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, and PTPRB. Post‐RT AS cases were graded according to a previously reported breast AS grading system. AVL cases showed a low number of HRAS and hTERT mutations, whereas post‐RT AS cases showed a high frequency of EGFR, TP53, HRAS and hTERT mutations. 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 shared HRAS and hTERT mutations, suggesting a relationship between the two lesions. [ABSTRACT FROM AUTHOR]