Endobronchial Pagetoid Spread of a Breast Carcinoma Metastatic to the Lung: A Case Report

A case of endobronchial pagetoid spread of a breast carcinoma metastatic to the lung is described. A 73-year-old woman underwent wedge lung resection after the cytological diagnosis of lung metastasis from ductal invasive breast carcinoma. The breast carcinoma had been surgically removed 6 years previously; at the time of diagnosis it was a T1N0, grade 3 invasive ductal carcinoma, with HER-2 amplification. The lung metastasis measured 1,9 cm and showed the same histology and biological profile of the primary tumor. In addition, numerous neoplastic cells, with large cytoplasm and atypical nuclei, appear to spread along the mucosa of the bronchi adjacent to the metastatic lesion as well as that of the main lobar bronchus, intermingled with the columnar ciliated cells. The neoplastic elements were negative for TTF-1 and strongly HER-2 positive; these features appeared consistent with endobronchial pagetoid spread by the metastatic breast carcinomatous cells

Cytological Features of Palisaded Mammary-Type Myofibroblastoma

Palisaded mammary-type myofibroblastoma is a rare variant of benign stromal spindle cell tumor whose histological features are well known. Nevertheless, no cytological features have been reported to date. In this article, we describe the cytological features of a case of palisaded mammary-type myofibroblastoma in which a preoperative fine needle aspirate was obtained. Smears were moderately cellular, characterized by clusters of spindle cells, disposed in a parallel fashion and immersed in myxoid background. Although the lesion is rare, it is worth distinguishing from benign and malignant spindle cell tumors

Simultaneous EUS-FNA Diagnosis and TNM Staging of a Pancreatic Neuroendocrine Tumor in a Patient with an Unrecognized MEN Type 1

We report the case of a woman who, during oncological followup for bronchial carcinoid (diagnosed in 2005), papillary thyroid carcinoma, and bilateral parathyroid adenoma (simultaneously diagnosed in 2007), performed a pancreatic endoscopic ultrasonography with fine needle agobiopsy (EUS-FNA) for a positron emission tomography (PET) suspicion of pancreatic and hepatic lesions; during the procedure, the pancreatic and liver lesions were confirmed, and a peripancreatic lymph node involvement was found, allowing a complete pTNM staging during the same procedure

Dynamics of fungi and related mycotoxins during cereal storage in silo bags

The aim of this work was to investigate the dynamics of fungi and related mycotoxins during cereal storage in silo bags. A 2-year trial was organised (2009-2011); in each year, two silo bags, filled with maize and durum wheat respectively, were prepared . During storage, meteorological data were collected from a close station and temperature, CO2 and O2 were measured inside the silos. Grain was sampled from silo filling (September) every 40 days until June (7/8 samples per silo per year). Water activity of grain, colony forming units (CFU) and mycotoxin content (fumonisins, aflatoxins and ochratoxin in maize, deoxynivalenol and ochratoxin in wheat) were determined. Temperature inside the silo bags followed the trend of external temperature, with a more limited variation. A decrease of O2 was observed from 16.4% to 2.0% in maize and from 15.7% to 15.1% in wheat; the decrease was balanced by CO2 increase. Minor variations were registered in grain water activity and CFU and mycotoxin content did not change significant throughout the storage period; the results were consistent in the two years. On the basis of these results, silo bags prove to be suitable for safe cereal storage

Next generation sequencing improves the accuracy of KRAS mutation analysis in endoscopic ultrasound fine needle aspiration pancreatic lesions.

The use of endoscopic ultrasonography has allowed for improved detection and pathologic analysis of fine needle aspirate material for pancreatic lesion diagnosis. The molecular analysis of KRAS has further improved the clinical sensitivity of preoperative analysis. For this reason, the use of highly analytical sensitive and specific molecular tests in the analysis of material from fine needle aspirate specimens has become of great importance. In the present study, 60 specimens from endoscopic ultrasonography fine needle aspirate were analyzed for KRAS exon 2 and exon 3 mutations, using three different techniques: Sanger sequencing, allele specific locked nucleic acid PCR and Next Generation sequencing (454 GS-Junior, Roche). Moreover, KRAS was also tested in wild-type samples, starting from DNA obtained from cytological smears after pathological evaluation. Sanger sequencing showed a clinical sensitivity for the detection of the KRAS mutation of 42.1%, allele specific locked nucleic acid of 52.8% and Next Generation of 73.7%. In two wild-type cases the re-sequencing starting from selected material allowed to detect a KRAS mutation, increasing the clinical sensitivity of next generation sequencing to 78.95%. The present study demonstrated that the performance of molecular analysis could be improved by using highly analytical sensitive techniques. The Next Generation Sequencing allowed to increase the clinical sensitivity of the test without decreasing the specificity of the analysis. Moreover we observed that it could be useful to repeat the analysis starting from selectable material, such as cytological smears to avoid false negative results

Overexpression of parkin rescues the defective mitochondrial phenotype and the increased apoptosis of Cockayne Syndrome A cells

The ERCC8/CSA gene encodes a WD-40 repeat protein (CSA) that is part of a E3-ubiquitin ligase/COP9 signalosome complex. When mutated, CSA causes the Cockayne Syndrome group A (CS-A), a rare recessive progeroid disorder characterized by sun sensitivity and neurodevelopmental abnormalities. CS-A cells features include ROS hyperproduction, accumulation of oxidative genome damage, mitochondrial dysfunction and increased apoptosis that may contribute to the neurodegenerative process. In this study, we show that CSA localizes to mitochondria and specifically interacts with the mitochondrial fission protein dynamin-related protein (DRP1) that is hyperactivated when CSA is defective. Increased fission is not counterbalanced by increased mitophagy in CS-A cells thus leading to accumulation of fragmented mitochondria. However, when mitochondria are challenged with the mitochondrial toxin carbonyl cyanide m-chloro phenyl hydrazine, CS-A fibroblasts undergo mitophagy as efficiently as normal fibroblasts, suggesting that this process remains targetable to get rid of damaged mitochondria. Indeed, when basal mitophagy was potentiated by overexpressing Parkin in CSA deficient cells, a significant rescue of the dysfunctional mitochondrial phenotype was observed. Importantly, Parkin overexpression not only reactivates basal mitophagy, but plays also an anti-apoptotic role by significantly reducing the translocation of Bax at mitochondria in CS-A cells. These findings provide new mechanistic insights into the role of CSA in mitochondrial maintenance and might open new perspectives for therapeutic approaches

Proposed algorithm for the detection of <i>KRAS</i> mutations in EUS-FNA material from pancreatic lesions.

<p>Ex, Exon; WT, Wild-Type.</p

Percentage of mutated <i>KRAS</i> samples according to preoperative cytology evaluation.

<p>ASLNAqPCR, Allele Specific Locked Nucleic Acid qPCR; NGS, Next Generation Sequencing; PDAC, Pancreatic Ductal AdenoCarcinoma; Not PDAC, malignant neoplasia but not Pancreatic Ductal Adenocarcinoma; NA, cytology not available.</p