50. Personalized medicine in practice: Comprehensive cytogenomic profiling of a lung adenocarcinoma leads to re-classification of a concurrent lymphoma

Abstract

Through the use of comprehensive genomic characterization, a personalized medicine approach has the potential to improve diagnosis, ameliorate prognostication and identify actionable molecular alterations. Herein, we describe a 77-year old patient under surveillance for untreated CLL, diagnosed via flow cytometry and further characterized by cytogenetic and molecular studies. In a peripheral blood specimen, FISH analyses identified trisomy 12 in 77% of nuclei and loss of TP53 in 9% of nuclei and was negative for all other markers tested including: loss of 13q14 and/or ATM and IGH-CCND1 rearrangement. Concurrent molecular studies detected a TP53 p.V157F mutation. PET-CT scan for surveillance of patient's CLL incidentally identified multiple bilateral pulmonary nodules, concerning for primary lung cancer. A pulmonary wedge resection confirmed the presence of a lung adenocarcinoma which was profiled using a targeted Next-Generation Sequencing (NGS) panel. This analysis revealed an actionable EGFR mutation (in frame exon 19 deletion), two TP53 mutations (p.P152Q and p.V157F) as well as an IGH-CCND1 rearrangement. Follow-up immunohistochemistry (IHC) studies performed on the intrapulmonary nodules showed positive staining for cyclin D1 (CCND1) and negative staining for SOX11. Together, the presence of the TP53 p.V157F in the lung resection, IGH-CCND1 rearrangement and IHC positivity for CCND1 were most suggestive of an infiltration of an extra-nodal mantle cell lymphoma (MCL) within the lung adenocarcinoma. Genomic characterization of this tumor led to the identification of a CCND1-IGH rearrangement, pathognomonic of MCL, which was misdiagnosed at the onset of the disease due to a cytogenetically cryptic event. This led to the re-evaluation of the patient's heme disorder which was reclassified as a CCND1-positive, SOX11-negative indolent MCL. This further highlights the importance of holistic genomic characterization for accurate classification of neoplasms and disease management.