Kiran Batra

Telomere-related lung fibrosis is diagnostically heterogeneous but uniformly progressive.

Heterozygous mutations in four telomere-related genes have been linked to pulmonary fibrosis, but little is known about similarities or differences of affected individuals. 115 patients with mutations in telomerase reverse transcriptase (TERT) (n=75), telomerase RNA component (TERC) (n=7), regulator of telomere elongation helicase 1 (RTEL1) (n=14) and poly(A)-specific ribonuclease (PARN) (n=19) were identified and clinical data were analysed. Approximately one-half (46%) had a multidisciplinary diagnosis of idiopathic pulmonary fibrosis (IPF); others had unclassifiable lung fibrosis (20%), chronic hypersensitivity pneumonitis (12%), pleuroparenchymal fibroelastosis (10%), interstitial pneumonia with autoimmune features (7%), an idiopathic interstitial pneumonia (4%) and connective tissue disease-related interstitial fibrosis (3%). Discordant interstitial lung disease diagnoses were found in affected individuals from 80% of families. Patients with TERC mutations were diagnosed at an earlier age than those with PARN mutations (51±11 years versus 64±8 years; p=0.03) and had a higher incidence of haematological comorbidities. The mean rate of forced vital capacity decline was 300 mL·year−1 and the median time to death or transplant was 2.87 years. There was no significant difference in time to death or transplant for patients across gene mutation groups or for patients with a diagnosis of IPF versus a non-IPF diagnosis. Genetic mutations in telomere related genes lead to a variety of interstitial lung disease (ILD) diagnoses that are universally progressive. Mutations in four telomere-related genes lead to progressive pulmonary fibrosis, regardless of ILD diagnosis http://ow.ly/TH2B300Yjvt

Pleuroparenchymal fibroelastosis: a pattern of chronic lung injury ☆ ☆☆

Pleuroparenchymal fibroelastosis (PPFE) is a rare condition currently described as an upper lobe subpleural and interstitial proliferation of predominantly elastic fibers. The etiology is unknown, and no specific diagnostic criteria have been reported. Here we report 5 cases of PPFE, 1 man and 4 women, 3 of them diagnosed at the time autopsy, 1 diagnosed in an explanted lung, and 1 diagnosed on a surgical wedge biopsy. The average age of diagnosis among this series is 73 years, and the duration of pulmonary symptoms ranged from 14 months to at least 9 years. Two patients had been exposed to specific medications (daptomycin and dapsone) preceding the development of pulmonary symptoms, and 1 patient developed eosinophilic pneumonia in the course of the disease. Four patients had clinical evidence of fibrous interstitial pneumonia. We found evidence of diffuse parenchymal fibroelastosis involving both upper and lower lobes in all 5 cases, suggesting that the disease may be a more diffuse condition than previously reported. PPFE may actually represent a pattern of chronic lung injury rather than a specific entity and may be seen in association with a variety of clinicoradiologic conditions. Based on our findings in this series and the most recent publications of the subject, we propose the following set of diagnostic criteria for PPFE: multilobar subpleural and/or centrilobular fibrous interstitial pneumonia characterized by an extensive (>80%) proliferation of elastic fibers in nonatelectatic lung, along with absent to mild chronic inflammation, and absent to rare granulomas.

The MUC5B promoter polymorphism and telomere length in patients with chronic hypersensitivity pneumonitis: an observational cohort-control study

SUMMARY Background Patients with hypersensitivity pneumonitis (HP) may develop lung fibrosis, which is associated with reduced survival. Families with pulmonary fibrosis can present with members diagnosed with idiopathic pulmonary fibrosis (IPF) or chronic HP (cHP), suggesting that fibrotic HP may share risk factors with IPF. Methods In an observational study of two independent cohorts of patients with cHP (UCSF n=145, UTSW n=72), we measured two common single nucleotide polymorphisms associated with IPF (MUC5B rs35705950 & TOLLIP rs5743890) and peripheral blood leukocyte telomere length and evaluated their associations with cHP disease, survival, and clinical-radiograph-pathologic features. Findings The frequency of the MUC5B minor allele, but not the TOLLIP minor allele, was significantly increased in cHP patients in both cohorts (UCSF MAF 24.4% & UTSW MAF 32.3%) compared to healthy controls (MAF 10.7%; p-values for comparison = <0.0001 for both cohorts) and similar to IPF (UCSF MAF 33.3% & UTSW MAF 32.0%, p-values for comparison=0.10 & 0.95, respectively). The MUC5B minor allele (adjusted OR 1.91, p=0.045) and shorter telomere length (adjusted OR 0.23, p=0.002) were associated with extent of radiographic fibrosis and other measures of lung remodeling and fibrosis in the combined cHP cohorts. Shorter telomere length had a significant association (adjusted HR 0.18, p=0.001) with reduced survival in the combined cHP cohorts. Interpretation The MUC5B promoter polymorphism rs35705950 and shorter telomere length are associated with extent of fibrosis in cHP. Shorter telomere length is associated with histopathology findings typical of usual interstitial pneumonia and reduced survival in cHP. Funding NIH grants KL2TR001870, T32HL098040, UL1TR001105, R01HL093096, and the Nina Ireland Program for Lung Health.

Spectrum of Suprascapular Nerve Lesions: Normal and Abnormal Neuromuscular Imaging Appearances on 3-T MR Neurography

OBJECTIVE. In this article, we will review the normal anatomy and imaging features of various neuromuscular abnormalities related to suprascapular neuropathy. CONCLUSION. Suprascapular neuropathy can be difficult to distinguish from rotator cuff pathology, plexopathy, and radiculopathy. Electrodiagnostic studies are considered the reference standard for diagnosis; however, high-resolution 3-T MR neurography (MRN) can play an important role. MRN enables direct visualization of the nerve and simultaneous assessment of the cervical spine, brachial plexus, and rotator cuff.

Revisions to the Tumor, Node, Metastasis staging of lung cancer (8th edition): Rationale, radiologic findings and clinical implications

The Tumor, Node, Metastasis (TNM) staging system, adopted by the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC), has been recently revised, with the new 8th edition of the staging manual being published in January 2017. This edition has few but important evidence-based changes to the TNM staging system used for lung cancer. Radiologists should be aware of the updated classification system to accurately provide staging information to oncologists and oncosurgeons. In this article, we discuss the rationale, illustrate the changes with relevance to Radiology, and review the clinical implications of the 8th edition of the UICC/AJCC TNM staging system with regards to lung cancer.

Pleuroparenchymal fibroelastosis associated with telomerase reverse transcriptase mutations

We thank H. Nunes and colleagues for their interest in our study of patients with telomere-related gene mutations associated with pleuroparenchymal fibroelastosis (PPFE) [1]. Their cohort of five patients with PPFE and rare variants in telomerase reverse transcriptase (TERT) is similar to ours with regard to its female predominance. Here we provide additional details of our eight cases to point out additional similarities and differences between these two cohorts (table 1). A diagnosis of PPFE is linked to pathogenic variants in three different telomere-related genes http://ow.ly/eGOq30aPkgx

Series of rare lung diseases mimicking imaging patterns of common diffuse parenchymal lung diseases

Diffuse parenchymal lung diseases (DPLDs) encompass a variety of restrictive and obstructive lung pathologies. In this article, the authors discuss a series of rare pulmonary entities and their high-resolution computed tomography imaging appearances, which can mimic more commonly encountered patterns of DPLDs. These cases highlight the importance of surgical lung biopsies in patients with imaging findings that do not show typical imaging features of usual interstitial pneumonia.

Utility of Bronchoalveolar Lavage and Transbronchial Biopsy in Patients with Hypersensitivity Pneumonitis

IntroductionMaking the diagnosis of HP is challenging due to a lack of consensus criteria and variability of both pathologic and radiographic findings. The purpose of this retrospective study was to determine the diagnostic utility of the combination of BAL lymphocyte count and TBBX in patients with HP.MethodsWe conducted a retrospective cohort study of all patients with a MDD diagnosis of HP at a single center.Results155 patients were included in the study. 49% of patients who underwent BAL had a lymphocyte count > 20, 42% had a lymphocyte count > 30, and 34% had lymphocyte count > 40%. The median BAL lymphocyte count was higher in inflammatory HP compared to fibrotic HP. The addition of TBBX to BAL significantly increased the diagnostic yield regardless of the BAL lymphocyte cutoff used. The yield of bronchoscopy with TBBX and BAL when a lymphocyte count > 40% was used as a cutoff was 52%.ConclusionsOur study suggests that the combination of TBBX with BAL significantly increases the likelihood that the procedure will provide adequate additional information to allow a confident MDD diagnosis of HP and may reduce the need for SLB in the diagnostic workup of HP.

Pathology-radiology correlation of common and uncommon computed tomographic patterns of organizing pneumonia

Organizing pneumonia (OP) is a common pattern of lung injury that can be associated with a wide range of etiologies. Typical and not-so-typical imaging features of OP occur, as both common and rare lung pathologies can mimic the same imaging pattern as that of OP. This article will attempt to describe the difference between confusing terminologies that have been used in the past for OP and existence of primary versus secondary OP. The role of a multidisciplinary approach as an essential component to correctly diagnose and effectively manage challenging cases of OP will be highlighted. Additionally, we will discuss the limitation of transbronchial and importance of open lung biopsy to make the correct diagnosis. One example of an emerging diagnosis in the spectrum of OP and diffuse alveolar damage is acute fibrinous and organizing pneumonia. Ultimately, the reader should feel comfortable recognizing the many variable presentations of OP and be able to participate knowledgeably in a multidisciplinary team after reading this article. OP is a disease entity with variable radiographic and distinct histological characteristics that requires a multidisciplinary approach to correctly diagnose cryptogenic OP. Classic radiologic findings of OP occur in as low as 60% of cases. Secondary causes include infections, neoplasms, inflammatory disorders, and iatrogenic. Acute fibrinous and organizing pneumonia can appear similarly, but miliary nodules are a clue to diagnosis.

Pathology and radiology correlation of idiopathic interstitial pneumonias

By nature, idiopathic interstitial pneumonias have been diagnosed in a multidisciplinary manner. As classifications have been subject to significant refinement over the last decade, the importance of correlating clinical, radiologic, and pathologic information to arrive at a diagnosis, which will predict prognosis in any given patient, has become increasingly recognized. In 2013, the American Thoracic Society and European Respiratory Society updated the idiopathic interstitial pneumonias classification scheme, addressing the most recent updates in the field. The purpose of this review is to highlight the correlations between radiologic and pathologic findings in idiopathic interstitial pneumonias while using updated classification schemes and naming conventions.