CASE REPORT

Secondary Angiosarcoma of the Breast: Can ImagingFindings Aid in the Diagnosis?

Angela Moore, MD,* Aaron Hendon, MD,* Molly Hester, MD,* andLuis Samayoa, MD�

*Diagnostic Radiology and �Pathology and Laboratory Medicine, University of Kentucky,Lexington, KY

n Abstract: Secondary angiosarcomas, although rare, are aggressive tumors that can develop in breast tissue that hasundergone prior radiation therapy. We present three cases of secondary angiosarcoma of the breast in the setting of priorbreast irradiation. Imaging findings include cutaneous nodules and progressive skin or trabecular thickening in an area ofthe breast separate from the patient’s original breast carcinoma. These imaging findings may enable the radiologist to sug-gest this diagnosis, even when the clinical presentation is more benign. n

Key Words: angiosarcoma, breast, breast carcinoma, radiation therapy

The development of post-radiation sarcomas in the

breast, although rare, is a known occurrence (1–

13). Angiosarcoma, which arises from the endovascu-

lar tissues is one of the most common forms (11,13).

One review reported an estimated 0.04% risk of

acquiring a secondary breast angisoarcoma after

receiving radiation therapy, with a minimum radiation

dose range of 25–60 Gy (1). Breast cancer patients typ-

ically receive a dose of approximately 50–60 Gy (14).

Similar to primary angiosarcomas, which develop

in breast tissue that has not received prior radiation,

these secondary angiosarcomas can behave aggres-

sively and most commonly spread hematogeneously

(1–3). Recurrence rates approach 70% and 2-year

disease-free survival ranges from 0 to 35% (1–

3,5,6,11). Unlike the primary form, however, their

onset can be clinically subtle, often resulting in a

delay in diagnosis (11,12). Primary angiosarcomas

arise within the breast parenchymal tissue and usu-

ally present as an enlarging palpable mass (4). They

are most common between the ages of 20 and 40

(4,11). Overlying skin color changes (purple or bluish

discoloration) may be present, providing a clue to

the diagnosis (1). Primary angiosarcomas have a non-

specific appearance on both mammography and

sonography, often appearing as a noncalcified, soli-

tary, ill-defined, isodense, or hypoechoic mass (4,15).

In contrast, secondary angiosarcomas have a ten-

dency to affect only the skin (1,5). A history of prior

radiation therapy may be the predisposing factor for

this phenomenon (1). Because of their location, the

clinical onset of secondary angiosarcoma is often ini-

tially deceiving. Patients may complain of skin

changes such as skin thickening or discoloration

(1,12). Raised skin nodules, papules, or vesicles may

be noted (6,9,11). Some of these changes (such as

skin thickening) may be attributed to progressive

radiation changes, infection ⁄ inflammation, or even

recurrence of the patient’s original tumor (3,9–12).

The overlying skin discoloration may be dismissed as

mild trauma. Therefore, a high degree of clinical sus-

picion is required for the early diagnosis of these

potentially aggressive tumors.

Radiographic aid in the diagnosis of secondary

angiosarcoma has been reported to be limited

(1,6,10). We present three cases of secondary breast

angiosarcoma that developed in the setting of prior

breast irradiation to illustrate its various radiologic

presentations and discuss how the presence of certain

imaging findings might assist in recognition of these

tumors.

Address correspondence and reprints requests to: Angela R. Moore,

MD, 800 Rose Street, Lexington, KY, 40536, USA, or e-mail: armoor1@uky.

edu.

ª 2008 Blackwell Publishing, Inc., 1075-122X/08The Breast Journal, Volume 14 Number 3, 2008 293–298

CASE REPORTS

Patient 1

In 2004, a Gravida3 Para3 71-year-old woman pre-

sented with a 2-year history of increasing firmness and

skin changes involving her left breast. Her past medi-

cal history was significant for a left upper outer quad-

rant lumpectomy in 1992 to remove a 1.5 cm focus of

ductal carcinoma in situ. In addition, between August

25, 1992 and September 29, 1992, she underwent

radiation therapy receiving a total of 50 Gy to the left

breast. Her initial post-lumpectomy ⁄ radiation therapy

mammogram demonstrated some mild postoperative

changes involving the left upper outer quadrant

(Fig. 1). These changes were essentially resolved by

1999. She began to notice a change in the texture of

her left breast in 2002. She reported that her left

breast became contracted and more firm. Her most

recent mammogram (2004) revealed skin and trabecu-

lar thickening which was attributed to postsurgi-

cal ⁄ radiation changes (Fig. 2). In 2004 she developed

a skin lesion described as an ‘‘open wound’’ over the

left inferior breast measuring 1–2 cm in diameter.

Soon afterwards, she developed multiple cutaneous

nodules and areas of discoloration over the left breast.

A biopsy performed in November 2004 revealed an

angiosarcoma. Thereafter, she underwent a total left

mastectomy. Her final pathology revealed an anaplas-

tic epitheliod angiosarcoma involving the skin and

subcutaneous tissue of the breast (Fig. 3). Computed

tomography (CT) scan of the chest ⁄ abdomen ⁄ pelvis

revealed no evidence of distant metastasis. At this

point, the patient was referred to our institution.

Review of the patient’s prior mammographic exam-

inations revealed progressive skin and trabecular

thickening involving the sub-areolar and inferior

aspect of the left breast (Figs. 4 and 5). Of note, these

CC MLO Figure 1. Initial post-lumpectomy craniocaudal (CC) and medio-

lateral oblique (MLO) views of the left breast from 1994 demon-

strate some mild post-operative changes in the upper outer

quadrant.

CC MLO Figure 2. CC and MLO views (coned to the subareolar region) of

the left breast from 2004 demonstrate increased trabecular and

skin thickening involving the inferior and medial aspect of the

breast, an area separate from the patient’s lumpectomy bed.

Figure 3. Intermediate power (40x) photomicrograph of a repre-

sentative section of the patient’s mastectomy specimen reveals a

post-radiation high grade epithelioid angiosarcoma of the breast

with marked lymphocytic infiltrate.

294 • moore et al.

changes did not affect the upper outer quadrant lump-

ectomy bed region (delineated with a scar marker on

the mediolateral oblique view). The initial mammo-

graphic changes were seen in images from the year

2002. This was also the time the patient began to

first notice the physical changes in her left breast.

These changes were most noticeable when the recent

mammograms were compared with more remote

priors, including the baseline lumpectomy films from

1994.

Although angiosarcomas have a tendency to behave

aggressively, they can follow a more indolent course

(6,12,16). This patient was diagnosed with angiosar-

coma in 2004 but she began to report symptoms in

2002. After her mastectomy, the patient underwent

excision of two separate chest wall recurrences. In

addition, a follow-up CT scan of the chest in June

2005 revealed interval development of right axillary

adenopathy. Excision showed tumor with features

consistent with metastatic angiosarcoma. Angiosarco-

mas like other sarcomas usually spread hematogenous-

ly, although cases of axillary involvement by primary

angiosarcomas have been reported (4,6,17,18).

This patient has remained disease-free at this time.

Her prolonged course demonstrates the progressive

skin changes that can occur with secondary angiosar-

comas of the breast.

Patient 2

In 1998 an 87-year-old female presented with ill-

defined thickening involving the medial aspect of her

left breast as well as a soft tissue nodule with overly-

ing bluish discoloration. Her past medical history was

significant for a prior left upper outer quadrant lump-

ectomy to remove a 1.7 cm invasive well-differenti-

ated ductal adenocarcinoma (2 ⁄ 20 positive axillary

lymph nodes) 7 years prior to her presentation.

She also underwent adjuvant radiotherapy to the

left breast receiving a total of 45 Gy. Follow-up

mammograms revealed evolving post-lumpec-

tomy ⁄ radiation changes which decreased in promi-

nence over time (Fig. 6). Her most recent

mammogram was performed in December 2003,

8 months prior to her presentation.

The patient’s physical findings were initially attrib-

uted to a hematoma. The lesion continued to enlarge,

1994 1999 2002 2003 2004

Figure 5. Sequential CC views also demon-

strating the developing skin/trabecular thick-

ening representing the patient s secondary

angiosarcoma.

1994 1999 2002 2003 2004

Figure 4. Presented are sequential MLO

views of the left breast. Mammographic

changes begin to become apparent in 2001

and steadily progress. These changes are

most striking if comparison is made to the

older studies. Also, note changes in the size

of the breast.

Secondary Angiosarcoma of the Breast: Can Imaging Findings Aid in the Diagnosis? • 295

however, with erosion of the skin. CT scan of the

chest revealed diffuse skin thickening involving the

medial aspect of the left breast as well as an exophytic

mass arising from the lateral aspect of the breast

(Fig. 7). The patient did not undergo mammography

at this time. A biopsy of the exophytic lesion revealed

an epithelioid angiosarcoma. The patient underwent a

simple mastectomy. On pathology review, the tumor

measured 4.2 cm in size. She initially declined chemo-

therapy but developed a chest wall recurrence which

was resected. At this point, she agreed to chemother-

apy and was treated with doxorubicin. She declined

radiation therapy but subsequently developed a second

chest wall recurrence in April 2005. She consented to

chest wall radiotherapy and received a dose of

3,960 cGy to the chest as well as a boost of

1,440 cGy in the area of recurrence around the medial

chest wall scar.

She presented to our institution January 2006 with a

3-week history of lesions on her chest wall which were

clinically consistent with recurrent angiosarcoma. Phys-

ical exam revealed multiple skin nodules (at least 20)

extending across the entire chest wall and down onto

her upper abdomen and flank. These skin lesions were

not amenable to surgical resection. CT scan of her chest

and a bone scan were negative for metastatic disease.

This patient’s disease progressed fairly rapidly. Her

most recent prior mammogram in 2003 was essen-

tially negative. Within 8 months of this mammogram

she presented with the exophytic breast mass.

Although mammography was not performed at that

time, a CT scan of the chest revealed not only the

breast mass, but also associated marked skin thicken-

ing which was new. This secondary angiosarcoma fol-

lowed a more typical aggressive course. The patient

soon expired of the disease.

1998 2000 2003

Figure 6. Sequential post-lumpectomy MLO views of the left

breast demonstrate the breast trabecular and skin thickening had

been decreasing over time.

Figure 7. Axial CT scan of the chest at the level of the interventri-

cular septum demonstrates diffuse skin thickening involving the

medial aspect of the breast as well as an exophytic mass arising

from the lateral aspect of the breast.

Figure 8. Coned MLO view reveals a low density superficial

mass/contour bulge (arrows) along the superior aspect of the left

breast.

296 • moore et al.

Patient 3

A 63-year-old female presented in December 2004

with an erythematous skin lesion on the left breast

close to the nipple. Her past medical history was

significant for a left upper outer quadrant lumpec-

tomy in 1998 to remove a 1.4 cm invasive ductal

carcinoma (0 ⁄ 10 positive axillary lymph nodes). She

also received a total of 60.4 Gy to her left breast in

adjuvant radiotherapy. Mammography revealed a

superficial soft tissue bulge along the superior aspect

of the left breast, best seen on the mediolateral obli-

que view (Fig. 8). Left breast ultrasound revealed an

oval, hypoechoic mass with circumscribed borders

located in the subcutaneous tissue with associated

increased vascularity around the base of the mass

(Fig. 9). On physical examination, areas of discolor-

ation were present on the patient’s skin. The patient

was initially treated with oral antibiotics for possible

skin infection, but the lesions progressed rapidly. She

was eventually referred to a dermatologist who per-

formed a biopsy revealing an invasive poorly differen-

tiated angiosarcoma involving the nipple and skin

with invasion into the sub-areaolar periductal tissue.

A preoperative CT scan of abdomen ⁄ pelvis for radio-

graphic staging was negative for metastatic disease.

This same CT scan revealed skin thickening of the

left breast.

The patient underwent a left mastectomy on April

12, 2005 which revealed a 5.8 cm· 3.9 cm· 2.1 cm

high grade, poorly differentiated angiosarcoma with

involvement of the skin and nipple region. She initially

did well following mastectomy but several weeks later

developed a similar erythematous nodular type lesion

on the medial aspect of her mastectomy scar. Biopsy

of this lesion revealed an angiosarcoma. In August

2005 she underwent a wide excision of the left chest

with partial resection of the pectoralis muscle. Pathol-

ogy revealed a 2 cm · 1.1 cm lesion consistent with

angiosarcoma.

This case differs from the previous cases wherein

this patient did not develop significant skin thickening,

but rather a superficial lesion of the breast. Ultrasound

revealed the mass to be located within the subcutane-

ous tissue and to be associated with increased vascu-

larity, clues to a possible secondary angiosarcoma.

DISCUSSION

Secondary angiosarcomas are a rare but deadly

complication of prior radiation therapy and can occur

in patients who have undergone breast-conservation

surgery with adjuvant radiotherapy. Unfortunately,

this may happen even in patients who were origi-

nally treated for preinvasive or minimally invasive

carcinomas.

Radiologists must be aware of this clinical entity

when reviewing mammograms on patients who have

undergone breast irradiation. Although secondary

angiosarcomas have a predilection to occur within the

skin, they can produce imaging findings. One of the

most obvious mammographic changes is secondary to

the associated erythema or hemorrhage with subse-

quent thickening of the skin or trabecular pattern

(3,6). Radiation to the breast tissue also produces

similar skin and trabecular changes from resulting

edema and eventually fibrosis (3,19–21). It is the time-

line, however, that may provide the most relevant

clues. It is helpful to compare any follow-up mammo-

grams in patients who have undergone breast-conser-

vation surgery and breast irradiation to multiple prior

exams, not just the most recent study. If a pattern of

increasing skin or trabecular thickening is noted, com-

parison to the 6-month post-treatment baseline exam

should be performed. It is at this baseline exam that

the radiation changes should be most pronounced

(usually diffuse skin and trabecular thickening) (19–

21). Radiation changes would not be expected to

increase at a later date but rather decrease in promi-

nence over time (3,19,20). Secondary angiosarcomas

typically occur approximately 5–6 years following

radiation therapy but this may vary (1,2,4–

12,17,18,22). If progressive skin or trabecular thicken-

ing is noted after several years of stability the most

common entities to consider are recurrence of the

patient’s original carcinoma or an inflammatory ⁄ infec-

tious process (3,9). However, radiologists should also

Figure 9. Ultrasound evaluation of the

superficial mass revealed an oval, hypoe-

choic mass with circumscribed borders in the

subcutaneous tissue. Color Doppler analysis

indicated increased vascularity in the base of

the mass.

Secondary Angiosarcoma of the Breast: Can Imaging Findings Aid in the Diagnosis? • 297

be alerted to the possibility of a secondary angiosarco-

ma, especially if the changes occur in a quadrant of

the breast separate from the patient’s initial tumor.

Patients with angiosarcomas may present with pal-

pable cutaneous or subcutaneous masses. These

patients often undergo sonography in their diagnostic

work-up. The ultrasound appearance of these masses

is nonspecific, revealing a superficial hypoechoic mass.

Color Doppler analysis may be helpful if increased

vascularity is noted. Radiologists, however, must be

aware that secondary angiosarcomas are in the differ-

ential diagnosis for any superficial breast mass in the

setting of prior breast irradiation.

Magnetic resonance imaging may also prove to be a

useful tool in the diagnosis of secondary angiosarcoma

of the breast and has been reported in the literature

(6,22). MRI findings include enhancing skin lesions as

well as non-mass-like cutaneous enhancement (22).

In conclusion, secondary angiosarcomas that

develop in the setting of prior breast irradiation can

produce imaging findings that may enable the radiolo-

gist to suggest this diagnosis, even when the clinical

picture is more benign. In our review, we found that

radiologic studies performed in our series of cases

revealed abnormalities suggestive of angiosarcoma

before the clinical diagnosis was made. These included

progressive skin thickening in an area of the breast

separate from the patient’s prior lumpectomy site as

well as superficial mass formation with associated

increased vascularity. As we continue to offer more

women the choice of breast-conservation therapy, the

possibility of post-radiation sarcomas should be kept

in mind. If the patient’s referring clinician does not

suspect a secondary angiosarcoma, the radiologist

may be able to facilitate the diagnosis.

REFERENCES

1. Majeski J, Austin RM, Fitzgerald RH. Cutaneous angiosarco-ma in an irradiated breast after breast conservation therapy for can-

cer. J Surg Oncol 2000;74:208–13.

2. Autio P, Kariniemii AL. Angiosarcoma. A rare secondary

malignancy after breast cancer treatment. Eur J Dermatol1999;9:118–21.

3. Rubin E, Maddox WA, Mazier MT. Cutaneous angiosarcoma

of the breast seven years after lumpectomy and radiation therapy.

Radiology 1990;174:258–60.

4. Liberman L, Dershaw DD, Kaufman RJ, Rosen PP. Angiosar-

coma of the breast. Radiology 1992;183:649–54.

5. Vorburger SA, King Y, Hunt KK, et al. Angiosarcoma of thebreast. Cancer 2005;104:2682–8.

6. Monroe AT, Fiengenberg SJ, Mendenhall NP. Angiosarcoma

after breast conserving therapy. Cancer 2003;97:1832–40.7. Huang J, Mackillop WJ. Increased risk of soft tissue sarcoma

after radiotherapy in women with breast carcinoma. Cancer2001;92:172–80.

8. Fodor J, Orosa Z, Szabo E, et al. Angiosarcoma after conser-vation treatment for breast carcinoma: our experience and a review

of the literature. J Am Acad Dermatol 2006;54:499–504.

9. Gherardi G, Rossi S, Perrone S, Scanni A. Angiosarcoma after

breast-conserving therapy: fine-needle aspiration biopsy, immunocy-tochemistry and clinicopathologic correlates. Cancer Cytopathol2005;105:145–51.

10. Hanasono MM, Osborne MP, Dielubanza EJ, Petus SB, Ga-

yle LB. Radiation-induced angiosarcoma after mastectomy andTRAM flap breast reconstruction. Ann Plast Surg 2005;54:211–4.

11. Tahir M, Hendry P, Baird L, Qureshi NA, Ritchie D, Whit-

ford P. Radiation induced angiosarcoma a sequela of radiotherapyfor breast cancer following conservative surgery. Int Semin SurgOncol 2006;3:26.

12. Adhikari D, Hajdu S, Levine D. Post-radiation angiosarcoma

and bilateral mastectomy. Ann Clin Lab Sci 2000;32:428–33.13. Kirova YM, Vilcoq JR, Asselain B, Sastre-Garau X, Four-

quet A. Radiation-induced sarcomas after radiotherapy for breast

carcinoma: a large-scale single-institution review. Cancer2005;104:856–63.

14. Tobias JS, Vaidya JS, Keshtgar M, D’Souze DP, Baum M.

Reducing radiotherapy dose in early breast cancer: the concept of

conformal intraoperative brachytherapy. Br J Radiol 2004;77:279–84.

15. Glazebrook KN, Morton MJ, Reynolds C. Vascular tumors

of the breast: mammographic, sonographic, and MRI appearances.

Am J Roentgenol 2005;184:331–8.16. Rosen PP, Kimmel M, Ernsberger D. Mammary angiosarco-

ma: the prognostic significance of tumor differentiation. Cancer1988;62:2145–51.

17. Losanoff JE, Jaber S, Esuba M, Perry M, Sauter ER. Primaryangiosarcoma of the breast: do enlarged axillary nodes matter?

Breast J 2006;12:3750–3761.

18. Carter E, Ulusarac O, Dyess DL. Axillary lymph nodeinvolvement in primary epithelioid angiosarcoma of the breast.

Breast J 2005;11:219–20.

19. Brenner RJ, Pfaff JM. Mammographic features after conser-

vation therapy for malignant breast disease: serial findings standard-ized by regression analysis. Am J Roentgenol 1996;167:171–8.

20. Dershaw DW. Mammography in patients with breast cancer

treated by breast conservation (lumpectomy with or without radia-

tion). Am J Roentgenol 1995;164:309–16.21. Bassett LW, Jackson BP, Fu KL, et al. Diagnosis of Diseases

of the Breast, 2nd edn. Philadelphia: Elsevier Saunders, 2005.

22. Sanders LM, Groves AC, Schaefer S. Cutaneous angiosarco-

ma of the breast on MRI. Am J Roentgenol 2006;187:W143–6.

298 • moore et al.