Although breast cancer is the second most common cause of central nervous system (CNS) metastases with a notable increase of incidence, only few studies on brain-metastasizing breast cancer are available. In this immunohistochemical and fluorescence in situ hybridization (FISH) study, metastases to the CNS (n ¼ 85) and primary breast cancers, with known involvement of the CNS (n ¼ 44) including paired primary and metastasized tumours (n ¼ 23), were investigated retrospectively for the expression of oestrogen-(ER) and progesterone-(PR) hormone receptors, Her-2/neu, epidermal growth factor receptor (EGFR), Ki-67, and cytokeratins (CKs) 5/ 14. The majority of brain metastases were steroid hormone receptor negative (ER 66%, PR 82%) corresponding to the findings in primary tumours with known involvement of the CNS (68% ER-negative, 75% PR-negative). The frequency of HER-2/neu-overexpressing or -amplified cancers was increased in both groups (34 and 32%, respectively). EGFR expression was more frequent in metastases (41%) than in primary tumours (16%). The proportions of cases with a basal phenotype were 26 and 30%, respectively. In paired primary tumours and metastases to the CNS, constancy of Her-2/neu status was observed in 87% of cases with only one sample turning Her-2/neu-negative and two samples acquiring overexpression/amplification in brain metastases. In contrast, steroid hormone receptors exhibited more frequently a loss of expression (17%) than a gain (9%) with 74% revealing a constant phenotype. We conclude that brain-metastasizing breast cancer belongs predominantly to the basal type or Her-2/neu type. Primary and metastatic tumours differ from each other only in a minority of cases, leading rather to a loss of steroid hormone receptors and to a gain of EGFR and Her-2/neu.

These data clearly demonstrate the involvement of circulating fibroblastic precursor cells in the development of human fibrosing lung lesions and provide evidence that these cells are most probably bone marrow derived. These results may open new venues regarding the prevention of fibrosis in lung transplants and potentially in other organs.

AimsRecently, transcatheter aortic valve replacement (TAVR) has evolved as the standard treatment in patients with inoperable aortic valve stenosis. According to TAVR guidelines, body computed tomography (CT) is recommended for pre-procedural planning. Due to the advanced age of these patients, multiple radiological potentially malignant incidental findings (pmIFs) appear in this cohort. It is unknown how pmIFs influence the decision by the heart team to intervene and the mortality.Methods and resultsWe evaluated in a retrospective single-centre observational study 414 participants screened for TAVR with dual-source CT between October 2010 and December 2012. pmIFs are common and appeared in 18.7% of all patients screened for TAVR. The decision to intervene by TAVR or surgical aortic valve replacement (SAVR) was made by an interdisciplinary heart team and the role of pmIF in decision-making and time to treatment with TAVR or SAVR was analysed, retrospectively. The appearance of a pmIF vs. no pmIF did not significantly influence therapeutic decisions [odds ratio (OR) 1.14; P = 0.835] or time to treatment (91 ± 152 vs. 61 ± 109 days, respectively). Several findings, which are highly suspicious for malignancy, were less likely associated with invasive treatment (OR 0.207; P = 0.046). Patient survival was evaluated for at least 2 years until January 2014. Two-year survival of patients after TAVR or SAVR, treated according to the heart team decision, was ∼75% and independent from the presence of a non-severe (P = 0.923) or severe (P = 0.823) pmIF.ConclusionThe study indicates that frequently occurring radiologic pmIF did not influence 2-year survival after a decision to intervene was made by an interdisciplinary heart team.

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Medullary carcinoma of the breast has a relatively favorable prognosis despite its malignant histopathological appearance, providing a challenge for the pathologically based diagnosis of breast cancer. Macroscopic and microscopic findings combined provide diagnostic criteria. The importance of the immunophenotype of medullary carcinoma is not well defined. Because the reproducibility of morphological criteria is limited, we conducted an immunohistochemical study in search of markers that could facilitate histopathological classification. We examined 32 medullary carcinomas in comparison with 30 high grade ductal invasive carcinomas with similar morphology using 23 different immunohistochemical markers. The results showed an overlap with the so called basal like subtype of invasive breast cancer (negativity for steroid hormone receptor, positivity for basal cytokeratins). None of the immunohistochemical markers enabled a specific discrimination between the two groups. Medullary carcinomas overexpress EGF-R more frequently (P<0.004). In combining the characteristic morphological criteria and the immunohistochemical detection of the basal like phenotype and EGFR, a higher diagnostic accuracy can be achieved. The immunophenotype alone does not allow a definite classification of medullary carcinoma.

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