphangiosarcoma, less preferred term is “malignant hemangioendothelioma”

Epidemiology

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● Rare, < 0.2% of primary breast tumors (Ann Diagn Pathol 2009;13:147), 3-9% of breast sarcomas

● (a) young women with no prior history

● (b) women 5-10 years post-radiation therapy for breast carcinoma (in skin or breast, Cancer 2009;115:4055), or

● (c) skin of chronically edematous arm after axillary lymph node dissection (Stewart-Treves syndrome, incidence has decreased dramatically due to use of more conservative surgery)

● Note: post-radiation and post-axillary dissection cases have more prominent cutaneous involvement

Clinical

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● Clinically forms bulky mass associated with bruise-like cutaneous changes

● Estimated incidence of 0.14% after breast conserving therapy (J Am Acad Dermatol 2006;54:499)

● Precursor lesion is “atypical vascular lesion”, which occurs after surgery and radiation of the breast (Am J Surg Pathol 2008;32:943)

● May resemble recurrent breast carcinoma clinically (Clin Breast Cancer 2008;8:94)

Xray

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● Solitary mass on mammography without calcifications or skin thickening, at site of prior surgical incision

Case reports

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● Tumor post-radiation therapy #1 (Archives 2002;126:989), #2 (Univ Oklahoma), #3 (Int Semin Surg Oncol 2006;3:26), #4-low grade tumor (Hum Pathol 1992;23:710), #5-bilateral tumor with Paget’s disease (Mod Pathol 1995;8:1)

● 26 year old woman with epithelioid angiosarcoma (Am J Surg Pathol 1997;21:599)

Treatment and prognosis

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● Treatment is complete excision

● Post-radiation cases have shorter latency period and no edema, compared to Stewart-Treves syndrome cases (Am J Surg Pathol 2004;28:781)

● Tumors have similar behavior with or without prior radiation therapy (Cancer 2005;104:2682)

● Median survival of 3-6 years (Am J Clin Oncol 2009 Jul 2 [Epub ahead of print])

● Often recurs locally

● Grading may not have prognostic significance (Am J Surg Pathol 2008;32:1896, but see Am J Surg Pathol 1983;7:53)

Clinical images

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Hemorrhagic lesion Post-radiotherapy Erythema and ulceration

51 year old woman with high grade tumor

Gross description

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● Soft, spongy, hemorrhagic

● May have blue nodules at site of prior scar

● Mean 5 cm

● Usually poorly circumscribed

Gross images

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Well circumscribed mass (AFIP) Infiltrative mass Intermediate grade

with hemorrhage tumor with hemorrhage

High grade tumor

Contributed by anonymous pathologist:

Mastectomy post radiation and Hemorrhagic mass

chemotherapy for ductal carcinoma

Microscopic description

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● Anastomosing vascular channels lined by atypical endothelial cells with pleomorphic, hyperchromatic nuclei

● Infiltrative margins

● Microscopic heterogeneity common within same tumor, so sample thoroughly

● Variable mitotic activity

● Usually no fibrous septae, no epithelial component

● Post-radiation tumors are typically high grade

Grade I (well differentiated):

● Anastomosing vascular channels dissect interlobular stroma

● Vessels have wide lumina with red blood cells

● Endothelium lining vessels have prominent and hyperchromatic nuclei, may resemble benign vascular tumors

Grade II (moderately differentiated):

● 75% of tumor is well differentiated, but solid foci are also found (Am J Surg Pathol 1981;5:629)

Grade III (poorly differentiated):

● Interanastomosing vascular channels are intermingled with solid endothelial or spindled areas, with necrosis and mitotic figures

● At least 50% of tumor is composed of solid or spindled areas without vascular channels

Micro images

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Neoplastic vascular Solid areas and neoplastic Markedly pleomorphic tumor cells,

channels vascular channels mitotic figures and apoptotic cells

Focal spindle cells Large vascular cavities in which epithelioid

endothelial cells in a peritheliomatous configuration,

resembling a papillary intravascular growth

Various images

Complex anastomosing vascular pattern

Fig 1: Infiltrating vascular lesion with spindle cell proliferation in dermis

Fig 2/3: Pleomorphic spindle cells with “blood lakes” and brisk mitotic activity

Low grade tumor recurring as high grade tumor

Low grade angiosarcoma

Low grade angiosarcoma (contributed by anonymous pathologist)

Well differentiated tumor

Intermediate grade angiosarcoma

Dilated vascular spaces contain Focal solid neoplastic vascular

endothelial cells and red blood cells proliferation in fat

Focal spindle cell and small Focal complex capillary and Spindle cells and

vessel proliferation endothelial cell proliferation mitotic figure

High grade angiosarcoma

Irregular spaces resemble Anastomosing vascular

adenocarcinoma channels

High grade tumor

Anastomosing vascular channels Solid growth and hemorrhagic necrosis

with spindle and papillary foci

Spindle cells with indistinct Plump spindle cells Blood lakes (foci of

vascular spaces with mitoses hemorrhagic necrosis)

29 year old woman with poorly differentiated tumor:

H&E

Factor VIII

Post-mastectomy (AFIP):

Atypical vascular proliferation in dermis and Vascular channels in superficial dermis

subcutis and changes of chronic lymphedema with endothelial atypia

Anastomosing vascular channels with papillary Focal solid pattern of atypical endothelial cells

proliferation of atypical endothelial cells

Post-radiotherapy:

Skin tumor

Stains

H&E and Ki-67 Factor VIII+ endothelial

cells (AFIP)

H&E, Ki-67 and Skp2 CD31

Cytology description

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● Moderate to highly cellular with variable cellular aggregates

● Cells are epithelioid and spindled

● May have subtle angioformative changes (Cancer 2005;105:145)

Cytology images

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Large, three dimensional cellular aggregates Cells are round/oval, epithelioid or spindled with

and smaller sheets with looser elements and occasional cytoplasmic prolongations; an abundant

noncohesive cells in a bloody background (Pap) network of thin, arborizing vessels is seen (Pap)

Cells have round nuclei with smooth contours, Angioformative changes: (A) loosely aggregated

moderate cytoplasm, 1+ nucleoli of variable cells may cluster in a rosette-like configuration

size and irregular configuration; also a cell (arrows), (B) in three-dimensional aggregates,

with nuclear grooves and scattered, single spindled and epithelioid cells appear to cluster

elements with long cytoplasmic prolongations around vascular lumina as whorls or palisades

CD31 expression in the cytoplasm of spindled and epithelioid cells in this three-dimensional aggregate

Positive stains

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● Vimentin, Factor VIII

● ER (variable)

● CD31 and CD34 (well differentiated areas)

● High Ki-67 (Archives 2007;131:538)

Negative stains

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● Keratin

Electron microscopy

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● Prominent pinocytic vesicles and cell-cell junctions

Differential diagnosis

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● Metaplastic carcinoma

● Acantholytic squamous cell carcinoma - has at least focal areas of squamous differentiation, keratin+, negative for vascular markers

● Hemangioma - well circumscribed, no atypia

● Atypical vascular lesions - more circumscribed, less atypia than low grade angiosarcoma

● Pseudoangiomatous stromal hyperplasia

Additional references

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● Am J Surg Pathol 2004;28:781, Am J Surg Pathol 1983;7:329 (Stewart-Treves syndrome), Stanford University

End of Breast – Malignant, Males, Children > Angiosarcoma

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