ArticleFrontiers in oncology2026
Evidence for the transformation of a subset of pulmonary carcinoids to small cell lung carcinomas through shared molecular alterations.
Article in Frontiers in oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Pulmonary carcinoid and small cell lung carcinomas represent fundamentally distinct tumors in terms of molecular pathogenesis, pathological features, treatment, and prognosis. Whether any pathogenic link exists between pulmonary carcinoids and small cell carcinomas remains poorly understood. Elucidating the potential for carcinoids to undergo transformation into small cell lung carcinomas is critical for early intervention, treatment personalization, and prognostic assessment. Methods: H&E staining was performed to assess histomorphological transitions between pulmonary atypical carcinoids and small cell lung carcinomas. Immunohistochemistry was subsequently applied to compare the immunophenotypic profiles of two tumors. Molecular profiling was conducted to evaluate clonal relatedness and the presence of progressive genetic alterations, thereby providing evidence for transformation. Results: In addition to the atypical carcinoid and small cell lung carcinomas morphological characteristics, the lesion areas also present hybrid morphological characteristics of both tumors. Immunohistochemical analysis demonstrated distinct profiles between the two tumors: atypical carcinoids exhibited a low Ki67 proliferative index, high TP53 expression, and loss of RB1 expression, whereas small cell lung carcinomas showed a high Ki67 proliferative index, low TP53 expression, and loss of RB1 expression. Furthermore, clonal evolution analysis revealed that the two tumor components shared a set of 160 identical somatic mutations (accounting for approximately 16% of the total mutations in each component). Conclusion: This study delineates a dynamic evolutionary process within the pulmonary neuroendocrine tumor spectrum, confirming that a subset of atypical carcinoids can progress to small cell lung carcinoma through a transformation pathway.
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