Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH) with multifocal carcinoid tumours

A 69-year-old female non-smoker presented with a 6-month history of progressive breathlessness. She had no relevant past medical history or drug history. Spirometry showed FEV1 32% predicted and a flow-volume loop suggesting severe small airway disease. Transthoracic echocardiogram was normal.

High Resolution Computed Tomography (HRCT): There is widespread mosaicism with geographic air-trapping, exacerbated in expiration (figure 1).  There are multiple peribronchovascular and endobronchial smoothly lobulated solid nodules and masses throughout both mid and lower zones, the largest in the anterior segment of the right upper lobe measures 33mm with a density of 32 Hounsfield Units (HU) (figures 2 & 3). The mass described is airway-centric, with thickening of the proximal airway (figure 3) and plugging of the distal airway (figure 4).  Multiple other airways are also distally plugged.

Post-contrast CT thorax/abdomen/pelvis: The right upper lobe pulmonary mass demonstrates heterogeneous enhancement (68 HU) with some patchy areas of less marked enhancement anteriorly (figure 5). Nodules in the middle lobe, left upper and lower lobes also enhance, some avidly. No extra-thoracic primary tumour identified. No lymphadenopathy or metastases below the diaphragm.

18-gauge CT-guided coaxial biopsy of the largest mass yielded carcinoid tumour.

Background

Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH) is a rare pulmonary condition first described in 1992 since confined to case reports and small case series[1,2]. The World Health Organisation defines DIPNECH as a preinvasive condition on a spectrum of neuroendocrine cells proliferation and a precursor to carcinoid tumour[3]. Neuroendocrine cells confined to airway mucosa proliferate into aggregates that may extend through the basement membrane to cause constrictive bronchiolitis[2,4]. Neuroendocrine aggregates are defined by size; <5mm (tumourlets) and >5mm (carcinoid)[3,4]. 

Clinical perspective

Middle-aged females with a history of chronic cough or asthma[2,4,5].  There is no relationship with smoking. Pulmonary function tests demonstrate an obstructive or mixed obstructive/restrictive pattern, although can be normal[2,4,5]. Imaging plays an important role due to non-specific clinical features, although often cases are initially misdiagnosed[4]. When present, pulmonary carcinoid tumours are divided by location into central or peripheral; the former more symptomatic due to the sequelae of airway obstruction[6,7]. Carcinoid syndrome is uncommon (<5%)[6,7].

Imaging perspective

HRCT findings include mosaic attenuation due to constrictive bronchiolitis causing air-trapping and small (<5mm) random pulmonary nodules (absence of nodularity does not exclude DIPNECH)[4]. Bronchial wall thickening, mucus plugging/impaction and bronchiectasis are also reported. When present, pulmonary carcinoid tumours are usually central and may be multiple[6,7]. Carcinoid tumours are smoothly defined, rounded/lobulated, <5cm and homogenously enhance due to increased vascularity [4,6,7]. If present, calcification is coarse and eccentric. Fluorodeoxyglucose-positron emission tomography (FDG-PET) is of limited utility (low-moderate uptake, ~25% false-negative rate)[6,7]. Somatostatin receptor-PET demonstrates higher sensitivity and specificity; Gallium-68 DOTATATE Octreotide-PET/CT being the evolving modality that out-performs traditional Octreotide scintigraphy, although is limited by centre availability[7,8].

Outcome

No consensus treatment or follow-up protocols exist due to rarity. Somatostatin analogues and inhaled corticosteroids have been used with varying success to treat small airways disease[2,4]. CT follow up is generally accepted given risk of developing carcinoid tumours[4]. When carcinoid is present, surgical resection is the treatment of choice for localised disease[6].

Take-home messages

Although rare, DIPNECH is being increasingly described with typical clinical and radiological findings, especially when mosaicism and either random nodules or endobronchial tumours are present. The radiologist may be first to suggest the diagnosis. Ultimately histological sampling of larger nodules/tumours is required to confirm carcinoid. Giving intravenous contrast is a simple step to differentiate carcinoid on background DIPNECH from bronchoceles on background small airways disease/asthma or allergic bronchopulmonary aspergillosis.

Written informed patient consent for publication has been obtained.