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INSM1 Demonstrates Superior Performance to the Individual and Combined Use of Synaptophysin, Chromogranin and CD56 for Diagnosing Neuroendocrine Tumors of the Thoracic Cavity

Rooper, Lisa M. MD*; Sharma, Rajni PhD*; Li, Qing Kay MD, PhD*; Illei, Peter B. MD*; Westra, William H. MD*,†,‡

The American Journal of Surgical Pathology: November 2017 - Volume 41 - Issue 11 - p 1561–1569
doi: 10.1097/PAS.0000000000000916
Original Articles
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Despite the importance of recognizing neuroendocrine differentiation when diagnosing tumors of the thoracic cavity, the sensitivity of traditional neuroendocrine markers is suboptimal, particularly for high-grade neuroendocrine carcinomas such as small cell lung carcinoma and large cell neuroendocrine carcinoma. To increase sensitivity, neuroendocrine markers are routinely ordered as panels of multiple immunostains where any single positive marker is regarded as sufficient evidence of neuroendocrine differentiation. Insulinoma-associated protein 1 (INSM1) is a well-validated transcription factor of neuroendocrine differentiation that has only recently been evaluated for diagnostic use. We performed INSM1 immunohistochemistry on a large series of thoracic neuroendocrine and non-neuroendocrine tumors and compared its performance to synaptophysin, chromogranin, and CD56. INSM1 was positive in 94.9% of small cell lung carcinomas and 91.3% of large cell neuroendocrine carcinomas, compared with 74.4% and 78.3% with the combined panel of traditional markers. INSM1 also stained all (100%) of the atypical carcinoids, typical carcinoids and mediastinal paragangliomas, but only 3.3% of adenocarcinomas and 4.2% of squamous cell carcinomas. Overall, INSM1 demonstrated a sensitivity of 96.4% across all grades of thoracic neuroendocrine tumors, significantly more than the 87.4% using the panel of traditional markers (P=0.02). INSM1 is sufficiently sensitive and specific to serve as a standalone first-line marker of neuroendocrine differentiation. A more restrained approach to immunohistochemical analysis of small thoracic biopsies is appropriate given the expanding demand on this limited material for therapeutic biomarker analysis.

Departments of *Pathology

Oncology

Otolaryngology, The Johns Hopkins University School of Medicine, Baltimore, MD

A portion of this data was presented in abstract form at the 2017 USCAP Annual Meeting in San Antonio, TX.

Conflicts of Interest and Source of Funding: Supported by the Joseph C. Eggleston Award in Surgical Pathology at The Johns Hopkins Hospital. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Correspondence: Lisa M. Rooper, MD, The Johns Hopkins Medical Institutions, 401 N. Broadway, Weinberg 2249, Baltimore, MD 21231-2410 (e-mail: rooper@jhmi.edu).

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