Morphological and genetic heterogeneity in multifocal lung adenocarcinoma: The case of a never-smoker woman.
Discrimination 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.
['Bonanno|Laura|L|', 'Calabrese|Fiorella|F|', 'Nardo|Giorgia|G|', 'Calistri|Daniele|D|', 'Tebaldi|Michela|M|', 'Tedaldi|Gianluca|G|', 'Polo|Valentina|V|', 'Vuljan|Stefania|S|', 'Favaretto|Adolfo|A|', 'Conte|PierFranco|P|', 'Amadori|Alberto|A|', 'Rea|Federico|F|', 'Indraccolo|Stefano|S|']
D000230:Adenocarcinoma D000077192:Adenocarcinoma of Lung D000368:Aged D004252:DNA Mutational Analysis D003937:Diagnosis, Differential D018572:Disease-Free Survival D066246:ErbB Receptors D005260:Female D059014:High-Throughput Nucleotide Sequencing D006801:Humans D008113:Liver Neoplasms D008175:Lung Neoplasms D009154:Mutation D009362:Neoplasm Metastasis D009378:Neoplasms, Multiple Primary D049268:Positron-Emission Tomography D047428:Protein Kinase Inhibitors D016896:Treatment Outcome
EGFR Mutate allele frequency Next generation sequencing Multifocal lung tumors Non-small cell lung cancer Pathology