Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare, but increasingly recognized entity that primarily affects middle-aged and elderly women. It is characterized by abnormal proliferation of pulmonary neuroendocrine cells (PNECs) and is considered a preinvasive lesion for carcinoid tumorlets/tumors. Sometimes, DIPNECH is accompanied by constrictive bronchiolitis which usually manifests as chronic cough and/or dyspnea, along with airflow limitation on spirometry. The telltale imaging sign of DIPNECH is the presence of multiple noncalcified pulmonary nodules and mosaic attenuation on CT. However, these clinico-radiologic features of DIPNECH are characteristic but nonspecific; thus, histopathologic confirmation is usually necessary. DIPNECH has an indolent course and only rarely leads to respiratory failure or death; progression to overt neuroendocrine tumor (carcinoid) of the lung occurs in a minority of patients. Of available therapies, somatostatin analogs and mechanistic target of rapamycin inhibitors are the most promising. In this review, we provide an update regarding the diagnosis and management of DIPNECH and describe critical gaps in our understanding of this entity, including the central terms ‘diffuse’ and ‘idiopathic.’ We also summarize the inconsistencies in definitions employed by recent studies and discuss the pitfalls of the DIPNECH definitions proposed by the World Health Organization in 2021. In this context, we propose an objective and reproducible radio-pathologic case definition intended for implementation in the research realm and seeks to enhance homogeneity across cohorts. Furthermore, we discuss aspects of PNECs biology which suggest that PNEC hyperplasia may contribute to the pathogenesis of phenotypes of lung disease aside from constrictive bronchiolitis and carcinoid tumorlets/tumors. Finally, we steer attention to some of the most pressing and impactful research questions awaiting to be unraveled.

弥漫性特发性肺神经内分泌细胞增生症（DIPNECH）是一种罕见但越来越被认识的疾病，主要影响中老年女性。其特征是肺神经内分泌细胞（PNEC）异常增殖，被认为是类癌小瘤/肿瘤的浸润前病变。有时，DIPNECH 伴有缩窄性细支气管炎，通常表现为慢性咳嗽和/或呼吸困难，以及肺活量测定中的气流受限。DIPNECH 的影像学征象是 CT 上存在多个非钙化肺结节和马赛克衰减。然而，DIPNECH 的这些临床放射学特征是特征性的，但非特异性；因此，通常需要组织病理学证实。DIPNECH 病程呈惰性，很少会导致呼吸衰竭或死亡；少数患者会进展为明显的肺部神经内分泌肿瘤（类癌）。在可用的疗法中，生长抑素类似物和雷帕霉素抑制剂的机制靶点是最有前途的。在这篇综述中，我们提供了有关 DIPNECH 诊断和治疗的最新信息，并描述了我们对该实体的理解中的关键差距，包括中心术语“弥漫性”和“特发性”。我们还总结了最近研究中使用的定义的不一致之处，并讨论了世界卫生组织在 2021 年提出的 DIPNECH 定义的缺陷。在这种背景下，我们提出了一个客观且可重复的放射病理病例定义，旨在在研究领域实施并寻求增强群体之间的同质性。此外，我们讨论了 PNEC 生物学的各个方面，这表明 PNEC 增生可能与缩窄性细支气管炎和类癌肿瘤/肿瘤之外的肺部疾病表型的发病机制有关。最后，我们将注意力转向一些有待解决的最紧迫和最有影响力的研究问题。