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.
Dr. Hughes, a member of the CAP Cytopathology Committee, is with Laboratory Medicine Consultants Ltd., Las Vegas