Neuroendocrine Markers Insulinoma-Associated Protein 1, Chromogranin, Synaptophysin, and CD56 Show Rare Positivity in Adenocarcinoma Ex-Goblet Cell Carcinoids

Background: Adenocarcinoma ex-goblet cell carcinoid (AdexGCC) was considered a neuroendocrine adenocarcinoma, despite majority of tumor cells being negative for conventional neuroendocrine markers such as chromogranin and synaptophysin. Recently, insulinoma-associated protein 1 (INSM1) has been identified as a novel neuroendocrine marker that is more sensitive than chromogranin. synaptophysin, and CD56 in pulmonary neuroendocrine tumors. Methods: We studied this marker in conjunction with chromogranin, synaptophysin, and CD56 in 36 appendiceal AdexGCCs (21 primaries, 15 metastatic). Results: Primary AdexGCCs showed staining for INSM1, chromogranin, synaptophysin, and CD56 in 13/21 (62%), 18/21 (86%), 18/21 (86%), and 9/19 (47%) cases, respectively. However, the mean proportion of tumor cells stained for INSM1, chmmogranin, synaptophysin, and CD56 was only 8.0% (median 1%, range 0-70%), 15.7% (median 2%, range 0-70%), 19.9% (median 5%, range 0-90%), and 5.6% (median 0%, range 0-50%), respectively. Metastatic AdexGCCs showed staining for INSM1, chromogranin, synaptophysin, and CD56 in 8/15 (53%), 11/15 (73%), 12/15 (80%), and 3/14 (21%) cases. The mean proportion of tumor cells stained for INSM1, chromogranin, synaptophysin, and CD56 in metastatic tumors was 1% (median 1%, range 0-3%), 12% (median 1%, range 0-85%), 17% (median 5%, range 0-85%), and 2% (median 0%, range 0-20%), respectively. Conclusions: Primary and metastatic AdexGCCs showed no difference in INSM1, chromogranin, synaptophysin, or CD56 staining. INSM1 exhibits low expression in AdexGCCs and is expressed by a lower proportion of tumor cells compared to chromogranin and synaptophysin.