The spectrum of changes in adults with multifocal pulmonary neuroendocrine proliferations: what is the minimum set of pathologic criteria to diagnose DIPNECH?

Diffuse idiopathic neuroendocrine cell hyperplasia (DIPNECH) can be difficult to diagnose in resections for lung tumors and other conditions, as variable diagnostic criteria and definitions of "diffuse" and/or "idiopathic" have been used in the literature. We reviewed 70 consecutive lung wedge biopsies and resection specimens with multifocal neuroendocrine cell proliferations (NEP) including neuroendocrine cell hyperplasia (NECH) and/or carcinoid tumorlets to identify pathologic findings significantly associated with neuroendocrine neoplasms. The presence of pathologic changes other than NEP (eg, interstitial fibrosis, bronchiectasis, others) and the number of tumorlets were recorded to identify "idiopathic NEP." Cases were classified into 4 groups: A: NECH only, B: >1 tumorlet without NECH, C: NECH + 2 tumorlets, and D: NECH + >2 tumorlets. Proportions of neuroendocrine neoplasms and presence/absence of pathologic changes other than NEP were compared by group with χ(2) statistics. Carcinoids were seen in 8 (22.8%) of 35 and in 21 (72.4%) of 29 groups B and D cases, respectively. Of the 21 group D carcinoids, 18 (85.7%) lacked other associated pathologic changes, and the incidence of these tumors in this group was significantly higher (P < .001) than in group B. Three high-grade neuroendocrine carcinomas were seen, 1 each in groups A to C. Because group D cases had a significantly higher proportion of carcinoid tumors and a significant lack of association with conditions that could result in secondary NECH, the presence of multifocal NECH combined with 3 or more carcinoid tumorlets is proposed as minimum pathologic criteria for the diagnosis of DIPNECH.