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

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. 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. 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. 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. 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.