Neuroendocrine (NE) neoplasms of the lung are a spectrum of tumors including typicalcarcinoid (TC), atypical carcinoid tumor (ACT), small cell lung carcinoma (SCLC), and large cell NEcarcinoma (LCNEC). Given the overlapping features within these tumors, misclassification is a known risk, with significant treatment consequences.
A search of the pathology archives from The Johns Hopkins Hospital yielded 390 cases of TC diagnosed over 20 years. Sixty-three cytology cases with corresponding surgical material were identified. The cytology specimens were comprised of 49 cases of lung fine-needle aspiriation specimens and 14 cases of lung brushings/washings.
Among 63 paired cases, 32 cases (51%) demonstrated concordant and 31 cases (49%) demonstrated discordant diagnoses. Among discordant cases, the most notable findings included overdiagnosis of TC as SCLC (4 cases; 6%), ACT (4 cases; 6%), and poorly differentiated carcinoma with NE features (5 cases; 8%) as well as misdiagnosis of other lesions as TC (4 cases; 6%) on cytology.
The significant morphologic factors for distinguishing low-grade TC from ACT, SCLC, or carcinoma remain the critical evaluation of nuclear features, chromatin patterns, and assessment of nucleoli. Nuclear molding and crowding are not discernible features because they may be found on smears with increased cellularity. Crush artifact can occur in both low-grade and high-grade NE neoplasms and may cause a misinterpretation of SCLC. Other artifacts resulting from delayed fixation or poor processing and sampling error are potential causes of incorrect interpretations. Ki-67 staining may be useful in difficult cases.