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

Sep 22, 2026

Lepidic-patterned lung adenocarcinoma frequently mimics pneumonia on radiology, creating major diagnostic difficulty when material is limited to small cytology samples. A 57-year-old female non-smoker presented with persistent cough, massive sputum production, and diffuse bilateral lesions resembling infection, rapidly progressing to acute respiratory failure despite antibiotics. Sputum cell block and CK7+/TTF-1+ staining confirmed lung adenocarcinoma. Next-generation sequencing identified an EGFR L858R mutation, with first-line osimertinib producing rapid clinical and radiological improvement before progression after 9 months; repeat testing showed persistent L858R with rising VAF and no secondary resistance alterations, suggesting non-genetic resistance. The case supports multidisciplinary diagnosis and early molecular testing.

LanguageEnglish

CategoryHealthcare

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Pages7

Reading Time18 min

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Case presentation

CASE REPORT published: 02 April 2026 doi: 10.3389/bjbs.2026.16119 *Correspondence Thoi Van Dang, [dvthoi@dhktyduocdn.edu.vn](dvthoi@dhktyduocdn.edu.vn)[ ](dvthoi@dhktyduocdn.edu.vn)†These authors have contributed equally to this work Received: 22 December 2025 Revised: 01 March 2026 Accepted: 12 March 2026 Published: 02 April 2026 Citation: Pham Nguyen C, Phan LT, Phan PT, Phan DQT, Pham Nguyen T and Dang TV (2026) Challenges in Diagnosis of Lepidic Subtype in Lung Cancer According to W.H.O Classification: A Case Report. Br. J. Biomed. Sci. 83:16119. doi: 10.3389/bjbs.2026.16119 Challenges in Diagnosis of Lepidic Subtype in Lung Cancer According to W. H.O Classification: A Case Report Cuong Pham Nguyen 1†, Long Thien Phan 2†, Phuong Thi Phan3, Do Quyen Thi Phan4, Tuong Pham Nguyen4 and Thoi Van Dang5 * 1Department of Pathology, Hue Central Hospital, Hue, Vietnam, 2Department of Oncology, International Medical Center, Hue Central Hospital, Hue, Vietnam, 3Pulmonary Disease Department, Hue Central Hospital, Hue, Vietnam, 4Oncology Center, Hue Central Hospital, Hue, Vietnam, 5Da Nang University of Medical Technology and Pharmacy, Da Nang, Vietnam 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. Keywords: EGFR mutations, lepidic adenocarcinoma, osimertinib, pathology, respiratory Insufficiency INTRODUCTION Lung cancer is one of the most common cancers worldwide with high incidence and mortality, heterogeneous clinical features, and complex histologic and molecular patterns. Non-small cell lung cancer (NSCLC) accounts for the majority of cases (approximately 85%), with adenocarcinoma being one of the most frequent subtypes [ 1, 2]. Bronchoalveolar carcinoma (BAC) is a rare subtype of NSCLC that accounting for 3%–6% of lung cancer, usually occurs in the lung periphery along alveolar walls, without invasion of the lung parenchyma [3]. Since 2015, World Health Organization (WHO) has replaced the term BAC from the 2010 WHO classification with “lepidicadenocarcinoma,” based on the predominant histopathological pattern where lepidic growth is the most prominent feature. The lepidic growth pattern involves the proliferation of atypical British Journal of Biomedical Science | Published by Frontiers 1 April 2026 | Volume 83 | Article 16119 pneumocytes or Clara cells along the alveolar walls [4] . Besides, lepidic adenocarcinoma often coexists with other invasive components, requiring the pathologist to carefully assess the percentage of each component. Minimally Invasive Adenocarcinoma (MIA) is a key concept related to the lepi

FAQs

Why is diagnosing lepidic-patterned lung tumors challenging?

Lepidic adenocarcinoma often shows atypical radiological patterns that mimic pneumonia, and limited material from small cytology samples makes accurate assessment difficult.

What confirmed the diagnosis in this case?

A sputum cell block with immunoprofiles CK7+ and TTF-1+ confirmed lung adenocarcinoma.

How did genomic testing and treatment influence outcomes?

Next-generation sequencing identified an EGFR L858R mutation, and first-line osimertinib led to rapid clinical and radiological response. After 9 months, progression occurred without secondary resistance mutations on repeat biopsy and NGS re-evaluation.

Sep 22, 2026

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