Updates in the molecular pathology of non-small cell lung cancer.

An understanding of the molecular pathology of non-small cell lung cancer (NSCLC) is important for pathologists as molecular characterization is now required for treatment decisions in advanced stage disease. While assessment for EGFR mutations, ALK and ROS1 fusions, and in some countries BRAF mutations, is now standard practice, other oncogenic mutations are also emerging that may impact routine clinical practice including alterations involving KRAS, NTRK, RET, MET and HER2. In addition, molecular pathology alterations of NSCLC are associated with responses to immune checkpoint therapy and are being increasingly investigated. Finally, specific molecular pathological alterations define some rarer subtypes of NSCLC such as salivary gland tumours, NUT carcinoma and SMARCA4-deficient undifferentiated tumour, and an understanding of the molecular pathology is important for their accurate diagnosis. In this review, the molecular pathology of NSCLC is discussed with a focus on clinically relevant molecular alterations.

[INDENA SPA company's patent portfolio of Ginkgo biloba preparation].

INDENA SPA Company in Italy is a multi-national company that produces and sells plant extracts. Based on its own re- search advantages in the field of Ginkgo biloba preparation, the company protects its own products market effectively through building patent portfolio around the patents of its opponent. Based on the multi-angle analysis for patent portfolio of G. biloba preparation from the aspects of application time, legal status, technical development route, and patent portfolio layout, this article provides technical reference on research and development of G. biloba preparation, and the author suggest that Chinese applicants learn techniques and layout experiences of other patents fully to enhance the level of research and patent protection level.

[SCHWABE Company's patent portfolio of Ginkgo biloba preparation].

SCHWABE Company in German is the first and largest manufacturer of Ginkgo biloba preparation. The company not only has leading technology in this field, but also protects its own market effectively through the high quality of patent drafting and exactly patent layout. Based on multi-angle analysis for patent portfolio of G. biloba preparation at application time, legal status, globally layout, Chinese layout, the article provides technical reference of research and development of G. biloba, also provides valuable experience of traditonal Chinese medicine patent portfolio layout for Chinese enterprises.

[Global patent overview of Ginkgo biloba preparation].

With related global patent data as analysis samples, worldwide patent overview of Ginkgo biloba preparation is analyzed in application, applicant, technical distribution and so on. This research shows that the most important areas of G. biloba preparation are Europe and China. The European applicants start earliest along with developing smoothly, moreover, their patents have best quality. The Chinese applicants start late along with the fastest growing, and have already certain research capabilities, moreover, their patents' quality needs to be improved. This research result provides reference for development of G. biloba preparation. The author suggest that Chinese applicants learn techniques and layout experiences of other's patents fully to enhance the level of new drug development and patent protection.

A single tertiary institution review of the international system for serous fluid cytopathology and the impact of cell block and ancillary studies on its performance.

INTRODUCTION: We sought to assess the utility of the International System for Serous Fluid Cytopathology (TIS) in the context of our department's routine practice. MATERIALS AND METHODS: We examined 1028 archived effusion cytology (pleural, peritoneal, and pericardial) cases from 2018 to 2019, and re-classified them along the international system into the following diagnostic categories: nondiagnostic (ND), negative for malignancy (NFM), atypia cells of undetermined significance (AUS), suspicious for malignancy (SFM), and malignant (MAL). RESULTS: The full distribution of the cases examined was as follows: ND 2.0%; NFM 66.1%; AUS 6.0%; SFM 4.7%; MAL 21.2%. Overall risk of malignancy for each category was calculated as: ND 30.0%; NFM 18.0%; AUS 61.9%; SFM 100%; MAL 94.4%. The overall performance attributes of TIS were as follows: sensitivity 57.1%; specificity 98.3%; positive predictive value 94.4%; negative predictive value 82.0%; diagnostic accuracy 84.5%. CONCLUSIONS: The new classification was simple and intuitive to use and our results appear to fall within the expected ranges of the new guidelines, with risk of malignancy and accuracy comparable to similar studies. The availability of a cell block allowed for refinement of the diagnosis in a majority of cases with equivocal cytology, though this was dependent on the cell yield.

Molecular testing in non-small cell lung cancer: A consensus recommendation.

Introduction: Lung cancer remains an important cause of cancer-related mortality in Singapore, with a greater proportion of non-smokers diagnosed with non-small cell lung cancer (NSCLC) in the past 2 decades. The higher prevalence of targetable genomic alterations in lung cancer diagnosed in Singapore compared with countries in the West, as well as the expanding therapeutic landscape for NSCLC in the era of precision medicine, are both factors that underscore the importance of efficient and effective molecular profiling. Method: This article provides consensus recommendations for biomarker testing for early-stage to advanced NSCLC. These recommendations are made from a multidisciplinary group of lung cancer experts in Singapore with the aim of improving patient care and long-term outcomes. Results: The recommendations address the considerations in both the advanced and early-stage settings, and take into account challenges in the implementation of biomarker testing as well as the limitations of available data. Biomarker testing for both tumour tissue and liquid biopsy are discussed. Conclusion: This consensus statement discusses the approaches and challenges of integrating molecular testing into clinical practice for patients with early- to late-stage NSCLC, and provides practical recommendations for biomarker testing for NSCLC patients in Singapore.

Obtaining spatially resolved tumor purity maps using deep multiple instance learning in a pan-cancer study.

Tumor purity is the percentage of cancer cells within a tissue section. Pathologists estimate tumor purity to select samples for genomic analysis by manually reading hematoxylin-eosin (H&E)-stained slides, which is tedious, time consuming, and prone to inter-observer variability. Besides, pathologists' estimates do not correlate well with genomic tumor purity values, which are inferred from genomic data and accepted as accurate for downstream analysis. We developed a deep multiple instance learning model predicting tumor purity from H&E-stained digital histopathology slides. Our model successfully predicted tumor purity in eight The Cancer Genome Atlas (TCGA) cohorts and a local Singapore cohort. The predictions were highly consistent with genomic tumor purity values. Thus, our model can be utilized to select samples for genomic analysis, which will help reduce pathologists' workload and decrease inter-observer variability. Furthermore, our model provided tumor purity maps showing the spatial variation within sections. They can help better understand the tumor microenvironment.

Periprostatic schwannoma mimicking metastatic lymphadenopathy in a case of multifocal prostate adenocarcinoma.

Schwannomas of the prostate are a rare entity and usually diagnosed incidentally following surgical management of presumed benign prostate hyperplasia or prostate adenocarcinoma. We present a case of sporadic periprostatic schwannoma diagnosed in conjunction with multifocal prostate adenocarcinoma on pre-operative multiparametric magnetic resonance imaging.

Recurrent pneumothoraces with diffuse small ground-glass and solid nodules.

Multifocal micronodular pneumocyte hyperplasia (MMPH) is the lesser known pulmonary manifestation of tuberous sclerosis. It manifests radiologically as diffuse small ground-glass and solid nodules. Accurate diagnosis is essential as it can be mistaken for miliary tuberculosis or malignant lesions which necessitates specific treatment. Constellation of radiological features such as multicentric disease at onset and stability over time can help to distinguish MMPH from its differentials. Histologically, MMPH is characterized by hamartomatous proliferation of type II pneumocytes with a lack of high nuclear to cytoplasmic ratio. MMPH confers a benign prognosis unlike its differentials. Therefore, accurate diagnosis is paramount in ensuring appropriate care is delivered. Here, we describe the radiological and histological features of MMPH in a patient with genetically proven tuberous sclerosis complex and co-existing lymphangioleiomyomatosis.

Chronic Cough With Non-Resolving Mass-like Consolidation.

CASE PRESENTATION: A 72-year-old Chinese man presented with a 5-month history of chronic dry cough, weight loss, and progressive dyspnea. There was no associated hemoptysis, hoarseness, epistaxis, or fever on systemic review. He was a nonsmoker and had no family history of malignancy. He was treated for pulmonary TB 40 years ago. A chest radiograph (Fig 1) showed mass-like consolidation in the right midzone with loss of the right hilar border, a small right pleural effusion, and bi-apical scarring. On physical examination, he was afebrile and normotensive, and he had pulse oxygen saturation of 97%. Examination of the chest was remarkable only for reduced breath sounds over the right chest. He did not have digital clubbing, distended neck veins, or cervical lymphadenopathy.

High-Dimensional Characterization of the Systemic Immune Landscape Informs on Synergism Between Radiation Therapy and Immune Checkpoint Blockade.

PURPOSE: Improved antitumor responses have been observed in patients after combination radiation therapy (RT) and immune checkpoint blockade (ICB). Whether these clinical responses are linked to the host systemic immune system has not been elucidated. METHODS AND MATERIALS: In this single-institution prospective observational study, peripheral blood was longitudinally collected from 10 patients with metastatic disease who had responded to anti-PD-1/anti-PD-L1 ICB and received RT (8-50 Gy in 1-5 fractions) upon disease progression at the following timepoints: baseline (pre-RT), 1 to 2 weeks post-RT, and post-ICB (cycle 1) on reintroduction post-RT. To thoroughly characterize the interaction between combined RT-ICB and the host immune system, we performed high-dimensional, mass cytometry-based immunophenotyping of circulating lymphocytes using a 40-marker panel addressing lineage, differentiation, activation, trafficking, cytotoxicity, and costimulatory and inhibitory functions. Phenotypic expression of circulating lymphocytes was compared across patients and time points and correlated with post-RT tumor responses. RESULTS: Foremost, we demonstrated excellent posttreatment clinical responses, including 4 local responses with >50% reduction in radiated tumor size, 1 out-of-field response, and 4 patients who resumed ICB for >1 year. Baseline and post-RT immune states were highly heterogeneous among patients. Despite this interindividual heterogeneity in baseline immune states, we observed a systemic immune reaction to RT-ICB common across patients, histology, and radiation sites; a subset of pre-existing Ki-67+ CD8+ T cells were increased post-RT and further expanded upon reintroduction of ICB post-RT (2.3-fold increase, P = .02). Importantly, RT did not alter the phenotypic profile of these Ki-67+ CD8+ T cells, which was characterized by a distinct activated and differentiated effector phenotype. CONCLUSIONS: Collectively, these findings point toward a sustained reinvigoration of host antitumor immunity after RT-ICB and suggest an expansion in activated Ki-67+ CD8+ T cells as a possible demonstration of this synergy, thereby providing new insights that may support the development of optimal sequencing strategies.