Objective To investigate the clinical and pathological characteristics, tumor immune microenvironment (TIME), and prognostic differences among various pathological subtypes of pulmonary pleomorphic carcinoma (PC), seeking to provide insights for the stratified management and individualized treatment of patients with PC.

Methods A retrospective analysis was conducted on clinical and pathological data from 46 patients with pulmonary PC admitted to the Affiliated Hospital of Inner Mongolia Medical University from June 2016 to December 2022. Univariate and multivariate Cox proportional hazards regression analyses were performed to assess the factors influencing overall survival (OS), including gender, age, tumor size, clinical stage, epithelial markers, and histological subtypes (mixed and pure). The expression of PD-L1, characteristics of immune cell infiltration, and TIME heterogeneity were evaluated in the mixed and pure subtypes.

Results Univariate analysis identified clinical stage (P=0.019) as a risk factor, and pathological subtype (P=0.048) and neutrophil infiltration (P=0.007) as protective factors affecting patient OS. Multivariate analysis confirmed the clinical stage (P=0.044) and neutrophil infiltration (P=0.003) as independent factors influencing patient survival. PD-L1 expression analysis and TIME classification revealed that the mixed subtype exhibited a higher level of CD4⁺T lymphocyte infiltration than that of the pure subtype (P=0.009). Conversely, compared to the mixed subtype, the pure subtype demonstrated higher expression levels of PD-L1 and greater density of CD163⁺M2 tumor-associated macrophages (TAM) (P=0.002). The mixed subtype predominantly displayed type Ⅱ and Ⅲ TIME, while the pure subtype exhibited type Ⅰ and Ⅲ TIME.

Conclusions Pulmonary PC has heterogeneous morphology and a unique TIME, and stratified management based on morphology and TIME is necessary to improve the effectiveness of immunotherapy.