Probable hereditary familial overlap syndrome with multiple synchronous lung tumors.
Here we report a case of a young, never-smoker Hispanic woman with a hereditary familial overlap syndrome (Li-Fraumeni plus CDH1). The patient developed multiple synchronous primary lung adenocarcinomas related to Intra-Alveolar Tumor Spread (STAS) several years after the diagnosis of a locally advanced lower limb osteosarcoma. Comprehensive genomic profiling by next generation sequencing (NGS) was performed on 90 cancer-related genes over each lung lesion (including two nodules of acinar adenocarcinoma, one lepidic spread tumor and in the STAS area). Likewise, the broad genomic analysis was performed on archival tissue from the previous bone tumor. Lung tumors were found to harbor PIK3CA (invasive lesions) and a rare in-frame insertion of nucleotides in exon 19 of EGFR (lepidic tumor). STAS area showed KRAS and BRAF mutations in two different segments, and osteosarcoma tested positive for well known PIK3CA, KRAS and CDH1 alterations. This unique case raises practical questions as to the challenges of molecular testing and highlights the potential association of germline TP53 and CDH1 mutations with concurrent somatic alterations that elucidate the basis of tumor heterogeneity.
['Cardona|Andrés F|AF|', 'Zatarain-Barrón|Zyanya Lucia|ZL|', 'Rubio|Cladelis|C|', 'Martínez|Stella|S|', 'Ruiz-Patiño|Alejandro|A|', 'Ricaurte|Luisa|L|', 'Serna|Adriana|A|', 'Barrios|Rodolfo|R|', 'Garzón|Juan Carlos|JC|', 'Navarrete|Constanza|C|', 'Balaguera|Alberto|A|', 'Corrales|Luis|L|', 'Rojas|Leonardo|L|', 'Arrieta|Oscar|O|']
D000230:Adenocarcinoma D000328:Adult D015703:Antigens, CD D015820:Cadherins D058534:Class I Phosphatidylinositol 3-Kinases D066246:ErbB Receptors D005260:Female D059014:High-Throughput Nucleotide Sequencing D006801:Humans D016864:Li-Fraumeni Syndrome D008175:Lung Neoplasms D009154:Mutation D009378:Neoplasms, Multiple Primary D048493:Proto-Oncogene Proteins B-raf D016283:Proto-Oncogene Proteins p21(ras) D055815:Young Adult
Osteosarcoma Familial cancer syndrome Li fraumeni Lung cancer