Pulmonary Large Cell Carcinoma Is Clinicopathologically and Molecularly Similar to Solid Subtype Adenocarcinoma
David H Hwang, Anthony S Perry, Lynette M Sholl. Brigham and Women's Hospital, Boston, MA; Banner MD Anderson Cancer Center, Gilbert, AZ
Background: Accurate histologic subtyping of non small cell lung carcinoma is critical to clinical management. According to the World Health Organization (WHO), large cell carcinoma (LCC) encompasses tumors that are not readily diagnosed as adenocarcinoma (ACA) or squamous cell carcinoma on morphologic grounds; however, the diagnosis of LCC can lead to confusion when it comes to triaging for molecular analysis. We have noted a high degree of morphologic similarity between solid-predominant ACA and many tumors diagnosed as LCC. This study compares the clinicopathologic and molecular features of solid ACA and LCC.
Design: Cases diagnosed as LCC or solid ACA on pulmonary resection specimens (excluding biopsies) were retrieved from the pathology department archives from 2000-2012. Diagnoses were confirmed following review of H&E, mucicarmine, and TTF-1 and P63 immunohistochemistry (IHC) stains. Tumors with solid growth and lack of squamous or neuroendocrine differentiation were included. Distinction between solid ACA and LCC was made according to WHO criteria (≥ 5 intracellular mucin droplets in at least 2 HPF for solid ACA). Targeted genotyping was performed for KRAS codons 12-13 and EGFR L858R and exon 19 deletions, and FISH and/or IHC (clone D5F3) for ALK rearrangement. Patient outcomes were derived from the electronic medical record following approval from the hospital institutional review board.
Results: 29 solid ACA and 30 LCC were included. There was no difference in the ratio of female patients (56 v 52%), median age (60 v 66), stage at diagnosis (64 v 69% were stage I) and percent smokers (96 v 97%) between solid ACA and LCC cohorts, respectively. Other than the presence or absence of mucin droplets, the dominant pathology in both groups was similar, with solid nests of polygonal cells with moderate cytoplasm, frequent clear cell change, vesicular chromatin, and prominent nucleoli. KRAS was mutated in 32% of solid ACA versus 41% of LCC (p = 0.5); 55% of KRAS mutations were G12C. No EGFR mutations were identified. One ALK rearrangement was detected in the solid ACA group. Risk of progression at 5 years was 21% for solid ACA v 27% for LCC (p=0.76).
Conclusions: LCC (without neuroendocrine features) appears to be morphologically, molecularly, and clinically indistinguishable from solid-subtype ACA. These tumors occur in smokers and have a preponderance of smoking-associated KRAS mutations. We propose that these tumors be reclassified as mucin-poor solid adenocarcinomas.
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 288, Monday Morning