Subtyping of Non-Small Cell Lung Cancer in the Era of Bevacizumab
TU Lang, PA Navarro, B Weinstein, AE Fraire, M Garcia-Moliner. Tufts Medical Center, Boston, MA; University of Massachusetts Medical School, Worcester, MA
Background: The management of advanced non-small-cell lung cancer (NSCLC) has evolved considerably in recent years with the emergence of Bevacizumab as an adjunct therapy. Bevacizumab showed overall progression-free survival benefit in Phase I & II trials for the treatment of recurrent or refractory NSCLC. However, it is not free of side effects. A reported rare complication associated with necrotic cavitated squamous cell carcinoma is major pulmonary hemorrhage. Therefore in this era, the pathologists role to accurately subtype NSCLC is critical to the appropriate use of Bevacizumab in non-squamous NSCLC.
Design: Representative H&E stained slides of 37 patients accessioned between 2001-2007 with initial fine needle aspiration (FNA) and subsequent resection of NSCLC lung tumor were retrieved. The slides were independently reviewed by 3 pathologists. Each pathologist subtyped the tumors into 5 categories: squamous, adeno, adenosquamous, undetermined/NOS or others. Statistical analysis was used to determine the degree of concordance.
Results: Our study comprised of 16 male and 21 female patients with a mean age of 65 years (range 38-82). The statistic of concordance for 3 pathologists and 5 possible outcomes was 0.31 and 0.69 for FNA and resection specimens respectively. A value of this magnitude is defined as being fair agreement for FNA specimens and substantial agreement for resection specimens. In 71% of FNA and 97.3% of resection specimens, there was unanimous agreement or only one discordant designation. 29% of FNA and 2.7% of resection specimens had two or more discordant interpretations. The correlated subtyping of FNA to resected specimen for each pathologist was 70.3%, 78.4% and 86.5%.
Conclusions: Today, pathologists face the critical task of subtyping NSCLC using FNA materials. This allows the patient to be treated with the appropriate regime and to avoid pulmonary hemorrhage. Surprisingly, the concordance rate for subtyping NSCLC on FNA materials is fair at best. Reasons attributed to high rate of discordance are diagnostic language, mixed tumor differentiation, poorly differentiated tumor, unusual tumor morphology, tumor necrosis and inflammation. Our study highlights several issues for pathologists in the current era of bevacizumab use. Is NSCLC an acceptable diagnostic category for FNA? Should bevacizumab be used in a mixed tumor with adeno and squamous features? What is the role of immunohistochemistry to distinguish the tumor on FNA materials?
Monday, March 9, 2009 1:00 PM
Poster Session II # 223, Monday Afternoon