Clinico-pathological and biomolecular findings in Italian patients with multiple cutaneous neurofibromas

<p>Abstract</p> <p>Background</p> <p>Neurofibroma occurs as isolated or multiple lesions frequently associated with neurofibromatosis type 1 (NF1), a common autosomal dominant disorder affecting 1 in 3500 individuals. It is caused by mutations in the <it>NF1 </it>gene, which comprises 60 exons and is located on chromosome 17q11.2. <it>NF1 </it>is a fully penetrant gene exhibiting a mutation rate some 10-fold higher compared with most other disease genes. As a consequence, a high number of cases (up to 50%) are sporadic. Mutation detection is complex due to the large size of the <it>NF1 </it>gene, the presence of pseudogenes and the great variety of lesions.</p> <p>Methods</p> <p>110 patients with at least two neurofibroma lesions recorded in the files of the Pathology Department of the University of Modena during the period 1999-2010, were included in this study. Through interviews and examination of clinical charts, pedigrees were drawn for all patients who were affected by at least two neurofibromas. We attempted to delineate the clinical features of NF1 and the mutational spectrum in the cohort of 11 NF1 families identified. For each proband, the whole coding sequence and all splice sites were studied for mutations, either by the protein truncation test (PTT), or, more frequently, by denaturing high performance liquid chromatography (DHPLC). Two GIST tumors of NF1 patients were tested for somatic NF1 mutations.</p> <p>Results</p> <p>NF1 germline mutations were identified in 7 (68%) patients. A novel mutation, c.3457_3460delCTCA in exon 20, was detected in two unrelated patients and was associated with different clinical features. No NF1 somatic mutations were detected in the GIST tumors. A wide phenotypic and genotypic variability was registered, both in the spectrum of skin lesions and visceral neoplasms, even among members of the same family who had different clinical manifestations. A proclivity to multiple tumors arising in the same subject, and a higher tumor burden per family were the most relevant findings observed in patients affected with the NF1 mutation.</p> <p>Conclusions</p> <p>We report a novel NF1 mutation and we contribute data for the refinement of the NF1 genotype-phenotype spectrum.</p

Diagnostic accuracy and complication rate of CT-guided fine needle aspiration biopsy of lung lesions: a study based on the experience of the cytopathologist.

BACKGROUND: CT-guided transthoracic needle biopsy is a well-established technique for the diagnosis of focal lung lesions. Fine needle aspiration biopsy (FNAB) requires the presence of a cytopathologist on-site to assess the adequacy of samples. For this reason FNAB is less and less used, and core biopsy is the first-line procedure when an experienced cytopathologist is not immediately available. PURPOSE: To evaluate the accuracy and complication rate of CT-guided FNAB of lung lesions according to the experience of the cytopathologist on-site. MATERIAL AND METHODS: A total of 321 consecutive biopsies were considered. Immediate cytological assessment was performed by an experienced cytopathologist for the first 165 procedures (group A) and by two training pathologists for the remaining 156 biopsies (group B). At the time of FNAB the pathologist assigned a semiquantitative score (0-3) to each specimen to assess its diagnostic quality. All variables between the two groups were analyzed by chi-square and Student's t test. A P value <0.05 was considered statistically significant. RESULTS: For all procedures, overall diagnostic accuracy was 80% for cytology alone, with no statistical difference between the two groups for diagnostic accuracy and sample score assigned. In all, 75% of the cytological samples (75% group A, 74% group B) obtained a higher score with a specific diagnosis of histotype. A post biopsy pneumothorax was detected in 27% of biopsies (25% group A, 28% group B). Thirteen patients (4.0%) required chest tube insertion for treatment. For all cases, the pneumothorax rate was significantly affected by the number of samples obtained (P=0.02), but not by the pleural punctures (P=0.15). There was no statistically significant difference between the two groups concerning the number of needle passes and complication rate (P>0.05). CONCLUSION: The efficacy and safety of CT-guided FNAB is not significantly affected by the training level of the cytopathologist on-site. Moreover, the number of specimens obtained for each procedure is a risk factor for pneumothorax

The Pioneering Contribution of Italian Surgeons to Skull Base Surgery

The origin of neurosurgery as a modern, successful, and separate branch of surgery could be dated back to the end of the 19th century. The most important development of surgery occurred in Europe, particularly in Italy, where there was a unique environment, allowing brilliant open-minded surgeons to perform, with success, neurosurgical operations. Neurosurgery began at the skull base. In everyday practice, we still pay tribute to early Italian neuroanatomists and pioneer neurosurgeons who represented a starting point in a new, obscure, and still challenging field of medicine and surgery during their times. In this paper, we report at a glance the contributions of Tito Vanzetti from Padua (1809-1888), for his operation on a destructive skull base cyst that had, indeed, an intracranial expansion; of Davide Giordano (1864-1954) from Venice, who described the first transnasal approach to the pituitary gland; and, most importantly, of Francesco Durante from Messina (1844-1934), who was the first surgeon in the history of neurosurgery to successfully remove a cranial base meningioma. They carried out the first detailed reported surgical excision of intracranial lesions at the skull base, diagnosed only through clinical signs; used many of the advances of the 19th century; and conceived and performed new operative strategies and approaches. Their operations were radical enough to allow the patient to survive the surgery and, in the case of Durante, for the first time, to obtain more than 12 years of good survival at a time when a tumor of this type would have been fatal

Insights into prion biology: Integrating a protein misfolding pathway with its cellular environment

Protein misfolding and assembly into ordered, self-templating aggregates (amyloid) has emerged as a novel mechanism for regulating protein function. For a subclass of amyloidogenic proteins known as prions, this process induces transmissible changes in normal cellular physiology, ranging from neurodegenerative disease in animals and humans to new traits in fungi. The severity and stability of these altered phenotypic states can be attenuated by the conformation or amino-acid sequence of the prion, but in most of these cases, the protein retains the ability to form amyloid in vitro. Thus, our ability to link amyloid formation in vitro with its biological consequences in vivo remains a challenge. In two recent studies, we have begun to address this disconnect by assessing the effects of the cellular environment on traits associated with the misfolding of the yeast prion Sup35. Remarkably, the effects of quality control pathways and of limitations on protein transfer in vivo amplify the effects of even slight differences in the efficiency of Sup35 misfolding, leading to dramatic changes in the associated phenotype. Together, our studies suggest that the interplay between protein misfolding pathways and their cellular context is a crucial contributor to prion biology