Testing for Neuroendocrine Immunohistochemical Markers Should Not Be Performed in Poorly Differentiated NSCCs in the Absence of Neuroendocrine Morphologic Features according to the 2015 WHO Classification
Authors: William D. Travis, Elisabeth Brambilla, Andrew G. Nicholson
Journal: Journal of Thoracic Oncology (2016)

In contrast to the recommendations of the 2015 World Health Organization (WHO) classification of tumors,1Travis W.D. Brambilla E. Burke A.P. Marx A. Nicholson A.G. WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart.4th ed. International Agency for Research on Cancer, Lyon2015Google Scholar Derks et al. suggest that testing for neuroendocrine (NE) immunohistochemical markers should be performed on all poorly differentiated non–small cell carcinomas (NSCCs) lacking NE morphologic features and reported.2Derks J.L. Speel E.J. Dingemans A.M. An unmet need in the WHO 2015 biopsy classification: poorly differentiated NSCCs with positive neuroendocrine markers.J Thorac Oncol. 2015; 11: e25-e26Abstract Full Text Full Text PDF Scopus (6) Google Scholar We considered this suggestion in our preparation of the WHO classification, and the topic was discussed in detail. For the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society lung adenocarcinoma classification, we conducted an evidence-based review that addressed this topic specifically.3Travis W.D. Brambilla E. Noguchi M. et al.The new IASLC/ATS/ERS international multidisciplinary lung adenocarcinoma classification.J Thorac Oncol. 2011; 6: 244-285Abstract Full Text Full Text PDF PubMed Scopus (3581) Google Scholar Because there are no consistent evidence-based data in the literature to support any clinical relevance (diagnostic, prognostic, or therapeutic) of a positive NE marker in the absence of NE morphologic features, the 2015 WHO Classification recommends that testing for NE markers not be performed on all poorly differentiated NSCCs in the absence of NE morphologic features.1Travis W.D. Brambilla E. Burke A.P. Marx A. Nicholson A.G. WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart.4th ed. International Agency for Research on Cancer, Lyon2015Google Scholar This recommendation is specifically presented on page 20 of the WHO blue book,1Travis W.D. Brambilla E. Burke A.P. Marx A. Nicholson A.G. WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart.4th ed. International Agency for Research on Cancer, Lyon2015Google Scholar and this detail could not be included in the short review provided for the Journal of Thoracic Oncology.4Travis W.D. Brambilla E. Nicholson A.G. et al.The 2015 World Health Organization classification of lung tumors: impact of genetic, clinical and radiologic advances since the 2004 classification.J Thorac Oncol. 2015; 10: 1243-1260Abstract Full Text Full Text PDF PubMed Scopus (2591) Google Scholar Only if there is a suggestion of NE morphologic features is testing for NE immunohistochemical markers appropriate. In addition, the problem of NSCC with NE differentiation is addressed on page 71 of the WHO blue book, where it also stated that NE stains are not recommended for routine use in tumors lacking NE morphologic features.1Travis W.D. Brambilla E. Burke A.P. Marx A. Nicholson A.G. WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart.4th ed. International Agency for Research on Cancer, Lyon2015Google Scholar The WHO committee did not consider this problem important enough to warrant a formal title in the classification; however, the recommendation that testing for NE immunohistochemical markers in the absence of NE morphologic features not be performed in either the nonresection or resection specimen settings is important and should not be overlooked. An Unmet Need in the WHO 2015 Biopsy Classification: Poorly Differentiated NSCCs with Positive Neuroendocrine MarkersJournal of Thoracic OncologyVol. 11Issue 2PreviewIt is with great interest that we read the recent World Health Organization (WHO) Classification 2015 of lung tumors and the state-of-the-art concise review by Travis et al. published in the Journal of Thoracic Oncology.1 The diagnostic criteria for small biopsy specimens are especially interesting and clinically relevant. Full-Text PDF Open Archive