Insulinoma‐associated protein 1 is a sensitive and specific marker of neuroendocrine lung neoplasms in cytology specimens

BACKGROUND Recent studies suggest that insulinoma‐associated protein 1 (INSM1) is a sensitive and specific marker of neuroendocrine neoplasms. The aims of this study were to determine whether INSM1 can be reliably used in cytology (Cellient) cell blocks, to ascertain whether staining correlates with paired surgical pathology specimens, and to compare its sensitivity and specificity with those of synaptophysin (SYN), chromogranin (CHR), and CD56 for neuroendocrine lung tumors. METHODS Seventy‐four primary lung neoplasms diagnosed on cytology were stained with INSM1, SYN, CHR, and CD56: 41 small cell lung carcinomas (SCLCs), 1 large cell neuroendocrine carcinoma (LCNEC), 10 carcinoid tumors, 11 adenocarcinomas, 9 squamous cell carcinomas, 1 mesothelioma and 1 poorly differentiated non–small cell lung carcinoma, not otherwise specified. In 20 cases, a paired surgical pathology specimen was also stained with INSM1. RESULTS INSM1 was positive in 48 of 52 primary lung neuroendocrine neoplasms (92%), including 38 of 41 SCLCs (93%), the only LCNEC (100%), and 9 of 10 carcinoid tumors (90%), and it was negative in all 22 non‐neuroendocrine primary lung tumors. For SCLC, the sensitivity of INSM1 (93%) was lower than the sensitivity of CD56 (100%), equal to the sensitivity of SYN (93%), and higher than the sensitivity of CHR (35%). For carcinoid tumors, the sensitivity of INSM1 (90%) was lower than the sensitivity of all other markers (100% each). The specificity of INSM1 for neuroendocrine neoplasms as a group was 100%. INSM1 staining was concordant with surgical pathology specimens in all 20 paired cases. CONCLUSIONS INSM1 can be used in cytopathology cell blocks, and it is sensitive and highly specific for neuroendocrine lung tumors. INSM1 staining in cytology cell blocks correlates well with surgical pathology specimens. Cancer Cytopathol 2018;126:243‐52. © 2018 American Cancer Society. Insulinoma‐associated protein 1, a nuclear marker of neuroendocrine neoplasms, can be reliably used in Cellient cell blocks from lung tumors, and it combines high sensitivity (slightly less than the sensitivity of CD56) with high specificity (similar to the specificity of chromogranin). Insulinoma‐associated protein 1 staining in cytology cell block samples correlates well with corresponding surgical pathology specimens.