[Pulmonary neuroendocrine tumors in the new WHO 2015 classification: Start of breaking new grounds?]

In the recently published 4th edition of the World Health Organization (WHO) classification of tumors of the lungs, pleura, thymus and heart, all neuroendocrine tumors of the lungs (pNET) are presented for the first time in one single chapter following adenocarcinoma and squamous cell carcinoma and before large cell carcinoma. In this classification, high grade small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) are differentiated from intermediate grade atypical carcinoids (AC) and low grade typical carcinoids as well as from preinvasive lesions (DIPNECH). In the 3rd WHO classification from 2004, which dealt with resection specimens, SCLC and carcinoids each had a separate chapter and LCNEC was previously listed in the chapter on large cell carcinoma of the lungs. The new WHO classification is for the first time also applicable to lung biopsies.

Normally, common features of all pNET are a neuroendocrine morphology (as far as detectable in small biopsies) and expression of the neuroendocrine (NE) markers (chromogranin A, synaptophysin and CD56/NCAM). An immunohistochemical positive staining of at least one NE marker was already recommended in the 3rd edition of the WHO classification (2004) only for LCNEC. Differentiating features are a small or large cell cytomorphology/histomorphology, nuclear criteria and the mitotic rate (for SCLC >10 with a median of 80, for LCNEC >10 median 70, for AC 2 - 10, for TC < 2 each per 2 mm(2)). Tumor cell necrosis usually occurs in SCLC and LCNEC, partially in AC and not in TC. The guideline Ki67 proliferation rates are given for the first time in the new WHO classification for SCLC as 50-100 %, for LCNEC 40-80 %, for AC up to 20 % and for TC up to 5 %.

Molecular alterations occur in SCLC and LCNEC in large numbers and are very variable in quality. In AC and TC they occur much less frequently and are relatively similar.

The direct comparison of all pNET in one chapter facilitates the differential diagnostics of these tumors, provides a better transparency especially of LCNEC and allows a further comprehensive development of the clinical practical and scientific evaluation of pNET. Although a separate terminology of pNET is maintained for the lungs, a careful approach towards the gastroentero-pancreatic NET (gepNET) can be observed.