Summary

Lung cancer may exhibit marked morphological and molecular heterogeneity, posing relevant diagnostic and therapeutic challenges. We present a case of lung adenocarcinoma that raises important questions regarding the distinction between collision tumors, intratumoral molecular heterogeneity, subclonal alterations, and aberrant mutation profiles. A 76-year-old man was diagnosed with a lung lesion composed of two spatially distinct adenocarcinomas in the same mass, one harboring the EGFR L858R mutation and the other showing the ALK rearrangement. Integrated gross, histopathological, and molecular assessment was essential to establish the diagnosis of a dual-driver collision tumor. This case highlights the need for careful pathological-molecular correlation and emphasizes the role of MTB in managing complex presentations in lung cancer.

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Authors

Lorenzo Nibid - Research Unit of Anatomical Pathology, Department of Medicine and Surgery, Università Campus Bio-Medico Di Roma, Rome, Italy https://orcid.org/0000-0001-8583-0596

Alessia Capozzi - Research Unit of Anatomical Pathology, Department of Medicine and Surgery, Università Campus Bio-Medico Di Roma, Rome, Italy https://orcid.org/0009-0003-0733-4804

Veronica Vicomandi - Research Unit of Anatomical Pathology, Department of Medicine and Surgery, Università Campus Bio-Medico Di Roma, Rome, Italy https://orcid.org/0000-0001-5207-8764

Giovanna Sabarese - Anatomical Pathology Operative Research Unit, Fondazione Policlinico Universitario Campus Bio-Medico

Daniela Righi - Anatomical Pathology Operative Research Unit, Fondazione Policlinico Universitario Campus Bio-Medico

Marco Russano - Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Roma, Italy.

Alessio Cortellini - Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Roma, Italy.

Luisella Righi - Department of Genetics, Biology, and Biochemistry, Laboratory of Immunogenetics, University of Torino Medical School, Torino, Italy

Giuseppe Perrone - Research Unit of Anatomical Pathology, Department of Medicine and Surgery, Università Campus Bio-Medico Di Roma, Rome, Italy

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Copyright (c) 2026 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology

How to Cite
Nibid, L., Capozzi, A., Vicomandi, V., Sabarese, G., Righi, D., Russano, M., Cortellini, A., Righi, L., & Perrone, G. (2026). When one tumor isn’t one: a case of dual driver lung adenocarcinoma. Pathologica - Journal of the Italian Society of Anatomic Pathology and Diagnostic Cytopathology, 118(4). https://doi.org/10.32074/1591-951X-2497
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