All pure flat atypical atypia lesions of the breast diagnosed using percutaneous vacuum-assisted breast biopsy do not need surgical excision.

BACKGROUND: The purposes of this study were to evaluate the outcome of women with pure flat atypical atypia (FEA) diagnosed at vacuum-assisted breast biopsy (VABB) targeting microcalcifications and to determine whether clinical, radiological and pathologic parameters are able to predict which lesions will be upgraded to malignancy. MATERIALS: 2414 cases of consecutive VABB for microcalcifications using VA 8-, 10- or 11-Gauge stereotactically guided core biopsy performed between January 2005 and December 2011 from two french breast cancer centers were evaluated. Data of women with VABB-diagnosed pure FEA who underwent either excisional surgery or mammographic follow-up were analyzed. Cases with mass lesions or ipsilateral cancers were excluded. Two pathologists (FA,PM) reviewed the results of procedures performed. Clinical, radiological, as well as histological criteria have been studied in order to determine the correlation between these factors and carcinoma underestimation. RESULTS AND CONCLUSION: This study included 70 cases of pure FEA. Twenty women underwent surgical excision and 50 had clinical and mammographic surveillance only. In three women FEA was upgraded to breast cancer on excision. Clinical and mammographic follow-up for a mean of 56 months ±â€¯27 in the group without excision showed two cancers in the same breast (Intermediate grade DCIS, and invasive ductal carcinoma 84 and 48 months respectively after VABB). Three factors were significantly predictive of underestimation or occurence of cancer for pure FEA when the radiologic lesions are calcifications: age≥ 57 years, radiologic size >10 mm and number of FEA foci ≥4.

Different inactivating mutations of the mineralocorticoid receptor in fourteen families affected by type I pseudohypoaldosteronism.

We have analyzed the human mineralocorticoid receptor (hMR) gene in 14 families with autosomal dominant or sporadic pseudohypoaldosteronism (PHA1), a rare form of mineralocorticoid resistance characterized by neonatal renal salt wasting and failure to thrive. Six heterozygous mutations were detected. Two frameshift mutations in exon 2 (insT1354, del8bp537) and one nonsense mutation in exon 4 (C2157A, Cys645stop) generate truncated proteins due to premature stop codons. Three missense mutations (G633R, Q776R, L979P) differently affect hMR function. The DNA binding domain mutant R633 exhibits reduced maximal transactivation, although its binding characteristics and ED(50) of transactivation are comparable with wild-type hMR. Ligand binding domain mutants R776 and P979 present reduced or absent aldosterone binding, respectively, which is associated with reduced or absent ligand-dependent transactivation capacity. Finally, P979 possesses a transdominant negative effect on wild-type hMR activity, whereas mutations G633R and Q776R probably result in haploinsufficiency in PHA1 patients. We conclude that hMR mutations are a common feature of autosomal dominant PHA1, being found in 70% of our familial cases. Their absence in some families underscores the importance of an extensive investigation of the hMR gene and the role of precise diagnostic procedures to allow for identification of other genes potentially involved in the disease.