Post-radiotherapy vascular lesions of the breast: immunohistochemical and molecular features of 74 cases with long-term follow-up and literature review

Aims A wide range of post-radiotherapy (RT) vascular lesions can occur, ranging from benign lymphangiomatous papules of the skin (BLAPs), to atypical vascular lesions (AVLs) and post-RT angiosarcomas (ASs). The relationship between benign and malignant post-RT breast lesions and their prognostic features are still controversial. The aims of this study were to investigate the relationship between benign and malignant mammary post-RT vascular lesions and to define post-RT AS prognostic features. Methods and results Seventy-four post-RT vascular lesion cases were obtained and stained with antibodies against CD34, CD31, D2-40, Ki67, and c-Myc. Mutational analysis was performed by deep sequencing for the following genes:KRAS,NRAS,HRAS,BRAF,PIK3CA,TP53,NOTCH1,PTEN,CDKN2A,EGFR,AKT1,CTNNB1,hTERT, andPTPRB. Post-RT AS cases were graded according to a previously reported breast AS grading system. AVL cases showed a low number ofHRASandhTERTmutations, whereas post-RT AS cases showed a high frequency ofEGFR,TP53,HRASandhTERTmutations. On follow-up, all BLAP and AVL patients were alive with no evidence of disease. Post-RT AS 5-year overall survival declined with the increase in grade, as follows: 85.7% for grade 1, 83.3% for grade 2, and 40.4% for grade 3. Conclusions Our findings confirm that BLAP and AVL have a good prognosis, and that post-RT AS prognosis is strongly related to histological grading. On molecular analysis, AVL and post-RT AS sharedHRASandhTERTmutations, suggesting a relationship between the two lesions.