Association of small foci of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) with adenocarcinoma of the lung.

DIPNECH is regarded as a precursor lesion of neuroendocrine lung tumors, specifically carcinoids. A relationship with lung adenocarcinomas has not been clearly established so far. We present a series of four cases with a concomitant presence of adenocarcinoma and DIPNECH in the lung. The cases were retrieved from the archives of the Institutes of Pathology of the Jena University Hospital and the Charité, Berlin. The clinical data were collected from the hospital information system. The microscopic findings of adenocarcinoma and DIPNECH were reviewed. A panel of neuroendocrine and epithelial markers was analyzed immunohistochemically. In addition, the H&E slides of a series of 82 lung carcinomas were reevaluated for the presence of DIPNECH foci and the parameters of the IASLC/ATS/ERS classification for lung adenocarcinoma. DIPNECH foci were composed of small intramucosal nests of proliferating pulmonary neuroendocrine cells alongside or at the periphery of terminal airways. All detected foci measured less than 5mm in maximal diameter and showed a consistent reactivity against Synaptophysin. They did not express epithelial markers of squamous cell carcinoma and adenocarcinoma. In three cases, the DIPNECH foci were clearly associated with the adenocarcinoma, while in one case, they were observed in the non-neoplastic lung tissue. The adenocarcinoma with DIPNECH inside mainly showed low grade histology, while the fourth case was intermediate to high grade. The histologic evaluation of the HE slides of the other 82 lung cancer cases showed no suspected or definite DIPNECH foci. Within this series, we could confirm the prognostic significance of the IASLC/ATS/ERS classification of lung adenocarcinoma. Our series suggest that a subset of lung adenocarcinoma is characterized by the concomitant presence of DIPNECH within the tumor, suggesting a causal relationship. These adenocarcinomas seem to be low grade ones, and may have a particular tumorigenesis and clinical behavior. These observations need to be confirmed in larger tumor collectives. We could confirm the prognostic relevance of the new adenocarcinoma classification.