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Reggio nell'Emilia, Italy

Zalaudek I.,Skin Cancer Unit | Zalaudek I.,Medical University of Graz | Ciarrocchi A.,Laboratory of Molecular Biology | Piana S.,Pathology Unit | And 8 more authors.
Journal of the European Academy of Dermatology and Venereology | Year: 2015

Background: In the context of amelanotic melanoma, little is known on the genetic or molecular background that determines the onset of this peculiar phenotype of melanoma and its sites of metastatic spread. However, it appears that amelanotic melanomas frequently lack BRAF mutations. Objective: To report the genetical analysis of one case amelanotic melanoma developing oral metastasis. Methods: The BRAF mutational status of the primary lesion was assessed by both Sanger sequencing and pyrosequencing. Results: Both methodologies showed changes in three nucleotides: C1796T; G1798A and T1799A. These mutations should result in a rare double aminoacid substitution in codons 599 and 600 of the BRAF protein (BRAF T599I/V600K). Conclusion: This unusual mutation was associated with an uncommon clinical phenotype of the primary tumour and with an unusual site of metastatic spread. In the lack of comparable data, a potential association between the unusual mutation and clinical findings remains a matter of further studies. © 2014 European Academy of Dermatology and Venereology.

Pelosi G.,University of Milan | Barbareschi M.,Operative Unit of Pathology | Cavazza A.,Arcispedale S. Maria Nuova IRCCS | Graziano P.,IRCCS Casa Sollievo della Sofferenza | And 2 more authors.
Lung Cancer | Year: 2015

Large cell carcinoma (LCC) is a merely descriptive term indicating a subtype of lung cancer with no specific features of small-cell lung cancer (SCLC), adenocarcinoma (ADC) or squamous cell carcinoma (SQC). This diagnosis is allowed on surgical specimens only, whereas its counterpart in biopsy/cytology samples is non-small-cell lung carcinoma (NSCLC), not otherwise specified (NOS). Although these two terms do not fulfill the same concept, they can be interchangeable synonyms at the clinical level, reflecting, in different ways, the inability to define a specific subtype. Immunohistochemistry (IHC), next generation sequencing (NGS) analysis and, historically, electron microscopy have been unveiling diverse cell differentiation lineages in LCC, resulting in LCC-favor ADC, LCC-favor SQC and LCC-favor large-cell neuroendocrine carcinoma (LCNEC), the latter hopefully to be included into the neuroendocrine tumor (NET) group in the future. Paradoxically, however, the interpretation issues of LCC/NSCLC-NOS are not diminishing, but even increasing albeight an accurate diagnosis is oncologically required and crucial. Also, rare LCC/NSCLC-NOS cases exhibiting null/unclear phenotype, are difficult to classify, and this terminology could be maintained for the sake of classification (basically these tumors are serendipitous ADC, as also confirmed by the lack of p40). In this review article, seven relevant issues to LCC have been addressed by using a question-answer methodology, with final key points discussing major interpretation issues. In conclusion, most LCC/NSCLC-NOS may be eventually re-classified and addressed by exploiting IHC and/or molecular testing to satisfy the criteria of precision medicine (the right drug, to the right patient, at the right time). © 2015 Elsevier Ireland Ltd.

Kermani T.A.,University of California at Los Angeles | Crowson C.S.,Mayo Medical School | Muratore F.,Arcispedale S. Maria Nuova IRCCS | Schmidt J.,Amiens University Hospital | And 2 more authors.
Seminars in Arthritis and Rheumatism | Year: 2015

Objective: To compare clinical and imaging characteristics of patients with giant cell arteritis (GCA) and upper extremity (UE) arterial involvement to patients with Takayasu arteritis (TAK). Methods: A cohort of patients seen at the Mayo Clinic with TAK diagnosed between 1984 and 2009 and a cohort of patients with GCA and UE arterial involvement diagnosed between 1999 and 2008 were studied. Results: The TAK cohort consisted of 125 patients (91% female); the mean age (±SD) at diagnosis was 30.9 (±10) years. The cohort of patients with GCA and UE involvement comprised of 120 patients (80% female); the mean age (±SD) at diagnosis was 67.8 (±7.5) years. The mean time from onset of symptoms to diagnosis was significantly longer in TAK (3.2 years) than GCA (0.5 years), p < 0.001. UE claudication was reported in 40% with TAK and 53% with GCA, p = 0.04. UE blood pressure discrepancy was present in 65% with TAK versus 28% with GCA, p < 0.001. Involvement of the thoracic aorta, abdominal aorta, carotid arteries, innominate artery, mesenteric artery, and left renal artery was more frequently observed in TAK (p < 0.05). Among patients with luminal changes of the thoracic aorta, stenotic/occlusive lesions were predominant in TAK (81% compared to 0% in GCA), whereas aneurysmal disease was more common in GCA (100% compared with 19% in TAK, p < 0.001). Conclusion: Patients with GCA and UE involvement differ from patients with TAK in clinical and imaging characteristics. Aortic aneurysms were more common in GCA, while stenotic changes of the aorta were more common in TAK, suggesting different pathophysiologic mechanisms or vascular response to injury. © 2015 Elsevier Inc.

Pietrangeli V.,Ospedale G.B. Morgagni | Piciucchi S.,Ospedale G.B. Morgagni | Tomassetti S.,Ospedale G.B. Morgagni | Ravaglia C.,Ospedale G.B. Morgagni | And 5 more authors.
Lung | Year: 2015

A 74-year-old non-smoker female presented to our attention with a history of dyspnea and cough. CT scan revealed multiple areas of patchy ground glass attenuation associated to a diffuse mosaic oligoemia. Scattered bilateral subcentimetric pulmonary nodules were also present. Patient underwent a surgical lung biopsy. Specimens showed features of diffuse neuroendocrine hyperplasia, microhoneycombing, fibroblast foci. A final diagnosis of diffuse neuroendocrine hyperplasia with obliterative bronchiolitis and UIP was rendered. © 2015, Springer Science+Business Media New York.

Santoro A.,Humanitas Cancer Center | Rimassa L.,Humanitas Cancer Center | Borbath I.,Cliniques universitaires Saint Luc | Daniele B.,G. Rummo Hospital | And 21 more authors.
The Lancet Oncology | Year: 2013

Background: Tivantinib (ARQ 197), a selective oral inhibitor of MET, has shown promising antitumour activity in hepatocellular carcinoma as monotherapy and in combination with sorafenib. We aimed to assess efficacy and safety of tivantinib for second-line treatment of advanced hepatocellular carcinoma. Methods: In this completed, multicentre, randomised, placebo-controlled, double-blind, phase 2 study, we enrolled patients with advanced hepatocellular carcinoma and Child-Pugh A cirrhosis who had progressed on or were unable to tolerate first-line systemic therapy. We randomly allocated patients 2:1 to receive tivantinib (360 mg twice-daily) or placebo until disease progression. The tivantinib dose was amended to 240 mg twice-daily because of high incidence of treatment-emergent grade 3 or worse neutropenia. Randomisation was done centrally by an interactive voice-response system, stratified by Eastern Cooperative Oncology Group performance status and vascular invasion. The primary endpoint was time to progression, according to independent radiological review in the intention-to-treat population. We assessed tumour samples for MET expression with immunohistochemistry (high expression was regarded as ≥2+ in ≥50% of tumour cells). This study is registered with ClinicalTrials.gov, number NCT00988741. Findings: 71 patients were randomly assigned to receive tivantinib (38 at 360 mg twice-daily and 33 at 240 mg twice-daily); 36 patients were randomly assigned to receive placebo. At the time of analysis, 46 (65%) patients in the tivantinib group and 26 (72%) of those in the placebo group had progressive disease. Time to progression was longer for patients treated with tivantinib (1·6 months [95% CI 1·4-2·8]) than placebo (1·4 months [1·4-1·5]; hazard ratio [HR] 0·64, 90% CI 0·43-0·94; p=0·04). For patients with MET-high tumours, median time to progression was longer with tivantinib than for those on placebo (2·7 months [95% CI 1·4-8·5] for 22 MET-high patients on tivantinib vs 1·4 months [1·4-1·6] for 15 MET-high patients on placebo; HR 0·43, 95% CI 0·19-0·97; p=0·03). The most common grade 3 or worse adverse events in the tivantinib group were neutropenia (ten patients [14%] vs none in the placebo group) and anaemia (eight [11%] vs none in the placebo group). Eight patients (21%) in the tivantinib 360 mg group had grade 3 or worse neutropenia compared with two (6%) patients in the 240 mg group. Four deaths related to tivantinib occurred from severe neutropenia. 24 (34%) patients in the tivantinib group and 14 (39%) patients in the placebo group had serious adverse events. Interpretation: Tivantinib could provide an option for second-line treatment of patients with advanced hepatocellular carcinoma and well-compensated liver cirrhosis, particularly for patients with MET-high tumours. Confirmation in a phase 3 trial is needed, with a starting dose of tivantinib 240 mg twice-daily. Funding: ArQule, Daiichi Sankyo (Daiichi Sankyo Group). © 2013 Elsevier Ltd.

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