Pulmonale neuroendokrine Tumoren in der neuen WHO-Klassifikation 2015

Abstract

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.

Comparative evaluation of three proliferation markers, Ki-67, TOP2A, and RacGAP1, in bronchopulmonary neuroendocrine neoplasms: Issues and prospects

“…The distinction between the four BP-NEN entities is clinically very important because the subsequent classification-based diagnostic and therapeutic approaches differ due to their differential aggressiveness [3, 5, 6, 29, 30]. Mitosis counting is part of the classification procedure (based on the WHO and IASLC criteria); it is a very time-consuming process, and has a relatively high inter-observer variability [6, 8, 9].…”

“…Therefore, one aim of our study was to reevaluate Ki-67 expression in the tumor samples of a large cohort of BP-NEN patients. The different methods routinely used in clinical practice for the determination of Ki-67 expression levels were compared in this context [5, 12]. …”

“…This relationship is particularly true in the well-industrialized northern hemisphere, where lung cancer comprises 20–25% of the malignancies of neuroendocrine origin. The 2015 WHO classification system (first proposed in 1998 by Travis et al [1]) classifies these bronchopulmonary neuroendocrine neoplasms (BP-NEN) into the less aggressive, well-differentiated, and low-grade typical carcinoids (TC), the intermediate-grade atypical carcinoids (AC), and the poorly-differentiated and aggressive large cell neuroendocrine lung carcinomas (LCNEC) and small cell lung cancers (SCLC) [1–5]. Correct diagnostic classification of these four tumor entities is of major clinical importance because the prognostic, diagnostic, and therapeutic consequences differ greatly between them.…”

“…Correct diagnostic classification of these four tumor entities is of major clinical importance because the prognostic, diagnostic, and therapeutic consequences differ greatly between them. The current grading system for NEN of the lung and thymus is based on WHO and International Association for the Study of Lung Cancer (IASLC) criteria: The grade is mainly determined by counting the number of mitotic figures in 10 high-power fields (HPFs) in combination with the presence or absence of necrosis [5, 6]. Counting mitoses is a very time-consuming process with a high inter-observer variability and cytomorphological overlap among the BP-NEN entities is not uncommon.…”

“…A uniform evaluation system (manual counting, eyeballing, digital image analysis), inter-observer variability of manual immunohistochemical evaluation, and the correct cut-off values to distinguish the BP-NEN entities are issues for further study [8, 9, 12–14]. The 2015 WHO classification for pulmonary neuroendocrine tumors recommends only very rough Ki-67 limits (TC ≤ 5%, AC ≤ 20%, SCLC 50–100%, and LCNEC 40–80%) and calls for additional studies to generate more data [5]. …”