Large-cell neuroendocrine carcinoma of the lung: proposed criteria for cytologic diagnosis.

The category of large-cell neuroendocrine carcinoma (LCNEC) of the lung, proposed to expand the traditional scheme of typical carcinoid, atypical carcinoid (AC), and small-cell carcinoma (SCC), based on histologic features, has not been defined in cytology. We attempt to describe LCNEC cytologically. Cytologic features in 16 histologically confirmed LCNECs in fine-needle aspiration biopsies, cell blocks, bronchial brushes, washes, and sputum specimens stained with Diff-Quik, Papanicolaou, hematoxylin-eosin, chromogranin, and synaptophysin were analyzed. Three poorly differentiated nonsmall-cell carcinomas, 4 SCCs, and 2 atypical carcinoids were studied similarly. Twenty specimens from 16 histologically confirmed cases of LCNEC with original cytologic diagnoses including high-grade neuroendocrine carcinoma, large-cell carcinoma, nonsmall-cell carcinoma, poorly differentiated carcinoma, adenocarcinoma, and SCC, were examined. Features included flattened three-dimensional clusters with peripheral palisading, moderate to large single cells with scant (alcohol-fixed) or moderate (air-dried) cytoplasm; and large, oval, or polygonal nuclei with irregular contours, thickened nuclear membranes, and finely or coarsely granular chromatin, showing some molding and crush artifact. Nucleoli were generally present, and occasionally prominent. Mitosis and necrosis were apparent. Neuroendocrine stains were applied to all specimens, with at least one marker, commonly synaptophysin, positive in 18/20 specimens. LCNEC can be diagnosed in cytologic material, using morphology confirmed by immunocytochemistry. Treatment can be offered on the basis of cytologic examination.