Pictorial ReviewDIPNECH: when to suggest this diagnosis on CT
Introduction
Pulmonary neuroendocrine cells (PNECs), also known as Kulchitsky-type cells, are epithelial cells of the pulmonary bronchial wall, found from the trachea to the terminal bronchioles. They play a role in lung development during foetal life and act as chemoreceptors to hypoxaemia in adulthood.1 It has been known for decades that lung carcinoid tumours originate from PNEC and that PNEC can show reactive hyperplasia to chronic lung diseases.2 However, it was only in 1992 that diffuse idiopathic PNECs proliferation (DIPNECH) was reported as a separate entity by Aguayo et al.2 Seven years later, this new condition has been recognized by the 1999 World Health Organization International Histological Classification of Tumours as the only pre-invasive lesion for lung carcinoid tumours.3
Although DIPNECH reported prevalence among patients with resected lung carcinoid tumours reaches 5.4%4 it remains an under-recognized disease and symptomatic patients often have a long history of respiratory symptoms before diagnosis. In those patients, several CT airway abnormalities can lead to the right diagnosis. DIPNECH diagnosis is more difficult in asymptomatic patients, especially those undergoing CT for cancer follow-up, in which nodules must not be mistaken for diffuse lung metastases. An awareness of DIPNECH imaging features can help diagnosis and distinction from other airways diseases.
The aim of this review is to describe DIPNECH-related CT features, and correlate them with histology, in order to help radiologists diagnose this under-recognized condition and distinguish it from other causes of mosaic perfusion due to blood flow redistribution observed in other airway diseases or of thromboembolic origin.
Section snippets
Pathophysiology
During foetal life, PNECs are the first cells to form and differentiate in the lung epithelium.1 They play a part in paracrine regulation of lung development.2 They are specialized epithelial cells, located throughout the entire respiratory tract, and usually exist as solitary cells, but sometimes aggregate to form small nodules termed neuro-epithelial bodies.1 During foetal life, PNECs release various amine and peptides, including serotonin, calcitonin, neuron-specific enolase, chromogramin A,
Clinical presentation
Demographic characteristics of DIPNECH are different from those of reactive PNECs proliferation and of carcinoid tumours unrelated to DIPNECH. DIPNECH preferentially affects women (89%) with a mean age of 58 years.10 In contrast, carcinoid tumours preferentially occur in younger patients (average age of 46 years) without marked sex predilection.11 There is no evidence of female predominance in reactive proliferation of PNECs.9 By definition, patients with DIPNECH are free of diseases that might
Pathology
DIPNECH is defined as a proliferation of pulmonary neuroendocrine cells that do not cross the basement membrane.7 The histological appearance may comprise a generalized proliferation of scattered PNECs, small nodules (neuroendocrine bodies), or a linear proliferation of pulmonary endocrine cells (Fig 1). Although it is diffuse, DIPNECH shows spatial heterogeneity; more severe involvement of lung bases has been reported in a few cases.15
Secretion of peptides by hyperplasic PNECs can lead to
CT findings
Because DIPNECH is characterized by cell proliferation in the bronchial wall, CT signs are those of airway-related diseases, and include bronchial wall thickening, mild bronchiectasis, mucoid impactions, with mosaic perfusion being the most important and suggestive feature. Lesions are almost always bilateral—only one case of unilateral involvement has been reported to date.24 A case of normal CT in a patient with histologically proven DIPNECH has also been reported but expiratory CT was not
Differential diagnosis
Clinically, patients are often misdiagnosed with asthma.12, 13, 16, 18, 19 Histologically, PNEC hyperplasia, tumorlets, and carcinoid tumours can be seen as distinct entities and are not necessarily associated with DIPNECH. Unique or multiple DIPNECH-unrelated tumorlets are incidental findings of no clinical significance that can be encountered in the same conditions as reactive PNEC hyperplasia. Similarly, the vast majority of carcinoid tumours are not associated with DIPNECH, which are
Positive diagnosis
CT is insufficient to establish a definite diagnosis, as radiological signs are non-specific and inconstant. However, the association of mosaic perfusion with multiple lung nodules in a middle-aged woman referred for chronic cough and wheezing should point first towards the diagnosis of DIPNECH36 (Figure 9, Figure 10).
A positive diagnosis always requires histopathological confirmation of diffuse PNEC proliferation.17 Due to spatial heterogeneity of PNEC hyperplasia, biopsy specimens should be
Management and prognosis
To date, there are no evidence-based guidelines for the management of DIPNECH. The various treatments reported in the literature vary from conservative management, oral and inhaled steroids, somatostatin analogues, chemotherapy to surgical lung resection, and even lung transplantation.2, 10, 17 Despite being a pre-invasive condition leading to lung carcinoid, DIPNECH typically remains an indolent disorder. Data on long-term follow-up and outcome are limited, but prognosis may not depend on
Conclusion
DIPNECH is an under-recognized disease characterized by small airway obstruction of variable severity. Expiratory CT can help detection by demonstrating air-trapping. Although often associated with lung carcinoids tumours, which for DIPNECH is regarded as pre-invasive condition, prognosis mainly depends on respiratory symptoms. DIPNECH should be suspected when diffuse mosaic perfusion in middle-aged women is demonstrated at CT, particularly if multiple lung nodules are also seen.
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Prognostic Significance of Pulmonary Multifocal Neuroendocrine Proliferation With Typical Carcinoid
2022, Annals of Thoracic SurgeryCitation Excerpt :Therefore, the complex pathophysiology and the real clinical meaning of MNEP with TC remain to be better clarified.24-26 The assessment of preoperative imaging studies, risk factors, and clinical symptoms may be crucial to confirm the clinical origin of pulmonary neuroendocrine tumors.26-28 In the PNECH setting, a high-resolution CT scan with an expiratory study has a role in detecting mosaic attenuation, bronchial wall thickening, air trapping, and bronchiectasis in association with pulmonary nodules.2,16,28,29
Neuroendocrine neoplasms of the lung
2022, Practical Pulmonary Pathology: A Diagnostic ApproachA case of multiple lung carcinoid tumors localized in the right lower lobe
2022, Respiratory Medicine Case ReportsCitation Excerpt :HR-CT features include more peripheral multiple small nodules than in segmental bronchi, mosaic perfusion, and air trapping sings. MIP reformation is useful for the detection of peripheral nodules, while MinIP reformation is useful for the detection of mosaic perfusion [11]. Mosaic perfusion reflects the attenuation of vessels and the pulmonary parenchyma following constrictive bronchiolitis, which bronchial obstruction arising from NECH causes.