Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH)

Epidemiology and Etiology:

• Very rare (see DDx below)
• Women primarily
• Tumorlets (<0.5 cm) are usually incidental histologic findings of no clinical significance (solitary)
• Associated with inflammatory and/or fibrotic conditions (bronchiectasis, interstitial fibrosis, chronic abscesses, tuberculosis)
• DIPNECH:
• Widespread peripheral airway NE cell hyperplasia and/or multiple tumorlets
• Preinvasive lesion for carcinoids
• DDx of NE cell hyperplasia and/or multiple tumorlets:
• NE cell hyperplasia and tumorlets found associated with bronchiolar inflammation / fibrosis (most often scenario)
• Considered reactive, typically without progression to carcinoid)
• found in lung surrounding up to 75% of carcinoid tumours
• frequently seen in lungs resected for carcinoid tumors (45-75%)
• both in the vicinity and away (?) from the tumour
• it is unclear whether DIPNECH diagnosis is appropriate in this scenario
• the possibility of diffuse NE proliferations in unresected lung could be raised in a note

· progression to carcinoid tumours may occur

· rarely, patients may develop respiratory symptoms

· tumourlets may be detected by CT scans as multiple nodules

· may mimic a military pattern of metastasis

Common sites:

• peripheral airways

Gross features:

• may have clinical features of ILD due to frequent association with bronchiolar fibrosis
• may be mistaken for metastatic carcinoma clinically

Histologic features:

• prominent NE cell hyperplasia and/or
• multiple tumorlets (< 0.5 cm)
• note: tumorlets should be distinguished from minute meningothelioid nodules (chemodectoma-like bodies) which are frequently seen in multiples
• perivenular location
• stellate-like extension into alveolar walls
• whorls and intranuclear inclusions similar to meningioma
• lack of associated fibrosis
• negative for NE markers and cytokeratins
• background lung is relatively normal (ex. no bronchiectasis or airway fibrosis)
• carcinoid(s) in some
• normal:
• rare single cells (Kulchitsky cells) or small cell clusters of 4-10 cells (neuroepithelial bodies)
• NE cell hyperplasia:
• Inconspicuous on H&E
• Groups of cells with pale cytoplasm
• Retraction of the underlying stroma frequently
• Intraluminal fingerlike projections of the overlying respiratory epithelium maybe

Immunophenotype:

Marker:

Sensitivity:

Specificity:

Molecular features:

Other features:

• diffuse involvement of peripheral airways with neuroendocrine hyperplasia and tumourlets.
• May present as interstitial lung disease with airway obstruction

References:

• Travis WD. Pathology of Lung Cancer. Clinics in Chest Medicine 2002; 23(1): 65-81.
• Travis WD. Advances in neuroendocrine lung tumors. Annals of Oncology 2010;21(Supp. 7): vii65–vii71.