Smoking and FGFR2 rs2981582 variant independently modulate male breast cancer survival: A population-based study in Tuscany, Italy

Aim: Male breast cancer (MBC) is a rare disease and recommendations for its clinical management are often extrapolated from those for female breast cancer, even if breast cancer (BC) has different characteristics in the two sexes. The purpose of this study was to assess the influence of several individual characteristics including clinico-pathological, lifestyle and genetic factors on overall survival (OS) of a relatively large and well characterized population-based series of 166 MBCs enrolled in Tuscany. Methods: We genotyped MBC cases at BRCA1/2 genes and at 9 candidate BC susceptibility SNPs. Kaplan-Meier method and multivariate Cox regression, adjusted for several individual characteristics were used. To reduce a possible selection bias related to the interval between diagnosis and enrolment of MBC cases into the study, we used the date of blood donation as the date of the start of observation for survival analysis. Results: Only smoking habits had a significant effect on OS at 10 years (for current smokers, HR: 3.34; 95% CI 1.45–7.68; p = 0.004), while lymph node status fell short of reaching statistical significance (for pN positive, HR: 2.07; 95% CI 0.93–4.55; p = 0.07). In the same multivariate analysis we found a significantly higher OS in cases with FGFR2 rs2981582 variant in the dominant transmission model (HR: 0.29; 95% CI: 0.13–0.62; p = 0.028). A sensitivity analysis with left truncation showed similar results. Conclusions: Our results may contribute to shed light on factors influencing MBC survival suggesting an important role for cigarette smoking and FGFR2 rs2981582 variant, and provide clues for better patient management

Comparison of Pre- and Postsurgical Concentrations of Blood HER-2 mRNA and HER-2 Extracellular Domain Reflects HER-2 Status in Early Breast Cancer

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Classic and follicular variant of papillary thyroid microcarcinoma: 2 different phenotypes beyond tumor size

Context: Despite the wide revision of current guidelines, the management of papillary thyroid microcarcinoma (mPTC) still has to be decided case by case. There is conflicting evidence about the role of more frequent histological subtypes, and no data about potential differences at presentation. Objective: Our aim was to compare the phenotype of the 2 most frequent mPTC variants, namely, classical papillary thyroid microcarcinoma (mPTCc) and the follicular variant of papillary thyroid microcarcinoma (mFVPTC). Methods: Retrospective observational study, from January 2008 to December 2017 of a consecutive series of patients with mPTCc and mFVPTC. All cases were classified according to the 2015 American Thyroid Association (ATA) risk classification. Clinical and preclinical features of mPTCc and mFVPTC at diagnosis were collected. The comparison was also performed according to the incidental/nonincidental diagnosis and differences were verified by binary logistic analysis. Results: In total, 235 patients were eligible for the analysis (125 and 110 mPTCc and mFVPTC, respectively). Compared with mPTCc, mFVPTCs were more often incidental and significantly smaller (4 vs 7mm) (P <. 001 all), possibly influenced by the higher rate of incidental detection. mFVPTC and incidental (P <. 001 both) tumors were significantly more often allocated within the low-risk class. A logistic regression model, with ATA risk class as the dependent variable, showed that both mFVPTC (OR 0.465 [0.235-0.922]; P =. 028]) and incidental diagnosis (OR 0.074 [0.036-0.163]; P <. 001) independently predicted ATA risk stratification. Conclusion: mFVPTC shows some differences in diagnostic presentation compared with mPTCc, and seems to retain a significant number of favorable features, including a prevalent onset as incidental diagnosis

Nodal-Stage Classification in Invasive Lobular Breast Carcinoma: Influence of Different Interpretations of the pTNM Classification

Purpose Application of current nodal status classification is complicated in lobular breast carcinoma metastases. The aim of this study was to define the optimal interpretation of the pTNM classification in sentinel node (SN) -positive patients to select patients with limited or with a high risk of non-SN involvement. Patients and Methods SN metastases of 392 patients with lobular breast carcinoma were reclassified according to interpretations of the European Working Group for Breast Screening Pathology (EWGBSP) and guidelines by Turner et al, and the predictive power for non-SN involvement was assessed. Results Reclassification according to definitions of EWGBSP and Turner et al resulted in different pN classification in 73 patients (19%). The rate of non-SN involvement in the 40 patients with isolated tumor cells according to Turner et al and with micrometastases according to EWGBSP was 20%, which is comparable to the established rate for micrometastases. The rate of non-SN involvement in the 29 patients with micrometastases according to Turner et al and with macrometastases according to EWGBSP was 48%, which is comparable to the established rate for macrometastases. Therefore, the EWGBSP method to classify SN tumor load better reflected the risk of non-SN involvement than the Turner et al system. Conclusion Compared with the guidelines by Turner et al, the EWGBSP definitions better reflect SN metastatic tumor load and allow better differentiation between patients with lobular breast carcinoma who have a limited or a high risk of non-SN metastases. Therefore, we suggest using the EWGBSP definitions in these patients to select high-risk patients who may benefit from additional local and/or systemic therapy

Hyperplasia of parathyroid gland in a five-year old child affected by MEN 2A

Primary hyperparathyroidism (HPT) is observed in 20-30% of patients with multiple endocrine neoplasia type 2A (MEN 2A). The age of diagnosis ranges from seven to seventy one year old (with median of thirty eight years) in patients affected by HPT in MEN 2A. We diagnosed primary HPT in a 5 year old boy carrier of RET gene mutation associated with MEN 2A,submitted to prophylactic total thyroidectomy (TT). The RET mutated gene carriers are submitted to prophylactic TT at different ages. Recent studies demonstrated that based on the type of RET gene mutation the timing of TT varies, as the transforming potential of RET-mutations are codon-dependentwith significant correlations between genotype and clinical phenotype in MEN 2A patients. In particular, the medullary thyroid carcinoma (MTC) occurs earlier in the patients with codon 634 mutations than in those with other mutations, and these patients have also a higher frequency of pheochromocytoma and hyperparathyroidism. This genotype-phenotype correlation is confirmed in the patient described in this report, who was carrier of a germline mutation in the 634 codon (Cys→Trp) and showed early expression of MTC and parathyroid pathology. The young age of this patient represents an exception, as other Authors report the absence of parathyroid pathology in children or in adolescents submitted to prophylactic TT. The patient underwent a partial parathyroidectomy in agreement with the preferred surgical treatment of HPT in MEN 2A, which consists in removing only the parathyroid(s) with increased volume. Indeed, the experiences with subtotal or total parathyroidectomy associated to autograft are very limited, with results supporting lack of major differences and, therefore, suggesting a more conservative surgical approach HPT in MEN 2A. We diagnosed primary HPT in a 5 year old boy carrier of RET gene mutation associated with MEN 2A, submitted to prophylactic total thyroidectomy (TT). The RET mutated gene carriers are submitted to prophylactic TT at different ages. Recent studies demonstrated that based on the type of RET gene mutation the timing of TT varies, as the transforming potential of RET-mutations are codon-dependent with significant correlations between genotype and clinical phenotype in MEN 2A patients. In particular, the medullary thyroid carcinoma (MTC) occurs earlier in the patients with codon 634 mutations than in those with other mutations, and these patients have also a higher frequency of pheochromocytoma and hyperparathyroidism. This genotype-phenotype correlation is confirmed in the patient described in this report, who was carrier of a germline mutation in the 634 codon (Cys→Trp) and showed early expression of MTC and parathyroid pathology. The young age of this patient represents an exception, as other Authors report the absence of parathyroid pathology in children or in adolescents submitted to prophylactic TT. The patient underwent a partial parathyroidectomy in agreement with the preferred surgical treatment of HPT in MEN 2A, which consists in removing only the parathyroid(s) with increased volume. Indeed, the experiences with subtotal or total parathyroidectomy associated to autograft are very limited, with results supporting lack of major differences and, therefore, suggesting a more conservative surgical approac