Primary Angiosarcoma of Breast: a Case Series of Rare Disease

Abstract

Primary angiosarcoma of breast (PAB) is a very rare disease and it accounts for only 0.05% of all malignant breast tumors. We present the clinical radiological and pathological features, treatment given, and outcome of this rare disease in our institute in a period of 5 years, aiming at contributing to the knowledge of prognostic factors of this rare disease. We report a case of PAB treated at our hospital along with 2 more cases of PAB we found on retrospective analysis. The basic criterion for inclusion in the study was the presence of histopathologically confirmed primary angiosarcoma of the breast: graded into low (G1, G2) and high (G3) grades. Surgeons must be aware about its high systemic metastatic potential, atypical presentation, and diffuse nature of infiltration so that it will be diagnosed early, and undergo a margin negative excision with reconstruction after a proper metastatic evaluation.

Introduction

Primary angiosarcoma of the breast (PAB) is a very rare disease, accounting for only 0.05% of all malignant breast tumors [1]. Primary angiosarcoma of the breast occurs in the younger age group and radiation-induced angiosarcoma occurs in the relatively older age group [2]. PAB patients present with a sensation of fullness in the breast or swelling with rapid growth [3]. Although surgery (mastectomy /breast conservation surgery) is the mainstay of treatment, multimodality treatment is scarce owing to the rarity of the disease. We present the clinical, radiological, and pathological features, treatment given, and outcome of this rare disease in our institute over 5 years, aiming at contributing to the knowledge of prognostic factors of this rare disease.

Findings

We report a case of PAB treated at our hospital, along with 2 more cases of PAB that we found on retrospective analysis. The basic criterion for inclusion in the study was the presence of histopathologically confirmed primary angiosarcoma of the breast: graded into low (G1, G2) and high (G3) grades. Specific data such as age at diagnosis, sex, and symptoms at presentation, as well as clinical history—tumor size, side, clinical condition, prior radiotherapy, rendered treatment, presence of local recurrence and distant metastasis, and patient survival—were evaluated based on the available medical records and then analyzed. Table 1 summarizes the clinicopathological features of our 3 patients diagnosed with PAB.

Table 1.

Case details (MMG mammogram, MRI magnetic resonance imaging, BIRADS breast imaging reporting and data system, NA not applicable, MRM modified radical mastectomy)

CASE	AGE	SEX	SIDE	IMAGING	BIRADS	SIZE	TREATMENT
1	46	F	Left	MMG, PET-CT and MRI	III	6.4 × 4.6 cm	Excision >  > left MRM >  > RE wide excision
2	16	F	Bilateral	MRI	III both sides	11 × 10 cm on right and 1.4 × 1 cm on left	WLE both breast
3	63	F	Right	NA	NA	10 × 10 cm	Right MRM

Case No. 1

The first patient presented with a breast lump without any pain, ulcer, or skin discoloration. She didn’t have any family history of cancer or history of irradiation to the chest. Mammogram showed a relatively well-defined 6 × 4 cm BIRADS III lesion in the upper inner quadrant of the left breast, likely suggestive of hamartoma. MRI breast showed malignant-looking heterogeneously enhancing vascular lesion with infiltrating borders involving the overlying skin and areola (Fig. 1). Patient initially underwent wide excision from a local hospital, the pathology report of which came as PAB (CD 31 Positive) and margins were positive (Fig. 2A, B). She then underwent a left modified radical mastectomy, from the local hospital. The histopathology report of that came as a residual disease with medial margin and deep margins positive for malignancy (15 axillary nodes—all reactive). She was then referred to us and she underwent a re-wide excision with en bloc resection of the medial part of the pectoralis major muscle, HPR of which showed no residual disease. She was started on adjuvant chemotherapy. Upon searching our case records, we could find 2 more cases of PAB treated at our center within the last 6 years which are also discussed below.

Fig. 1.

MRI image showing T2 hyper enhancing lesion in the left breast with infiltrating borders

Fig. 2.

A H&E slide showing anastomosing vascular channels lined by pleomorphic cells with prominent eosinophilic nucleoli. B Immunohistochemistry showing positive for CD31 in endothelial cells

Case No. 2

The second patent presented with bilateral breast lumps, with no history of pain or ulceration. She had no family history of cancer or history of irradiation to the chest. MRI breast showed a large vascular lesion with contrast enhancement in the right breast, resembling a large hemangioma, categorized as a BIRADS-III lesion. The left breast lesion was smaller and also classified as BIRADS-III. Subsequently, she underwent wide excision of both lesions. Both lesions were margin positive. She developed local recurrence in the right breast after a month and on evaluation for re-wide excision, she was detected to have liver and brain metastasis. She was started on palliative chemotherapy and passed away 1 month after detecting the recurrence.

Case No. 3

The third patient also presented with a breast lump and an ulcer. She had no family history of cancer or history of irradiation to the chest. On examination, a 10 × 10 cm mass was noted involving the entire right breast, with blackish discoloration and ulceration of the overlying skin. The lump was mobile within the breast, and there were no palpable enlarged axillary nodes. The patient underwent a right MRM with curative intent. She passed away after 1 month. The cause of death is unknown. No further details of this case are available.

Discussion

Primary breast sarcomas are rare, accounting for 0.1% of all breast malignancies [4]. Angiosarcoma is the most common primary breast sarcoma reported in many of the large series [5, 6]. Studies on PAB are few, which shows its rarity [7–10].

PAB occurs mainly in young women between 30 and 50 years of age [11]. It presents with a poorly defined mass with or without reddish-blue skin discoloration, which may mimic a rash [12]. Like in our 3 cases, the clinical presentation of this disease can vary from skin discoloration through a small lump to a large lump with or without an ulcer. Hence, a high index of clinical suspicion is needed to diagnose an angiosarcoma of the breast. A rare scenario of patients presenting with a large breast lump and consumption coagulopathy has also been reported [13].

Ultrasonography or mammography is not specific and has a high false negativity [14]. MR mammogram is the imaging of choice. Hyperintensity on T2-weighted images with high-grade tumors shows swift enhancement and washout kinetics [15]. Prolonged enhancement in MRI is typical of vascular tumors, so the histological features and imaging appearance have to be combined and correlated to get a diagnosis. Our patients had an MRI done, which showed a vascular lesion with hyper-enhancement, which is diagnostic of angiosarcoma. The mass demonstrated predominantly low T1 signal, extremely high T2 signal with rapid wash-in, and prolonged enhancement on the dynamic phase.

Benign lesions like capillary hemangiomas, papillary endothelial hyperplasia, or pseudoangiomatous stromal hyperplasia can mimic angiosarcoma histologically [16]. The use of vascular markers helps make this distinction, and the positivity of vascular markers is important for the diagnosis of angiosarcoma (CD31, CD34, and D2-40). Hemangiomas can be distinguished from angiosarcoma by a lower proliferation index, as shown with immunostaining for Ki-67, and absence of expression of Skp2. Angiolipoma can be characterized by the absence of an infiltrative growth pattern and endothelial atypia or multilayering, and the typical fibrin micro-thrombi are also useful diagnostic clues, especially in needle biopsies. Core biopsy is reported to have a high false-negative rate in angiosarcoma [17]. Our first case was diagnosed after a margin positive-excision biopsy after a false-negative core biopsy report. Microscopy of our cases also showed the presence of well-formed anastomosing vascular channels lined by endothelial cells with focal multilayering (Fig. 2A).

Proper diagnosis and differentiation from carcinoma are essential for optimal therapy and avoidance of unnecessary radical surgery. The preferred treatment for breast angiosarcoma is mastectomy rather than wide local excision given the high chance of local recurrence [18]. In our study, all patients initially underwent wide excision. In all three cases, margins were positive, which means that because of the diffuse nature of the disease margin assessment is difficult. A proper preoperative assessment with MRI is needed to study the exact extent of the disease. Additionally, patients must be planned for wide excision with extra gross margins and reconstruction to achieve a proper negative margin in the first surgery itself. Patients undergoing multimodality treatment are reported to have a better prognosis. Shearwood et al. reported that the extent of surgery and radiotherapy were not associated with survival, and adjuvant chemotherapy for lesions more than 5 cm was associated with survival improvement [19]. Although there are only 10 cases in his study, Johnstone et al. reported that there is excellent local control with adjuvant radiotherapy for PAB [20]. The responsiveness of metastatic breast angiosarcoma to combination cytotoxic chemotherapy (48% overall response rate) suggests that it is likely to be a chemosensitive disease, specifically in terms of anthracycline-ifosfamide and gemcitabine-taxane combinations. In young patients, PAB behaves more aggressively, as in our second case [21]. Tumor size and grade also have been reported as prognostic factors [4, 22, 23].

Conclusion

PAB is a very rare and aggressive malignancy. Surgeons must be aware of their atypical presentation, diffuse nature of infiltration, and high systemic metastatic potential. This awareness will help in early diagnosis, multidisciplinary team discussion on management, a proper margin-negative excision with reconstruction after a proper metastatic evaluation, and adjuvant treatment.

Declarations

Conflict of Interest

The authors declare no competing interests.