Lung tumor
Neuroendocrine tumors
Diffuse idiopathic pulmonary neuroendocrine hyperplasia (DIPNECH)


Topic Completed: 24 December 2019

Minor changes: 24 December 2019

Copyright: 2019, PathologyOutlines.com, Inc.

PubMed Search: Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia [title]

Andréanne Gagné, M.D., M.Sc.
Philippe Joubert, M.D., Ph.D.
Page views in 2019: 38
Page views in 2020 to date: 1,058
Cite this page: Gagné A, Joubert P. Diffuse idiopathic pulmonary neuroendocrine hyperplasia (DIPNECH) . PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/lungtumordipnech.html. Accessed June 7th, 2020.
Definition / general
Essential features
  • Diffuse idiopathic pulmonary neuroendocrine hyperplasia (DIPNECH) is considered a pre-invasive lesion that may progress into tumorlets or carcinoid tumors, usually typical carcinoid
  • Histologic features comprise a generalized intramucosal proliferation of pulmonary neuroendocrine cells in monolayers or small groups that can penetrate through the bronchial basement membrane to form tumorlets
  • Diagnostic criteria are still debated; WHO defines diffuse idiopathic pulmonary neuroendocrine hyperplasia with histologic features but some authors consider it a syndrome with a distinctive clinical presentation, typical radiological findings and a pathological demonstration
  • Has to be differentiated from secondary DIPNECH, which is a localized neuroendocrine proliferation secondary to another chronic lung disease
  • Symptomatic patients present with insidious onset of a nonproductive chronic cough with dyspnea and wheezing, mimicking asthma, chronic obstructive pulmonary disease or gastroesophageal reflux
ICD coding
  • ICD-O: 8040/0 - tumorlet, benign
  • ICD-10: D3A.8 - other benign neuroendocrine tumors
Epidemiology
Sites
Pathophysiology
Etiology
Clinical features
Diagnosis
Laboratory
Radiology description
  • CT scan:
    • Bilateral mosaic perfusion with air trapping is the most important feature (Clin Radiol 2015;70:317, Clin Imaging 2015;39:243)
      • Better evaluated on expiratory CT scan
      • Secondary to a disturbed airflow caused by the proliferation of tumor cells within small airways and constrictive bronchiolitis
    • Multiple bronchiolocentric parenchymal nodules of a solid or ground glass appearance (Clin Radiol 2015;70:317)
      • Representing aggregates of neuroendocrine cells, tumorlets or carcinoid tumors
Radiology images

Contributed by Andréanne Gagné, M.D., M.Sc. and Philippe Joubert, M.D., Ph.D.
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CT scan: mosaic perfusion

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CT scan: nodules

Prognostic factors
  • Poorly understood
  • Prognosis mostly linked to the progressive worsening of pulmonary function (Chest 2015;147:415)
    • Progression can be rapid (within two years) or over a long period
    • Presence of constrictive bronchiolitis on histology is not a prognostic factor
Case reports
Treatment
Gross description
  • Not visible macroscopically
Frozen section description
Microscopic (histologic) description
  • Generalized intramucosal proliferation of pulmonary neuroendocrine cells forming monolayers or small groups that can protrude into bronchial lumen (IARC: WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart, 4th Edition, 2015)
  • Cells do not cross the mucosal basal lamina
  • Cells are round, oval or spindle shaped, have a moderate amount of eosinophilic cytoplasm and have round to oval nuclei with a salt and pepper chromatin
  • A minimal number of foci of proliferating neuroendocrine cells and tumorlets has been proposed but no consensus exists: (Hum Pathol 2015;46:176)
    • Presence of ≥ 5 neuroendocrine cells distributed in a linear fashion or in clusters within the basement membrane in ≥ 3 bronchioles
    • And association to ≥ 3 tumorlets
  • If neuroendocrine cells cross the mucosal basal lamina = tumorlet
    • Poorly defined nodules with infiltrative margins in a fibrotic stroma, usually found in relation to an airway
    • Size < 5 mm with < 2 mitoses / 2 mm2 and absence of necrosis
  • Has to be differentiated from secondary DIPNECH, which is a localized neuroendocrine proliferation associated to an underlying lung pathology
  • Can be associated with constrictive bronchiolitis (44% of patients) (Chest 2015;147:415)
Microscopic (histologic) images

Contributed by Andréanne Gagné, M.D., M.Sc. and Philippe Joubert, M.D., Ph.D.
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Small nodules

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Linear proliferation

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Nodule occluding a bronchiole

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Discrete proliferation

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Tumorlet


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Tumorlet

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Salt and pepper chromatin

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Chromogranin

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Synaptophysin

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CD56

Virtual slides

Images hosted on other servers:
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Wedge resection with DIPNECH

Positive stains
Molecular / cytogenetics description
Sample pathology report
  • Lung, left upper lobe, wedge resection:
    • Multiple foci of neuroendocrine proliferation (neuroendocrine hyperplasia and neuroendocrine tumorlet) (see comment)
    • Comment: The presence of foci of neuroendocrine proliferation raises the possibility of a diffuse idiopathic pulmonary neuroendocrine cells hyperplasia (DIPNECH). Correlation with clinical symptoms, pulmonary function tests and high resolution chest CT scan with an expiratory phase is recommended to confirm this diagnosis.
Differential diagnosis
Board review style question #1

    A 55 year old woman with a long history of chronic cough and asthma undergoes an upper right lobectomy for a lung nodule. The final diagnosis is a typical carcinoid tumor. The adjacent lung parenchyma presents numerous lesions diffusely throughout the lobectomy as depicted in the image. Concerning this diagnosis, which of the following is true?

  1. Diagnostic criteria are well defined and combine histological, radiological and clinical findings
  2. EGFR mutations are frequently found
  3. Constrictive bronchiolitis can be found
  4. Most patients are men
Board review answer #1
C. Constrictive bronchiolitis can be found

Explanation: The diagnosis here is diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH). Diagnostic criteria for this entity are still debated (A). The WHO classification defines diffuse idiopathic pulmonary neuroendocrine cell hyperplasia with histologic features and some authors have proposed precise diagnostic criteria. However, other groups consider it a syndrome with a distinctive clinical presentation, typical radiological findings and a pathological demonstration. No specific molecular alterations have been described in diffuse idiopathic pulmonary neuroendocrine cell hyperplasia lesions (B). Mengoli et al. (Am J Surg Pathol 2018;42:646) tested a panel of targetable genes and have not found any specific molecular alterations. Concerning histologic findings, constrictive bronchiolitis can be found and is thought to be secondary to the production of peptides by the neuroendocrine cells (C). Finally, an overwhelming majority of patients with diffuse idiopathic pulmonary neuroendocrine cell hyperplasia are women (F:M > 10:1) (D).

Reference: Diffuse idiopathic pulmonary neuroendocrine hyperplasia

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Board review style question #2
    Regarding the histologic features of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH), which of the following is true?

  1. There is a generalized intramucosal proliferation of pulmonary neuroendocrine cells
  2. There is a localized intramucosal proliferation of pulmonary neuroendocrine cells around bronchiectasis
  3. Tumorlets can have a size of > 5 mm
  4. A tumorlet is a nodule of neuroendocrine cells that is limited to the bronchial mucosa
Board review answer #2
A. There is a generalized intramucosal proliferation of pulmonary neuroendocrine cells

Explanation: A generalized intramucosal proliferation of pulmonary neuroendocrine cells (A) is found in diffuse idiopathic pulmonary neuroendocrine cell hyperplasia cases. It has to be differentiated from localized pulmonary neuroendocrine cell proliferations that can be found associated to chronic lung diseases (B). Tumorlets are, by definition, < 5 mm (C) and cross the basal membrane of the mucosa (D).

Reference: Diffuse idiopathic pulmonary neuroendocrine hyperplasia

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