Distinguishing carcinoid tumor from small
  cell carcinoma of the lung

October 2005
PAP/NGC Programs Review

Jonathan H. Hughes, MD, PhD

Carcinoid tumor and small cell carcinoma both belong to the general category of neuroendocrine lung tumors. It is important to distinguish these two types of tumor from one another because the prognosis and treatment for them are very different. Although the cytomorphologic features of carcinoid tumor and small cell carcinoma are well described, data generated from the CAP nongynecologic cytology program indicate that over-diagnosis of carcinoid tumor as small cell carcinoma is a common interpretative error among the program participants.

In a recent article, Andrew A. Renshaw and colleagues studied the ability of CAP nongyn program participants to distinguish cases of carcinoid tumor from small cell carcinoma and attempted to identify the cytologic features that led to interpretative errors (Renshaw AR, Haja J, Lozano RL, Wilbur DC. 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. Arch Pathol Lab Med. 2005;129:614–618). The investigators reviewed 1,100 interpretations from 26 different cases of carcinoid tumor in lung fine-needle aspiration specimens in the nongyn program. The cases were divided into those that were frequently misclassified as small cell carcinoma (at least 20 percent of the responses, 19 cases) and those that were infrequently misclassified as small cell carcinoma (<10 percent of responses, seven cases). The cases were independently reviewed by three cyto pa thol ogists, who looked specifically for cytologic features that might be responsible for misclassification. All seven cases of carcinoid tumor that were infrequently misclassified as small cell carcinoma 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 these seven cases showed a prominent streaming vascular pattern with tumor cells attached to the endothelial cell core. In contrast, cases that were frequently misclassified as small cell carcinoma had one of six patterns that were not seen in cases that were rarely misclassified. These six patterns were: (1) poorly preserved and pale-staining cells with fine chromatin and a suggestion of molding (five cases); (2) numerous large, well-preserved, spindle-shaped cells (two cases); (3) numerous cells varying markedly in size and shape (both round and spindle-shaped cells), with a common finding of degenerated, smudgy, small round and spindle-shaped cells (nine cases); (4) hypocellular specimens (eight cases); (5) obscureness of cells by blood (two cases); and (6) tumor cells present predominantly in groups, with few isolated cells (eight cases). In none of these cases were mitoses or true necrosis identified.

The results of Renshaw’s study strongly suggest that there are specific patterns found in some cases of carcinoid tumor that are rarely misclassified as small cell carcinoma and other patterns that are more commonly misinterpreted as small cell carcinoma. Specifically, cases with numerous monotonous and well-preserved round, or round and spindle, cells were rarely misclassified. In addition, cases having the typical streaming pattern of vessels and attached tumor cells well represented within the aspirated material were also infrequently misclassified. In contrast, cases with large spindle cells, even when well preserved, were found to be commonly misinterpreted as small cell carcinoma. Recognizing and paying close attention to these features should improve overall accuracy in the diagnosis of carcinoid tumor in lung FNA specimens.