{"doi":"10.3389/fpubh.2026.1847300","title":"Conditional dependence of the “male–SCC, female–ADC” teaching heuristic in lung cancer: shifts in exposure pathways and the need for pathology education reform","abstract":"<jats:p>The classic pathological teaching aphorism that “male lung cancer is predominantly squamous cell carcinoma (squamous cell carcinoma, SCC), whereas female lung cancer is predominantly adenocarcinoma (adenocarcinoma, ADC)” remains widely used in medical education, yet it is now markedly discordant with contemporary epidemiological evidence. We argue that this discrepancy does not indicate that the aphorism was historically incorrect; rather, the three exposure premises on which it was originally founded have been fundamentally altered in the modern era. The substantial global decline in male smoking prevalence has weakened the population basis of SCC, cigarette filter ventilation design, as a hypothetical contributing factor, has altered the intrapulmonary deposition pattern of inhaled carcinogens, while fine particulate matter (PM2.5) can activate pre-existing driver mutations in lung epithelial cells through inflammatory signaling, thereby establishing a tobacco-independent carcinogenic pathway favoring ADC. The convergence of these exposure shifts has enabled ADC to replace SCC as the most common lung cancer subtype in both men and women across most countries and regions. However, the teaching aphorism has never been explicitly annotated with its historical conditional boundaries. As a result, a screening cognition framework still centered on the “smoking–SCC” paradigm may generate substantial blind spots in clinical practice, potentially contributing to missed detection and diagnostic misclassification. We therefore advocate replacing this static mnemonic with a conditional and dynamic teaching framework structured around temporal, exposure, and population dimensions, and call for prioritizing risk-stratified lung cancer screening strategies for never-smokers together with individual-level causal validation of the PM2.5-driven carcinogenic pathway.</jats:p>","journal":"Frontiers in Public Health","year":2026,"id":649459,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1693064,"name":"Mu-Wei Dai","orcid":null,"position":1,"is_corresponding":false},{"id":1056867,"name":"Li-Nan Chen","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Conditional dependence of the “male–SCC, female–ADC” teaching heuristic in lung cancer: shifts in exposure pathways and the need for pathology education reform","abstract":"<jats:p>The classic pathological teaching aphorism that “male lung cancer is predominantly squamous cell carcinoma (squamous cell carcinoma, SCC), whereas female lung cancer is predominantly adenocarcinoma (adenocarcinoma, ADC)” remains widely used in medical education, yet it is now markedly discordant with contemporary epidemiological evidence. We argue that this discrepancy does not indicate that the aphorism was historically incorrect; rather, the three exposure premises on which it was originally founded have been fundamentally altered in the modern era. The substantial global decline in male smoking prevalence has weakened the population basis of SCC, cigarette filter ventilation design, as a hypothetical contributing factor, has altered the intrapulmonary deposition pattern of inhaled carcinogens, while fine particulate matter (PM2.5) can activate pre-existing driver mutations in lung epithelial cells through inflammatory signaling, thereby establishing a tobacco-independent carcinogenic pathway favoring ADC. The convergence of these exposure shifts has enabled ADC to replace SCC as the most common lung cancer subtype in both men and women across most countries and regions. However, the teaching aphorism has never been explicitly annotated with its historical conditional boundaries. As a result, a screening cognition framework still centered on the “smoking–SCC” paradigm may generate substantial blind spots in clinical practice, potentially contributing to missed detection and diagnostic misclassification. We therefore advocate replacing this static mnemonic with a conditional and dynamic teaching framework structured around temporal, exposure, and population dimensions, and call for prioritizing risk-stratified lung cancer screening strategies for never-smokers together with individual-level causal validation of the PM2.5-driven carcinogenic pathway.</jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"42433424","pmcid":null,"openalex_id":null,"authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":null,"license":"https://creativecommons.org/licenses/by/4.0/","oa_locations":[{"url":"https://www.frontiersin.org/articles/10.3389/fpubh.2026.1847300/full","host_type":"publisher"}],"fields_of_study":[],"mesh_terms":["Humans","Adenocarcinoma","Carcinoma, Squamous Cell","Lung Neoplasms","Pathology","Education, Medical","Female","Male"],"keywords":["Lung cancer","Adenocarcinoma","Squamous cell carcinoma","Medical education","Public Health","Pm2.5","Histological Subtype"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-10T03:44:46.002149Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}