Orthopedia homeobox protein (OTP) is a sensitive and specific marker for primary pulmonary carcinoid tumors in cytologic and surgical specimens

Abstract

Orthopedia homeobox protein (OTP) was recently demonstrated to be a pulmonary neuroendocrine marker showing specificity for pulmonary carcinoid tumors in histologic sections. Little is known of OTP performance and specificity for pulmonary neuroendocrine tumors in lung fine-needle aspiration (FNA) cell blocks (CBs), however. We evaluated OTP expression in lung non-neuroendocrine and neuroendocrine tumor CBs to determine its diagnostic utility in these specimens. Pulmonary typical carcinoid (TC) and atypical carcinoid (AC), small-cell lung cancer (SCLC) and large-cell neuroendocrine carcinoma (LCNEC), and squamous cell carcinoma (SQ) and adenocarcinoma (ADC) CBs were retrieved along with matched surgical cases and assessed for nuclear OTP expression with immunohistochemistry. Nuclear OTP was seen in 82% TCs (9 of 11) and 83% ACs (10 of 12), but not in SCLC (0 of 9), LCNEC (0 of 9), SQ (0 of 10) or ADC (0 of 6) cytology cases. Similar to the cytologic specimens, nuclear OTP was seen in 82% TCs (9 of 11) and 80% ACs (8 of 10) but in none of the SCLC (0 of 8), LCNEC (0 of 7), SQ (0 of 8) or ADC (0 of 6) resections. Both AC and TC CBs showed a similar percentage of cells expressing nuclear OTP. By contrast, in resection specimens, 30% ACs (3 of 10) compared with 73% TC (8 of 11) cases showed >40% of cells nuclear OTP staining. Nuclear OTP demonstrated 80-83% sensitivity and 100% specificity for pulmonary carcinoid tumors in cytology and surgical specimens. In the context of pulmonary malignancies, nuclear OTP immunohistochemistry is highly sensitive and specific in distinguishing carcinoid tumors from other pulmonary neuroendocrine and non-neuroendocrine malignancies in cytologic and surgical specimens.