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Background: Mesenchymal-to-epithelial transition (MET) exon 14 skipping mutations and MET gene amplification occur in 3-5% of non-small cell lung cancer (NSCLC) patients. Tyrosine kinase inhibitors (TKIs) targeting MET alterations have shown promising results in these patients.Objective: The aim of this study was to describe the genomic profile, PD-L1 expression and clinicopathological features of MET dysregulated NSCLC.Patients and Methods: We identified 188 patients with advanced-stage NSCLC with data on MET expression by immunohistochemistry (IHC). IHC for PD-L1 expression was performed in 131 patient samples, and next-generation sequencing (NGS) analysis was performed in 109 patient samples.Results: MET exon 14 skipping alterations were identified in 16 (14.7%) samples, MET amplifications with cut-off ≥4 copy number variations were identified in 11 (10.1%) samples, and an oncogenic MET mutation (MET p.D1228N) was identified in 1 (0.9%) sample. 12/15 tumors (80.0%) harboring MET exon 14 alterations and 7/11 (63.6%) MET-amplified tumors expressed PD-L1 in ≥1% of tumor cells. Tumors harboring MET exon 14 skipping alterations expressed PD-L1 more frequently than MET wild-type IHC-positive tumors (p = 0.045). Twenty-five percent of MET exon 14-altered cases and 33% of MET-amplified cases harbored potentially targetable oncogenic co-mutations in KRAS, BRAF, and EGFR. The most frequent co-occurring mutations in all MET-altered tumors were TP53, KRAS, BRAF, and CDK4.Conclusions: We demonstrated that MET exon 14 skipping alterations and MET amplification are not mutually exclusive to other oncogenic co-mutations, and report the association of genomic MET alterations with PD-L1 expression. Since genomic MET alterations are emerging targets requiring upfront treatment, optimal understanding of the co-mutational landscape for this patient population is needed. [ABSTRACT FROM AUTHOR]

Soluble αKlotho (sKl) is a disease-specific biomarker that is elevated in patients with acromegaly and declines after surgery for pituitary adenoma. Approximately 25% of patients do not achieve remission after surgery, therefore a risk stratification for patients early in the course of their disease may allow for the identification of patients requiring adjuvant treatment. Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) have been assessed as biomarker for disease activity, however the value of sKl as a predictive biomarker of surgical success has not been evaluated yet. In this study, we measured serum biomarkers before and after transsphenoidal pituitary surgery in 55 treatment-naïve patients. Based on biochemical findings at follow-up (7–16 years), we divided patients into three groups: (A) long-term cure (defined by normal IGF-1 and random low GH (< 1 μg/l) or a suppressed GH nadir (< 0.4/μg/l) on oral glucose testing); (B) initial remission with later disease activity; (C) persistent clinical and/or biochemical disease activity. sKl levels positively related to GH, IGF-1 levels and tumor volume. Interestingly, there was a statistically significant difference in pre- and postoperative levels of sKl between the long-term cure group and the group with persistent disease activity. This study provides first evidence that sKl may serve as an additional marker for surgical success, decreasing substantially in all patients with initial clinical remission while remaining high after surgery in patients with persistent disease activity. [ABSTRACT FROM AUTHOR]

A nuclear protein of testis (NUT) carcinoma, also known as NUT midline carcinoma, is a rare subtype of squamous carcinoma known for its aggressive growth behaviour. It can form anywhere in the body. Although, it usually occurs along midline structures (head, neck, lungs). The authors present the first report of intrasellar NUT carcinoma with cavernous sinus infiltration in a 47-year-old patient. MRI showed an inhomogeneous, gadolinium-enhancing lesion with intra- and suprasellar growth, invasion of the cavernous sinus without clear differentiation from normal pituitary tissue. Given the lymphoma diagnosis in the frozen section and invasion of the cavernous sinus, the patient underwent endoscopic, transnasal, and transsphenoidal subtotal resection only. Local tumour and spinal metastases showed a good response to radio-chemotherapy. Despite combined radio-chemotherapy, the patient died of pulmonary insufficiency due to rapid progression of pulmonary metastasis 6 months after the initial diagnosis. [ABSTRACT FROM AUTHOR]

Primary Olfactory Neuroblastoma Masquerading as a Pituitary Adenoma: Case Report and Review of the Literature Incidental sellar masses are found in 4-20% of the general population at autopsy or by computed tomography (CT)/magnetic resonance imaging (MRI). Cerebral magnetic resonance imaging (MRI) revealed a multilobulated mass in the sella turcica (pituitary fossa), measuring 4 × 4.2 × 3.7 cm, with suprasellar extension, impinging on the hypothalamus and infiltrating the cavernous sinus and Meckel's cave. [Extracted from the article]

Purpose: Preoperative embolization of radiographically suspected meningiomas is often performed to facilitate tumor resection. Its effects on the subsequent disease course of meningioma patients have not been studied in detail and randomized trials are lacking. The purpose of this study was to explore associations of preoperative meningioma embolization with postoperative outcome.Patients and methods: Patients undergoing resection of an intracranial meningioma at the University Hospital Zurich 2000-2013 (N = 741) were reviewed for the inclusion of pre-operative embolization in the management strategy. Annotations included demographics, radiographic, surgical, histological and hematological parameters, cardiovascular risk factors, pre- and postoperative neurological function and gene methylation-based classification. Binary regression and Cox proportional hazards models were applied to determine factors associated with outcome.Results: Pre-operative embolization was performed in 337 patients (42%). Cardiovascular events after surgery comprised mostly deep vein thrombosis (N = 39) and pulmonary embolisms (N = 64). On multivariate analyses of post-operative cardiovascular adverse events controlling for established risk factors, there were associations with embolization (OR 2.38, 95% CI 1.37-4.00), and with female gender (OR 2.18, 95% CI 1.17-4.08). Recurrence-free survival (RFS) of embolized patients was less favorable among patients with WHO grade II or grade III meningiomas (median RFS: 4.3 vs. 7.0 years, P = 0.029) or in patients with intermediate or malignant gene methylation subtype meningiomas (median RFS: 2.0 vs. 8.2 years, P = 0.005).Conclusion: Pre-operative meningioma embolization may cause adverse outcomes. Randomized trials to determine benefit-risk ratios are warranted to clarify the role of pre-operative embolization for the treatment of meningioma patients. [ABSTRACT FROM AUTHOR]