PURPOSE:The aim of this study was to determine the utility of cytology and a fluorescence in situ hybridization (FISH) reflex assay for the detection of primary lung carcinoma in peripheral lung nodules.
METHODS:Bronchial brushing specimens were collected between June 2006 and March 2008 as part of clinical practice for cytology and FISH testing from 172 patients with an indeterminate peripheral nodule. Nineteen specimens were excluded from analysis due to the absence of clinical follow-up (N=2), a biopsy diagnosis of metastases to lung (N=8), lymphoma (N=7) or carcinoid tumor (N=2). Due to the high specificity of positive cytology diagnoses, FISH was not performed on cytology specimens diagnosed as positive. FISH testing with the LaVysionÖ (Abbott Molecular Inc. Des Plaines, IL) probe set was performed on residual specimen from the remaining samples diagnosed as negative or equivocal by cytology. FISH was positive if ≥5 cells demonstrated gains of two or more loci/chromosomes. Pathology confirmation and/or clinical indication of disease progression were considered evidence of malignancy.
RESULTS:Cytology with FISH reflex (Cyto+FISH) was more sensitive (54% vs. 24%; P<0.001) than cytology alone in all patients while the specificity of Cyto+FISH was similar to cytology alone (95% vs. 100%; P=0.13). The sensitivity of Cyto+FISH was significantly higher than cytology alone in patients with nodules <2 cm (n=53; 45% vs. 5%; P<0.005) and in patients with nodules >2cm (n=100; 57% vs. 30%; P<0.001) while there was no significant difference in specificity among the two groups. The positive predictive value (PPV) of Cyto+FISH was 91%, 69% and 100% for all patients, nodules <2 cm and >2cm, respectively, while the PPV of cytology alone was 100% for all categories.
CONCLUSION:FISH is a useful adjunctive test for detecting primary lung carcinoma in peripheral lung lesions when used with routine cytology.
CLINICAL IMPLICATIONS:The increase in diagnostic yield of Cyto+FISH is similar to new bronchoscopic techniques without need for additional equipment or invasive testing. Studies are needed to better define the clinical utility of this reflex assay.
DISCLOSURE:Otis Rickman, Grant monies (from industry related sources) Dr. Kevin Halling and the Department of Anatomic Pathology, Mayo Clinic receive grant support from Abbott Molecular Inc. for the development of FISH probe sets.; Other Dr. Kevin Halling receives royalties from the sale of the LaVysion probe set discussed in this study.; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. The LaVysion probe set used in this study is considered an Analyte Specific Reagent and is not approved by the FDA. The performance characteristics of this assay were developed and validated by the Mayo Clinic.