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Peer-reviewedCC BYThoracic cancer

Non-Small Cell Lung Carcinoma With Bilayered Architecture and TP53 Alteration: A Diagnostic Pitfall and a Potential Distinct Entity.

  • Yao Liu1
  • Biao Zhang1
  • Xiaobin Cui1
  • Fanqing Meng1
  1. 1Department of Pathology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China.
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Abstract

The presence of a continuous basal cell layer is generally regarded as a defining feature of bronchiolar adenoma/ciliated muconodular papillary tumor (BA/CMPT), and preservation of this bilayered architecture is commonly used as a surrogate marker of benign behavior. We report a 1.1-cm pulmonary nodule detected in a 75-year-old never-smoker that exhibited marked high-grade cytologic atypia in both luminal and basal cells. Immunohistochemical analysis demonstrated diffuse strong P53 expression and an increased proliferative index (Ki-67 approximately 10%). Targeted next-generation sequencing revealed a pathogenic TP53 mutation (p.A161T). Despite the intact basal layer, the diffuse high-grade cytology and shared strong P53 expression in both compartments indicate that this lesion represents a fully malignant carcinoma rather than a benign BA/CMPT. In practice, it can only be classified as non-small cell lung cancer (NSCLC), NOS, with a distinctive bilayered phenotype. This case emphasizes that a preserved basal cell layer does not always equate to benignity, and it highlights a rare tumor type that may mimic BA/CMPT, carrying a risk of underdiagnosis. Integrating cytology, immunophenotype, and molecular findings is crucial for correct classification.

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Cite

BibTeXRIS
BibTeX
@article{liu2026nonsmall,
  title = {{Non-Small Cell Lung Carcinoma With Bilayered Architecture and TP53 Alteration: A Diagnostic Pitfall and a Potential Distinct Entity.}},
  author = {Yao Liu and Biao Zhang and Xiaobin Cui and Fanqing Meng},
  journal = {Thoracic cancer},
  year = {2026},
  month = oct,
  doi = {10.1111/1759-7714.70411},
  url = {https://europepmc.org/article/MED/42958874},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Non-Small Cell Lung Carcinoma With Bilayered Architecture and TP53 Alteration: A Diagnostic Pitfall and a Potential Distinct Entity.
AU  - Yao Liu
AU  - Biao Zhang
AU  - Xiaobin Cui
AU  - Fanqing Meng
PY  - 2026
DA  - 2026/10/29
JO  - Thoracic cancer
DO  - 10.1111/1759-7714.70411
UR  - https://europepmc.org/article/MED/42958874
AB  - The presence of a continuous basal cell layer is generally regarded as a defining feature of bronchiolar adenoma/ciliated muconodular papillary tumor (BA/CMPT), and preservation of this bilayered architecture is commonly used as a surrogate marker of benign behavior. We report a 1.1-cm pulmonary nodule detected in a 75-year-old never-smoker that exhibited marked high-grade cytologic atypia in both luminal and basal cells. Immunohistochemical analysis demonstrated diffuse strong P53 expression and an increased proliferative index (Ki-67 approximately 10%). Targeted next-generation sequencing revealed a pathogenic TP53 mutation (p.A161T). Despite the intact basal layer, the diffuse high-grade cytology and shared strong P53 expression in both compartments indicate that this lesion represents a fully malignant carcinoma rather than a benign BA/CMPT. In practice, it can only be classified as non-small cell lung cancer (NSCLC), NOS, with a distinctive bilayered phenotype. This case emphasizes that a preserved basal cell layer does not always equate to benignity, and it highlights a rare tumor type that may mimic BA/CMPT, carrying a risk of underdiagnosis. Integrating cytology, immunophenotype, and molecular findings is crucial for correct classification.
SN  - 1759-7706
SN  - 1759-7714
ER  -