Next Article in Journal
Mammography Datasets for Neural Networks—Survey
Previous Article in Journal
Quantifiable Measures of Abdominal Wall Motion for Quality Assessment of Cine-MRI Slices in Detection of Abdominal Adhesions
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
J. Imaging
Volume 9
Issue 5
10.3390/jimaging9050094
jimaging-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

Angiosarcoma of the Breast: Overview of Current Data and Multimodal Imaging Findings

by
Marco Conti
1,
Francesca Morciano
2,
Claudia Rossati
3,
Elisabetta Gori
2,
Paolo Belli
1,2,
Francesca Fornasa
3,
Giovanna Romanucci
3 and
Rossella Rella
4,*
1
UOC di Radiologia Toracica e Cardiovascolare, Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy
2
Facoltà di Medicina e Chirurgia, Università Cattolica Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy
3
UOSD Breast Unit ULSS9, Ospedale di Marzana, Piazzale Lambranzi, 1, 37142 Verona, Italy
4
UOC Diagnostica per Immagini, Ospedale G.B. Grassi, Via Gian Carlo Passeroni, 28, 00122 Rome, Italy
*
Author to whom correspondence should be addressed.
J. Imaging 2023, 9(5), 94; https://doi.org/10.3390/jimaging9050094
Submission received: 31 March 2023 / Revised: 25 April 2023 / Accepted: 26 April 2023 / Published: 30 April 2023
Browse Figures
Versions Notes

Abstract

:
Angiosarcoma of the breast is a rare breast cancer, which can arise de novo (primary breast angiosarcoma, PBA) or as a secondary malignancy (secondary breast angiosarcoma, SBA) as a result of a biological insult. In the latter case, it is usually diagnosed in patients with a previous history of radiation therapy following a conserving treatment for breast cancer. Over the years, the advances in early diagnosis and treatment of breast cancer, with increasing use of breast-conserving surgery and radiation therapy (instead of radical mastectomy), brought about an increased incidence of the secondary type. PBA and SBA have different clinical presentations and often represent a diagnostic challenge due to the nonspecific imaging findings. The purpose of this paper is to review and describe the radiological features of breast angiosarcoma, both in conventional and advanced imaging to guide radiologists in the diagnosis and management of this rare tumor.

1. Introduction

Angiosarcoma of the breast (BA) is a rare malignant breast cancer, representing around 0.04% of all breast cancers and 8% of breast sarcomas [1,2]. It can arise de novo (primary breast angiosarcoma, PBA) or develop after a biological insult, e.g., radiation therapy (secondary breast angiosarcoma, SBA) [3]. These two entities are clinically and pathologically different: PBA usually originates from breast parenchyma and may affect the skin, with different degrees of cutaneous and subcutaneous involvement; conversely, SBA originates from the skin previously included in an irradiation field or at its limits, in the so-called “twilight zone” where radiation is inhomogeneous, with a subsequent potential invasion of the underlying breast tissue [4,5,6,7,8]. They also differ for the median age of presentation: around 40 years for PBA and 70 years for SBA, with a median of 72 months postradiotherapy [5,9].
When breast-conserving treatment (BCT) was not so common, SBA was generally seen after mastectomy and axillary dissection in association with lymphedema, in the so-called Stewart–Treves syndrome [10,11,12]. Nowadays, it is mostly linked to a previous history of radiation therapy [10]. For this reason, in recent years, the number of diagnosed SBAs is increasing in parallel with the number of patients treated with breast-conserving surgery and adjuvant radiotherapy [3]. In the USA, the absolute risk of radiation-associated SBA is estimated at 7 per 100,000 person-years post-BCT [13].
The purpose of this paper is to describe the radiological features of this rare tumor and provide a comprehensive review of the available literature about its presentation in both conventional and advanced imaging to guide radiologists in its diagnosis and management.

2. Clinical Presentation

PBA and SBA are two different histopathological entities with different clinical presentations.
PBA is a rare entity, with unknown risk factors, which affects younger women. Most PBA presents as a palpable mass with rapid growth, with a mean tumor size ranging from 5.7 cm to 7.3 cm according to previously published studies [9,14,15], located within the mammary gland and which can extend to the skin causing ulceration [14]. Rarely, PBA presents with diffuse swelling of the entire breast, sensation of fullness or alteration of the breast shape [9,14]. PBA can also be associated with Kasabach–Merritt syndrome (KMS), a disease with a poor prognosis, more frequently diagnosed in children with giant hemangiomas [9,16,17]. KMS is characterized by thrombocytopenia, due to platelets sequestration in a large vascular lesion, and consumptive coagulopathy with a bleeding diathesis [18].
About SBA, it has cutaneous and/or subcutaneous localization [19,20,21,22] so it often presents with cutaneous changes and lesions, either in the chest wall or residual breast parenchyma, rather than a palpable mass. Cutaneous lesions are predominantly represented by erythematous or violaceous plaques, nodules, ecchymosis [6], skin discoloration, erythematous areas, bluish to reddish or black nodules, and edema [23] (Figure 1). Ulceration may or may not be present [19].
Concerning the dimension of skin lesions in SBA, Ginter et al. remarked that their extension is usually greater than 2 cm, helping to differentiate SBA from benign vascular tumors, which commonly are infracentimetric [19].
SBA diagnosis is often delayed because it usually arises in a postirradiated or postsurgical breast. Therefore, it could be difficult to differentiate it from post-actinic skin changes (i.e., radiodermatitis) [24]. Any cutaneous lesion in postirradiated residual breast parenchyma or chest wall should be further investigated in the suspicion of SBA.
For these reasons, clinical examination is crucial in the suspicion of BA and photographic documentation can be a helpful tool in this field.

3. Pathogenesis

The pathogenesis of angiosarcomas and especially BA is certainly a multifactorial process. BReast CAncer 1 and 2 (BRCA1 and BRCA2) are two of the most studied genes in the development of breast and ovarian cancer. These genes are involved in cellular homeostasis and protection against radiation-induced DNA damage, thus their connection with the development of SBA has been speculated; West et al. and Kadouri et al. reported some cases of SBA in BRCA1 and BRCA2 mutation carriers [25,26]. The transcription factor p53 and its main inhibitor MDM2 were linked to development of angiosarcomas both on an animal model [27,28] and in patients with BA, also associated with upregulation of vascular endothelial growing factor (VEGF) expression [29,30,31]. Amplification of MYC gene, which codes for a transcription factor, has been reported to be present in cases of secondary angiosarcoma [32,33]; Guo et al. hypothesized that Fms-related tyrosine kinase (FLT4), encoding a tyrosine kinase receptor for vascular endothelial growth factors, may be a potential candidate for this gene amplification [34]. Finally, the PIK3CA/AKT/mTOR pathway may also be directly or indirectly linked to the development of angiosarcoma and may represent a possible target for therapy [35].
PBA can also arise during pregnancy [36]. Nevertheless, the only publication that specifically investigated and reported the presence of steroid receptors (i.e., estrogens, progesterone, glucocorticoids) in these tumors evaluated only two cases of BA: the first case showed the expression of estrogens and progesterone receptors, the latter only the estrogens ones [37]. Conversely, the research of these hormonal receptors (estrogen and progesterone) in the published cases of PBA diagnosed during pregnancy resulted negative [38,39]. Further studies should be performed, with a larger population, to determine if hormonal receptors and thus endocrine aspects could be involved in PMA development during pregnancy.

4. Imaging Findings

4.1. Mammography

BA is a rare entity so only a few studies evaluated mammographic appearance of both primary and secondary BA.
Focusing on PBAs, Wu et al. investigated their features on mammography, concluding that they are nonspecific [40]. Indeed, the authors describe PBAs as lobulated or oval masses, large diffuse asymmetries with irregular density, alterations of breast trabecular structure, thickened local vessels, irregular densities of subcutaneous fat, and skin thickening. Nevertheless, no enlarged axillary lymph nodes were reported. The authors did not find associated microcalcifications: this could be explained by the origin of PBA from parenchymal rather than ductal structures (where the calcium is deposited) and/or by its rapid growth [40]. Another retrospective study published by Wang et al. investigated PBAs on 36 patients and agreed on the nonspecificity of their mammographic characteristics: circumscribed noncalcified masses were described in most of the patients and no remarkable findings were found in 43.8% of patients [14]. However, patients diagnosed with PBA were more likely to present with a clinically and radiographically detectable parenchymal mass than those with SBA (p < 0.002) [3]. Additionally, BA might manifest as a focal asymmetry and this can be explained by its infiltrating nature [1] (Figure 2).
About SBA, its mammographic appearance can overlap postirradiation modifications of breast post-BCT, which include skin thickening, retraction, and architectural distortion of the breast parenchyma, or an ill-defined mass [5,41,42] (Figure 3).
However, it should be noted that mammography can give false negative results even after skin changes [43,44,45,46]. Indeed, some authors estimate that approximately 33% of radiation-associated SBA could present with a completely normal mammography [42]. Therefore, it is important to highlight that in the follow-up of women post-BCT, skin thickening is expected to decrease two years after radiotherapy [47]. Any increase in cutaneous thickness after this period should raise the suspicion of malignancy, for example, of carcinomatous mastitis or SBA. When this sign is detected on mammography, radiologists should reconsider the patient’s cancer history and carry out a clinical examination that can reveal the presence of skin discoloration, edema, skin papules, nodules, and/or vesicles [20,42] (Figure 4 and Figure 5).
A recently published multicentric study investigated the role of imaging in primary and secondary BA in a large geographical area and over a long interval of time (25 years). In this paper, authors found that SBA is more likely to manifest as skin changes rather than parenchymal findings (i.e., masses) [3].
To the best of our knowledge, there is only one published case that examined the characteristics of SBA on contrast-enhanced mammography. In this case, the patient had a history of BCT, and, at clinical examination, skin discoloration and multiple dermal lesions were found in the previously treated breast, with a mean size of about 8 cm. When compared with previous mammograms, the last one showed both skin and trabecular thickening, while recombined views highlighted a considerable subcutaneous nonmass enhancement. A targeted ultrasound (US) examination was performed which confirmed skin thickening with increased vascularity. A US-guided core needle biopsy was performed and the presence of SBA was histologically proved [48].

4.2. Ultrasound

US examination is an essential tool in breast imaging, which allows the characterization of lesions, with high sensitivity also in dense breasts, as in younger women, in whom the sensitivity of mammography is lower and the presence of breast lesions, such as BA, may be obscured [49].
A study published by Yang et al. retrospectively reviewed the US features of 21 BAs: most of them appeared as solid masses with an oval shape and circumscribed margins, without posterior acoustic phenomena, and, in a minority of cases, with lobular shape and indistinct or microlobulated margins. In addition, almost half of mass lesions are hypoechogenic, while the others may show hyperechogenicity or mixed features: this could be explained by the vascular nature of the tumor with the presence of multiple interfaces of vascular channels [1] (Figure 6, Figure 7 and Figure 8).
Focusing on the differential diagnosis with other hyperechoic breast lesions, it should be highlighted that the majority of them are benign. These include: lipoma, angiolipoma, haematoma, seroma, fat necrosis, silicone granuloma, sebaceous or epidermal inclusion cyst, abscess, pseudoangiomatous stromal hyperplasia (PASH), galactocele or lactating adenoma, ductal ectasia, and apocrine metaplasia [50]. On the other hand, even other malignant lesions can be hyperechoic: infiltrating ductal or invasive lobular carcinomas, but also some uncommon tumors, such as lymphoma or metastatic lesions [50].
Another US feature may be the presence of anechoic components, linked to hemorrhage and necrosis [51].
When Color doppler imaging is performed, BA presents an increased vascularity [1,52] or variable internal blood flow [3].
However, as previously described, BA can also be characterized by cutaneous changes and lesions: in these cases, US often shows nonspecific findings or demonstrates skin edema or thickening with associated suspicious hypoechoic intracutaneous lesions, as reported by Salminen et al. [53].
To date, only two case reports investigated the features of BAs on contrast-enhanced ultrasound (CEUS), both about PBA: the first one, described by Yang et al., was characterized by peripheral irregular and rapid enhancement with slow washout, and with a central area of nonenhancement, probability due to perfusion defects [54]; the second one was described by Qin et al. as a mass with scattered and inhomogeneous early enhancement, suggesting an increased vascularization within the mass when compared with normal breast parenchyma [55].

4.3. Magnetic Resonance Imaging

Given the possibility of false negatives and nonspecific findings on conventional imaging, magnetic resonance imaging (MRI) could be useful in the differential diagnosis and in the evaluation of the extent of the disease when BA is suspected [1,53,56,57]. Moreover, MRI was proven to be the most sensitive technique for the detection of SBA associated with radiation therapy [53].
In a study conducted on thirteen women, BA showed both heterogeneous and slightly or significantly high homogeneous with hypointense necrotic or cystic components on T1-weighted images and inhomogeneous high signal on T2-weighted (w) images. About half of them presented as hemorrhagic lesions characterized by hyperintensity on both T1-w and T2-w images or with a hemosiderin ring (resulting from long-term hemorrhage). On post-contrast images, a vivid heterogeneous enhancement was demonstrated [40]. In particular, the kinetic enhancement is strictly linked to tumor grade: the kinetic curve shows a rapid enhancement with rapid washout in the highest grades, while a plateau or a persistent enhancement is seen in the lower ones [58,59,60,61,62,63,64]. In addition, high-grade tumors may also present hemorrhage or vascular lakes, displayed as focal areas of hyperintensity on T1-w images [58] (Figure 9).
Focusing on radiation-associated SBA, the published papers reported various MRI morphological appearance: a retrospective study analyzed the MRI features of 16 cases finding out that the majority of them (81.3%) showed diffuse heterogeneous skin enhancement, sometimes associated with T2-hypointense nodular skin foci of rapid early arterial enhancement with washout [56]. Authors hypothesized that postradiation inflammatory changes may explain skin thickening with diffuse high signal on T2-w images whilst tumoral cells would actually manifest as hypointense foci [56].
However, other MRI appearance of SBA were described: in a case report by Sanders et al., a infracentimetric enhancing skin lesion was described [57], while Vuille-dit-bille et al. reported a nonspecific thickening and enhancement of the skin, without focal nodularity or masses in the underlying breast parenchyma [65]; in three MRI examinations performed at diagnosis, Bentley et al. found a parenchymal mass associated to nonmass enhancement and cutaneous thickening or nodularity/masses and nipple enlargement [3]. Finally, Bentley et al. also analyzed the MRI appearance of recurrent disease in two patients previously treated for BA, reporting a skin nodule in the first case and a chest wall and subcutaneous nodules in the second one [3] (Figure 10 and Figure 11).

4.4. Computed Tomography

Computed tomography (CT) has no broad application in the diagnosis of breast lesions but, in this setting, it is essential for staging purposes.
CT can be useful to find distant localizations of disease in case of metastatic spread. In particular, lung parenchyma is the most frequent localization, but metastasis were reported also in liver, skin, bone, central nervous system, spleen, lymph nodes, ovary, and heart [3,61,66,67,68] (Figure 12).
In addition, Salminen et al. retrospectively reviewed the available imaging of a nationwide cohort of patients with SBA, finding out that CT has similar sensitivity to MRI in the evaluation of SBA, warning that both techniques could be falsely negative [53] (Figure 13).
Moreover, taking into account that BA might present with compromised local conditions (i.e., breast swelling, skin induration, or ulcerations), it could be uncomfortable for patients to undergo MRI examination, due to prone position and lengthy acquisition time; in this setting, CT could be used as a valid alternative.

4.5. PET-CT

There is a lack of knowledge about the role of positron emission tomography-computed tomography (PET-CT) in breast angiosarcoma. The few case reports available in the current literature show that PBA and SBA are avid of F-18 fluoro-2-deoxy-D-glucose (FDG) in both primary and metastatic localizations [4,69,70] (Figure 14).
A report of thirteen lesions found that the two subtypes are visually and statistically different in maximum standardized uptake value (SUVmax); nevertheless, lesions with the highest SUVmax presented a worse prognosis regardless of the subtype [70].
To our knowledge, no study investigated the role of PET/MRI.
Although further research is needed, this imaging technique may be helpful for the initial staging of BA and to evaluate therapeutic response in follow-up by demonstrating the resolution of metabolic activity.

5. Histopathology

Immunohistochemistry is very important in this setting to differentiate BA from invasive carcinomas. The endothelial markers of angiosarcoma are CD 34, CD 31, and factor VIII. Higher Ki67 index is linked with poor prognosis [71].
After surgical resection, histopathological and immunohistochemical analysis of the entire specimen are mandatory and represent the gold standard for diagnosis: indeed, fine needle aspiration and core needle biopsy may result falsely negative for malignancy (with an estimated 37% of cases), because of the existence of well differentiated histotypes as well as the presence of necrotic and fatty tissue or hemorrhage [40].
Differential diagnoses concerning low-grade BA include angiolipoma, hemangioma, and benign proliferative lesions; instead for the higher grades, mastitis, fibromatosis, but especially to invasive mammary carcinoma [66].
BAs can present with different grades: low-grade angiosarcoma, consisting of well-formed anastomosing vascular channels, intermediate grade angiosarcoma (characterized by an important neoplastic vascular growth), and high-grade angiosarcoma, that show localized necrosis, infarction, and hemorrhage [36,40].

6. Treatment and Prognosis

Given the rarity of this cancer, there is no real consensus on treatment and the management varies depending on the institution, ranging from simple wide excision to radical mastectomy [2,21,72,73,74,75]. Like all soft tissue sarcomas, BA presents better outcomes when managed in a multidisciplinary team [76].
The majority of the authors agree that nodal involvement is not common in BA [21,72,75,77,78,79,80]. Nevertheless, while lymphatic dissemination is unusual, early metastases can usually be found due to preferential hematogenous pathways, potentially involving any anatomic location, especially lungs [81,82].
Treatments vary according to the stage of the disease (localized vs. metastatic) [76]. About localized disease, the gold standard is surgery with R0 (microscopically margin-negative) resection: as BA are infiltrative tumors, wide margins are recommended; positive margins are linked to worse prognosis with a high risk of local recurrence [76]. Indeed, R0 resections are proven to have significantly higher survival rates in radiation-associated SBA when compared to R1 (microscopically irradical) or R2 (macroscopically irradical) resections [83]. Regarding radiation-associated BA, some authors considered surgical margins to be safe when reaching 2–4 cm [84,85,86]; however, a case report reported a successful local control with just 1 cm of clear margins [46].
The effectiveness of adjuvant chemotherapy is still not clear as published results are discordant [87,88] and represented by case reports, which mainly suggest its efficacy for locally recurrent and metastatic SBA [89,90,91], or small-scale studies, which found an improved survival in patients with SBA but not in PBA [92].
Although some authors suggested that chemotherapy regimens, like gemcitabine, doxorubicin, and taxanes, have cytotoxic effects in BA, their efficacy on long-term survival remains uncertain [93,94].
Focusing on SBA, many studies found that survival and local recurrence rates were poor even when surgery was combined with standard adjuvant chemotherapy [83,95,96,97] A retrospective study conducted by Lagrange et all. reported no significant difference in survival rates when comparing patients treated with surgery alone with those treated with surgery and chemotherapy [98]. Nevertheless, several studies found that adjuvant chemotherapy can be beneficial after surgery with wide clear margins [23,72,99,100,101,102,103]. Rosen et al. reported that adjuvant chemotherapy improved disease-free survival rate of higher-grade BA [72].
The use of radiotherapy is also controversial, in particular in radiation-associated SBA: in these cases, skin was already irradiated, raising concerns about an increased toxicity [89]. However, Palta et al. evaluated the outcomes of 14 cases of radiation-associated BA treated with hyperfractionated and accelerated radiotherapy, with or without surgery, finding encouraging results in terms of local control, disease-free likelihood, and overall survival [104].
About BA prognosis, it is influenced by margin involvement after surgical treatment, histological grade, and tumor dimension. Gutkin et al. reviewed 58 patients with nonmetastatic BA finding that 5-year overall survival was 73.7% for PBA and 63.5% for SBA, with an improved local control when resection margins were superior to 5 mm [92]. Regarding radiation-associated BA, the 5-year survival rate and disease-free survival rate were reported around 27–48% [105,106] and 35%, respectively [107]. An important prognostic factor was the number of cutaneous lesions: the 2-year survival rate increases from 0% to 50% depending on the presence of multiple or single lesions [20,108]. Moreover, low-grade tumors are linked to longer disease-free survival intervals [98,109]. Brady et al. described lesion dimension (with a cutoff of 5 cm), metastatic spread, and surgery as the most important prognostic factors, with impact on mortality rate [95].

7. Conclusions

Breast angiosarcoma is a rare and highly malignant breast tumor. Unfortunately, only a few studies were published on this topic, mainly represented by case reports and small-scale studies. For these reasons, BA often represents a diagnostic challenge for breast radiologists. It is important to be familiar with clinical presentation and imaging features of BA to achieve early diagnosis. When BA is suspected, anamnestic information should be properly collected, with particular regard to previous breast cancer history.

Author Contributions

Conceptualization, M.C. and F.M.; methodology, M.C. and R.R.; validation, R.R., G.R., P.B., F.F. and C.R.; formal analysis, M.C.; investigation, F.M. and C.R.; resources, F.M., E.G. and C.R.; data curation, F.M. and C.R; writing—original draft preparation, M.C., F.M. and C.R.; writing—review and editing, R.R.; supervision, P.B., F.F., G.R. and R.R.; project administration, R.R. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

No new data were created.

Acknowledgments

The authors want to thank Fondazione Policlinico Agostino Gemelli—IRCCS, Ospedale di Marzana and Ospedale G.B. Grassi for their support.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Yang, W.T.; Hennessy, B.T.J.; Dryden, M.J.; Valero, V.; Hunt, K.K.; Krishnamurthy, S. Mammary Angiosarcomas: Imaging Findings in 24 Patients. Radiology 2007, 242, 725–734. [Google Scholar] [CrossRef] [PubMed]
  2. Hui, A.; Henderson, M.; Speakman, D.; Skandarajah, A. Angiosarcoma of the Breast: A Difficult Surgical Challenge. Breast Edinb. Scotl. 2012, 21, 584–589. [Google Scholar] [CrossRef]
  3. Bentley, H.; Roberts, J.; Hayes, M.; Wilson, C.; Simmons, C.; Nichol, A.; Smrke, A.; Martin, T. The Role of Imaging in the Diagnosis of Primary and Secondary Breast Angiosarcoma: Twenty-Five-Year Experience of a Provincial Cancer Institution. Clin. Breast Cancer 2023, 23, e45–e53. [Google Scholar] [CrossRef]
  4. Glazebrook, K.N.; Magut, M.J.; Reynolds, C. Angiosarcoma of the Breast. AJR Am. J. Roentgenol. 2008, 190, 533–538. [Google Scholar] [CrossRef] [PubMed]
  5. Abbott, R.; Palmieri, C. Angiosarcoma of the Breast Following Surgery and Radiotherapy for Breast Cancer. Nat. Clin. Pract. Oncol. 2008, 5, 727–736. [Google Scholar] [CrossRef] [PubMed]
  6. Brenn, T.; Fletcher, C.D.M. Radiation-Associated Cutaneous Atypical Vascular Lesions and Angiosarcoma: Clinicopathologic Analysis of 42 Cases. Am. J. Surg. Pathol. 2005, 29, 983–996. [Google Scholar] [CrossRef]
  7. Brenn, T.; Fletcher, C.D.M. Postradiation Vascular Proliferations: An Increasing Problem. Histopathology 2006, 48, 106–114. [Google Scholar] [CrossRef] [PubMed]
  8. Verdin, V.; Mattart, L.; Cusumano, P.G.; De Hertogh, O.; De Meester, C.; Francart, D.; Kirova, Y.M.; Nelissen, X.; Sacino, F.; Vanderick, J.; et al. Angiosarcoma Associated with Radiation Therapy after Treatment of Breast Cancer. Retrospective Study on Ten Years. Cancer/Radiothérapie 2021, 25, 114–118. [Google Scholar] [CrossRef]
  9. Nascimento, A.F.; Raut, C.P.; Fletcher, C.D.M. Primary Angiosarcoma of the Breast: Clinicopathologic Analysis of 49 Cases, Suggesting That Grade Is Not Prognostic. Am. J. Surg. Pathol. 2008, 32, 1896–1904. [Google Scholar] [CrossRef]
  10. Morgan, E.A.; Kozono, D.E.; Wang, Q.; Mery, C.M.; Butrynski, J.E.; Baldini, E.H.; George, S.; Nascimento, A.F.; Raut, C.P. Cutaneous Radiation-Associated Angiosarcoma of the Breast: Poor Prognosis in a Rare Secondary Malignancy. Ann. Surg. Oncol. 2012, 19, 3801–3808. [Google Scholar] [CrossRef]
  11. Yap, J.; Chuba, P.J.; Thomas, R.; Aref, A.; Lucas, D.; Severson, R.K.; Hamre, M. Sarcoma as a Second Malignancy after Treatment for Breast Cancer. Int. J. Radiat. Oncol. Biol. Phys. 2002, 52, 1231–1237. [Google Scholar] [CrossRef]
  12. Brady, M.S.; Garfein, C.F.; Petrek, J.A.; Brennan, M.F. Post-Treatment Sarcoma in Breast Cancer Patients. Ann. Surg. Oncol. 1994, 1, 66–72. [Google Scholar] [CrossRef]
  13. Uryvaev, A.; Moskovitz, M.; Abdach-Bortnyak, R.; Hershkovitz, D.; Fried, G. Post-Irradiation Angiosarcoma of the Breast: Clinical Presentation and Outcome in a Series of Six Cases. Breast Cancer Res. Treat. 2015, 153, 3–8. [Google Scholar] [CrossRef] [PubMed]
  14. Wang, L.; Lao, I.W.; Yu, L.; Yang, W.; Wang, J. Primary Breast Angiosarcoma: A Retrospective Study of 36 Cases from a Single Chinese Medical Institute with Clinicopathologic and Radiologic Correlations. Breast J. 2017, 23, 282–291. [Google Scholar] [CrossRef]
  15. Abdou, Y.; Elkhanany, A.; Attwood, K.; Ji, W.; Takabe, K.; Opyrchal, M. Primary and Secondary Breast Angiosarcoma: Single Center Report and a Meta-Analysis. Breast Cancer Res. Treat. 2019, 178, 523–533. [Google Scholar] [CrossRef]
  16. Malolan, A.; Chowdary, P.B.; Sadashivaiah, S.B. Recurrent Primary Angiosarcoma of the Breast Presenting as Kasabach-Merritt Syndrome: A Case Report and Review of Literature. J. Clin. Diagn. Res. JCDR 2016, 10, XD04–XD07. [Google Scholar] [CrossRef]
  17. Bernathova, M.; Jaschke, W.; Pechlahner, C.; Zelger, B.; Bodner, G. Primary Angiosarcoma of the Breast Associated Kasabach-Merritt Syndrome during Pregnancy. Breast Edinb. Scotl. 2006, 15, 255–258. [Google Scholar] [CrossRef] [PubMed]
  18. Maguiness, S.; Guenther, L. Kasabach-Merritt Syndrome. J. Cutan. Med. Surg. 2002, 6, 335–339. [Google Scholar] [CrossRef] [PubMed]
  19. Ginter, P.S.; McIntire, P.J.; Shin, S.J. Vascular Tumours of the Breast: A Comprehensive Review with Focus on Diagnostic Challenges Encountered in the Core Biopsy Setting. Pathology (Phila.) 2017, 49, 197–214. [Google Scholar] [CrossRef]
  20. Fodor, J.; Orosz, Z.; Szabó, E.; Sulyok, Z.; Polgár, C.; Zaka, Z.; Major, T. Angiosarcoma after Conservation Treatment for Breast Carcinoma: Our Experience and a Review of the Literature. J. Am. Acad. Dermatol. 2006, 54, 499–504. [Google Scholar] [CrossRef] [PubMed]
  21. Fraga-Guedes, C.; Gobbi, H.; Mastropasqua, M.G.; Botteri, E.; Luini, A.; Viale, G. Primary and Secondary Angiosarcomas of the Breast: A Single Institution Experience. Breast Cancer Res. Treat. 2012, 132, 1081–1088. [Google Scholar] [CrossRef]
  22. Wang, X.Y.; Jakowski, J.; Tawfik, O.W.; Thomas, P.A.; Fan, F. Angiosarcoma of the Breast: A Clinicopathologic Analysis of Cases from the Last 10 Years. Ann. Diagn. Pathol. 2009, 13, 147–150. [Google Scholar] [CrossRef]
  23. Marchal, C.; Weber, B.; de Lafontan, B.; Resbeut, M.; Mignotte, H.; du Chatelard, P.P.; Cutuli, B.; Reme-Saumon, M.; Broussier-Leroux, A.; Chaplain, G.; et al. Nine Breast Angiosarcomas after Conservative Treatment for Breast Carcinoma: A Survey from French Comprehensive Cancer Centers. Int. J. Radiat. Oncol. Biol. Phys. 1999, 44, 113–119. [Google Scholar] [CrossRef]
  24. Bonito, F.J.P.; de Almeida Cerejeira, D.; Dahlstedt-Ferreira, C.; Oliveira Coelho, H.; Rosas, R. Radiation-Induced Angiosarcoma of the Breast: A Review. Breast J. 2020, 26, 458–463. [Google Scholar] [CrossRef]
  25. West, J.G.; Weitzel, J.N.; Tao, M.L.; Carpenter, M.; West, J.E.; Fanning, C. BRCA Mutations and the Risk of Angiosarcoma after Breast Cancer Treatment. Clin. Breast Cancer 2008, 8, 533–537. [Google Scholar] [CrossRef]
  26. Kadouri, L.; Sagi, M.; Goldberg, Y.; Lerer, I.; Hamburger, T.; Peretz, T. Genetic Predisposition to Radiation Induced Sarcoma: Possible Role for BRCA and P53 Mutations. Breast Cancer Res. Treat. 2013, 140, 207–211. [Google Scholar] [CrossRef] [PubMed]
  27. Donehower, L.A.; Harvey, M.; Slagle, B.L.; McArthur, M.J.; Montgomery, C.A.; Butel, J.S.; Bradley, A. Mice Deficient for P53 Are Developmentally Normal but Susceptible to Spontaneous Tumours. Nature 1992, 356, 215–221. [Google Scholar] [CrossRef] [PubMed]
  28. Chen, C.-M.; Chang, J.-L.; Behringer, R.R. Tumor Formation in P53 Mutant Ovaries Transplanted into Wild-Type Female Hosts. Oncogene 2004, 23, 7722–7725. [Google Scholar] [CrossRef]
  29. Domfeh, A.B.; Fichera, M.; Hunt, J.L. Allelic Loss of 3 Different Tumor Suppressor Gene Loci in Benign and Malignant Endothelial Tumors of the Head and Neck. Arch. Pathol. Lab. Med. 2006, 130, 1184–1187. [Google Scholar] [CrossRef] [PubMed]
  30. Naka, N.; Tomita, Y.; Nakanishi, H.; Araki, N.; Hongyo, T.; Ochi, T.; Aozasa, K. Mutations of P53 Tumor-Suppressor Gene in Angiosarcoma. Int. J. Cancer 1997, 71, 952–955. [Google Scholar] [CrossRef]
  31. Momand, J.; Zambetti, G.P.; Olson, D.C.; George, D.; Levine, A.J. The Mdm-2 Oncogene Product Forms a Complex with the P53 Protein and Inhibits P53-Mediated Transactivation. Cell 1992, 69, 1237–1245. [Google Scholar] [CrossRef]
  32. Manner, J.; Radlwimmer, B.; Hohenberger, P.; Mössinger, K.; Küffer, S.; Sauer, C.; Belharazem, D.; Zettl, A.; Coindre, J.-M.; Hallermann, C.; et al. MYC High Level Gene Amplification Is a Distinctive Feature of Angiosarcomas after Irradiation or Chronic Lymphedema. Am. J. Pathol. 2010, 176, 34–39. [Google Scholar] [CrossRef] [PubMed]
  33. Mentzel, T.; Schildhaus, H.U.; Palmedo, G.; Büttner, R.; Kutzner, H. Postradiation Cutaneous Angiosarcoma after Treatment of Breast Carcinoma Is Characterized by MYC Amplification in Contrast to Atypical Vascular Lesions after Radiotherapy and Control Cases: Clinicopathological, Immunohistochemical and Molecular Analysis of 66 Cases. Mod. Pathol. 2012, 25, 75–85. [Google Scholar] [CrossRef] [PubMed]
  34. Guo, T.; Zhang, L.; Chang, N.; Singer, S.; Maki, R.G.; Antonescu, C.R. Consistent MYC and FLT4 Gene Amplification in Radiation-Induced Angiosarcoma but Not in Other Radiation-Associated Atypical Vascular Lesions. Genes Chromosomes Cancer 2011, 50, 25–33. [Google Scholar] [CrossRef] [PubMed]
  35. Wada, M.; Horinaka, M.; Yasuda, S.; Masuzawa, M.; Sakai, T.; Katoh, N. PDK1 Is a Potential Therapeutic Target against Angiosarcoma Cells. J. Dermatol. Sci. 2015, 78, 44–50. [Google Scholar] [CrossRef]
  36. Chen, K.T.; Kirkegaard, D.D.; Bocian, J.J. Angiosarcoma of the Breast. Cancer 1980, 46, 368–371. [Google Scholar] [CrossRef]
  37. Brentani, M.M.; Pacheco, M.M.; Oshima, C.T.; Nagai, M.A.; Lemos, L.B.; Góes, J.C. Steroid Receptors in Breast Angiosarcoma. Cancer 1983, 51, 2105–2111. [Google Scholar] [CrossRef] [PubMed]
  38. Wang, J.; Fisher, C.; Thway, K. Angiosarcoma of the Breast with Solitary Metastasis to the Ovary during Pregnancy: An Uncommon Pattern of Metastatic Disease. Case Rep. Oncol. Med. 2013, 2013, 209610. [Google Scholar] [CrossRef]
  39. Velidedeoğlu, M.; Bilgin, İ.A.; Karaduman, Z.; Kılıç, F.; Öztürk, T.; Aydoğan, F. A Case Report of Primary Breast Angiosarcoma Causing Hemorrhagic Shock in Pregnancy. Turk. J. SurgeryUlusal Cerrahi Derg. 2014, 30, 54–56. [Google Scholar] [CrossRef]
  40. Wu, W.-H.; Ji, Q.-L.; Li, Z.-Z.; Wang, Q.-N.; Liu, S.-Y.; Yu, J.-F. Mammography and MRI Manifestations of Breast Angiosarcoma. BMC Womens Health 2019, 19, 73. [Google Scholar] [CrossRef]
  41. Alves, I.; Marques, J.C. Radiation-Induced Angiosarcoma of the Breast: A Retrospective Analysis of 15 Years’ Experience at an Oncology Center. Radiol. Bras. 2018, 51, 281–286. [Google Scholar] [CrossRef] [PubMed]
  42. Lim, R.F.; Goei, R. Best Cases from the AFIP: Angiosarcoma of the Breast. Radiogr. Rev. Publ. Radiol. Soc. N. Am. Inc. 2007, 27 (Suppl. S1), S125–S130. [Google Scholar] [CrossRef]
  43. Mermershtain, W.; Cohen, A.D.; Koretz, M.; Cohen, Y. Cutaneous Angiosarcoma of Breast after Lumpectomy, Axillary Lymph Node Dissection, and Radiotherapy for Primary Breast Carcinoma: Case Report and Review of the Literature. Am. J. Clin. Oncol. 2002, 25, 597–598. [Google Scholar] [CrossRef] [PubMed]
  44. Deutsch, M.; Rosenstein, M.M. Angiosarcoma of the Breast Mimicking Radiation Dermatitis Arising after Lumpectomy and Breast Irradiation: A Case Report. Am. J. Clin. Oncol. 1998, 21, 608–609. [Google Scholar] [CrossRef] [PubMed]
  45. Williams, E.V.; Banerjee, D.; Dallimore, N.; Monypenny, I.J. Angiosarcoma of the Breast Following Radiation Therapy. Eur. J. Surg. Oncol. J. Eur. Soc. Surg. Oncol. Br. Assoc. Surg. Oncol. 1999, 25, 221–222. [Google Scholar] [CrossRef]
  46. Fant, J.; Grant, M.; May, S.; Talaasen, L.; Watkins, D. Angiosarcoma of the Breast: Mammographic, Clinical, and Pathologic Correlation. Breast J. 2003, 9, 252–253. [Google Scholar] [CrossRef]
  47. Peters, M.E.; Fagerholm, M.I.; Scanlan, K.A.; Voegeli, D.R.; Kelcz, F. Mammographic Evaluation of the Postsurgical and Irradiated Breast. Radiographics 1988, 8, 873–899. [Google Scholar] [CrossRef]
  48. Kacen, M.G.; Sangle, N.; Kornecki, A. Contrast-Enhanced Mammography in the Diagnosis of Breast Angiosarcoma. Case Rep. Radiol. 2021, 2021, 5542786. [Google Scholar] [CrossRef]
  49. Liu, X.; Zheng, S.; Li, Y.; He, W. Use of Extended Field-of-View Ultrasound Imaging in Giant Primary Breast Angiosarcoma: A Case Description. Quant. Imaging Med. Surg. 2022, 12, 868–873. [Google Scholar] [CrossRef]
  50. Gao, Y.; Slanetz, P.J.; Eisenberg, R.L. Echogenic Breast Masses at US: To Biopsy or Not to Biopsy? Radiographics 2013, 33, 419–434. [Google Scholar] [CrossRef]
  51. Mouhoub, M.; Miry, A.; Haloui, A.; Karich, N.; Kamaoui, I.; Benkirane, S.; Bennani, A. Primary Angiosarcoma of the Breast: A Case Report. Pan Afr. Med. J. 2019, 33. [Google Scholar] [CrossRef]
  52. Matsumoto, R.A.E.K.; Hsieh, S.J.K.; Chala, L.F.; de Mello, G.G.N.; de Barros, N. Sarcomas of the Breast: Findings on Mammography, Ultrasound, and Magnetic Resonance Imaging. Radiol. Bras. 2018, 51, 401–406. [Google Scholar] [CrossRef] [PubMed]
  53. Salminen, S.H.; Sampo, M.M.; Böhling, T.O.; Salo, J.; Tarkkanen, M.; Blomqvist, C.P.; Hukkinen, K. Radiation-Associated Angiosarcoma of the Breast: Analysis of Diagnostic Tools in a Registry-Based Population. Acta Radiol. Stockh. Swed. 1987 2022, 63, 22–27. [Google Scholar] [CrossRef] [PubMed]
  54. Yang, O.O.; Lan, T.; He, J.L.; Xu, H.B.; Hao, L.; Shu, C.; Hu, Z.J.; Luo, H. Magnetic Resonance Imaging and Contrast-Enhanced Ultrasound Findings of a Recurrent Primary Breast Angiosarcoma. Medicine (Baltimore) 2021, 100, e24625. [Google Scholar] [CrossRef] [PubMed]
  55. Qin, X.; Wu, Y.; Yu, L.; Lv, Q.; Xie, M. Metastasis of Primary Breast Angiosarcoma to Axillary and Supraclavicular Lymph Nodes: A Rare Case Diagnosed Using Imaging Data. J. Int. Med. Res. 2021, 49, 3000605211002337. [Google Scholar] [CrossRef] [PubMed]
  56. Chikarmane, S.A.; Gombos, E.C.; Jagadeesan, J.; Raut, C.; Jagannathan, J.P. MRI Findings of Radiation-Associated Angiosarcoma of the Breast (RAS). J. Magn. Reson. Imaging JMRI 2015, 42, 763–770. [Google Scholar] [CrossRef]
  57. Sanders, L.M.; Groves, A.C.; Schaefer, S. Cutaneous Angiosarcoma of the Breast on MRI. AJR Am. J. Roentgenol. 2006, 187, W143–W146. [Google Scholar] [CrossRef]
  58. O’Neill, A.C.; D’Arcy, C.; McDermott, E.; O’Doherty, A.; Quinn, C.; McNally, S. Magnetic Resonance Imaging Appearances in Primary and Secondary Angiosarcoma of the Breast. J. Med. Imaging Radiat. Oncol. 2014, 58, 208–212. [Google Scholar] [CrossRef]
  59. Liberman, L.; Dershaw, D.D.; Kaufman, R.J.; Rosen, P.P. Angiosarcoma of the Breast. Radiology 1992, 183, 649–654. [Google Scholar] [CrossRef]
  60. Kikawa, Y.; Konishi, Y.; Nakamoto, Y.; Harada, T.; Takeo, M.; Ogata, M.; Yamamoto, M.; Usuki, N.; Toyoshima, M.; Katsuyama, E. Angiosarcoma of the Breast - Specific Findings of MRI. Breast Cancer 2006, 13, 369–373. [Google Scholar] [CrossRef]
  61. Marchant, L.K.; Orel, S.G.; Perez-Jaffe, L.A.; Reynolds, C.; Schnall, M.D. Bilateral Angiosarcoma of the Breast on MR Imaging. AJR Am. J. Roentgenol. 1997, 169, 1009–1010. [Google Scholar] [CrossRef] [PubMed]
  62. Brown, A.L.; Wahab, R.A. MRI of Primary Angiosarcoma of the Breast. Radiology 2020, 297, 31. [Google Scholar] [CrossRef]
  63. Ooe, Y.; Terakawa, H.; Kawashima, H.; Ikeda, H.; Inaki, N. Bilateral Primary Angiosarcoma of the Breast: A Case Report. J. Med. Case Rep. 2023, 17, 60. [Google Scholar] [CrossRef] [PubMed]
  64. Perretta, T.; Meucci, R.; Serio, M.L.; Caliandro, A.; Censi, M.; Beninati, E.; Collura, A.; Vanni, G.; Giacobbi, E.; Anemona, L.; et al. Small Vascular Lesions of the Breast Diagnosed by Magnetic Resonance Imaging-guided Vacuum Assisted Biopsy: Report of 2 Cases. Radiol. Case Rep. 2022, 17, 2492–2500. [Google Scholar] [CrossRef]
  65. Vuille-dit-Bille, R.N.; Sauter, D.; Pfofe, D.; Zagralioglu, O.; Jandali, A.R.; Nadig, J.; Dinçler, S.; Muff, B. High-Grade Cutaneous Angiosarcoma of the Breast 8.5 Years after Radiotherapy. Breast J. 2013, 19, 435–436. [Google Scholar] [CrossRef]
  66. Varghese, B.; Deshpande, P.; Dixit, S.; Koppiker, C.B.; Jalnapurkar, N. Primary Angiosarcoma Of the Breast: A Case Report. J. Radiol. Case Rep. 2019, 13, 15–25. [Google Scholar] [CrossRef]
  67. Chesebro, A.L.; Chikarmane, S.A.; Gombos, E.C.; Giardino, A.A. Radiation-Associated Angiosarcoma of the Breast: What the Radiologist Needs to Know. AJR Am. J. Roentgenol. 2016, 207, 217–225. [Google Scholar] [CrossRef] [PubMed]
  68. Ohta, M.; Tokuda, Y.; Kuge, S.; Okumura, A.; Tanaka, M.; Kubota, M.; Tajima, T.; Akatsuka, A.; Osamura, R.Y.; Tamaoki, N.; et al. A Case of Angiosarcoma of the Breast. Jpn. J. Clin. Oncol. 1997, 27, 91–94. [Google Scholar] [CrossRef] [PubMed]
  69. Zeng, W.; Styblo, T.M.; Li, S.; Sepulveda, J.N.; Schuster, D.M. Breast Angiosarcoma: FDG PET Findings. Clin. Nucl. Med. 2009, 34, 443–445. [Google Scholar] [CrossRef]
  70. Cassou-Mounat, T.; Champion, L.; Bozec, L.; Laurence, V.; Huchet, V.; Luporsi, M.; Jehanno, N. Primary and Secondary Breast Angiosarcoma: FDG PET/CT Series. Clin. Nucl. Med. 2019, 44, e33. [Google Scholar] [CrossRef]
  71. Tang, C.; Zhan, C.; Qin, Y.; Hu, Q.; Ai, T. Primary Angiosarcoma of the Breast: Two Case Reports and Brief Review of the Literature. Radiol. Case Rep. 2023, 18, 1671–1675. [Google Scholar] [CrossRef]
  72. Rosen, P.P.; Kimmel, M.; Ernsberger, D. Mammary Angiosarcoma. The Prognostic Significance of Tumor Differentiation. Cancer 1988, 62, 2145–2151. [Google Scholar] [CrossRef] [PubMed]
  73. Luini, A.; Gatti, G.; Diaz, J.; Botteri, E.; Oliveira, E.; Cecilio Sahium de Almeida, R.; Veronesi, P.; Intra, M.; Pagani, G.; Naninato, P.; et al. Angiosarcoma of the Breast: The Experience of the European Institute of Oncology and a Review of the Literature. Breast Cancer Res. Treat. 2007, 105, 81–85. [Google Scholar] [CrossRef]
  74. Abraham, J.A.; Hornicek, F.J.; Kaufman, A.M.; Harmon, D.C.; Springfield, D.S.; Raskin, K.A.; Mankin, H.J.; Kirsch, D.G.; Rosenberg, A.E.; Nielsen, G.P.; et al. Treatment and Outcome of 82 Patients with Angiosarcoma. Ann. Surg. Oncol. 2007, 14, 1953–1967. [Google Scholar] [CrossRef] [PubMed]
  75. Monroe, A.T.; Feigenberg, S.J.; Mendenhall, N.P. Angiosarcoma after Breast-Conserving Therapy. Cancer 2003, 97, 1832–1840. [Google Scholar] [CrossRef] [PubMed]
  76. Spiker, A.M.; Mangla, A.; Ramsey, M.L. Angiosarcoma. In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2023. [Google Scholar]
  77. Biswas, T.; Tang, P.; Muhs, A.; Ling, M. Angiosarcoma of the Breast: A Rare Clinicopathological Entity. Am. J. Clin. Oncol. 2009, 32, 582–586. [Google Scholar] [CrossRef] [PubMed]
  78. Bousquet, G.; Confavreux, C.; Magné, N.; de Lara, C.T.; Poortmans, P.; Senkus, E.; de Lafontan, B.; Bolla, M.; Largillier, R.; Lagneau, E.; et al. Outcome and Prognostic Factors in Breast Sarcoma: A Multicenter Study from the Rare Cancer Network. Radiother. Oncol. J. Eur. Soc. Ther. Radiol. Oncol. 2007, 85, 355–361. [Google Scholar] [CrossRef]
  79. Sher, T.; Hennessy, B.T.; Valero, V.; Broglio, K.; Woodward, W.A.; Trent, J.; Hunt, K.K.; Hortobagyi, G.N.; Gonzalez-Angulo, A.M. Primary Angiosarcomas of the Breast. Cancer 2007, 110, 173–178. [Google Scholar] [CrossRef]
  80. Ragavan, S.; Lim, H.J.; Tan, J.W.-S.; Hendrikson, J.; Chan, J.Y.; Farid, M.; Chia, C.S.; Tan, G.H.C.; Soo, K.C.; Teo, M.C.C.; et al. Axillary Lymph Node Dissection in Angiosarcomas of the Breast: An Asian Institutional Perspective. Sarcoma 2020, 2020, 4890803. [Google Scholar] [CrossRef]
  81. Maeda, T.; Tateishi, U.; Hasegawa, T.; Ojima, H.; Arai, Y.; Sugimura, K. Primary Hepatic Angiosarcoma on Coregistered FDG PET and CT Images. AJR Am. J. Roentgenol. 2007, 188, 1615–1617. [Google Scholar] [CrossRef]
  82. Freudenberg, L.S.; Rosenbaum, S.J.; Schulte-Herbrüggen, J.; Eising, E.G.; Lauenstein, T.; Wolff, A.; Bockisch, A. Diagnosis of a Cardiac Angiosarcoma by Fluorine-18 Fluordeoxyglucose Positron Emission Tomography. Eur. Radiol. 2002, 12 Suppl 3, S158–S161. [Google Scholar] [CrossRef]
  83. Thijssens, K.M.J.; van Ginkel, R.J.; Suurmeijer, A.J.H.; Pras, E.; van der Graaf, W.T.A.; Hollander, M.; Hoekstra, H.J. Radiation-Induced Sarcoma: A Challenge for the Surgeon. Ann. Surg. Oncol. 2005, 12, 237–245. [Google Scholar] [CrossRef] [PubMed]
  84. Rao, J.; Dekoven, J.G.; Beatty, J.D.; Jones, G. Cutaneous Angiosarcoma as a Delayed Complication of Radiation Therapy for Carcinoma of the Breast. J. Am. Acad. Dermatol. 2003, 49, 532–538. [Google Scholar] [CrossRef] [PubMed]
  85. Plotti, F.; Di Donato, V.; Zullo, M.A.; Angioli, R.; Panici, P.B. An Unusual Case of Secondary Fibrosarcoma after Treatment for Breast Cancer. Gynecol. Oncol. 2006, 103, 1133–1136. [Google Scholar] [CrossRef] [PubMed]
  86. Borman, H.; Safak, T.; Ertoy, D. Fibrosarcoma Following Radiotherapy for Breast Carcinoma: A Case Report and Review of the Literature. Ann. Plast. Surg. 1998, 41, 201–204. [Google Scholar] [CrossRef]
  87. Depla, A.L.; Scharloo-Karels, C.H.; de Jong, M.A.A.; Oldenborg, S.; Kolff, M.W.; Oei, S.B.; van Coevorden, F.; van Rhoon, G.C.; Baartman, E.A.; Scholten, R.J.; et al. Treatment and Prognostic Factors of Radiation-Associated Angiosarcoma (RAAS) after Primary Breast Cancer: A Systematic Review. Eur. J. Cancer Oxf. Engl. 1990 2014, 50, 1779–1788. [Google Scholar] [CrossRef]
  88. Torres, K.E.; Ravi, V.; Kin, K.; Yi, M.; Guadagnolo, B.A.; May, C.D.; Arun, B.K.; Hunt, K.K.; Lam, R.; Lahat, G.; et al. Long-Term Outcomes in Patients with Radiation-Associated Angiosarcomas of the Breast Following Surgery and Radiotherapy for Breast Cancer. Ann. Surg. Oncol. 2013, 20, 1267–1274. [Google Scholar] [CrossRef]
  89. Lewcun, J.A.; Pameijer, C.; Kass, R.; Cream, L.; Hershock, D.; Brooks, A.J.; Dodge, D.G. Doxorubicin, Paclitaxel, and Cisplatin Based Chemotherapy for the Treatment of Angiosarcoma: Two Case Reports. Int. J. Surg. Case Rep. 2020, 68, 83–87. [Google Scholar] [CrossRef]
  90. Gambini, D.; Visintin, R.; Locatelli, E.; Bareggi, C.; Galassi, B.; Runza, L.; Blundo, C.; Sosnovskikh, I.; Tomirotti, M. Secondary Breast Angiosarcoma and Paclitaxel-Dependent Prolonged Disease Control: Report of Two Cases and Review of the Literature. Tumori 2015, 101, e60–e63. [Google Scholar] [CrossRef]
  91. Suzuki, Y.; Taniguchi, K.; Hatono, M.; Kajiwara, Y.; Abe, Y.; Kawada, K.; Tsukioki, T.; Kochi, M.; Nishiyama, K.; Iwamoto, T.; et al. Recurring Radiationinduced Angiosarcoma of the Breast That Was Treated with Paclitaxel Chemotherapy: A Case Report. Surg Case Rep. 2020, 6, 25. [Google Scholar] [CrossRef]
  92. Gutkin, P.M.; Ganjoo, K.N.; Lohman, M.; von Eyben, R.; Charville, G.W.; Nazerali, R.S.; Dirbas, F.M.; Horst, K.C. Angiosarcoma of the Breast: Management and Outcomes. Am. J. Clin. Oncol. 2020, 43, 820–825. [Google Scholar] [CrossRef]
  93. Stacchiotti, S.; Palassini, E.; Sanfilippo, R.; Vincenzi, B.; Arena, M.G.; Bochicchio, A.M.; De Rosa, P.; Nuzzo, A.; Turano, S.; Morosi, C.; et al. Gemcitabine in Advanced Angiosarcoma: A Retrospective Case Series Analysis from the Italian Rare Cancer Network. Ann. Oncol. Off. J. Eur. Soc. Med. Oncol. 2012, 23, 501–508. [Google Scholar] [CrossRef] [PubMed]
  94. Leu, K.M.; Ostruszka, L.J.; Shewach, D.; Zalupski, M.; Sondak, V.; Biermann, J.S.; Lee, J.S.-J.; Couwlier, C.; Palazzolo, K.; Baker, L.H. Laboratory and Clinical Evidence of Synergistic Cytotoxicity of Sequential Treatment with Gemcitabine Followed by Docetaxel in the Treatment of Sarcoma. J. Clin. Oncol. 2004, 22, 1706–1712. [Google Scholar] [CrossRef] [PubMed]
  95. Brady, M.S.; Gaynor, J.J.; Brennan, M.F. Radiation-Associated Sarcoma of Bone and Soft Tissue. Arch. Surg. 1960 1992, 127, 1379–1385. [Google Scholar] [CrossRef] [PubMed]
  96. Kuten, A.; Sapir, D.; Cohen, Y.; Haim, N.; Borovik, R.; Robinson, E. Postirradiation Soft Tissue Sarcoma Occurring in Breast Cancer Patients: Report of Seven Cases and Results of Combination Chemotherapy. J. Surg. Oncol. 1985, 28, 168–171. [Google Scholar] [CrossRef] [PubMed]
  97. Cafiero, F.; Gipponi, M.; Peressini, A.; Queirolo, P.; Bertoglio, S.; Comandini, D.; Percivale, P.; Sertoli, M.R.; Badellino, F. Radiation-Associated Angiosarcoma: Diagnostic and Therapeutic Implications--Two Case Reports and a Review of the Literature. Cancer 1996, 77, 2496–2502. [Google Scholar] [CrossRef]
  98. Lagrange, J.L.; Ramaioli, A.; Chateau, M.C.; Marchal, C.; Resbeut, M.; Richaud, P.; Lagarde, P.; Rambert, P.; Tortechaux, J.; Seng, S.H.; et al. Sarcoma after Radiation Therapy: Retrospective Multiinstitutional Study of 80 Histologically Confirmed Cases. Radiology 2000, 216, 197–205. [Google Scholar] [CrossRef]
  99. Barrow, B.J.; Janjan, N.A.; Gutman, H.; Benjamin, R.S.; Allen, P.; Romsdahl, M.M.; Ross, M.I.; Pollock, R.E. Role of Radiotherapy in Sarcoma of the Breast—A Retrospective Review of the M.D. Anderson Experience. Radiother. Oncol. J. Eur. Soc. Ther. Radiol. Oncol. 1999, 52, 173–178. [Google Scholar] [CrossRef]
  100. Guram, S.; Covelli, A.M.; O’Neill, A.C.; Shultz, D.B.; Demicco, E.G.; Gupta, A.A.; Gladdy, R.A. Multidisciplinary Intervention in Radiation-Associated Angiosarcoma of the Breast: Patterns of Recurrence and Response to Treatment. Ann. Surg. Oncol. 2022, 29, 522–532. [Google Scholar] [CrossRef]
  101. Brenin, C.M.; Small, W.; Talamonti, M.S.; Gradisher, W.J. Radiation-Induced Sarcoma Following Treatment of Breast Cancer. Cancer Control J. Moffitt Cancer Cent. 1998, 5, 425–432. [Google Scholar] [CrossRef]
  102. Chapelier, A.R.; Bacha, E.A.; de Montpreville, V.T.; Dulmet, E.M.; Rietjens, M.; Margulis, A.; Macchiarini, P.; Dartevelle, P.G. Radical Resection of Radiation-Induced Sarcoma of the Chest Wall: Report of 15 Cases. Ann. Thorac. Surg. 1997, 63, 214–219. [Google Scholar] [CrossRef] [PubMed]
  103. Feigenberg, S.J.; Mendenhall, N.P.; Reith, J.D.; Ward, J.R.; Copeland, E.M. Angiosarcoma after Breast-Conserving Therapy: Experience with Hyperfractionated Radiotherapy. Int. J. Radiat. Oncol. Biol. Phys. 2002, 52, 620–626. [Google Scholar] [CrossRef] [PubMed]
  104. Palta, M.; Morris, C.G.; Grobmyer, S.R.; Copeland, E.M.; Mendenhall, N.P. Angiosarcoma after Breast-Conserving Therapy: Long-Term Outcomes with Hyperfractionated Radiotherapy. Cancer 2010, 116, 1872–1878. [Google Scholar] [CrossRef]
  105. Quadros, C.A.; Vasconcelos, A.; Andrade, R.; Ramos, R.S.; Studart, E.; Nascimento, G.; Trajano, A. Good Outcome after Neoadjuvant Chemotherapy and Extended Surgical Resection for a Large Radiation-Induced High-Grade Breast Sarcoma. Int. Semin. Surg. Oncol. 2006, 3, 18. [Google Scholar] [CrossRef] [PubMed]
  106. Erel, E.; Vlachou, E.; Athanasiadou, M.; Hassan, S.; Chandrasekar, C.R.; Peart, F. Management of Radiation-Induced Sarcomas in a Tertiary Referral Centre: A Review of 25 Cases. Breast Edinb. Scotl. 2010, 19, 424–427. [Google Scholar] [CrossRef]
  107. Strobbe, L.J.; Peterse, H.L.; van Tinteren, H.; Wijnmaalen, A.; Rutgers, E.J. Angiosarcoma of the Breast after Conservation Therapy for Invasive Cancer, the Incidence and Outcome: An Unforseen Sequela. Breast Cancer Res. Treat. 1998, 47, 101–109. [Google Scholar] [CrossRef] [PubMed]
  108. Sheth, G.R.; Cranmer, L.D.; Smith, B.D.; Grasso-LeBeau, L.; Lang, J.E. Radiation-Induced Sarcoma of the Breast: A Systematic Review. The Oncologist 2012, 17, 405–418. [Google Scholar] [CrossRef]
  109. Billings, S.D.; McKenney, J.K.; Folpe, A.L.; Hardacre, M.C.; Weiss, S.W. Cutaneous Angiosarcoma Following Breast-Conserving Surgery and Radiation: An Analysis of 27 Cases. Am. J. Surg. Pathol. 2004, 28, 781–788. [Google Scholar] [CrossRef]
Jimaging 09 00094 g001 550
Figure 1. An 85-year-old patient with a history of carcinoma of the right breast treated with quadrantectomy and radiotherapy. (a–c) Clinical examination revealed papillary erythematous lesion, skin thickening, and multiple reddish nodules.
Figure 1. An 85-year-old patient with a history of carcinoma of the right breast treated with quadrantectomy and radiotherapy. (a–c) Clinical examination revealed papillary erythematous lesion, skin thickening, and multiple reddish nodules.
Jimaging 09 00094 g001
Jimaging 09 00094 g002 550
Figure 2. A 60-year-old patient with a history of gastric lymphoma treated 30 years previously. Clinical examination revealed an erythematous area on the right breast. (a) Craniocaudal and (b) mediolateral oblique mammograms of the right breast show an irregular mass. A core needle biopsy was performed with the simultaneous placement of a clip marker (white dot) and the presence of a primary BA was histologically proven.
Figure 2. A 60-year-old patient with a history of gastric lymphoma treated 30 years previously. Clinical examination revealed an erythematous area on the right breast. (a) Craniocaudal and (b) mediolateral oblique mammograms of the right breast show an irregular mass. A core needle biopsy was performed with the simultaneous placement of a clip marker (white dot) and the presence of a primary BA was histologically proven.
Jimaging 09 00094 g002
Jimaging 09 00094 g003 550
Figure 3. A 70-year-old patient with a history of carcinoma of the left breast treated with quadrantectomy and radiotherapy. Three years after completion of radiotherapy, clinical examination revealed a reddish cutaneous area and a palpable mass in the surgical scar location. (a) Craniocaudal and (b) mediolateral oblique mammograms of the left breast show a high density, irregular mass below the scar associated to skin thickening. The white lines represent the surgical clips released at the time of the quadrantectomy.
Figure 3. A 70-year-old patient with a history of carcinoma of the left breast treated with quadrantectomy and radiotherapy. Three years after completion of radiotherapy, clinical examination revealed a reddish cutaneous area and a palpable mass in the surgical scar location. (a) Craniocaudal and (b) mediolateral oblique mammograms of the left breast show a high density, irregular mass below the scar associated to skin thickening. The white lines represent the surgical clips released at the time of the quadrantectomy.
Jimaging 09 00094 g003
Jimaging 09 00094 g004 550
Figure 4. A 58-year-old patient with a history of carcinoma of the left breast treated with quadrantectomy and radiotherapy. Seven years after completion of radiotherapy, clinical examination revealed an erythematous lesion in the scar location. (a) Craniocaudal and (b) mediolateral oblique mammograms of the left breast show only skin thickening without mass or calcifications association. Due to the persistence of the cutaneous lesion, a punch biopsy was performed revealing an SBA.
Figure 4. A 58-year-old patient with a history of carcinoma of the left breast treated with quadrantectomy and radiotherapy. Seven years after completion of radiotherapy, clinical examination revealed an erythematous lesion in the scar location. (a) Craniocaudal and (b) mediolateral oblique mammograms of the left breast show only skin thickening without mass or calcifications association. Due to the persistence of the cutaneous lesion, a punch biopsy was performed revealing an SBA.
Jimaging 09 00094 g004
Jimaging 09 00094 g005 550
Figure 5. A 75-year-old patient with a history of lobular invasive carcinoma of the right breast treated with quadrantectomy and radiotherapy. Clinical examination revealed skin discolouring and teleangectasis five years after completion of radiotherapy. (a) Right craniocaudal (RCC) and (b) mediolateral oblique (MLO) mammograms show scar remodeling and skin thickening. No mass or suspicious calcifications were detected. A histological diagnosis of SBA was made with a punch biopsy.
Figure 5. A 75-year-old patient with a history of lobular invasive carcinoma of the right breast treated with quadrantectomy and radiotherapy. Clinical examination revealed skin discolouring and teleangectasis five years after completion of radiotherapy. (a) Right craniocaudal (RCC) and (b) mediolateral oblique (MLO) mammograms show scar remodeling and skin thickening. No mass or suspicious calcifications were detected. A histological diagnosis of SBA was made with a punch biopsy.
Jimaging 09 00094 g005
Jimaging 09 00094 g006 550
Figure 6. A 60-year-old patient with a palpable mass. US image of a PBA characterized by a voluminous heterogeneous hyperechoic mass, with non-circumscribed margins, with associated skin thickening.
Figure 6. A 60-year-old patient with a palpable mass. US image of a PBA characterized by a voluminous heterogeneous hyperechoic mass, with non-circumscribed margins, with associated skin thickening.
Jimaging 09 00094 g006
Jimaging 09 00094 g007 550
Figure 7. A 58-year-old patient with a history of carcinoma of the left breast treated with quadrantectomy and radiotherapy. US image of an SBA characterized by a diffuse skin thickening and an oval-shaped hypoechoic lesion with circumscribed margins.
Figure 7. A 58-year-old patient with a history of carcinoma of the left breast treated with quadrantectomy and radiotherapy. US image of an SBA characterized by a diffuse skin thickening and an oval-shaped hypoechoic lesion with circumscribed margins.
Jimaging 09 00094 g007
Jimaging 09 00094 g008 550
Figure 8. A 75-year-old patient with a history of lobular invasive carcinoma of the right breast treated with quadrantectomy and radiotherapy. US image of an SBA characterized by skin thickening and an irregular mass with indistinct margins in the retroareolar area. A US-guided core needle biopsy was performed, revealing a single focus of atypical cellular proliferation. Then, a punch biopsy was performed and an SBA was histologically proven.
Figure 8. A 75-year-old patient with a history of lobular invasive carcinoma of the right breast treated with quadrantectomy and radiotherapy. US image of an SBA characterized by skin thickening and an irregular mass with indistinct margins in the retroareolar area. A US-guided core needle biopsy was performed, revealing a single focus of atypical cellular proliferation. Then, a punch biopsy was performed and an SBA was histologically proven.
Jimaging 09 00094 g008
Jimaging 09 00094 g009 550
Figure 9. A 60-year-old patient with PBA. (a) T2-weighted, (b) axial 3D gradient echo T1-weighted post-contrast and (c) sagittal 3D gradient echo T1-weighted post-contrast images show an irregular mass, with non-circumscribed margins, characterized by heterogeneous enhancement, with skin thickening and invasion.
Figure 9. A 60-year-old patient with PBA. (a) T2-weighted, (b) axial 3D gradient echo T1-weighted post-contrast and (c) sagittal 3D gradient echo T1-weighted post-contrast images show an irregular mass, with non-circumscribed margins, characterized by heterogeneous enhancement, with skin thickening and invasion.
Jimaging 09 00094 g009
Jimaging 09 00094 g010 550
Figure 10. A 58-year-old patient with a history of carcinoma of the left breast treated with quadrantectomy and radiotherapy. (a) T2-weighted and (b) 3D gradient echo T1-weighted post-contrast images show skin thickening near the scar and late contrast enhancement. Punch biopsy revealed SBA.
Figure 10. A 58-year-old patient with a history of carcinoma of the left breast treated with quadrantectomy and radiotherapy. (a) T2-weighted and (b) 3D gradient echo T1-weighted post-contrast images show skin thickening near the scar and late contrast enhancement. Punch biopsy revealed SBA.
Jimaging 09 00094 g010
Jimaging 09 00094 g011 550
Figure 11. A 48-year-old patient with a history of left breast cancer treated with quadrantectomy and radiotherapy. (a) T2-weighted, (b) axial 3D gradient echo T1-weighted post-contrast and (c) sagittal 3D gradient echo T1-weighted post-contrast images show skin thickening and an oval-shaped mass, with circumscribed margins, characterized by homogenous enhancement. US-guided core needle biopsy reveals SBA.
Figure 11. A 48-year-old patient with a history of left breast cancer treated with quadrantectomy and radiotherapy. (a) T2-weighted, (b) axial 3D gradient echo T1-weighted post-contrast and (c) sagittal 3D gradient echo T1-weighted post-contrast images show skin thickening and an oval-shaped mass, with circumscribed margins, characterized by homogenous enhancement. US-guided core needle biopsy reveals SBA.
Jimaging 09 00094 g011
Jimaging 09 00094 g012 550
Figure 12. A 65-year-old patient with a history of PBA treated with right mastectomy, right axillary lymph node dissection and radiotherapy of the right axilla. A 2-year follow-up with CT scan revealed metastatic disease: (a) Mediastinal window showing a voluminous mass in the left breast, an enlarged lymph node in the right axilla, and a nodular thickening in the subcutaneous soft tissues of the right arm and of the left lateral chest wall. (b) Parenchymal window showing numerous bilateral pulmonary nodules.
Figure 12. A 65-year-old patient with a history of PBA treated with right mastectomy, right axillary lymph node dissection and radiotherapy of the right axilla. A 2-year follow-up with CT scan revealed metastatic disease: (a) Mediastinal window showing a voluminous mass in the left breast, an enlarged lymph node in the right axilla, and a nodular thickening in the subcutaneous soft tissues of the right arm and of the left lateral chest wall. (b) Parenchymal window showing numerous bilateral pulmonary nodules.
Jimaging 09 00094 g012
Jimaging 09 00094 g013 550
Figure 13. A 75-year-old patient with a history of lobular invasive carcinoma of the right breast treated with quadrantectomy and radiotherapy. Mediastinal window of a follow-up CT scan shows skin thickening of the right breast.
Figure 13. A 75-year-old patient with a history of lobular invasive carcinoma of the right breast treated with quadrantectomy and radiotherapy. Mediastinal window of a follow-up CT scan shows skin thickening of the right breast.
Jimaging 09 00094 g013
Jimaging 09 00094 g014 550
Figure 14. A 65-year-old patient with a history of PBA treated with right mastectomy, right axillary lymph node dissection, and radiotherapy of the right axilla. A 2-year follow-up with 18F FDG PET-CT scan revealed metastatic disease: (a,b) hypermetabolic lesions are observed in breasts, lungs, and bones.
Figure 14. A 65-year-old patient with a history of PBA treated with right mastectomy, right axillary lymph node dissection, and radiotherapy of the right axilla. A 2-year follow-up with 18F FDG PET-CT scan revealed metastatic disease: (a,b) hypermetabolic lesions are observed in breasts, lungs, and bones.
Jimaging 09 00094 g014
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Conti, M.; Morciano, F.; Rossati, C.; Gori, E.; Belli, P.; Fornasa, F.; Romanucci, G.; Rella, R. Angiosarcoma of the Breast: Overview of Current Data and Multimodal Imaging Findings. J. Imaging 2023, 9, 94. https://doi.org/10.3390/jimaging9050094

AMA Style

Conti M, Morciano F, Rossati C, Gori E, Belli P, Fornasa F, Romanucci G, Rella R. Angiosarcoma of the Breast: Overview of Current Data and Multimodal Imaging Findings. Journal of Imaging. 2023; 9(5):94. https://doi.org/10.3390/jimaging9050094

Chicago/Turabian Style

Conti, Marco, Francesca Morciano, Claudia Rossati, Elisabetta Gori, Paolo Belli, Francesca Fornasa, Giovanna Romanucci, and Rossella Rella. 2023. "Angiosarcoma of the Breast: Overview of Current Data and Multimodal Imaging Findings" Journal of Imaging 9, no. 5: 94. https://doi.org/10.3390/jimaging9050094

APA Style

Conti, M., Morciano, F., Rossati, C., Gori, E., Belli, P., Fornasa, F., Romanucci, G., & Rella, R. (2023). Angiosarcoma of the Breast: Overview of Current Data and Multimodal Imaging Findings. Journal of Imaging, 9(5), 94. https://doi.org/10.3390/jimaging9050094

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop