Which type of cancer is detected in breast screening programs? Review of the literature with focus on the most frequent histological features.

Breast cancer is the most frequent type of cancer affecting female patients. The introduction of breast cancer screening programs led to a substantial reduction of mortality from breast cancer. Nevertheless, doubts are being raised on the real efficacy of breast screening programs. The aim of the present paper is to review the main pathological type of cancers detected in breast cancer screening programs. Specifically, attention will be given to: in situ carcinoma, invasive carcinoma histotypes and interval cancer.

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.

Asbestos exposure as an additional risk factor for small duct intrahepatic cholangiocarcinoma: a pilot study.

Intrahepatic cholangiocarcinoma (iCCA) is a rare malignancy, recently classified in small duct and large duct morphological subtypes. Growing evidence suggests asbestos as a putative risk factor for iCCA, albeit no correlation between asbestos and iCCA morphology has been investigated so far. The aim of the present study was to assess the relationship between asbestos exposure and iCCA morphological subtype. Forty patients with surgically removed iCCA were prospectively enrolled: asbestos exposure was assessed according to the Italian National Mesothelioma Register questionnaire. From the surgical iCCA specimens the main histopathological variables were collected, including the small duct (sd-iCCA, 32 patients) and large duct subtypes (ld-iCCA, 8 patients). Five sd-iCCA cases had a definite/probable occupational exposure to asbestos, while no cases of ld-iCCA were classified as being occupationally exposed (definite/probable). Other kind of asbestos exposure (i.e. possible occupational, familial, environmental) were recorded in 16 sd-iCCA and 3 ld-iCCA. Cases with unlikely exposure to asbestos were 11 sd-iCCA (35.5%) and 5 ld-iCCA (62.5%). In conclusion, these findings seem to indicate that sd-iCCA might be more frequently associated to asbestos exposure rather than ld-iCCA, suggesting that asbestos fibres might represent a parenchymal, rather than a ductal risk factor for iCCA. This pilot study must be confirmed by further case-control studies or large independent cohorts.

Chromosome X aneusomy and androgen receptor gene copy number aberrations in apocrine carcinoma of the breast.

Carcinomas with apocrine differentiation (CAD) of the breast are rare tumours typically presenting high immunohistochemical expression of androgen receptor (AR) which is a target molecule for personalised therapy. To date, no studies have evaluated the genetic changes that are associated with AR immunohistochemical expression in CADs. The present work aims to characterise AR status in CADs. Twenty CAD tumours were studied with immunohistochemistry, in situ fluorescence hybridization and DNA methylation analysis, to evaluate AR expression and its regulator status. All tumours demonstrated high AR immunohistochemical expression, with over 95% of the neoplastic cells showing AR positivity in 19/20 cases. CADs showed AR gene copy loss in a percentage of neoplastic cells ranging from 5 to 84% (mean 48.93%). AR regulator genes, including the MAGE family, UXT and FLNA, presented variable methylation levels, but were mainly hypomethylated and therefore all transcriptionally active. The results of this study indicate that CADs present AR monosomy, paralleled by higher transcriptional activity of the gene with potential to influence response to AR deprivation therapy.

The morphological spectrum of salivary gland type tumours of the breast.

Salivary gland like tumours of the breast constitute a wide spectrum of entities each one showing peculiar features and clinical behaviour. They can be subdivided as follows: (1) tumours showing pure myoepithelial cell differentiation, such as pure benign and malignant myoepitheliomas; (2) tumours with mixed epithelial and myoepithelial cell differentiation, such as pleomorphic adenoma, adenomyoepithelioma and adenoid cystic carcinoma; and (3) tumours with pure epithelial cell differentiation, such as acinic cell carcinoma, oncocytic carcinoma, mucoepidermoid carcinoma and polymorphous adenocarcinoma. These tumours share similar features with the salivary gland counterparts, but different clinical behaviour. Most salivary gland type tumours of the breast are negative for oestrogen and progesterone receptor and lack HER2 gene amplification, therefore they are classified as 'triple negative' tumours. Nevertheless, some of the malignant entities (such as classical adenoid cystic carcinoma) exhibit good behaviour and do not need any treatment in addition to local control. The aim of the present paper is to review the morphological and prognostic features of salivary gland like tumours of the breast, in order to highlight the correct clinical management.