Head and neck paragangliomas: Recent advances in translational and clinical research and guidelines for patient care.

Head and neck paragangliomas (HNPGLs), rare neuroendocrine tumors that mainly arise from parasympathetic ganglia along the cranial nerves, are challenging due to anatomic origin, tendency to aggressive neurovascular and skull base infiltration, unpredictable metastatic potential, radio-chemoresistance, and risk of multiplicity. Symptoms range from mild to life threatening depending on location/size, but rarely relate to catecholamine excess. Risk factors include female sex and pathogenic germline variants in genes affecting hypoxia signaling (foremost succinate dehydrogenase genes).

DNA methylation variations in familial female and male breast cancer.

In total, ~25% of familial breast cancer (BC) is attributed to germline mutations of the BRCA1 and BRCA2 genes, while the rest of the cases are included in the BRCAX group. BC is also known to affect men, with a worldwide incidence of 1%. Epigenetic alterations, including DNA methylation, have been rarely studied in male breast cancer (MBC) on a genome-wide level.

A Developmental Perspective on Paragangliar Tumorigenesis.

In this review, we propose that paraganglioma is a fundamentally organized, albeit aberrant, tissue composed of neoplastic vascular and neural cell types that share a common origin from a multipotent mesenchymal-like stem/progenitor cell. This view is consistent with the pseudohypoxic footprint implicated in the molecular pathogenesis of the disease, is in harmony with the neural crest origin of the paraganglia, and is strongly supported by the physiological model of carotid body hyperplasia. Our immunomorphological and molecular studies of head and neck paragangliomas demonstrate in all cases relationships between the vascular and the neural tumor compartments, that share mesenchymal and immature vasculo-neural markers, conserved in derived cell cultures.

Novel BRAF mutation in melanoma: A case report.

In melanoma, a number of specific genetic and genomic aberrations have been identified to be important in tumorigenesis. In particular, the mutant B-Raf proto-oncogene, Serine/Threonine kinase (BRAF) gene is the target of tailored therapy with kinase inhibitor molecules. Identification of the array of mutations in patients with melanoma will be useful in determining a genetic profile of the tumor with potential implications for treatment decisions.

Correction to: Paragangliomas arise through an autonomous vasculo-angio-neurogenic program inhibited by imatinib.

The given and family names of two co-authors were incorrect in the published article. The correct spelling should read as: Sampath Chandra Prasad and Vinagolu K Rajasekhar.

Paragangliomas arise through an autonomous vasculo-angio-neurogenic program inhibited by imatinib.

Tumours can be viewed as aberrant tissues or organs sustained by tumorigenic stem-like cells that engage into dysregulated histo/organogenetic processes. Paragangliomas, prototypical organoid tumours constituted by dysmorphic variants of the vascular and neural tissues found in normal paraganglia, provide a model to test this hypothesis. To understand the origin of paragangliomas, we built a biobank comprising 77 cases, 18 primary cultures, 4 derived cell lines, 80 patient-derived xenografts and 11 cell-derived xenografts.

Strong Notch activation hinders bevacizumab efficacy in advanced colorectal cancer.

Aim: To assess the role of Notch activation in predicting bevacizumab efficacy in colorectal cancer (CRC).

Materials & Methods: Notch activation was evaluated by immunohistochemistry (IHC) on 65 CRC enrolled within randomized clinical trials assessing first-line bevacizumab-based chemotherapy and on 21 CRC treated with chemotherapy alone.

Results: Strong Notch (IHC 3+) activation was negatively associated with response (18 vs 62% in low Notch cases [IHC 0, 1, 2+]; p = 0.

Primary squamous cell carcinoma of the breast after cured bilateral breast cancer.

Background: Primary squamous cell carcinoma (SCC) of the breast is a rare and aggressive neoplasm that constitutes approximately 0.1% of all breast carcinomas. Before the tumor can be classified as a true SCC of the breast, certain criteria need to be fulfilled.

Salivary gland choristoma of the middle ear.

Choristoma of the middle ear is a rare condition characterized by the presence of normal salivary gland tissue in the middle ear space. Salivary gland choristomas are benign lesions that are frequently associated with ossicular chain and facial nerve anomalies. Total surgical excision is indicated when there is no risk of damaging the facial nerve.

HER2-positive gastric cancer showing marked thickening of the gastric wall on ultrasonographic and computed tomographic scans. a chance phenomenon or a specific behaviour of this cancer type? Report of three cases.

Worldwide, gastric cancer is the fourth most commonly diagnosed type of cancer and the second most common cause of cancer-related death. Recently, it was demonstrated that 15-20% of advanced gastro-oesophageal carcinomas overexpress human epidermal receptor 2 (HER2), one of a family of four identified human epidermal receptors. As in HER2-positive breast cancer, trastuzumab, a monoclonal antibody targeting HER2 receptor, with chemotherapy improves prognosis, time-to-progression and overall survival in patients with advanced gastric cancer.

Solitary fibrous tumors of the pleura: a case report and review of the literature.

Background: Solitary fibrous tumors of the pleura are rare and slow-growing neoplasms originating from the mesenchymal tissue underlying the mesothelial layer of the pleura. These tumors may have an unpredictable clinical course. Most cases occur in the sixth or seventh decades of life with no gender predilection, and more than 80% of cases are benign.

Giant cell tumors of the skull base: case series and current concepts.

Objective: To study the clinical features, tumor characteristics and outcomes of giant cell tumors (GCTs) in the skull base based on long-term follow-up. We also report the largest series of GCTs in the temporal bone and the lateral skull base.

Materials And Methods: A retrospective study was conducted of all GCTs managed at the Gruppo Otologico, a quaternary referral skull base institute, in Italy from 1993 to 2013.

Integrative genetic, epigenetic and pathological analysis of paraganglioma reveals complex dysregulation of NOTCH signaling.

Head and neck paragangliomas, rare neoplasms of the paraganglia composed of nests of neurosecretory and glial cells embedded in vascular stroma, provide a remarkable example of organoid tumor architecture. To identify genes and pathways commonly deregulated in head and neck paraganglioma, we integrated high-density genome-wide copy number variation (CNV) analysis with microRNA and immunomorphological studies. Gene-centric CNV analysis of 24 cases identified a list of 104 genes most significantly targeted by tumor-associated alterations.

Laser-assisted surgery with different wavelengths: a preliminary ex vivo study on thermal increase and histological evaluation.

Since the introduction of laser in clinical practice, different wavelengths have been used for oral surgery on the basis of the different characteristics and affinities of each one. The aim of this study was a comparison of different laser wavelengths in relation to both thermal increase and "histological quality" in a model of soft tissue surgery procedures. Thermal evaluation was realized, during laser-assisted surgery excision performed on a bovine tongue, by a thermal camera device to evaluate thermal increase on the surface of the sample and with four thermocouples to evaluate thermal increase on the depth of the specimen; temperature was recorded before starting surgical procedure and at the peak of every excision.

The Gruppo Otologico experience of endolymphatic sac tumor.

Objective: Endolymphatic sac tumor (ELST) is a rare low grade adenocarcinoma of the skull base. During the past decade the number of the reported cases has increased. This study exposes our experience in the management of ELST with a review of the literature.

Malignancy in vestibular schwannoma after stereotactic radiotherapy: a case report and review of the literature.

Objectives/hypothesis: A relation between conventional radiotherapy and the development of intracranial neoplasma is well known, but radiation-associated tumor following stereotactic radiotherapy of vestibular schwannoma is underestimated. In this article we will study this relation by doing a complete literature review on all the malignant intracranial tumors that appeared following radiosurgery and adding a case of malignant vestibular schwannoma following stereotactic radiotherapy in a Neurofibromatosis type 2 patient.

Methods: Literature review and discussion.

Molecular and functional characterization of allogantigen-specific anergic T cells suitable for cell therapy.

Background: CD4(+) regulatory T cells are a specialized subset of T cells that actively control immune responses. Several experimental protocols have been used to expand natural regulatory T cells and to generate adaptive type 1 regulatory T cells for regulatory T-cell-based therapies.

Design And Methods: The ability of exogenous recombinant human interleukin-10 to induce alloantigen-specific anergy in T cells was investigated and compared to that of interleukin-10 derived from tolerogenic dendritic cells, in mixed lymphocyte cultures.

Unusual myogenic and melanocytic differentiation of soft tissue pPNETs: an immunohistochemical and molecular study of 3 cases.

All of the members of the peripheral primitive neuroectodermal tumor family (Ewing sarcomas, neuroectodermal tumors of bone, peripheral neuroepitheliomas, and Askin tumors) have similar morphologic and immunophenotypical features (ie, the proliferation of small and medium-sized round cells in a fibrous background showing strong and diffuse immunohistochemical positivity for CD99), and the common cytogenetic abnormality of a nonrandom translocation involving the EWS gene and one of several members of the erythroblastosis virus transforming sequence family of transcription factors. The combination of clinical information and morphologic/immunophenotypical characteristics is usually sufficient for a correct diagnosis, but there are rare cases in which an unusual predominant or multidirectional immunophenotypical differentiation makes diagnosis a challenge and requires the use of molecular cytogenetic or molecular techniques. We describe 3 such cases in which we employed fluorescence in-situ hybridization analysis to detect translocation involving the EWS gene and reverse transcription polymerase chain reaction followed by sequencing to detect the fusion transcript EWS-FLI1.

High grade B-cell gastric lymphoma with complete pathologic remission after eradication of Helicobacter pylori infection: report of a case and review of the literature.

Background: Treatment of primary gastric diffuse large B-cell lymphoma is still controversial. The treatment of localized disease was based on surgery alone, or followed by chemotherapy and/or radiotherapy. High-grade gastric lymphomas are generally believed to be Helicobacter pylori (HP)-independent growing tumors.

Naive HIV/HCV-coinfected patients have higher intrahepatic pro-inflammatory cytokines than coinfected patients treated with antiretroviral therapy.

In the era of antiretroviral therapy, liver disease has emerged as an important cause of morbidity and mortality in HIV/hepatitis C virus (HCV) coinfected patients. It is believed that HCV is a non-cytopathic virus and that T-cell-mediated events (including the production of pro-inflammatory cytokines) have an important role in promoting both liver damage and viral clearance. Whether HIV coinfection or antiretroviral therapies influence such events is still unclear.

Minimal focal steatosis of liver after islet transplantation in humans: a long-term study.

Several reports have been published on islet transplantation in humans, but few data are available on the effect of islet infusion on the hepatic structure. Our aim was to evaluate in a longitudinal study the impact on the liver of intrahepatic islet transplantation. Clinical outcome and liver imaging were evaluated in 31 cases of islet-kidney transplantation (follow-up 38 +/- 4 months, range 12-96 months).

Liver fibrosis in HIV-positive patients with hepatitis C virus: role of persistently normal alanine aminotransferase levels.

Background: Liver fibrosis requiring treatment in HIV/hepatitis C virus (HCV)-coinfected patients with persistently normal alanine aminotransferase (ALT) values (PNAL) is currently not well defined; in this study clinical and histologic features of PNAL were compared with those of subjects with elevated ALT (EAL).

Methods: A total of 326 liver biopsies of HIV/HCV-coinfected patients, performed from 1997-2003, were retrospectively identified. Subjects with at least 3 consecutive normal ALT determinations during a prebiopsy follow-up of 12 months were grouped as PNAL (24 patients) and compared with EAL subjects (302 patients).