Cytomorphology of Non-Small Cell Lung Carcinoma (NSCLC) with Anaplastic Lymphoma Kinase (ALK) Gene Rearrangement
Adam D Toll, Peter Illei, Zahra Maleki. Johns Hopkins, Baltimore, MD
Background: ALK is a receptor tyrosine kinase demonstrating activating mutations in several malignancies including a subset (1-5%) of non-small cell lung carcinomas (NSCLC). The classic presentation is a relatively young patient with a minimal or absent smoking history, and lacking EGFR and KRAS mutations. While demonstrating resistance to both standard chemotherapy and anti-EGFR therapies, targeting ALK fusion products has demonstrated response rates above 50% in clinical studies. Prior work examining the histologic features of these tumors found a spectrum of findings, notably a solid / acinar pattern with signet-ring cells, as well as a mucinous cribriform pattern. Herein we present the first study to date describing the cytomorphology of NSCLC harboring ALK rearrangements.
Design: A retrospective database search was conducted to identify cytologic specimens of NSCLC demonstrating ALK rearrangement. Cytogenetic analysis was performed with fluorescence in situ hybridization (FISH) to evaluate ALK gene rearrangement. A total of 13 cases were identified. The following features were noted in each case: background, cytomorphology, and nuclear detail. Our control population consisted of ten cases of NSCLC not harboring ALK rearrangements, and was evaluated using the same cytomorphologic features as the study group.
Results: A total of 13 specimens from 9 patients were obtained. The average age was 50.4 years (range 28-68 yrs) with a male predominance (78%). Five patients never smoked, and four patients had a remote smoking history. All cases demonstrated moderate to poor differentiation with a predominance of single cells showing anisonucleosis and frequent intracytoplasmic neutrophils. The cells were frequently plasmacytoid with bi- and multinucleation, as well as numerous signet ring cells. The background showed necrosis and acute inflammation, as well as rare mucin. The control cases showed cells with smaller, less pleomorphic nuclei and smaller nucleoli with more clusters / tissue fragments. Intracytoplasmic neutrophils were present focally in one case. The background showed less necrosis with more mucin.
Conclusions: Several unique cytomorphologic features were consistently identified in the study population relative to the control population and include a prominence of single, markedly enlarged tumor cells with plasmacytoid features and anisonucleosis, as well as intracytoplasmic neutrophils. Larger studies are warranted to confirm our preliminary findings, as these features may help establish a more cost-effective means to select patients being tested for ALK mutational analysis.
Monday, March 4, 2013 1:00 PM
Poster Session II # 101, Monday Afternoon