Genome-Wide Methylation Analysis in Two Wild-Type Non-Small Cell Lung Cancer Subgroups with Negative and High PD-L1 Expression.

We conducted a pilot study to analyze the differential methylation status of 20 primary acinar adenocarcinomas of the lungs. These adenocarcinomas had to be wild type in mutation analysis and had either high (TPS > 50%; = 10) or negative (TPS < 1%; = 10) PD-L1 status to be integrated into our study. To examine the methylation of 866,895 specific sites, we utilized the Illumina Infinium EPIC bead chip array.

HER2 copy number determination in breast cancer using the highly sensitive droplet digital PCR method.

Human epidermal growth factor receptor 2 (HER)-positive breast cancer (BC) is characterized by an aggressive clinical course. In the case of HER2 overexpression/amplification, patients benefit from HER2-targeting therapies. Standardized diagnostic HER2 assessment includes immunohistochemistry (IHC) and/or in situ hybridization (ISH).

Dissecting the Methylomes of -Amplified Glioblastoma Reveals Altered DNA Replication and Packaging, and Chromatin and Gene Silencing Pathways.

Glioblastoma IDH wildtype is the most frequent brain tumor in adults. It shows a highly malignant behavior and devastating outcomes. To date, there is still no targeted therapy available; thus, patients' median survival is limited to 12-15 months.

Methylome Profiling of PD-L1-Expressing Glioblastomas Shows Enrichment of Post-Transcriptional and RNA-Associated Gene Regulation.

Glioblastomas are the most frequent primary brain tumors in adults. They show highly malignant behavior and devastating outcomes. Since there are still no targeted therapies available, median survival remains in the range of 12 to 15 months for glioblastoma patients.

Amplification Is a Phenomenon of Wildtype and Mutated High-Grade Glioma: An Integrated Analysis Using Fluorescence In Situ Hybridization and DNA Methylome Profiling.

Gliomas are the most common intrinsic brain tumors in adults, and in accordance with their clinical behavior and patients' outcome, they are graded by the World Health Organization (WHO) classification of brain tumors. One very interesting candidate for targeted tumor therapy may be epidermal growth factor receptor () amplification. Here, we performed an integrated comparative analysis of amplification in 34 glioma samples using standard fluorescence in situ hybridization (FISH) and Illumina EPIC Infinium Methylation Bead Chip and correlated results with molecular glioma hallmarks.

Sustained response to brigatinib in a patient with refractory metastatic pheochromocytoma harboring R1192P anaplastic lymphoma kinase mutation: a case report from the Austrian Group Medical Tumor Therapy next-generation sequencing registry and discussion of the literature.

Metastatic pheochromocytoma and paraganglioma (PPGL) are rare diseases with dismal prognosis and standard therapies are lacking. We herein report the first case of a germline anaplastic lymphoma kinase (ALK) mutation in a patient with chemorefractory metastatic pheochromocytoma in the absence of mutations of known PPGL-associated predisposing genes. Therapy with the ALK inhibitor (ALKi) brigatinib led to dramatic and durable disease remission, despite previous disease progression on the ALKi alectinib.

Integrated analysis of programmed cell death ligand 1 expression reveals increased levels in high-grade glioma.

Purpose: Gliomas are the most frequent primary brain tumors of adults. Despite intensive research, there are still no targeted therapies available. Here, we performed an integrated analysis of glioma and programmed cell death ligand 1 (PD-L1) in 90 samples including 58 glioma and 32 control brain tissues.

Therapy Line and Associated Predictors of Response to PD-1/PD-L1-Inhibitor Monotherapy in Advanced Non-small-Cell Lung Cancer: A Retrospective Bi-centric Cohort Study.

Background: Evidence on PD-1/PD-L1-directed immune checkpoint inhibitor (ICI) therapy for advanced non-small-cell lung cancer (NSCLC) is mainly based on clinical trials in first- or second-line settings.

Objective: We aimed to investigate response and prognostic factors with special regard to third- or later-line therapy.

Patients And Methods: We retrospectively analyzed all patients who had received ICI monotherapy with nivolumab, pembrolizumab, or atezolizumab for advanced NSCLC.

Real-world prevalence of programmed death ligand 1 expression in locally advanced or metastatic non-small-cell lung cancer: The global, multicenter EXPRESS study.

Objectives: Tumor programmed death ligand 1 (PD-L1) expression is associated with improved clinical benefit from immunotherapies targeting the PD-1 pathway. We conducted a global, multicenter, retrospective observational study to determine real-world prevalence of tumor PD-L1 expression in patients with NSCLC.

Materials And Methods: Patients ≥18 years with histologically confirmed stage IIIB/IV NSCLC and a tumor tissue block (≤5 years old) obtained before treatment were identified in 45 centers across 18 countries.

Baseline Absolute Lymphocyte Count and ECOG Performance Score Are Associated with Survival in Advanced Non-Small Cell Lung Cancer Undergoing PD-1/PD-L1 Blockade.

Immune-checkpoint blockade in front-line or second-line treatment improves survival in advanced non-small cell lung cancer (aNSCLC) when compared with chemotherapy alone. However, easily applicable predictive parameters are necessary to guide immune-checkpoint inhibition in clinical practice. In this retrospective bi-centric analysis, we investigated the impact of baseline patient and tumor characteristics on clinical outcome in aNSCLC patients treated with programmed cell death protein 1(PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors.

PD-L1 testing, fit for routine evaluation? From a pathologist's point of view.

Tumours with high somatic mutation rates escape immune surveillance by upregulating receptors and ligands such as programmed death receptor-1 and its ligand (PD-1/PD-L1). Checkpoint inhibitors (ICI) provide encouraging therapeutic results in non-small cell lung cancers (NSCLC) and may soon be used in 2nd or 1st line therapy. Currently PD-L1 immunohistochemistry (IHC) expression assessed on tumour cells is used as a predictive biomarker, since better patient outcomes are often, but not always associated with increased tumour cell PD-L1 IHC expression.

First line crizotinib in anaplastic lymphoma kinase (ALK) rearranged squamous cell lung cancer.

Recently the superiority of Crizotinib to standard first-line pemetrexed-plus-platinum chemotherapy in patients with previously untreated advanced ALK-positive NSCLC has been demonstrated. We report of a 36-year-old never smoker with advanced squamous cell carcinoma, presenting with a left lower lobe lesion, N3 nodal disease and multiple metastases (pleura, adrenal, muscle, bone). Despite squamous histology we decided on molecular testing.

CYP39A1 polymorphism is associated with toxicity during intensive induction chemotherapy in patients with advanced head and neck cancer.

Background: Induction chemotherapy incorporating docetaxel, cisplatin and 5- fluorouracil before radiotherapy may improve the outcome of patients with advanced head and neck cancer. Nevertheless, the addition of docetaxel increases hematological toxicity and infectious complications. Therefore, genetic markers predicting toxicity and efficacy of this treatment regimen may help to identify patients, who would have the most benefit from this intensive treatment.

ROS1 mutation and treatment with crizotinib in a 30-year old Caucasian woman with stage IV non-small cell lung cancer/adenocarcinoma and complete remission.

In this case report we describe a 30 year-old Caucasian woman with a histopathological diagnosis of pulmonary adenocarcinoma in both lungs with lipidic and micropapillary growth pattern and ROS1 (C-ros oncogene 1, receptor tyrosine kinase) rearrangement. There is evidence that crizotinib can be used for molecular target therapy in these patients. We enrolled the patient in an off-label program for the treatment of ROS1 rearranged adenocarcinomas with the EML4/anaplastic lymphoma kinase inhibitor crizotinib.

Immunohistochemistry as a screening tool for ALK rearrangement in NSCLC: evaluation of five different ALK antibody clones and ALK FISH.

Aims: ALK FISH analysis is used as the reference standard to demonstrate ALK rearrangements, which qualify patients with pulmonary adenocarcinomas for therapy with ALK inhibitors. The aim of this study was to find screening ALK antibody clones with the best positive and best negative percentage agreement with ALK FISH.

Methods And Results: Three hundred and three pulmonary adenocarcinomas were evaluated with ALK FISH and stained with five ALK antibody clones (5A4; D5F3; ALK1; ALK01; SP8) with standardized detection systems.

A rare manifestation of sarcoidosis with sensomotoric neuropathy of the ulnar nerve as the only symptom.

A 79-year-old woman was admitted complaining of progressive weakness and numbness of the right hand. The patient was otherwise healthy. The patient's history was unremarkable.

[Pigmented lesions of the oral mucosa].

The oral mucosa contains melanocytes, even though one might not suspect this when examining white subjects. Drug-induced pigmentation is usually irregularly distributed over the oral mucosa; typical causes are contraceptives and tetracyclines. Localized traumatic pigmentation can be due to injuries contaminated by foreign material (dust).

Successful bronchoscopic cryorecanalization in a case of endobronchial lipoma.

Endobronchial lipomas are rare benign tumors; less than 150 cases have been reported so far. Bronchial occlusion usually leads to a misdiagnosis of asthma/COPD or malignancy. We report the case of a 67-year-old man with a history of heavy smoking (100 pack years), dyspnea on exertion, cough, and malaise who was treated for pneumonia for three weeks.

Cerebral localized marginal zone lymphoma presenting as hypothalamic-pituitary region disorder.

Introduction: Marginal zone B-cell lymphoma is a rare disease which can be considerably difficult to recognize and diagnose when signs of systemic involvement are absent.

Case Presentation: We report the case of a 57-year-old woman with initial olfactory disturbance, followed by psychosis, diabetes insipidus and hypothalamic eating disorder as an uncommon clinical presentation of marginal zone B-cell lymphoma.

Conclusion: Marginal zone B-cell lymphoma should be considered as a potential differential diagnosis in patients with hypothalamic disturbances.

Sentinel lymph node biopsy is precise after primary systemic therapy in stage II-III breast cancer patients.

Background: Sentinel lymph node biopsy (SLNB) without axillary lymph node dissection (ALND) in SLN negative patients is a standard of care for most breast cancer patients. SLNB for axillary staging after primary systemic therapy (PST) is still under discussion because of possibly reduced accuracy, while data are lacking. The purpose of this study was to evaluate the accuracy of SLNB after PST.

[Squamous cell carcinoma and potentially malignant disorders of the oral mucosa].

Squamous cell carcinoma is the most frequent malignant tumor of the oral mucosa. Various endogenous and exogenous factors promote its development. Therapy and prognosis depend mainly on tumor stage.

Successful antiangiogenic combination therapy for pseudomyxoma peritonei with bevacizumab and capecitabine.

Effective systemic therapy for advanced pseudomyxoma peritonei (PMP) is the focus of investigation. We describe a case of PMP arising from an adenoma of the appendix in a 58-year-old man. First, the patient underwent explorative laparotomy with ileocoecal resection, but without possibility of major tumor debulking due to adhesive gross tumor masses.

Methylated NEUROD1 promoter is a marker for chemosensitivity in breast cancer.

Purpose: Chemotherapy can be an integral component of the adjuvant management strategy for women with early stage breast cancer. To date, no tool is available to predict or monitor the efficacy of these therapies. The aim of this proof-of-principle study was to assess whether NEUROD1 DNA methylation is able to predict the response to neoadjuvant and adjuvant chemotherapy.