Birt-Hogg-Dubé syndrome (BHDS) is characterized by a clinical triad including cutaneous hamartomas originating from hair follicles, lung cysts/pneumothorax, and kidney tumors. Inactivating mutations of the tumor suppressor gene FLCN are identified in most families with BHDS. Usually, patients are referred for genetic examination by dermatologists because of the presence of typical multiple skin tumors with or without additional symptoms. However, because of phenotypic variability and incomplete penetrance, the clinical presentation of BHDS is not yet fully defined. Criteria for genetic testing and diagnosis that take into account variable manifestations have recently been proposed by the European BHD Consortium. We sequenced the FLCN gene coding region in a series of 19 patients selected for kidney and/or lung manifestations. Overall, FLCN mutations were found in 9 of 19 (47%) families and were detected only in probands who had either >2 components of the clinical triad or a single component (renal or pulmonary) along with a family history of another main BHDS manifestation. Typical cutaneous lesions were present only in 8 of 21 FLCN mutation carriers aged >20 years identified in the mutation-positive families. In addition, we provide clinical and molecular evidence that parotid oncocytoma, so far reported in six BHDS cases, is associated with this condition, based on the observation of a patient with bilateral parotid involvement and marked reduction of the wild-type FLCN allele signal in tumor DNA. Overall, the results obtained in this study contribute to the definition of the phenotypic characteristics that should be considered for BHDS diagnosis and FLCN mutation testing.

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Women who were previously treated for breast cancer (BC) are an important particular subgroup of women at intermediate BC risk. Their breast follow-up should be planned taking in consideration a 1.0–1.5 % annual rate of loco-regional recurrences and new ipsilateral or contralateral BCs during 15–20 years, and be based on a regional/district invitation system. This activity should be carried out by a Department of Radiology integrating screening and diagnostics in the context of a Breast Unit. We recommend the adoption of protocols dedicated to women previously treated for BC, with a clear definition of responsibilities, methods for invitation, site(s) of visits, methods for clinical and radiological evaluation, follow-up duration, role and function of family doctors and specialists. These women will be invited to get a mammogram in dedicated sessions starting from the year after the end of treatment. The planned follow-up duration will be at least 10 years and will be defined on the basis of patient’s age and preferences, taking into consideration organizational matters. Special agreements can be defined in the case of women who have their follow-up planned at other qualified centers. Dedicated screening sessions should include: evaluation of familial/personal history (if previously not done) for identifying high-risk conditions which could indicate a different screening strategy; immediate evaluation of mammograms by one or, when possible, two breast radiologists with possible addition of supplemental mammographic views, digital breast tomosynthesis, clinical breast examination, breast ultrasound; and prompt planning of possible further workup. Results of these screening sessions should be set apart from those of general female population screening and presented in dedicated reports. The following research issues are suggested: further risk stratification and effectiveness of follow-up protocols differentiated also for BC pathologic subtype and molecular classification, and evaluation of different models of survivorship care, also in terms of cost-effectiveness.

This video aimed to describe the role of intraoperative neuromonitoring (IONM) during transoral endoscopic thyroidectomy vestibular approach (TOETVA) with emphasis given to IONM technical and technological notes, the identification of recurrent laryngeal nerve (RLN). Standardized technique of IONM consist in identifying and monitoring both the vagus nerve and the RLNs before and after resection (V1, V2, R1, R2). According to this report, IONM during TOETVA is feasible and safe in providing identification and function of laryngeal nerves. IONM enable surgeons to feel more comfortable with their initial approach to TOETVA or extended indications. Larger series are needed for appropriated evaluation of IONM in reduction of the rates for RLN complications. general anesthesia; precedent radiation in the head, neck, or upper mediastinum; antecedent neck surgery; recurrent goiter; a gland volume of >45 mL or main nodule diameter of >50 mm; documentation of lymph node or distant metastases, tracheal/esophageal infiltration, preoperative laryngeal nerve palsy, hyperthyroidism, mediastinal goiter, or oral abscesses. Moreover, patients with poorly-or undifferentiated cancer, dorsal extrathyroidal radius, and/or lateral neck metastasis (N1b) are not favored for TOETVA (1-16).Candidates for TOETVA undergo same preoperative workup will offer a conventional open approach. Preoperative preparationThe 3 vestibular incisions determine a new communication between the oral cavity and neck and a poor oral heath may contribute the ability of the oral microbiota to invade the body. Good oral and dental hygiene can prevent possible postoperative infective complications. Therefore, it is suggested a preoperative oral/dental assessment by specialist. Patients undergo dental care about 1 month before TOETVA (1-9). This is recommended especially in high risk subjects as diabetic and cardiovascular patients.Moreover, pre-and post-operatively, patients are asked to gargle with Chlorhexidine mouth wash. Amoxicillin/ clavulanic acid is used for preoperative prophylactic antibiotic (1-9). Some authors suggest extending the antibiotic for 5 days postoperatively orally (1-9). Equipment preference cardMonitored TOETVA is performed according to standards of equipment set up, induction and maintenance anesthesia, correct tube positioning verification tests, EMG definitions described by the INMSG Guidelines (23).Nerve-monitoring formats as laryngeal palpation, glottic observation, glottic pressure monitoring, endoscopically placed intramuscular vocal cord electrodes, intramuscular electrodes placed through the cricothyroid membrane, and postcricoid surface electrodes are difficult to use in any endoscopic thyroid procedure (21,23,24). Thus, for safety, utility, simplicity, systems that rely on endotracheal tube-based surface electrodes were preferred monitoring equipment format for TOETVA.Pre-fashioned with integrated paired left and right stainless steel electrodes embedded within the endotracheal tube surface were used (NIM TriVantage ® E...

Introduction Double occurrence of TTF1 and ΔNp63/p40 (henceforth, p40) within the same individual cells is exceedingly rare in lung cancer. Little is known on their biological and clinical implications. Methods Two index cases immunoreactive for both p40 and TTF1 and nine tumors selected from The Cancer Genome Atlas (TCGA) according to the mRNA levels of the two relevant genes entered the study. Results The two index cases were peripherally located, poorly differentiated, and behaviorally unfavorable carcinomas, which shared widespread p40 and TTF1 decoration within the same individual tumor cells. They also retained SMARCA2 and SMARCA4 expression, while variably stained for p53, cytokeratin 5, and programmed death-ligand 1. A subset of basal cells p40+/TTF1+ could be found in normal distal airways. Biphenotypic glandular and squamous differentiation was unveiled by electron microscopy, along with EGFR , RAD51B , CCND3 , or NF1 mutations and IGF1R , MYC , CCND1 , or CDK2 copy number variations on next-generation sequencing analysis. The nine tumors from TCGA (0.88% of 1018 tumors) shared the same poor prognosis, clinical presentation, and challenging histology and had activated pathways of enhanced angiogenesis and epithelial-mesenchymal transition. Mutation and copy number variation profiles did not differ from the other TCGA tumors. Conclusions Double p40+/TTF1+ lung carcinomas are aggressive and likely underrecognized non–small cell carcinomas, whose origin could reside in double-positive distal airway stem-like basal cells through either de novo-basal-like or differentiating cell mechanisms according to a model of epithelial renewal.