Follicular Bronchiolitis Research Articles

Rare interstitial lung diseases: a narrative review.

Interstitial lung diseases (ILDs) encompass over 200 entities. Among them, fibrosing lung diseases, have recently generated special interest due to the emerging therapies for their management. However, it is important to deepen our knowledge of other less prevalent ILD, since many of them are associated with a poor prognosis. This narrative review aims to provide a practical and up-to-date description of some poorly recognized ILD. It covers rare idiopathic interstitial pneumonias and their histologic patterns, genetic disorders with interstitial lung involvement (Hermansky-Pudlak syndrome), and ILD associated with benign proliferation of pulmonary lymphoid tissue, namely follicular bronchiolitis and granulomatous-lymphocytic interstitial lung disease. Electronic searches of PubMed and Google Scholar using specific keywords were conducted. Articles underwent screening for relevance, covering review articles, meta-analyses, systematic reviews, case series, prospective studies, society guidelines, editorials in peer-reviewed journals; scientific books on the subject. The data included was limited to English and Spanish publications. Despite the low prevalence of these diseases, the increased recognition of radiological patterns, pathological features, and diagnostic procedures, have permitted their better characterization. This review highlights epidemiology, clinical presentation, diagnosis, natural history, and treatment. Lesser-studied ILD represent a diagnostic and therapeutic challenge and can be frequently misdiagnosed. Also, due to the lack of randomized controlled trials, there are no well-established therapeutic options. Further studies or registries are needed to improve accurate diagnosis and management.

Persistent and fatal severe acute respiratory syndrome coronavirus 2 infection in a patient with severe hypogammaglobulinemia: a case report

BackgroundViruses are constantly changing as a result of mutations, and new viral variants are expected to appear over time. The virus that causes coronavirus disease 2019, severe acute respiratory syndrome coronavirus 2, is not excluded from this condition. Patients with some types of immunodeficiency have been reported to experience symptoms that vary from mild to severe, or even death, after being infected with severe acute respiratory syndrome coronavirus 2. We report a case of a woman with severe hypogammaglobulinemia who developed a prolonged and fatal severe acute respiratory syndrome coronavirus 2 infection.Case presentationA 60-year-old mestizo female with a previous history of severe hypogammaglobulinemia manifested by recurrent pulmonary infections and follicular bronchiolitis. She received a monthly treatment of intravenous immunoglobulins and was admitted after report of a neurological manifestation related to a left thalamic inflammatory lesion, for a duration of 2 weeks of hospitalization, indicated for the study of her neurological condition, including brain biopsy. Both on admission and 1 week later, nasopharyngeal polymerase chain reaction tests for severe acute respiratory syndrome coronavirus 2 were performed and reported negative. In the third week of hospitalization, she developed pulmonary symptoms, and a positive test result for severe acute respiratory syndrome coronavirus 2 was evidenced. On Day 3, the patients’ condition worsened as the infection progressed to respiratory failure and required mechanical ventilation. On Day 8 after the coronavirus disease 2019 diagnosis, the polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2 showed persistent detection of the virus. Various bacterial coinfections, including Klebsiella pneumoniae and Enterobacter cloacae, were diagnosed and treated. On Day 35, her pulmonary symptoms worsened, and the results of the severe acute respiratory syndrome coronavirus 2 polymerase chain reaction test remained positive. On Day 36, despite all the respiratory support, the patient died. The severe acute respiratory syndrome coronavirus 2 virus was sequenced at the beginning and 8 days after the onset of the disease, and the strain, without obvious mutations in the gene that encodes spike protein, was identified.ConclusionsThis clinical case showed persistent severe acute respiratory syndrome coronavirus 2 detection after 35 days of infection in a patient with severe hypogammaglobulinemia. The sequencing of the virus showed no mutations on the spike protein at 8 days, indicating that, in this case, the persistence of the viral detection was associated with immunodeficiency instead of changes in the viral components.

Interstitial Lung Disease in Immunocompromised Children.

The range of pulmonary complications beyond infections in pediatric immunocompromised patients is broad but not well characterized. Our goal was to assess the spectrum of disorders with a focus on interstitial lung diseases (ILD) in immunodeficient patients. We reviewed 217 immunocompromised children attending a specialized pneumology service during a period of 23 years. We assigned molecular diagnoses where possible and categorized the underlying immunological conditions into inborn errors of immunity or secondary immunodeficiencies according to the IUIS and the pulmonary conditions according to the chILD-EU classification system. Among a wide array of conditions, opportunistic and chronic infections were the most frequent. ILD had a 40% prevalence. Of these children, 89% had a CT available, and 66% had a lung biopsy, which supported the diagnosis of ILD in 95% of cases. Histology was often lymphocyte predominant with the histo-pattern of granulomatous and lymphocytic interstitial lung disease (GLILD), follicular bronchiolitis or lymphocytic interstitial pneumonitis. Of interest, DIP, PAP and NSIP were also diagnosed. ILD was detected in several immunological disorders not yet associated with ILD. Specialized pneumological expertise is necessary to manage the full spectrum of respiratory complications in pediatric immunocompromised patients.

USE OF INHALED CORTICOSTERIODS/LONG-ACTING BETA AGONIST (ICS-LABA) IN PATIENTS WITH BRONCHIOLITIS CAUSED BY SJÖGREN SYNDROME DECREASES NEED FOR ORAL STEROIDS

USE OF INHALED CORTICOSTERIODS/LONG-ACTING BETA AGONIST (ICS-LABA) IN PATIENTS WITH BRONCHIOLITIS CAUSED BY SJÖGREN SYNDROME DECREASES NEED FOR ORAL STEROIDS

Pulmonary lymphoproliferative disorders in children: a practical review.

Pulmonary lymphoproliferative disorders represent an uncommon spectrum of proliferation of lymphoid tissue in the lung parenchyma ranging from benign hyperplasia to malignancy. They tend to occur in certain clinical situations and have typical imaging features that together can be used by the radiologist to suggest these entities as part of the differential diagnosis. We review key clinical, histopathological and computed tomography features of pulmonary lymphoproliferative disorders in children including follicular bronchiolitis, lymphoid interstitial pneumonia, granulomatous-lymphocytic interstitial lung disease, lymphoma and post-transplant lymphoproliferative disorder to familiarize the pediatric radiologist with this group of disorders.

DIAGNOSIS, MANAGEMENT, AND OUTCOMES IN BIOPSY PROVEN BRONCHIOLITIS

TOPIC: Diffuse Lung Disease TYPE: Original Investigations PURPOSE: Bronchiolitis refers to a variety of inflammatory diseases affecting the small airways. Patients usually present with subtle symptoms including shortness of breath, cough or wheezing, often misdiagnosed as asthma. We performed a retrospective review to describe diagnostic characteristics, treatment patterns, and outcomes of biopsy-proven bronchiolitis METHODS: We searched the electronic medical records of the Advanced Lung Disease Clinic at Baylor University Medical Center. We examined charts of patients with VATS biopsy-proven bronchiolitis between Feb 2001 and February 2021. Cases that developed following bone-marrow or solid organ transplant were excluded RESULTS: Forty patients met criteria. The median age was 61(±9), and 90% were female. 45% of patients had a history of smoking. The most common presenting symptom was shortness of breath, followed by cough. More than half of the patients were treated for asthma prior to diagnosis of bronchiolitis. 50% of patients had airflow limitation noted on spirometry, defined as an FEV1/FVC < 0.7, 40% had FVC< 60%. Fifty percent of subjects had no positive connective tissue disease serologies; the remainder had positive rheumatoid factor (12), ANA (6), anti-RNP (3), anti-Scl-70 (2). ESR and CRP was elevated in 50% of the patients. High-resolution computed tomography was available in 36 patients. The most commonly identified abnormalities were: air trapping (80%), ground-glass opacities (22%), centrilobular nodules (32%), and pleural abnormalities (22%). Forty percent of patients underwent bronchoscopy with bronchoalveolar lavage. Lymphocytosis (defined as >15%) was noted in 5 patients (31%) and eosinophilia (defined as >1%) was noted in 4 patients (10%). Lung pathology revealed constrictive bronchiolitis in 33 patients (83%), follicular bronchiolitis in 7 (17%), organizing pneumonia in 7 (17%), and granulomas in 5 (10%) patients. Fourteen (35%) patients were treated with azithromycin, 6 (15%) with oral prednisone, 16 (40%) with mycophenolate mofetil (MMF), 1 (2.5%) with azathioprine, and 1 (2.5%) with rituximab. Seven (50%) patients on azithromycin and 8 (50%) patients on MMF had spirometric improvement (defined as > 10% improvement in FVC at 6-month follow-up spirometry). Two underwent lung transplantation, and three patients died. The rest of the patients were treated with inhaled bronchodilators or inhaled steroids. Most of the patients remained stable at 6 months follow up, one had decline in FVC by 10%. Follow-up PFTs were missing in five of the patients. CONCLUSIONS: Bronchiolitis is often misdiagnosed as asthma before a definitive pathologic diagnosis is made, and so a high index of suspicion is important in patients who do not respond to usual asthma therapies. The most common imaging finding was air trapping, and lung function testing most commonly indicated restriction or a mixed obstructive and restrictive pattern. The most common pathologic finding was constrictive bronchiolitis. No significant difference in outcome noted in patients on immunosuppression or macrolides compared to not on any treatment. Patients with follicular pathology tend to do better compared to constrictive pathology. CLINICAL IMPLICATIONS: Bronchiolitis is often misdiagnosed as asthma before a definitive pathologic diagnosis is made, and so a high index of suspicion is important in patients who do not respond to usual asthma therapies. DISCLOSURES: No relevant relationships by Susan Mathai, source=Web Response no disclosure on file for Mark Millard; No relevant relationships by Joon Yong Moon, source=Web Response No relevant relationships by Sofiya Rehman, source=Web Response No relevant relationships by Ciara Wisecup, source=Web Response

EXTRA-NODAL PULMONARY MARGINAL ZONE LYMPHOMA ASSOCIATED WITH SJÖGREN DISEASE

TOPIC: Lung Cancer TYPE: Fellow Case Reports INTRODUCTION: Mucosal-associated lymphoid tissue (MALT), is a system of lymphoid tissue found within various organs that plays a role in regulating local immunity. As this tissue contains T, B, and plasma cells, it is the potential site for the development of lymphoma. MALT lymphomas are a form of B-cell extranodal lymphoma that can originate from marginal zone lymphocytes within the lung, referred to as pulmonary marginal zone lymphoma (PMZL). CASE PRESENTATION: We present a 42-year-old female referred to our clinic for evaluation of pulmonary nodules and mediastinal adenopathy. She had a one year history of Sjogren's syndrome. At that time she had no pulmonary or B symptoms. To evaluate her mediastinal adenopathy, she was referred for endobronchial ultrasound where pathologic evaluation revealed only a polymorphous lymphoid population and was negative for malignancy. She had several endobronchial hypervascular and polypoid nodules within the mainstem airways. Pathology from these nodules demonstrated an atypical lymphoid infiltrate, but was unable to be characterized any further.Given ongoing concern for a lymphoproliferative process, she was referred for video-assisted thoracoscopic surgery (VATS). Pathology from her left upper and lower lobar wedge resections demonstrated follicular bronchiolitis. Biopsy of a pleural nodule demonstrated a lymphoproliferative process concerning for a low-grade B-cell neoplasm, thought to be extranodal PMZL. She was referred to oncology where PET/FDG demonstrated hypermetabolic multi-station adenopathy suggesting stage IV disease. Given her asymptomatic nature and anticipated indolent course, it was decided to defer chemotherapy pending resolution of the COVID-19 pandemic. DISCUSSION: MALT lymphoma can develop in response to continuous antigen stimulation, as is seen in Sjogren's syndrome or tobacco use. Radiographic features of MALT lymphoma are numerous, including consolidations, nodules, and masses being the most frequent patterns observed in ~50% of patients. Endobronchial lesions as observed in this patient occur in ~85% of cases. PET/FDG imaging commonly demonstrates mild uptake within identifiable lesions. It has a very favorable prognosis with an overall 5-year survival of 90% due to its indolent nature and excellent response rate to chemoimmunotherapy, typically combination Bendamustine and Rituximab. CONCLUSIONS: MALT lymphoma is an uncommon neoplasm that can occur due to chronic antigen stimulation, especially in patients with Sjogren's syndrome. It has numerous radiographic features, the most common being endobronchial lesions. When given these clinical features, establishing a diagnosis is of utmost importance due to the excellent response rate to therapy and favorable long-term prognosis. REFERENCE #1: Borie R, Wislez M, Thabut G, et al. Clinical characteristics and prognostic factors of pulmonary MALT lymphoma. Eur Respir J. 2009;34(6):1408-1416. REFERENCE #2: Husnain M, Kuker R, Reis IM, et al. Clinical and radiological characteristics of patients with pulmonary marginal zone lymphoma: A single center analysis. Cancer Med. 2020;9(14):5051-5064. REFERENCE #3: Stefanovic A, Morgensztern D, Fong T, Lossos IS. Pulmonary marginal zone lymphoma: a single centre experience and review of the SEER database. Leuk Lymphoma. 2008;49(7):1311-1320. DISCLOSURES: No relevant relationships by Brandon Jakubowski, source=Web Response No relevant relationships by Rosechelle Ruggiero, source=Web Response

Rheumatoid arthritis-interstitial lung disease: manifestations and current concepts in pathogenesis and management.

Rheumatoid arthritis (RA) is a systemic inflammatory disorder, with the most common extra-articular manifestation of RA being lung involvement. While essentially any of the lung compartments can be affected and manifest as interstitial lung disease (ILD), pleural effusion, cricoarytenoiditis, constrictive or follicular bronchiolitis, bronchiectasis, pulmonary vasculitis, and pulmonary hypertension, RA-ILD is a leading cause of death in patients with RA and is associated with significant morbidity and mortality. In this review, we focus on the common pulmonary manifestations of RA, RA-ILD and airway disease, and discuss evolving concepts in the pathogenesis of RA-associated pulmonary fibrosis, as well as therapeutic strategies, and have revised our previous review on the topic. A rational clinical approach for the diagnosis and management of RA-ILD, as well as an approach to patients with clinical worsening in the setting of treatment with disease-modifying agents, is included. Future directions for research and areas of unmet need in the realm of RA-associated lung disease are raised.

English

The differential diagnosis of the cystic lung disease is extensive, ranging from an isolated incidental lung cyst to multiple diffuse lung cysts with other varied associated lung abnormalities. High resolution computed tomography (HRCT) thorax is the imaging modality of choice in the evaluation of these diseases, by improving the characterisation of the lung cysts (number, size, shape, distribution, wall thickness and regularity), and associated pulmonary and extrapulmonary abnormalities (like ground glass densities, nodules, interstitial fibrosis, mediastinal lymphadenopathy). After differentiating from the common cyst mimickers (cavity, centrilobular emphysema and cystic bronchiectasis), they should be grouped by location into subpleural cysts (paraseptal emphysema, bulla and honeycombing) and intraparenchymal cysts. Intraparenchymal cysts are in turn categorised into solitary / localised cysts (incidental cyst, congenital pulmonary airway malformations, intrapulmonary bronchogenic cyst and hydatid cyst) and multiple diffuse cysts. The next step will be the categorisation of these multiple diffuse cysts into those without other lung abnormalities (lymphangioleiomyomatosis and Birt-Hogg-Dube syndrome) and those with other lung abnormalities such as predominant ground glass densities (Pneumocystis jirovecii pneumonia, desquamative interstitial pneumonia, lymphoid interstitial pneumonia, subacute hypersensitivity pneumonitis and pneumatoceles) or predominant nodules (pulmonary Langerhans cell histiocytosis, amyloidosis, light chain deposition disease, follicular bronchiolitis, recurrent respiratory papillomatosis, cystic tuberculosis, cystic lung metastasis, sarcoidosis, and pulmonary mesenchymal cystic hamartomas). We conclude that this orderly radiologic approach in a given HRCT chest study of a cystic lung disease (in addition to correlation with clinical and laboratory findings), can lead us to a specific diagnosis in majority of instances, thereby optimising their treatment management, without the need of an invasive biopsy. KEY WORDS HRCT Thorax, Lung Cysts, Ground Glass Densities, Lung Nodules

Granulomatous-Lymphocytic Interstitial Lung Disease Mimicking Sarcoidosis.

Common variable immunodeficiency (CVID) is one of the most common primary immunodeficiency disorders characterized by hypogammaglobulinemia and inadequate antibody response to immunizations. The impaired antibody response occurs due to the failure of B cells to differentiate into plasma cells resulting in low immunoglobulins levels and increased frequency of infections. Granulomatous and Lymphocytic Interstitial Lung Disease (GLILD) is a non-infectious complication of CVID that is seen in 10-30% of cases. GLILD is a multisystem inflammatory disease involving the lungs, lymph node, liver, spleen and gastrointestinal tract that mimics sarcoidosis. This report describes a series of cases who presented with dyspnea, recurrent respiratory infections or autoimmunity and on further evaluation revealed features suggestive of GLILD. There is very limited understanding of GLILD in terms of clinical presentation, the histo-pathological logical findings, and the diagnostic criteria by itself are limited. A diagnosis of GLILD is established in cases of CVID when there is evidence of lymphoproliferation, cytopenia, autoimmune processes and a lung biopsy demonstrating lymphocytic interstitial pneumonia, follicular bronchiolitis, lymphoid hyperplasia, and/or non-necrotizing granulomas. We review the treatment strategies, including replacement of immunoglobulin and agents targeting B and T lymphocytes. Systematic characterization of GLILD cases and long term follow up studies are sorely needed to understand the natural history of GLILD.

Histology of Interstitial Lung Disease in Common Variable Immune Deficiency.

Interstitial lung disease (ILD) is an important non-infectious complication in several primary immune deficiencies. In common variable immune deficiency (CVID) it is associated with complex clinical phenotypes and adverse outcomes. The histology of ILD in CVID is heterogeneous and mixed patterns are frequently observed within a single biopsy, including non-necrotising granulomatous inflammation, lymphoid interstitial pneumonitis, lymphoid hyperplasia, follicular bronchiolitis, organizing pneumonia, and interstitial fibrosis; ILD has to be differentiated from lymphoma. The term granulomatous-lymphocytic interstitial lung disease (GLILD), coined to describe the histopathological findings within the lungs of patients with CVID with or without multisystem granulomata, is somewhat controversial as pulmonary granulomata are not always present on histology and the nature of infiltrating lymphocytes is variable. In this mini review we summarize the literature on the histology of CVID-related ILD and discuss some of the factors that may contribute to the inter- and intra- patient variability in the histological patterns reported. Finally, we highlight areas for future development. In particular, there is a need for standardization of histological assessments and reporting, together with a better understanding of the immunopathogenesis of CVID-related ILD to resolve the apparent heterogeneity of ILD in this setting and guide the selection of rational targeted therapies in different patients.

COMMON VARIABLE IMMUNODEFICIENCY-ASSOCIATED GRANULOMATOUS-LYMPHOCYTIC INTERSTITIAL LUNG DISEASE DIAGNOSED ON TRANSBRONCHIAL LUNG CRYOBIOPSY

SESSION TITLE: Medical Student/Resident Pulmonary Manifestations of Systemic Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Granulomatous-Lymphocytic Interstitial Lung Disease (GLILD) is a rare entity involving granulomatous and lymphoproliferative inflammation of the small airways and pulmonary interstitium. Imaging reveals lower lung predominant ground glass and/or consolidative opacities and nodules. Histopathology may have features of lymphocytic interstitial pneumonia, follicular bronchiolitis and/or organizing pneumonia. GLILD is often seen as a manifestation of common variable immunodeficiency (CVID). Diagnosis requires lung biopsy as imaging findings are nonspecific. Surgical lung biopsy (SLB) is the gold standard in diagnosing interstitial lung disease. However, the relatively new, less invasive approach of transbronchial lung cryobiopsy (TBLC) has been increasingly considered for diagnostic purposes for diffuse parenchymal lung disease (DPLD). CASE PRESENTATION: A 58 year old male with a history of idiopathic thrombocytopenic purpura status-post splenectomy and rituximab presented with dyspnea on exertion, chest pressure and a chronic cough. CT chest revealed areas of consolidation and ground glass opacities in a lower lung distribution on a background of pulmonary fibrosis. Pulmonary function tests showed mild restriction and low diffusing capacity. He underwent outpatient TBLC with histopathologic findings of organizing pneumonia, patchy chronic inflammation, fibrosis and peribronchial lymphoid hyperplasia. Labs revealed low IgG and IgA, absence of member B cells, and deficiency of T cells. The patient was diagnosed with GLILD in setting of CVID. He was started on prednisone and IVIG with improvement in imaging findings and symptoms. DISCUSSION: GLILD is a granulomatous and lymphoproliferative disorder that occurs in 8-25% of patients with CVID. Patients may have shortness of breath and cough, as well as splenomegaly, cytopenia, and adenopathy. The constellation of signs and imaging findings are suggestive but not specific. Biopsy is needed for diagnosis. SLB is associated with relatively higher morbidity and mortality compared to TBLC, and necessitates hospitalization. TBLC has been proposed as a less invasive alternative to SLB. Advantages include lower mortality and complication rate, and no requirement for hospitalization. In this case, we demonstrate the utility of TBLC done as an outpatient in obtaining a diagnostic tissue sample, with clinical improvement on steroids and IVIG. There is no standard treatment for GLILD, but corticosteroids are recommended as first line therapy. Success has also been shown with azathioprine, ritxumab and IVIG. CONCLUSIONS: Transbronchial lung cryobiopsy is emerging as a less invasive alternative modality for obtaining tissue with less morbidity, less mortality and the advantage of being performed in the outpatient setting. Further studies regarding safety, diagnostic accuracy and yield in SLB versus TBLC are required to establish TBLC as common practice. Reference #1: Granulomatous-lymphocytic interstitial lung disease (GLILD) in common variable immunodeficiency (CIVD). Park JH, Levinson AI. Clin Immunol. 2010; 134(2):97. Reference #2: Transbronchial Lung Cryobiopsy in Idiopathic Pulmonary Fibrosis: A State of the Art Review. Adv Ther (2019) 36:2193-2204. Reference #3: British Lung Foundation/United Kingdom Primary Immunodeficiency Network Consensus Statement on the Definition, Diagnosis, and Management of Granulomatous-Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency Disorders. Hurst JR, Verma N. Lowe D, Daxendale HE, Jolles S, Kelleher P, Longhurst HJ, Patel Sy, Renzoni EA, Sander CR, Avery GR, Babar JL, Buckland MS, Burns S, Egner W, Gompels MM, Gordins P, Haddock JA, Hart SP, Hayman GR, Herriot R, Hoyles RK, Huissoon AP, Jacob J, Nicholson AG, Rassl DM, Sargur RB, Savic S, Seneviratne SL, Sheaff M, Vaailta PM, Walters GI, Whitehouse JL, Wright PA, Condliffe AM. J Allergy Clin Immunol Pract. 2017;5(4):938. Epub 2017 Mar 25. DISCLOSURES: No relevant relationships by Lawrence Benjamin, source=Web Response Speaker/Speaker's Bureau relationship with Boehringer-Ingelheim Pharmaceuticals Please note: $5001 - $20000 Added 04/07/2020 by Jaime Betancourt, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Vapotherm, Inc Please note: $5001 - $20000 Added 04/07/2020 by Jaime Betancourt, source=Web Response, value=Honoraria No relevant relationships by Houda Boucekkine, source=Web Response No relevant relationships by Scott Oh, source=Web Response

Ultra-rare cystic disease.

Diffuse cystic lung diseases include a group of heterogeneous disorders characterised by the presence of cysts within the lung parenchyma, sometimes showing a characteristic computed tomography scan pattern that allows diagnosis. The pathogenetic mechanisms underlying cyst formation in the lung are still not clear and a number of hypotheses have been postulated according to the different aetiologies: ball-valve effect, ischaemic dilatation of small airways and alveoli related to infiltration and obstruction of small vessels and capillaries that supply the terminal bronchioles and connective tissue degradation by matrix metalloproteases. A wide number of lung cyst diseases have been classified into six diagnostic groups according to the aetiology: neoplastic, congenital/genetic, lymphoproliferative, infective, associated with interstitial lung diseases, and other causes. This article focuses on lymphangioleiomyomatosis, pulmonary Langerhans cell histiocytosis and Erdheim-Chester disease, Birt-Hogg-Dubé, follicular bronchiolitis and lymphocytic interstitial pneumonia, light-chain deposition disease and amyloidosis, congenital lung disease associated with aberrant lung development and growth, and cystic lung disease associated with neoplastic lesion. These cystic diseases are epidemiologically considered as ultra-rare conditions as they affect fewer than one individual per 50 000 or fewer than 20 individuals per million. Despite the rarity of this group of disorders, the increasing use of high-resolution computed tomography has improved the diagnostic yield, even in asymptomatic patients allowing prompt and correct therapy and management without the need for a biopsy.

Cryobiopsy in the diagnosis of bronchiolitis: a retrospective analysis of twenty-three consecutive patients

Bronchiolitis manifests as a variety of histological features that explain the complex clinical profiles and imaging aspects. In the period between January 2011 and June 2015, patients with a cryobiopsy diagnosis of bronchiolitis were retrospectively retrieved from the database of our institution. Clinical profiles, imaging features and histologic diagnoses were analysed to identify the role of cryobiopsy in the diagnostic process. Twenty-three patients with a multidisciplinary diagnosis of small airway disease were retrieved (14 females, 9 males; age range 31–74 years old; mean age 54.2 years old). The final MDT diagnoses were post-infectious bronchiolitis (n = 5), constrictive bronchiolitis (n = 3), DIPNECH (n = 1), idiopathic follicular bronchiolitis (n = 3), Sjogren’s disease (n = 1), GLILD (n = 1), smoking-related interstitial lung disease (n = 6), sarcoid with granulomatous bronchiolar disorder (n = 1), and subacute hypersensitivity pneumonitis (n = 2). Complications reported after the cryobiopsy procedure consisted of two cases of pneumothorax soon after the biopsy (8.7%), which were successfully managed with the insertion of a chest tube. Transbronchial cryobiopsy represents a robust and mini-invasive method in the characterization of small airway diseases, allowing a low percentage of complications and good diagnostic confidence.

Chest High-resolution Computed Tomography Imaging Features of Lung Involvement in Rheumatoid Arthritis

Objective To explore the chest high-resolution computed tomography (HRCT) features in patients with rheumatoid arthritis (RA) complicated with pulmonary involvement. Methods Totally 161 patients with RA with lung involvement were collected from June 2014 to May 2018. The chest HRCT findings were retrospectively analyzed. According to the imaging features as well as the results of history taking,pulmonary function test,pathology,and bronchoalveolar lavage fluid test,RA-related lung diseases (RA-LD) were classified and their clinical characteristics were compared. Results These 161 RA-LD patients (56 males and 105 females) whose mean age at diagnosis was (60.7±12.8) years (14-85 years) included 87 cases of usual interstitial pneumonia (UIP) (including 16 cases of possible UIP),44 cases of non-specific interstitial pneumonia (NSIP),10 cases of organizing pneumonia,7 cases of lymphocytic interstitial pneumonia,9 cases of small airway disease (SAD) (including 8 cases of bronchiolitis obliterans and 1 case of follicular bronchiolitis),and 4 other lung manifestations (including 3 cases of diffuse alveolar hemorrhage and 1 case of rheumatoid nodules). The UIP group had the oldest average age [(63.3±12.1) years old] and the highest smoking rate (41.4%). The SAD group had the youngest average age [(54.7±15.1) years old] and there was no smoking history. There were significant differences between these two groups (P=0.020,P<0.001). Seventy patients (43.5%) with RA-LD were complicated with pleural lesions. Conclusions RA involving the lung is common and has varied imaging manifestations,with interstitial lung diseases (mainly UIP and NSIP) being the most important manifestations. RA patients should undergo lung HRCT as early as possible to identify the lung involvement and related types.

Lymphocytic interstitial pneumonia and follicular bronchiolitis in children: A registry‐based case series

Pediatric lymphocytic interstitial pneumonia (LIP) and follicular bronchiolitis (FB) are poorly characterized lymphoproliferative disorders. We present and quantify demographics, radiological and histopathologic patterns, treatments and their responses, and outcomes in non-HIV-infected children with LIP and FB. This structured registry-based study included a retrospective chart review, blinded analysis of imaging studies and lung biopsies, genetic testing, and evaluation of treatments and outcomes. Of the 13 patients (eight females) studied, eight had FB, four had combined LIP/FB, and one had isolated LIP; diagnoses were highly concordant between the pathologists. Most patients became symptomatic during the first 2 years of life, with a mean lag time to diagnosis of 4 years. The most common symptoms were coughing and respiratory infections (11 out of 13 each), dyspnea (10 out of 13), and wheezing (eight out of 13). Autoantibodies were found in eight out of 13 patients. In three patients, disease-causing mutations in the COPA gene were identified. CT revealed hilar lymphadenopathy (five out of 12), ground-glass opacity (eight out of 12), consolidation (five out of 12), and cysts (four out of 13). Systemic steroids as intravenous pulses (11 out of 13) or oral intake (10 out of 13) were the main treatments and showed high response rates of 100% and 90%, respectively. Within the mean observation period of 68 months, all children had chronic courses, eight out of 13 hadsevere diseases, two died, and one worsened. Children with LIP/FB have chronic diseases that occurred in early childhood and were commonly associated with immune dysregulation as well as high morbidity and mortality. Early diagnosis and treatment may be crucial to improve the outcome.

Follicular Bronchiolitis: Two Cases with Varying Clinical and Radiological Presentation

Follicular bronchiolitis (FB) is a rare bronchiolar disorder associated with hyperplasia of the bronchial-associated lymphoid tissue (BALT). It is characterized by the development of lymphoid follicles with germinal centers in the walls of small airways. It falls under the category of lymphoproliferative pulmonary diseases (LPDs) and commonly occurs in relation to connective tissue disease, immunodeficiency, infections, interstitial lung disease (ILD), and inflammatory airway diseases. Computerized tomography (CT) findings include centrilobular nodules with patchy ground glass infiltrate, tree-in-bud findings, and air trapping. It can very rarely present as diffuse cystic lung disease. We present two cases of FB. The first case is associated with Human Immunodeficiency Virus (HIV) infection and asthma with diffuse cystic changes on the CT. The second case is associated with reactive airway disease and gastroesophageal reflux disease (GERD) with the classic centrilobular nodules and ground glass opacities on the CT.

1424 Follicular Cholangitis Presenting as Cholangiocarcinoma in a Patient With Serologic Evidence of Autoimmune Disease

INTRODUCTION: Follicular cholangitis is a rare sclerosing cholangitis of the biliary hilum that is difficult to distinguish from primary sclerosing cholangitis, immunoglobulin G4-related sclerosing cholangitis, and most imperatively, hilar cholangiocarcinoma. Pathological findings include fibrotic thickening of bile duct walls containing lymph follicles with germinal center formation. While autoimmune evaluations have previously been negative, we herein report the first case of follicular cholangitis found in the pretense of autoimmune hepatitis. CASE DESCRIPTION/METHODS: A 40-year-old female presented following a 2-month history of pruritis, fatigue, and elevation of hepatobiliary enzymes (AST 113 U/L, ALT132 U/L, ALP 499 U/L). Medical history was significant for cholestasis of pregnancy 10 years ago. Laboratory evaluation was positive for an ANA (1:160), an atypical pANCA (1:320), and an elevated F-actin (101 units) while negative for anti-mitochondrial antibody. Serum IgG levels were normal (1250 mg/dl; IgG4 subclass &lt;1). IgM level was elevated at 350 mg/dl. Liver biopsy showed dense portal lymphatic inflammation, including focal germinal center formation as well as paucity of bile ducts without florid ductal lesion or fibrosis. Initial treatment with glucocorticoids, azathioprine and ursodiol did not improve symptoms or liver chemistries. ERCP revealed a tight stricture with direct visualization (spyglass) of a biliary lesion in the distal third of the common bile duct (CBD). Cytology from the stricture returned atypical cells suspicious for adenocarcinoma. Bile duct biopsy revealed severe chronic inflammation and few atypical glands. IgG4 immunostaining was negative. She underwent pancreaticoduodenectomy due to concern for cholangiocarcinoma. Macroscopically, the CBD mucosa was diffusely granular and without mass lesions. Microscopically; bile duct fibrosis, lymphoid hyperplasia with prominent germinal centers, and rare IgG4-positive cells were consistent with severe follicular cholangitis. DISCUSSION: Unique to this case is the serological backdrop and histologic findings of autoimmune disease. Whereas previous cases have been strictly ANA negative, there appears to be an unexplored continuum of disease as evidenced by cases of follicular bronchiolitis which have been associated with autoimmune disease and have similar immunohistologic findings. Although the etiology remains unclear, the existence of an autoimmune association raises important considerations for medical therapies.

GRANULOMATOUS LYMPHOCYTIC INTERSTITIAL LUNG DISEASE: MOST COMMON NONINFECTIOUS PULMONARY COMPLICATION OF COMMON VARIABLE IMMUNODEFICIENCY

SESSION TITLE: Tuesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM INTRODUCTION: Common Variable Immunodeficiency (CVID) is the most common primary immunodeficiency. Patients with CVID suffer from recurrent sinopulmonary infections. Granulomatous lymphocytic interstitial lung disease (GLILD) is one of the dreaded noninfectious pulmonary complication of CVID. CASE PRESENTATION: A 28-year-old female was seen in Pulmonology clinic for evaluation of an abnormal CT scan of the chest, progressively worsening chest tightness, chronic productive cough and dyspnea on exertion for last 1 year. Patient had history of CVID, Chiari I malformation, and iron deficiency anemia. She worked with construction companies to monitor archeological changes. Vitals and physical exam on presentation were normal. Initial investigations showed thrombocytopenia; Sputum gram stain, fungal and acid-fast smear and aerobic and anaerobic cultures were unremarkable. CT scan of the chest, abdomen and pelvis with contrast showed diffuse reticulonodular pulmonary infiltrates predominantly in the basal lung fields, peri bronchial thickening in the lower lobes and mildly enlarged lymphadenopathy in the axilla, retroperitoneum and mesentery, and splenomegaly (13.5 cm). Differential diagnosis at the time were sarcoidosis, GLILD, fungal/atypical infections, vasculitis and malignancy. Bronchoscopy revealed acutely inflamed mucosa throughout the tracheobronchial tree, petechiae in right lower lobe. Bronchoalveolar lavage (BAL) in right medial segment and transbronchial biopsy (TBBx) in left lower lobe showed 54% lymphocytes, but no vasculitis, fungal/bacterial/viral infection, and malignancy. Working diagnosis was narrowed down to sarcoidosis and GLILD. Video assisted thoracoscopic surgery and open lung biopsy of right middle and lower lobes revealed nodular and diffuse mononuclear cell infiltrates and scattered non-necrotizing granulomas. 2nd opinion from a tertiary care center confirmed follicular bronchiolitis with associated non-necrotizing granulomatous inflammation and foci of fibrinous organizing pneumonia consistent with GLILD seen in CVID. DISCUSSION: GLLID is the most common cause of diffuse parenchymal lung disease in patients with CVID. It occurs in 8-22% of persons with CVID. The etiology of GLILD is unknown. It presents between the ages of 20 and 50. Presence of hypersplenism and polyarthritis increases the risk of GLILD in patients with CVID. Classic histopathologic pattern of GLILD is a cellular interstitial pneumonia with a combination of granulomatous and lymphoproliferative features. Optimal treatment is unknown. Glucocorticoids, IVIGs and immunosuppressive therapies have been tried. CONCLUSIONS: In patients with CVID development of respiratory signs or symptoms should be carefully evaluated for GLILD as presence of GLILD shortens the survival by approximately 50%. Reference #1: Fernández Perez ER. 2012 November. Granulomatous Lymphocytic Interstitial Lung Disease. Immunol Allergy Clin AM. 32(2012):621-32 Reference #2: Bates CA, Ellison MC, Lynch DA, et al. Granulomatous-lymphocytic lung disease shortens survival in common variable immunodeficiency. J Allergy Clin Immunol 2004;114(2):415–21. Reference #3: Tou w CM, van de Ven AA, de Jong PA, et al. Detection of pulmonary complications in common variable immunodeficiency. Pediatric Allergy Immunol 2010;21(5):793–805. DISCLOSURES: No relevant relationships by Shujaa Faryad, source=Web Response No relevant relationships by Rajamurugan Meenakshisundaram, source=Web Response

Pathological interpretation of connective tissue disease-associated lung diseases.

Connective tissue diseases (CTDs) can affect all compartments of the lungs, including airways, alveoli, interstitium, vessels, and pleura. CTD-associated lung diseases (CTD-LDs) may present as diffuse lung disease or as focal lesions, and there is significant heterogeneity between the individual CTDs in their clinical and pathological manifestations. CTD-LDs may presage the clinical diagnosis a primary CTD, or it may develop in the context of an established CTD diagnosis. CTD-LDs reveal acute, chronic or mixed pattern of lung and pleural manifestations. Histopathological findings of diverse morphological changes can be present in CTD-LDs airway lesions (chronic bronchitis/bronchiolitis, follicular bronchiolitis, etc.), interstitial lung diseases (nonspecific interstitial pneumonia/fibrosis, usual interstitial pneumonia, lymphocytic interstitial pneumonia, diffuse alveolar damage, and organizing pneumonia), pleural changes (acute fibrinous or chronic fibrous pleuritis), and vascular changes (vasculitis, capillaritis, pulmonary hemorrhage, etc.). CTD patients can be exposed to various infectious diseases when taking immunosuppressive drugs. Histopathological patterns of CTD-LDs are generally nonspecific, and other diseases that can cause similar lesions in the lungs must be considered before the diagnosis of CTD-LDs. A multidisciplinary team involving pathologists, clinicians, and radiologists can adequately make a proper diagnosis of CTD-LDs.