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Introduction
Lung cancer ranks among the most lethal and most prevalent oncological diseases worldwide. According to the latest ‘GLOBOCAN 2022’ review of global cancer statistics, it stands as the second most commonly diagnosed type of cancer, trailing only breast cancer. In 2022 alone, almost 2.5 million new cases of lung cancer were diagnosed. Notably, lung cancer holds the grim distinction of being the primary cause of mortality among patients afflicted by malignant diseases, claiming the lives of 1.8 million individuals in 2022. Typically, it manifests in individuals aged ≥70, emerging as the leading cause of oncological fatalities among those aged ≥40 (1,2).
The success of lung cancer treatment is dependent upon various factors, including the clinical characteristics of patients, the tumor histological type, the outcomes of predictive biomarker testing, and effective communications between pathologists, radiologists and oncologists. Over the past decade, substantial strides have been made in therapeutic development, mainly through identifying and utilizing predictive biomarkers (3).
Invasive non-mucinous adenocarcinoma is the most common type of lung cancer. It comprises malignant epithelial cells whose morphology or immunohistochemical phenotype suggest glandular differentiation, and thus it does not meet the criteria for any other type of adenocarcinoma (4).
Anaplastic lymphoma kinase (ALK) rearrangement encompasses a group of gene mutations encoding the transmembrane receptor tyrosine kinase, belonging to the insulin receptor protein superfamily. To date, >20 rearrangement partners of the ALK gene have been identified, with the most prevalent occurring in non-small cell lung cancer (NSCLC): an intra-chromosomal inversion of the short arm of chromosome 2, resulting in the fusion of the 2p21 gene locus of the echinoderm microtubule-associated protein-like protein 4 (EML4) gene and 2p23 ALK genes (5). Among the genomic alterations observed in NSCLC, the ALK rearrangement is a targetable alteration for therapy, providing a therapeutic response that extends patient survival (6,7). While the histological type of the majority of lung cancers with ALK rearrangement is adenocarcinoma, the studies available to date exploring the detailed histomorphological and cytomorphological characteristics of these samples are limited and have yielded contradictory results (8–12).
Epidermal growth factor receptor (EGFR) belongs to the family of tyrosine kinase protein receptors whose mutation leads to the uncontrolled proliferation of malignant cells, their invasion, metastatic spread, the inhibition of apoptosis, as well as tumor...