Challenges in Diagnosis of Lepidic Subtype in Lung Cancer According to W.H.O Classification: A Case Report

Background: Lepidic 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 presentation: A 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. Conclusion: This 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.