Expression of developing neural transcription factors in diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH)

Abstract

DIPNECH is characterized by neuroendocrine cell hyperplasia, tumorlets, and eventually carcinoid tumors. Although it is regarded by some authors as a preneoplastic condition, this issue is controversial. New pathologic criteria have recently been proposed for the diagnosis of DIPNECH, and a subgroup of carcinoid tumors expressing developing neural transcription factors (DNTFs), with clinicopathologic features similar to those of DIPNECH, has been recognized. This paper reports on the clinical and pathological findings in three cases of DIPNECH and investigates the expression of three DNTFs (TTF1, ASCL1, and POU3F2). All patients were female, with a mean age of 63 years, and all lesions were located in the periphery of the lung. In two cases, typical carcinoids were associated with a spindle-cell component. All neuroendocrine proliferations were DNTF positive. The morphologic (spindle-cell component), phenotypic (DNTF expression), and clinicopathologic (peripheral tumors, female predominance) similarities suggest that DIPNECH may be a preneoplastic lesion for peripheral carcinoids.

Molecular alterations of neuroendocrine tumours of the lung

“…Immunophenotypically, DIPNECH is frequently characterised by expression of thyroid transcription factor 1 (TTF‐1), CD10 and gastrin‐releasing peptide (GRP)/bombesin‐like peptide, mechanistic target of rapamycin (mTOR), ribosomal protein S6 kinase beta‐1 (p70S6K), somatostatin receptor type 2 (SSTR2), Achaete–Scute family BHLH transcription factor 1 (ASCL1) and POU class 3 homeobox 2 (POU3F2) . According to Gosney and colleagues, focal expression of p53 and p16 as well as a relatively low (e.g.…”

Insights into Novel Prognostic and Possible Predictive Biomarkers of Lung Neuroendocrine Tumors

“…SCLCs and LCNECs unanimously expressed DNTFs, which were also expressed in a subset of carcinoids (27). DNTs have also been detected in the setting of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia, which is a debatable entity regarding its premalignant potential (29). LCNECs and SCLCs have also demonstrated a higher expression of nuclear survivin, which is essential for the completion of mitosis, in contrast to lung adenocarcinoma (30).…”