Morphologic and Molecular Features of Primary Lung Adenocarcinomas That Metastasize to Brain
Pallavi P Gopal, Christopher D Watt, Vania Aikawa, Anil Vachani, Ramesh Rengan, John Kucharczuk, Corey Langer, Steven Albelda, Vivianna VanDeerlin, Jennifer Morrissette, Michael D Feldman, Leslie A Litzky, Charuhas G Deshpande. University of Pennsylvania, Philadelphia; U Penn, Philadelphia
Background: Lung cancer, the leading cause of cancer-related deaths worldwide, has a 15% incidence of brain metastases within the first year of diagnosis. While morphologic and molecular heterogeneity occurs in lung adenocarcinomas, it is not known whether certain features predict the propensity to metastasize to the central nervous system (CNS). We hypothesize that lung adenocarcinomas which metastasize to the CNS show distinct morphologic and molecular features, when compared to those that are locoregionally confined.
Design: Primary lung adenocarcinoma resection specimen slides were retrieved (2001-2010) and studied retrospectively for morphologic differences between tumors that developed CNS metastases (n=16) and those that had locoregional spread only (n=149). The morphologic patterns of primary lung adenocarcinomas with and without brain metastases were classified according to the percentage of different morphologic patterns and then given a histologic score based on the two most predominant patterns [Am J Surg Pathol. 2010; 34(8):1155-62]. A Fischer-exact test was used to compare the morphologies of case and control groups. Adenocarcinomas that developed CNS metastases were analyzed by PCR for KRAS and EGFR mutations and by FISH for EML4-ALK translocations.
Results: Regardless of pathologic stage, lung adenocarcinomas which developed CNS metastases were more often histologic score 6 (6/16 cases) compared to control cases (3/149; p<0.001). No difference was observed between the number of histologic score 5 [(3,2) and (2,3)] cases in the CNS metastasis group (10/16) compared to control cases (91/149; p=0.6). Lung primaries which developed CNS metastases were more likely to have predominant solid/micropapillary pattern (12/16), score 5(3,2) or score 6, compared to controls (34/149; p<0.01). KRAS mutations were detected in 7 out of 16 lung adenocarcinomas with brain metastases; 4 of these 7 were KRAS G12C mutations. No EGFR mutations or EML4-ALK translocations were detected.
Conclusions: Lung adenocarcinomas which developed CNS metastases are more likely to be of higher histologic score 6(3,3) or 5(3,2), and preliminary data suggest they may be more likely to harbor KRAS mutations. The presence of a predominant solid or micropapillary pattern may morphologically predict primary lung adenocarcinomas that metastasize to the CNS, regardless of pathologic stage.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 288, Monday Morning