Testing of New IASLC/ATS/ERS Criteria for Diagnosis of Lung Adenocarcinoma (AD) in Small Biopsies: Minimize Immunohistochemistry (IHC) To Maximize Tissue for Molecular Studies.
James Suh, Natasha Rekhtman, Marc Ladanyi, Gregory J Riely, William D Travis. Memorial Sloan Kettering Cancer Center, New York, NY
Background: In advanced lung AD patients, recent advances have led to new therapeutic options that now require pathologists to make the distinction from squamous cell carcinoma (SQ) and non-small cell lung carcinoma (NSCLC) not otherwise specified (NOS). As 70% of lung cancer patients present in advanced stages this is a major paradigm shift for pathology diagnosis in small biopsies. A new IASLC/ATS/ERS Classification of lung adenocarcinoma provides new diagnostic criteria for small biopsies and recommends at most one AD marker or one SQ marker in tumors lacking clear AD or SQ morphology with the goal of preserving as much tissue as possible for molecular studies.
Design: Based on small biopsies from 115 patients suspected to have NSCLC all diagnoses made by one pathologist (WDT) during the past year using the new adenocarcinoma classification were reviewed. The number and type of stains utilized as well as the results of molecular testing for EGFR and KRAS mutation and EML4-ALK fusion testing by FISH were recorded.
Results: Diagnoses included: 58 AD, 13 NSCLC favor AD, 13 SQ, 8 NSCLC favor SQ, 4 NSCLC NOS (NOS), 2 NSCLC with giant cells (GC), 4 suspicious for AD (SAD), 2 metastatic breast cancer (MBC) and 1 metastatic malignant melanoma (MM). No immunostains were performed in 59 (51%) of cases as histologic classification was clear on H&E and/or the amount of tissue was so scant, all available tissue was needed for molecular testing. Positive TTF-1 in 41 AD confirmed a primary lung tumor. Negative TTF-1 in 17 cases suspected to be AD or NOS raised concern for metastasis or SQ: p63 staining in 4 of these cases confirmed SQ (n=4) while ER/PR or S100/HMB45 confirmed diagnosis of MBC (n=2) or MM (n=1). In 81 AD or Favor AD cases molecular testing was performed successfully in 72 (89%). EGFR mutations (7- Exon 19 deletion, 4- Exon 21 L858R mutation) were found in 11 (17%) KRAS mutations (8-G12C; 9-G12D; 3-G12V) in 20 (30%), and EML4-ALK fusion in 2 (3%). Both GC tested showed KRAS mutations (2-G12C). No mutations were found in 2 NOS cases.
Conclusions: Our data support that accurate diagnosis of lung AD in small biopsies can be achieved in most cases with minimal or no IHC rather than by using panels of multiple AD and SQ IHC markers. This aids in strategic management of tissue to maximize tissue available for molecular studies. This strategy results in a high yield (89%) of successful molecular testing.
Monday, February 28, 2011 2:15 PM
Platform Session: Section E, Monday Afternoon