I have been fortunate to spend my years of training in Anatomic and Clinical Pathology at Cedars-Sinai Medical Center. Prior to residency I had developed an interest in molecular genomics thanks to exposure during my undergraduate studies majoring in Biochemistry and Molecular Biology. It was only after committing to Pathology as a practice that I truly understood the awesome potential of molecular genomics. While training at CSMC I also developed a passion gastrointestinal pathology. My passion for both Molecular and GI Pathology led me to pursue fellowships in both disciplines at CSMC. Outside of work I enjoy supporting my favorite basketball team the Los Angeles Clippers, playing backgammon, and experiencing live music.
Elias Makhoul, Saleh Heneidi, Celeste Eno, Eric Vail
Cedars-Sinai Medical Center, Los Angeles, CA, USA
Introduction: High tumor mutation burden (TMB), having at least 10 mutations/megabase (mut/Mb), is reported to be as high as 42% of non small cell lung adenocarcinoma (LADC). Micropapillary adenocarcinoma is one of the most aggressive histologic subtypes of lung adenocarcinoma (LADC) and is often associated with a poor prognosis.
Methods: We performed next-generation sequencing (NGS) with and explored histologic and molecular features in 33 consecutive TMB High LADC utilizing the Ion Oncomine Comprehensive Panel Plus (OCAPlus).
Results: LADC with high tumor mutation burdens (TMBs) were more likely to display necrosis, as well as papillary and aggressive micropapillary features. Interestingly, RBM10 truncations were enriched in aggressive TMB LACD, seen in 2/2 cases of pleomorphic carcinoma and 4/7 cases with papillary or micropapillary features. BRAF class 2 mutations (non V600E) were also more likely to be seen in these aggressive tumors, identified in 5/33 cases of TMB high LADC, while no class 1 BRAF V600E mutations were observed.
Conclusions: A subset of high TMB LADC is especially aggressive, with histology including necrosis, micropapillary, and pleomorphic features. A subset of these tumors, with an especially poor overall survival rate contain either class 2 BRAF variants or truncated RBM10 mutations in 7/10 cases identified with these aggressive histologic features.