Cytomorphologic Criteria for the Distinction of Pulmonary Adenocarcinoma and Squamous Cell Carcinoma
Carlie S Sigel, Priscila Andrade, Maria A Friedlander, Andre L Moreira, Maureen F Zakowski, William D Travis, Natasha Rekhtman. Memorial Sloan-Kettering Cancer Center, New York, NY
Background: Accurate distinction of lung adenocarcinoma (ADC) and squamous cell carcinoma (SQCC) is essential for the selection of patients for novel targeted therapies. While the distinction between well-differentiated SQCC and ADC is usually straightforward, classification of moderately and poorly differentiated (M-PD) carcinomas can be a challenge. We tested 20 cytologic features for sensitivity/specificity in distinguishing histologically-proven M-PD ADC and SQCC, and assessed the causes of diagnostic difficulties.
Design: We selected 70 lung cytology samples with a subsequent resection diagnosis of M-PD ADC or SQCC. Of these, 40 cases had "diagnostic" cytomorphology, whereas 30 cases were "difficult" in that they required immunocytochemical stains or were misclassified. Scored features of SQCC included keratinization, keratin rings, intercellular bridges, ghost cells, cell streaming, sharp cell borders, spindle cells, dense cytoplasm, dark coarse chromatin, pearl-like cell arrangements, stratified cell groups, frayed group edges, and extensive necrosis; of ADC: three-dimensional (3-D) cell balls, flat honeycombs, picket-fences, fine chromatin, prominent nucleoli, eccentric nuclei, and vacuolated cytoplasm. The distribution of these features was compared in ADC vs SQCC and “diagnostic” vs “difficult” groups.
Results: All features, except dense cytoplasm, were differentially distributed in ADC vs SQCC (p=0.005 - p<0.0001). Only 3 features were entirely specific for SQCC: cytoplasmic keratinization, keratin rings, and intercellular bridges, but none of these features was highly sensitive (56%, 67%, and 36%, respectively). The only entirely specific feature for ADC was flat honeycombs, and this feature was also highly sensitive (94%). Features with specificity >90% were ghost cells for SQCC, and 3-D cell balls and picket fences for ADC. The features associated with diagnostic difficulties in ADC were cell streaming (p=0.002) and sharp cell borders (p=0.0134); and for SQCC: eccentric nuclei (p=0.009) and fine chromatin (p=0.0006).
Conclusions: Many cytomorphologic features widely regarded as diagnostic or highly characteristic for distinguishing ADC vs SQCC are not entirely specific and represent potential diagnostic pitfalls. The ADC-like morphology of M-PD SQCC is well known, and is confirmed here. We also identified “squamoid” features of some M-PD ADC as a cause of diagnostic difficulty. Recognition of these features of overlap should trigger a work-up with immunocytochemistry to determine the line of differentiation.
Wednesday, March 21, 2012 1:00 PM
Poster Session VI # 78, Wednesday Afternoon