• Laura Bonanno, Fiorella Calabrese, Giorgia Nardo, Daniele Calistri, Michela Tebaldi, Gianluca Tedaldi, Valentina Polo, Stefania Vuljan, Adolfo Favaretto, PierFranco Conte, Alberto Amadori, Federico Rea, and Stefano Indraccolo.
• Medical Oncology 2, Istituto Oncologico Veneto IRCCS, via Gattamelata 64, 35128 Padova, Italy. Electronic address: laura.bonanno@ioveneto.it.
• Lung Cancer. 2016 Jun 1; 96: 52-5.

AbstractDiscrimination of multifocal primary lung cancers from lung metastases is crucial to allow for an appropriate clinical management. We report here a case of multifocal lung adenocarcinomas with different morphological and molecular patterns. Radical surgery of one lung nodule was performed at the time of diagnosis, and subsequently on two other lung nodules. At the time of distant relapse, biopsy was repeated for molecular characterization. The patient was treated with EGFR tyrosine kinase inhibitor according to the detection of EGFR exon 21 mutation in metastatic sample and in one of the three lung tumors, characterized by lower mutated allele frequency. The progression free survival was three months according to radiological criteria and the treatment was provided for six months, until clinical progression. Following the assessment of EGFR mutations by pyrosequencing, tumor samples were analyzed by a 30-gene next generation sequencing (NGS) panel, allowing to study intra- and inter-tumor heterogeneity and to confirm the three lung tumors as independent. Different molecular profiles of synchronous tumors and identical EGFR, PIK3CA and TP53 mutations in one of three primary lung tumors and the metachronous metastasis were identified. In conclusion, morphological and molecular characterization of multiple lung nodules by NGS may help to define synchronous and metachronous adenocarcinomas, thus affecting surgical indication and systemic treatment. Intratumor heterogeneity may be associated with differential sensitivity to targeted treatment.Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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