AUTHOR=Pham Nguyen Cuong , Phan Long Thien , Phan Phuong Thi , Phan Do Quyen Thi , Pham Nguyen Tuong , Dang Thoi Van 
  
TITLE=Challenges in Diagnosis of Lepidic Subtype in Lung Cancer According to W.H.O Classification: A Case Report
  
JOURNAL=British Journal of Biomedical Science
  
VOLUME=Volume 83 - 2026
  
YEAR=2026
  
URL=https://www.frontierspartnerships.org/journals/british-journal-of-biomedical-science/articles/10.3389/bjbs.2026.16119
  
DOI=10.3389/bjbs.2026.16119
  
ISSN=2474-0896
  
ABSTRACT=BackgroundLepidic adenocarcinoma of the lung often presents with atypical radiological patterns mimicking pneumonia, posing significant diagnostic challenges, particularly from small cytology samples. This can lead to delayed diagnosis and advanced-stage presentation.Case presentationA 57-year-old non-smoking female presented with a persistent cough, massive sputum production, and diffuse bilateral pulmonary lesions on computed tomography scan, resembling pneumonia. The patient’s condition rapidly deteriorated into acute respiratory failure unresponsive to antibiotics. A sputum cell block confirmed lung adenocarcinoma (CK7+, TTF-1+). Liquid biopsy via Next-Generation Sequencing (NGS) identified an EGFR L858R mutation (VAF 80%). First-line Osimertinib induced a dramatic clinical and radiological response within days. However, disease progression occurred after 9 months. A repeat biopsy and NGS re-evaluation revealed a persistent L858R mutation with an increased VAF (89%), without secondary resistance mutations (T790M, C797S) or bypass alterations, suggesting non-genetic resistance mechanisms.ConclusionThis case underscores the critical difficulty of diagnosing lepidic-patterned tumors in an oncological emergency. It highlights the necessity of a multidisciplinary approach, combining cytology, radiology, and early molecular testing as a surrogate for traditional histopathology to guide urgent targeted therapy.