High-Grade Primary Angiosarcoma of the Breast with MYC Amplification: Case-Report of a 16-Year-Old Patient and Review of the Literature

    

    

    Figure 7: MYC amplification confirmed by FISH assay.
    

After discussion, our multidisciplinary oncologic team proposed an adjuvant treatment based comprising radiotherapy (RT) of the right chest wall (30 sessions for a total of 60 Grays) and prophylactic irradiation of the lymph nodes area (40 Grays). An alternating followup by clinical exam and CT-scan was proposed every 3 months. At 12 months of follow-up, our patient was free of any evidence of recurrence. At 16 months of follow-up, she showed bilateral lung and pleural metastases that were treated by chemotherapy (Adriamycinolaratumab) with good therapeutic response after six months but further progression of the disease within the next three months under olaratumab alone. Weekly chemotherapy with gemcitabine was then administered for three months but did not prevent further disease progression. Targeted treatment with pazopanib was then initiated and led to partial response after 3 months of therapy.

Discussion

ASB are rare entities. They represent 0.04 – 0.2% of all primary breast tumours and 8% of breast sarcomas [1-4], which corresponds to an incidence of 17 cases per million women [3]. Most ASB occur after previous RT treatment or chronic arm lymphoedema (Steward- Treves syndrom) but 20% occur de novo [5]. Compared to SASB, PASB usually occur in younger women (20-50 year-old) [1,4] with a median age at onset fluctuating between 53 years in the Kunkiel et al series [9] and 41 years in the Nascimento et al series [10] with a range from 15 to 82 years in these studies, in comparison to a median of 70 for SASB [5].

Diagnosis of PASB is not easy due to the insidious onset of the disease. We usually find a painless palpable mass with a fast growing rate associated with purplish, ecchymosis-like skin, without nipple retraction nor axillary node enlargement [3,4,9,11]. Tumour size generally exceeds 4 cm in diameter [10-13]. The differential diagnosis includes benign hemangioma, angiolipoma, fibromatosis, pseudoangiomatous stromal hyperplasia (PASH), cystosarcoma phyllodes, stromal sarcoma, metaplastic carcinoma, fibrosarcoma, liposarcoma, squamous cell carcinoma with sarcomatoid features, myoepithelioma and reactive spindle cell proliferative lesions [4,9].

Imaging of angiosarcoma is often limited. Mammograms frequently show non-specific changes because angioscarcomas do not have a proper pathological pattern and are found in young women with high density breast parenchyma, which may hinder the mass visualisation [3,14]. Sonography and doppler sonography are more helpful, showing angiosarcoma as a hypervascular heterogeneous hyperechoic mass associated with a disruption of normal breast architecture. MRI is usually more specific. ASB appear hypointense on T1-weighted and hyperintense on T2-weighted images while a rapid initial intense enhancement is followed by wash-out [2,3,5,15]. MRI is also useful in determining the tumour extent. The role of PET-Scan in ASB is poorly defined. As established by Cassou-Mounat et al. [16], it could help in differentiating PASB of SASB through a difference of maximum standardized uptake value (SUVmax). In our case for instance, in accordance with this study’s results, the lesion showed intense FDG avidity.

A FNA or a CNB must be performed in order to provide a histological diagnosis, even if Chen et al reported a false negative rate up to 37% [17]. If FNA or CNB is insufficient, surgical resection with microscopic examination can be performed. To avoid wrong or delayed diagnosis, as it is at best difficult, a large vascular breast mass should always be considered as an angiosarcoma until proven otherwise [4].

The neoplasm is of vascular origin. Donnell et al. [18] described three histologic grades (Table 1). Immunohistochemistry exams (CD31, CD 34, F VIII, FLI 1) may help to identify angiosarcoma [3,5,9]. There is no histological difference between PASB and RTinduced ASB. Even if these types of tumours are morphologically indistinguishable, several studies suggest that pathogenetic differences exist and propose to use MYC amplification to discriminate primary from secondary lesions in patients without relevant clinical history. Several studies showed MYC amplification in 100% of post-radiation breast angiosarcoma and nearly none in PASB [6,19-23]. However, in a molecular study investigating CIC, MYC, KDR, PLCG1 and FLT4 gene abnormalities in angiosarcomas of the breast and other somatic soft tissues, Huang et al found MYC amplification in 7% of primary angiosarcomas, in comparison to 91% of secondary angiosarcomas. Similarly, CIC alterations were found in 9% of primary angiosarcomas [24]. Our case is to be categorized within this small subset of PASB presenting with MYC amplification but without CIC alterations.

  

    
Grade I
    
Grade II
    
Grade III
  
  

    
= Low grade
      
Contains anastomosing vascular channels surrounding    breast ducts and infiltrating the adipose tissue. Blood vessels lined by a    single layer of endothelial cells with hyperchromatic nuclei showing little    mitosis with no endothelial tufting.
    
= Intermediate grade
      
Small foci of solid proliferation of    spindle-shaped cells associated with more    mitotic figures
    
= High grade
      
Contains more solid and atypical cell    proliferation with frequent necrotic area and blood lakes
  
  

    
 
    
 
    
 
  

Table 1: Angiosarcoma’s histopathological grades according to Donnell et al. [18].