Pulmonary Neuroendocrine Carcinomas in Situ: Do They Exist?

Introduction

Although precursor lesions of pulmonary squamous carcinoma, adenocarcinoma, and carcinoid tumor are well known and accepted entities, precursor lesions of pulmonary neuroendocrine carcinomas, i.e., small cell lung carcinoma and large cell neuroendocrine carcinoma, have never been identified. A small body of literature documenting intraepithelial involvement in cases of pulmonary neuroendocrine carcinomas begs the question of whether the intraepithelial lesion represents de novo intraepithelial neoplasia or invasion by underlying tumour.

Methods and Materials

The literature on cases of invasive neuroendocrine carcinomas with an intraepithelial component exhibiting a neuroendocrine immunophenotype was thoroughly and critically reviewed.

Results

The authors of the publications of cases of coexisting invasive and intraepithelial neuroendocrine carcinoma generally favour invasion as the explanation for the intraepithelial component. However, in practice, it is difficult or impossible to determine the direction of migration of tumor cells when there is both an invasive and intraepithelial component. Pulmonary neuroendocrine carcinomas in situ have been produced in genetically engineered mouse models.

Conclusions

Based on the illustrations in the literature of human cases and the production of pulmonary neuroendocrine carcinomas in situ in genetically engineered mice, it seems likely that these tumours also exist in humans. However, their existence and acceptance require definitive proof. Studies should be undertaken to identify bronchial and other lung biopsies with in situ carcinoma exhibiting a neuroendocrine immunophenotype and a subsequent negative resection specimen and no follow-up evidence of invasive carcinoma. Documenting such cases would provide definitive proof for the existence pulmonary neuroendocrine carcinomas in situ in humans.

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