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, chromogranin, 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.