Lung cancer is among the lethal and most prevalent oncological diseases globally. It is known that two types of mutations, namely anaplastic lymphoma kinase (ALK) gene rearrangement and epidermal growth factor receptor (EGFR) gene mutation, are responsible for the development of lung adenocarcinoma. The present study aimed to investigate the differences in the frequency of clinical, cytomorphological and histomorphological features of ALK and EGFR-positive lung adenocarcinomas. The present retrospective study comprised 101 patients diagnosed with lung adenocarcinoma. Based on the molecular findings, the patients were categorized into three groups as follows: The ALK-rearranged group (n=28), the EGFR group (n=42) and the negative group (n=31). The clinical features analyzed included sex, age, smoking status and disease stage. The cytomorphological and histomorphological features examined encompassed the following: Cell cluster size, the arrangement of tumor cells, the size of nuclei, nuclear atypia, the visibility of nucleoli, the presence of necrosis, intracytoplasmic vacuoles, signet ring cells, stromal characteristics and the presence of inflammatory infiltrate presence. The results indicated that the female sex was more prevalent in the EGFR group, but statistically significant differences (P<0.05) were observed between the EGFR and negative group. A significantly greater percentage of non-smokers was identified in the EGFR group compared with the ALK group (P<0.01). The majority of patients with confirmed ALK or EGFR mutations received onco-specific treatment. Focal and abundant necrosis was significantly less common in cytological samples in the EGFR group than in the other groups (21.43 vs. 57.14 and 51.61%, combined, P<0.01). No significant differences were observed in other cytomorphological features between the groups. Intracytoplasmic vacuoles, signet ring cells and cells with visible nucleoli were significantly more frequent in histological specimens of the ALK group (P<0.01). The predictive model composed of these features or combined with sex and smoking habits exhibited statistically significant differences for mutation status as a criterion (P<0.01). Collectively, the findings of the present study confirmed that, in addition to clinical characteristics, certain cytological and histological features of lung adenocarcinoma are associated with the mutational status of the tumor.
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