Distinguishing carcinoid tumor from small cell carcinoma of the lung: correlating cytologic features and performance in the College of American Pathologists Non-Gynecologic Cytology Program.

CONTEXT: The cytologic features of carcinoid tumor of the lung are well described. Nevertheless, some carcinoids may be difficult to distinguish from small cell carcinomas.
OBJECTIVE: To correlate the cytologic features of individual cases of carcinoid tumor of the lung in fine-needle aspiration specimens in the College of American Pathologists Non-Gynecologic Cytology Program with the frequency of misclassification as small cell carcinoma.
DESIGN: We reviewed 1100 interpretations from 26 different cases of carcinoid tumor in lung fine-needle aspiration specimens in the College of American Pathologists Non-Gynecologic Cytology Program and correlated the cytologic features with the performance in the program.
RESULTS: Cases were divided into those that were frequently misclassified as small cell carcinoma (at least 20% of the responses, 19 cases) and those that were infrequently misclassified as small cell carcinoma (<10% of all responses, 7 cases). All cases had areas with classic features of carcinoid tumor. Cases were reviewed independently by 3 cytopathologists specifically looking for cytologic features that might be responsible for misclassification as small cell carcinoma. All 7 cases that were infrequently misclassified consisted of numerous monotonous well-preserved tumor cells that were either entirely round or were a mixture of round and spindle-shaped cells. Six of 7 cases showed a prominent streaming vascular pattern with tumor cells attached to the endothelial cell core. In contrast, cases that were frequently misclassified had 1 of 6 patterns that were not seen in cases that were rarely misclassified. These 6 patterns were: (1) poorly preserved and pale-staining cells with fine chromatin and a suggestion of molding (5 cases); (2) numerous large, well-preserved, spindle-shaped cells (2 cases); (3) numerous cells varying markedly in both size and shape (both round and spindle-shaped cells), with a common finding of degenerated, smudgy, small round and spindle-shaped cells (9 cases); (4) hypocellular specimens (8 cases); (5) obscuration of cells by blood (2 cases); and (6) tumor cells present predominantly in groups, with few isolated cells (8 cases). In none of these cases were mitoses or true necrosis identified.
CONCLUSIONS: Frequent misclassification of carcinoid tumor as small cell carcinoma in lung fine-needle aspiration specimens in this program correlates strongly with specific cytologic features, some of which are common in small cell carcinoma (fine chromatin, molding, smudgy chromatin) and others that are not (spindle-shaped cells). In addition, hypocellular specimens or specimens with cellular obscuration performed poorly, along with specimens exhibiting absence of the commonly described carcinoid feature of streaming vascularity. Awareness of these patterns may aid in avoiding misdiagnosis.