Insulinoma-associated protein-1 (INSM-1) is a useful diagnostic marker for the evaluation of primary thymic neuroendocrine neoplasms: an immunohistochemical study of 27 cases.

Insulinoma-associated protein 1 (INSM1) immunohistochemistry has been established as a sensitive and reliable immunohistochemical marker for detecting neuroendocrine differentiation in tumors across various organ systems. However, this marker has not been adequately investigated in primary thymic neuroendocrine tumors. We have studied a series of 27 cases of primary neuroendocrine carcinomas of the thymus, including 3 typical carcinoids, 18 atypical carcinoids, 4 large cell neuroendocrine carcinomas, and 2 small cell carcinomas. Immunostaining on whole tissue sections for INSM-1 was evaluated. Results of immunostaining for chromogranin and synaptophysin were also evaluated. 26/27 tumors (96%) demonstrated nuclear positivity for INSM1. 18 tumors (67%) showed strong and diffuse nuclear staining (3 +), 3 tumors (11%) moderate (2 +) nuclear staining, and 5 tumors (19%) showed weak (1 +) nuclear staining. The average percentage of tumor cells positive for INSM1 was 76%. Only one tumor, a small cell carcinoma, was negative. All tumors were positive for synaptophysin, and 26/27 (96%) were positive for chromogranin A. This study confirms that INSM1 immunohistochemistry is a sensitive marker of neuroendocrine differentiation in primary thymic neuroendocrine neoplasms and demonstrates similar performance characteristics compared to other organ systems. The nuclear staining with this marker offers the advantage of eliminating some of the ambiguity in the interpretation sometimes encountered with other markers. An added advantage is the consistent staining across the entire spectrum of neuroendocrine tumors of this organ.