Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: a rare preneoplastic condition (original) (raw)
Related papers
Lung Cancer, 2017
Association of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) with lung adenocarcinoma: A radiologist's perspective To the Editor, We describe the case of an asymptomatic 66-year-old woman who was incidentally diagnosed with a lung nodule on a chest radiograph. A thoracic CT confirmed a 12-mm suspicious spiculated partly-solid lung nodule in the right lower lobe and unexpectedly detected multiple small nodules scattered throughout both lungs (Fig. 1). Given this presentation, small pulmonary metastases could not be completely ruled out. A videoassisted thoracoscopic lobectomy surgery (right lower lobectomy and a right middle lobe wedge resection) was performed, confirming a right lower lobe pT1a low-grade invasive mucinous adenocarcinoma and findings consistent with diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH). These findings were found both in the right lower lobectomy and right middle lobe wedge resection and encompassed the presence of nodular proliferations of neuroendocrine cells (including multiple tumorlets and even a small 6-mm carcinoid tumor) and areas of constrictive obliterative bronchiolitis. DIPNECH is a rare and poorly understood preneoplastic pulmonary disorder with less than 100 documented cases in the scientific literature and with no consolidated diagnostic radiological and/or pathological criteria that typically affects women [1]. According to the original description, DIPNECH is an entity characterized histologically by a diffuse proliferation of neuroendocrine cells and presence of constrictive obliterative bronchiolitis, radiologically by the presence of small pulmonary nodules, mosaic attenuation due to air trapping, and bronchial wall thickening, and clinically by symptoms of airflow limitation (dyspnea, chronic cough) [2]. However, the term DIPNECH is also used in asymptomatic patients with carcinoid tumors without radiological features of airway disease in whom incidental foci of neuroendocrine cell hyperplasia and tumorlets are found adjacent to the carcinoid tumor on the histopathological analysis [3]. To our knowledge this is the sixth reported case (third publication) describing the association of a lung adenocarcinoma with DIPNECH. Previous reports have focused on the pathologic findings of this rare association and have suggested that a subset of lung adenocarcinomas may have concomitant DIPNECH within the lung cancer, implying a causal relationship. Interestingly, this subset of lung adenocarcinomas may be low-grade tumors and exhibit a better prognosis than conventional (not DIPNECH-associated) lung adenocarcinomas [4,5]. This case reminds us that DIPNECH, whether it represents a fortuitous association with lung adenocarcinoma or not, may mimic metastatic pulmonary nodules in lung cancer patients. Therefore, we believe that DIPNECH should be considered in the differential diagnosis of patients with potentially resectable primary lung cancers presenting with small pulmonary nodules on imaging studies.
European Respiratory Journal, 2021
Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is considered a preinvasive lesion that may progress to carcinoid tumour [1]. Histologically, it is marked by a proliferation of neuroendocrine cells that is confined to the basement membrane (neuroendocrine cell hyperplasia; NECH), and/or has invaded past the basement membrane (carcinoid tumourlet) [2]. Tumourlets equal to or larger than 5 mm are classified as carcinoid tumours. Per the World Health Organization 2021 criteria, DIPNECH can be pathological (based solely on characteristic histological features) or clinical (diagnosed per characteristic symptoms and imaging findings, e.g. respiratory symptoms, bilateral pulmonary nodules, mosaic attenuation on computed tomography (CT)) [2]. In contrast to some lung diseases or neoplasms that can cause secondary, reactive NECH/tumourlets to form, DIPNECH is marked by such hyperplasia without an identifiable cause. Given only ∼ 200 cases have been reported in the literature [3], DIPNECH is still poorly understood, and as a result is frequently under-or misdiagnosed, especially as asthma/COPD given the symptomatology of chronic cough and dyspnoea. Although a few retrospective cohort studies have been published more recently [3, 4], there is still more to be learned about this rare entity, including the clinical presentation, the population affected, differences from secondary NECH/tumourlets, treatment algorithms and, importantly, the rate and frequency of progression to malignant carcinoid tumour. Here, we present a descriptive retrospective single institution study of 78 patients with NECH/tumourlets, comparing patients with secondary NECH/tumourlets to those with DIPNECH. A retrospective analysis of patients who were treated at Stanford Health Care from 1 January 2000 to 14 November 2020 was conducted, with institutional review board approval. Patients included had either pathological confirmation of NECH and/or carcinoid tumourlets, or were diagnosed with clinical DIPNECH after multidisciplinary review based on characteristic radiographic and clinical features [5]. NECH was defined pathologically as proliferation of neuroendocrine cells involving small airways without invasion through the basement membrane, while tumourlet was defined as nodular proliferation <5 mm with invasion beyond the membrane. Pathological and clinical DIPNECH were defined based on the 2021 WHO classification of thoracic tumours [2]. Pathological DIPNECH required NECH and/or multifocal tumourlets. Clinical DIPNECH was defined by symptoms related to airway obstruction, mosaic attenuation on CT and/or bilateral pulmonary nodules, and pathological confirmation of NECH/tumourlets was optional. Secondary NECH/tumourlets were defined by the co-occurrence of an alternative non-carcinoid lung disease identified on the same pathological specimen, or unifocal tumourlet with co-existing carcinoid tumour. An additional 145 patients with typical carcinoid, 34 patients with atypical carcinoid and 1771 patients with non-high grade, non-lung neuroendocrine tumours (NETs) were identified using the Stanford Neuroendocrine Tumor Database as comparison cohorts for demographics. Statistical analyses were performed using Fisher's exact test or Chi-squared analysis for categorical variables, or unpaired t-test for continuous variables.
Diffuse idiopathic pulmonary neuroendocrine hyperplasia
Introduction: Diffuse idiopathic pulmonary neuroendocrine cells hyperplasia (DIPNECH) is an extremely rare lesion of the lung, less than 400 cases are reported in the literature since its discovery in 1992. Observation: 51-year-old Patient hospitalized after the fortuitous discovery of a small nodule of the lobe apical right. The surgical pathologic examination of the scannoguided biopsy found a lung parenchyme the bronchial cells of which are replaced by neuroendocrine hyperplasiques making cells posing the diagnosis of a Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia with a tumor typical carcinoïde. The patient benefited a surgical resection of the nodule. The contrôle by a thoracic computed tomography scans don't objectivited a parenchymal recurrence, or appearance of other nodule. Conclusion: The current data of this disease concerning its diagnosis, treatment and prognosis are still little known. Several studies will be necessary to clear up the various persistent points about this pathology.
Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia
American Journal of Respiratory and Critical Care Medicine, 2011
Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIP-NECH) is being recognized with increasing frequency. Diagnostic and treatment information is limited. A systematic review is presented, focusing on patient demographics, clinical presentation, diagnosis, treatment options, and outcomes. A systematic electronic literature search was conducted for adult DIPNECH cases reported in the English literature during the past 6 years. Twenty-four DIPNECH cases were identified. Another case from our institution is contributed. Women represent 92% (23 of 25). Mean age at diagnosis was 58 years (range, 36-76 yr). Most were nonsmokers (16 of 24). Symptoms included cough (71%), dyspnea (63%), and wheezing (25%) occurring days to years before diagnosis. Pulmonary function testing showed obstructive ventilatory disease in 54%. Lung nodules were seen in 15 patients (63%), ground-glass attenuation in 7 patients (29%), and bronchiectasis in 5 patients (21%). Histological confirmation required surgical lung biopsy for 88%; however, transbronchial biopsies alone were diagnostic in three patients. Treatments strategies included systemic and inhaled corticosteroids, bronchodilators, and lung resection. Available followup data in 17 patients showed 6 clinically improved, 7 who remained stable, and 4 clinically deteriorated. The majority of patients presenting with DIPNECH are middle-aged females with symptoms of cough and dyspnea; obstructive abnormalities on pulmonary function testing; and radiographic imaging showing pulmonary nodules, ground-glass attenuation, and bronchiectasis. In general, the clinical course remains stable; however, progression to respiratory failure does occur. Long-term follow-up and treatment remains incomplete. Establishment of a national multicenter DIPNECH registry would allow formulation of optimal evidence-based guidelines for management of these patients.
Pathology - Research and Practice, 2013
DIPNECH is regarded as a precursor lesion of neuroendocrine lung tumors, specifically carcinoids. A relationship with lung adenocarcinomas has not been clearly established so far. We present a series of four cases with a concomitant presence of adenocarcinoma and DIPNECH in the lung. The cases were retrieved from the archives of the Institutes of Pathology of the Jena University Hospital and the Charité, Berlin. The clinical data were collected from the hospital information system. The microscopic findings of adenocarcinoma and DIPNECH were reviewed. A panel of neuroendocrine and epithelial markers was analyzed immunohistochemically. In addition, the H&E slides of a series of 82 lung carcinomas were reevaluated for the presence of DIPNECH foci and the parameters of the IASLC/ATS/ERS classification for lung adenocarcinoma. DIPNECH foci were composed of small intramucosal nests of proliferating pulmonary neuroendocrine cells alongside or at the periphery of terminal airways. All detected foci measured less than 5 mm in maximal diameter and showed a consistent reactivity against Synaptophysin. They did not express epithelial markers of squamous cell carcinoma and adenocarcinoma. In three cases, the DIPNECH foci were clearly associated with the adenocarcinoma, while in one case, they were observed in the non-neoplastic lung tissue. The adenocarcinoma with DIPNECH inside mainly showed low grade histology, while the fourth case was intermediate to high grade. The histologic evaluation of the HE slides of the other 82 lung cancer cases showed no suspected or definite DIPNECH foci. Within this series, we could confirm the prognostic significance of the IASLC/ATS/ERS classification of lung adenocarcinoma. Our series suggest that a subset of lung adenocarcinoma is characterized by the concomitant presence of DIPNECH within the tumor, suggesting a causal relationship. These adenocarcinomas seem to be low grade ones, and may have a particular tumorigenesis and clinical behavior. These observations need to be confirmed in larger tumor collectives. We could confirm the prognostic relevance of the new adenocarcinoma classification.
Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia A Systematic Overview
American Journal of Respiratory and Critical Care Medicine
Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is being recognized with increasing frequency. Diagnostic and treatment information is limited. A systematic review is presented, focusing on patient demographics, clinical presentation, diagnosis, treatment options, and outcomes. A systematic electronic literature search was conducted for adult DIPNECH cases reported in the English literature during the past 6 years. Twenty-four DIPNECH cases were identified. Another case from our institution is contributed. Women represent 92% (23 of 25). Mean age at diagnosis was 58 years (range, 36-76 yr). Most were nonsmokers (16 of 24). Symptoms included cough (71%), dyspnea (63%), and wheezing (25%) occurring days to years before diagnosis. Pulmonary function testing showed obstructive ventilatory disease in 54%. Lung nodules were seen in 15 patients (63%), ground-glass attenuation in 7 patients (29%), and bronchiectasis in 5 patients (21%). Histological confirmation requi...
Thorax, 2007
A review was undertaken of 19 patients diagnosed with diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) between 1992 and 2006. Most patients were women (n = 15) and non-smokers (n = 16). Clinical presentation was either with symptomatic pulmonary disease (group 1; n = 9) or as an incidental finding during investigation for another disorder, most frequently malignant disease (group 2; n = 10). In group 1, cough and dyspnoea were the most frequent symptoms, with an average duration of 8.6 years before diagnosis. Both groups showed mainly stable disease without treatment, although one patient progressed to severe airflow obstruction and one was diagnosed at single lung transplantation. Mosaicism with nodule(s) was the typical pattern of DIPNECH on high-resolution computed tomography, but one case had normal imaging despite airflow obstruction. Lung function tests showed obstructive (n = 8), mixed (n = 3) or normal (n = 5, all group 2) physiology. Two patients under...
A Rare Case of Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia
2018
We describe the case of a 53-year-old woman who visited many pneumologists without a diagnosis until finally being diagnosed with diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH). It is a relatively new disease characterized by neuroendocrine cell hyperplasia in small airways. She has stable DIPNECH and neuroendocrine carcinoma with somatostatin therapy.
Case Reports in Pulmonology, 2015
Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) and tumorlets are neuroendocrine cells proliferations smaller than 5 mm. The former confines to bronchial/bronchiolar wall, while the latter broke through epithelial basement membrane. The authors present 3 cases of DIPNECH and tumorlets associated with a typical peripheral carcinoid tumor without underlying lung disease. The patients presented with nonspecific pulmonary symptoms: 3 females, 60, 72, and 84 years old, whose CT-scans showed well-defined pulmonary nodules, 2.2, 1.6, and 1.4 cm, respectively; first patient was submitted to lobectomy and the others underwent surgical biopsy. Whitish/brownish lobulated tumors corresponded to typical carcinoids (less than 2 mitoses/2 mm2and without necrosis); polygonal/elongated cells under lobular pattern expressed CD56, chromogranin A, synaptophysin, and CK7; Ki-67 positivity was between 1 and 3%. Bronchial/bronchiolar wall neuroendocrine cell hyperplasia and several ...