Pathology of interstitial lung diseases (ILD) in patients with monogenic cause is poorly described. We investigated pathological and Computed Tomography (CT) features of ILD patients with telomere-related genes (TRG) mutations.

Patients diagnosed with ILD and TRG germline pathogenic variations at Bichat hospital between 2009 and 2020 and available lung samples were retrospectively included. CT and lung samples were reviewed by two radiologists and two pathologists assessing elementary lesions, primary diagnostic pattern and minor patterns.

Twenty-six patients (mean age: 54) with TERT (n=16), TERC (4), RTEL1 (5) and PARN (1) mutations were included. Multidisciplinary diagnoses were idiopathic pulmonary fibrosis (50%), unclassifiable fibrosis (UnF) (26.9%), hypersensitivity pneumonitis (HP) (11.5%), fibrosis and emphysema (7.6%), non-specific interstitial pneumonia (NSIP) (3.8%).

CT primary patterns were usual interstitial pneumonia (UIP) (38.5%), UnF (30.8%), pleuroparenchymal fibroelastosis (PPFE) (19.2%), NSIP (11.5%). Pathological primary patterns on 20 explants and 6 biopsies were UnF (34.6%), UIP (30.8%), PPFE (19.2%), NSIP (11.5%) and HP (3.8%). Radiology and pathology were fully or partially concordant in 22 cases. Combination of pathological patterns was frequent (61.5%). Including primary and minor features, the most frequent pathological patterns were UIP (61.5%), PPFE (34.6%) and HP (26.9%). In addition, an unusual pattern of continuous front of fibroblastic foci, inflammatory fibrosis and elastin-rich fibrosis was described in 8 cases.

Despite a high proportion of Unf, most patients showed UIP and PPFE patterns, consistent with aggressive course of TRG associated ILD.