Differentiating Separate Primary Lung Adenocarcinomas From Intrapulmonary Metastases With Emphasis on Pathological and Molecular Considerations: Recommendations From the International Association for the Study of Lung Cancer Pathology Committee.

Introduction: With the implementation of low-dose computed tomography screening, multiple pulmonary tumor nodules are diagnosed with increasing frequency and the selection of surgical treatments versus systemic therapies has become challenging on a daily basis in clinical practice. In the presence of multiple carcinomas, especially adenocarcinomas, pathologically determined to be of pulmonary origin, the distinction between separate primary lung carcinomas (SPLCs) and intrapulmonary metastases (IPMs) is important for staging, management, and prognostication.

Methods: We systemically reviewed various means that aid in the differentiation between SPLCs and IPMs explored by histopathologic evaluation and molecular profiling, the latter includes DNA microsatellite analysis, array comparative genomic hybridization, TP53 and oncogenic driver mutation testing and, more recently, with promising effectiveness, next-generation sequencing comprising small- or large-scale multi-gene panels.

Diagnosis and management of hypersensitivity pneumonitis in adults: A position statement from the Thoracic Society of Australia and New Zealand.

Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease (ILD) relating to specific occupational, environmental or medication exposures. Disease behaviour is influenced by the nature of exposure and the host response, with varying degrees of lung inflammation and fibrosis seen within individuals. The differentiation of HP from other ILDs is important due to distinct causes, pathophysiology, prognosis and management implications.

Data set for the reporting of lung cancer: recommendations from the International Collaboration on Cancer Reporting (ICCR).

Lung cancer is the leading cause of cancer related deaths worldwide, although some patients with early-stage disease can be cured with surgical resection. Standardised reporting of all clinically relevant pathological parameters is essential for best patient care and is also important for ongoing data collection and refinement of important pathological features that impact patient prognosis, staging and clinical care. Using the established International Collaboration on Cancer Reporting (ICCR) procedure, a representative international expert panel of nine lung pathologists as well as an oncologist was convened.

The histopathological spectrum and molecular changes associated with KRAS G12C mutation in non-small cell lung carcinoma.

KRAS G12C is the most common KRAS mutation in non-small cell lung carcinoma (NSCLC), for which targeted therapy has recently been developed. From the 732 cases of NSCLC that underwent next-generation sequencing at the Department of Anatomical Pathology, Liverpool Hospital, between July 2021 and May 2023, we retrieved 83 (11%) consecutive cases of KRAS G12C mutated NSCLC, and analysed their clinical, pathological, and molecular features. Of the 83 cases of KRAS G12C mutated NSCLC, there were 46 (55%) men and 37 (45%) women, with mean age of 72 years.

Disease Behaviour Classification: A pragmatic model for predicting outcomes in Interstitial Lung Disease.

Background And Objective: The interstitial lung diseases (ILD) are a heterogenous group of disorders with similar clinical presentation, but widely varying prognoses. The use of a pragmatic disease behaviour classification (DBC), first proposed in international guidelines in 2013, categorises diseases into five behavioural classes based on their predicted clinical course. This study aimed to determine the prognostic utility of the DBC in an ILD cohort.

Mesothelioma in the pleura, pericardium and peritoneum: Recommendations from the International Collaboration on Cancer Reporting (ICCR).

Aims: Mesothelioma is a rare malignancy of the serosal membranes that is commonly related to exposure to asbestos. Despite extensive research and clinical trials, prognosis to date remains poor. Consistent, comprehensive and reproducible pathology reporting form the basis of all future interventions for an individual patient, but also ensures that meaningful data are collected to identify predictive and prognostic markers.

Optimizing tissue stewardship in non-small cell lung cancer to support molecular characterization and treatment selection: statement from a working group of thoracic pathologists.

Many patients with non-small cell lung cancer do not receive guideline-recommended, biomarker-directed therapy, despite the potential for improved clinical outcomes. Access to timely, accurate, and comprehensive molecular profiling, including targetable protein overexpression, is essential to allow fully informed treatment decisions to be taken. In turn, this requires optimal tissue management to protect and maximize the use of this precious finite resource.

Dataset for reporting of thymic epithelial tumours: recommendations from the International Collaboration on Cancer Reporting (ICCR).

Aims: Thymic epithelial tumours (TET), including thymomas and thymic carcinomas and thymic neuroendocrine neoplasms, are malignant neoplasms that can be associated with morbidity and mortality. Recently, an updated version of the World Health Organization (WHO) Classification of Thoracic Tumours 5th Edition, 2021 has been released, which included various changes to the classification of these neoplasms. In addition, in 2017 the Union for International Cancer Control (UICC) / American Joint Committee on Cancer (AJCC) published the 8th Edition Staging Manual which, for the first time, includes a TNM staging that is applicable to thymomas, thymic carcinomas, and thymic neuroendocrine neoplasms.

A STAT3 protein complex required for mitochondrial mRNA stability and cancer.

Signal transducer and activator of transcription 3 (STAT3) is a potent transcription factor necessary for life whose activity is corrupted in diverse diseases, including cancer. STAT3 biology was presumed to be entirely dependent on its activity as a transcription factor until the discovery of a mitochondrial pool of STAT3, which is necessary for normal tissue function and tumorigenesis. However, the mechanism of this mitochondrial activity remained elusive.

International Association for the Study of Lung Cancer Study of Reproducibility in Assessment of Pathologic Response in Resected Lung Cancers After Neoadjuvant Therapy.

Introduction: Pathologic response has been proposed as an early clinical trial end point of survival after neoadjuvant treatment in clinical trials of NSCLC. The International Association for the Study of Lung Cancer (IASLC) published recommendations for pathologic evaluation of resected lung cancers after neoadjuvant therapy. The aim of this study was to assess pathologic response interobserver reproducibility using IASLC criteria.

Looking beyond workforce parity: addressing gender inequity in pathology.

While women pathologists have made up over one-third of pathologists in the Australian workforce for over 15 years and at least 50% since 2019, they are under-represented in senior leadership roles, scientific publications, grant recipients, editorial boards, key presentations, and professional awards. This is not unique to pathology and is seen in the broader medical and academic community. Barriers to gender equity and equality in pathology, medicine and academia include gender stereotypes, gender-based discrimination, structural and organisational barriers as well as broader social and cultural barriers.

NTRK fusions in solid tumours: what every pathologist needs to know.

Fusions involving the Neurotrophic tropomyosin receptor kinase (NTRK) gene family (NTRK1, NTRK2 and NTRK3) are targetable oncogenic alterations that are found in a diverse range of tumours. There is an increasing demand to identify tumours which harbour these fusions to enable treatment with selective tyrosine kinase inhibitors such as larotrectinib and entrectinib. NTRK fusions occur in a wide range of tumours including rare tumours such as infantile fibrosarcoma and secretory carcinomas of the salivary gland and breast, as well as at low frequencies in more common tumours including melanoma, colorectal, thyroid and lung carcinomas.

Dataset for the reporting of neoplasms of the heart, pericardium, and great vessels: recommendations from the International Collaboration on Cancer Reporting (ICCR).

The International Collaboration on Cancer Reporting (ICCR) was founded by major pathology organizations from around the world to produce internationally standardized and evidence-based datasets for pathologists' reporting of cancer. Its goal is to improve cancer patient outcomes worldwide and to advance international benchmarking in cancer management. The ICCR cancer dataset development schedule is aligned with revisions of the WHO Classification of Tumours ("Blue Book") series, and in 2015 ICCR developed an initial series of thoracic datasets including a dataset for neoplasms of the heart, pericardium, and great vessels.

Extracellular matrix profiles determine risk and prognosis of the squamous cell carcinoma subtype of non-small cell lung carcinoma.

Background: Squamous cell carcinoma (SqCC) is a subtype of non-small cell lung cancer for which patient prognosis remains poor. The extracellular matrix (ECM) is critical in regulating cell behavior; however, its importance in tumor aggressiveness remains to be comprehensively characterized.

Methods: Multi-omics data of SqCC human tumor specimens was combined to characterize ECM features associated with initiation and recurrence.

The Ring Study: an international comparison of PD-L1 diagnostic assays and their interpretation in non-small cell lung cancer, head and neck squamous cell cancer and urothelial cancer.

PD-L1 immunohistochemistry has been approved as a diagnostic assay for immunotherapy. However, an international comparison across multiple cancers is lacking. This study aimed to assess the performance of PD-L1 diagnostic assays in non-small cell lung cancer (NSCLC), head and neck squamous cell cancer (HNSCC) and urothelial cancer (UC).

Whole genome duplication in oral squamous cell carcinoma in patients younger than 50 years: implications for prognosis and adverse clinicopathological factors.

Introduction: Oral squamous cell carcinoma (OSCC) in the young (<50 years), without known carcinogenic risk factors, is on the rise globally. Whole genome duplication (WGD) has been shown to occur at higher rates in cancers without an identifiable carcinogenic agent. We aimed to evaluate the prevalence of WGD in a cohort of OSCC patients under the age of 50 years.