Kartik Viswanathan1, Momin T Siddiqui2, Alain C Borczuk2. 1. Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York. Electronic address: kav2009@nyp.org. 2. Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York.
Abstract
INTRODUCTION: Insulinoma-associated protein 1 (INSM1) is an immunohistochemical marker for neuroendocrine differentiation with potentially superior sensitivity and specificity. INSM1 performance in pulmonary cytology cell block material (CB) has not been well established, and large series demonstrating its performance have been few. MATERIALS AND METHODS: Typical and atypical carcinoid, small cell lung carcinoma, and large cell neuroendocrine carcinoma, squamous cell carcinoma, and adenocarcinoma CBs and 563 surgical specimens comprising 17 typical carcinoid, 14 atypical carcinoid, 8 small cell lung carcinoma, 10 large cell neuroendocrine carcinoma, 58 squamous cell carcinoma, 415 adenocarcinoma, and 17 large cell carcinoma cases and 24 other tumor types were immunostained with INSM1, CD56, synaptophysin, and chromogranin A. RESULTS: The INSM1 sensitivity, specificity, positive predictive value, and negative predictive value were 92.3%, 100%, 78.9%, and 99% in the CBs and 89.8%, 98.1%, 81.5%, and 99% in the surgical specimens, respectively, with 86.2% concordance. The sensitivity, specificity, positive predictive value, and negative predictive value for the other neuroendocrine markers were 97.4%, 93.3%, 97.4%, and 93.3% in the CBs and 93.9%, 93.6%, 58.2%, and 99.4% in the surgical specimens for CD56; 89.7%, 100%, 100%, and 75% in the CBs and 93.4%, 91.2%, 50.5%, and 99.4% in the surgical specimens for synaptophysin; 66.7%, 100%, 100%, and 53.6% in the CBs and 75.5%, 98.6%, 84.1%, and 97.7% in the surgical specimens for chromogranin A, respectively. Finally, INSM1, together with CD56, maximized the sensitivity to 100% with 93.3% specificity in the CBs. CONCLUSIONS: The results from our study have further established the high sensitivity and specificity of INSM1 in the largest pulmonary cytologic and surgical cohorts to date. INSM1 either matched or outperformed the performance of existing neuroendocrine markers, and its combination with CD56 appeared to maximize test performance.
INTRODUCTION:Insulinoma-associated protein 1 (INSM1) is an immunohistochemical marker for neuroendocrine differentiation with potentially superior sensitivity and specificity. INSM1 performance in pulmonary cytology cell block material (CB) has not been well established, and large series demonstrating its performance have been few. MATERIALS AND METHODS: Typical and atypical carcinoid, small cell lung carcinoma, and large cell neuroendocrine carcinoma, squamous cell carcinoma, and adenocarcinoma CBs and 563 surgical specimens comprising 17 typical carcinoid, 14 atypical carcinoid, 8 small cell lung carcinoma, 10 large cell neuroendocrine carcinoma, 58 squamous cell carcinoma, 415 adenocarcinoma, and 17 large cell carcinoma cases and 24 other tumor types were immunostained with INSM1, CD56, synaptophysin, and chromogranin A. RESULTS: The INSM1 sensitivity, specificity, positive predictive value, and negative predictive value were 92.3%, 100%, 78.9%, and 99% in the CBs and 89.8%, 98.1%, 81.5%, and 99% in the surgical specimens, respectively, with 86.2% concordance. The sensitivity, specificity, positive predictive value, and negative predictive value for the other neuroendocrine markers were 97.4%, 93.3%, 97.4%, and 93.3% in the CBs and 93.9%, 93.6%, 58.2%, and 99.4% in the surgical specimens for CD56; 89.7%, 100%, 100%, and 75% in the CBs and 93.4%, 91.2%, 50.5%, and 99.4% in the surgical specimens for synaptophysin; 66.7%, 100%, 100%, and 53.6% in the CBs and 75.5%, 98.6%, 84.1%, and 97.7% in the surgical specimens for chromogranin A, respectively. Finally, INSM1, together with CD56, maximized the sensitivity to 100% with 93.3% specificity in the CBs. CONCLUSIONS: The results from our study have further established the high sensitivity and specificity of INSM1 in the largest pulmonary cytologic and surgical cohorts to date. INSM1 either matched or outperformed the performance of existing neuroendocrine markers, and its combination with CD56 appeared to maximize test performance.