Distinguishing Small Cell Carcinoma From Non–Small Cell Carcinoma of the Lung: Correlating Cytologic Features and Performance in the College of American Pathologists Non-Gynecologic Cytology Program

Abstract Context.—The cytologic features of small cell carcinoma of the lung are well described. Nevertheless, some small cell carcinomas may be difficult to reproducibly distinguish from non–small cell carcinomas, and this distinction carries significant clinical importance. Objective.—To correlate the cytologic features of individual cases of small cell carcinoma of the lung in fine-needle aspiration specimens from the College of American Pathologists Non-Gynecologic Peer Comparison Cytology Program with the frequency of misclassification as non– small cell carcinoma. Design.—We reviewed 1185 interpretations of 23 different cases of small cell carcinoma in lung fine-needle aspiration specimens and correlated the cytologic features noted in these cases with performance in the program. Results.—Cases were divided into those that were frequently misclassified as non–small cell carcinoma (at least 10% of the responses, 11 cases) and those that were infrequently misclassified as non–small cell carcinoma (<5% of all responses, 12 cases). All cases had areas on the slides with classic features of small cell carcinoma. However, 10 of 11 cases that were frequently misclassified as non–small cell carcinoma had cells with either increased cytoplasm (4 cases), cytoplasmic globules (so-called paranuclear blue bodies) (3 cases), or apparent intracytoplasmic lumina (3 cases). These features were not identified in cases that were infrequently misclassified (P = .005). In addition, cases more frequently misclassified as non–small cell carcinoma tended to show better overall cellular and group preservation. Conclusions.—Frequent misclassification of small cell carcinoma as non–small cell carcinoma in lung fine-needle aspiration specimens in this program correlates strongly with the presence of cytoplasmic features that may suggest non–small cell carcinoma or with the presence of paranuclear blue bodies. Misclassification in this program may reflect a variety of factors, including the variation in the cytologic features of individual cases, but also the lack of wide recognition that some features of non–small cell carcinoma may also be noted in well-preserved cases of small cell carcinoma.