PMC6304384_01
Family tree. This study represents a 2-generation pedigree in which individuals from 2 generations had pulmonary fibrosis. Grey and unfiled shapes represent affected and unaffected individuals, respectively. Squares represent males and circles represent females. Strikethrough symbol (/) denotes deceased individuals. The patient is indicated by an arrow.
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The patient's family tree is shown in Fig. 1.
High resolution computed tomography (HRCT) scans at a presentation. (A-C) Transverse CT section and (D) coronal reconstruction showing honeycombing and reticulation along with traction bronchiectasis involving mainly the subpleural segments of middle and upper lobe but also the basal segments of the lower lobes. The overall radiologic pattern was typical for radiologic usual interstitial pneumonia (UIP).
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These radiological features were consistent with usual interstitial pneumonia (UIP) (Fig. 2).
Transbronchial lung cryobiopsy showing aspects suggestive of a pattern of usual interstitial pneumonia (UIP). (A) Low magnification showing pulmonary parenchyma with architecture distortion; heterogeneous appearance with areas of fibrosis and parenchymal areas more preserved (H & E, 25x). (B) Higher magnification reveals typical fibroblast foci with myofibroblast accumulation adjacent to areas of fibrosis (H & E, 200x).
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Transbronchial lung cryobiopsies obtained from the right lower lobe demonstrated scattered fibroblast foci in a background of chronic interstitial fibrosis, consistent with histologic UIP pattern, although no honeycomb change was seen (Fig. 3).
Sequence of the TERT gene in wild type (above) and patient DNA (bellow). A heterozygous missence mutation (c.2701C > T), located in exon 11 in TERT gene was identified in the patient (red square indicates the position of the mutation).
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A heterozygous mutation (c.2701C > T) located in exon 11 of the TERT gene that replaces arginine by tryptophan (Arg901Trp) was identified (Fig. 4).
High resolution computed tomography (HRCT) scans six months after treatment with nintedanib. (A-C) Transverse CT section and (D) coronal reconstruction showing progression of diffuse honeycombing involving mainly left lung.
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HRCT showed progressive honeycomb pattern (Fig. 5). He started long-term oxygen therapy and, subsequently, listed for lung transplantation.