Immune checkpoint inhibitor-related pneumonitis with atypical radiologic features in a patient with anti-aminoacyl-tRNA synthetase antibody.

A man with non-small-cell lung cancer who was negative for anti-nuclear antibodies was admitted for dyspnea after immune checkpoint inhibitor (ICI) administration. Computed tomography (CT) showed complexed radiologic features, including subpleural and basal predominant reticular shadow with cystic structures and peribronchovascular consolidation. Although we treated him with high-dose steroid under a diagnosis of ICI-related pneumonitis, he developed acute exacerbation of pneumonitis with progressive fibrosis and volume loss. A re-evaluation identified anti-aminoacyl-tRNA synthetase antibody in the serum collected before ICI administration. This case highlights the importance of re-evaluating pre-existing autoimmune disorders in patients who develop ICI-related pneumonitis with atypical radiologic features.

An 80-year-old woman with myelofibrosis and diffuse mosaic attenuation on chest computed tomography.

An 80-year-old woman with myelofibrosis sought evaluation for progressive dyspnea. Her past medical history included essential thrombocytosis, which transformed to myelofibrosis. Inspiratory computed tomography of chest showed diffuse mosaic attenuation with lymphadenopathy. Flexible bronchoscopy with lymph node and pulmonary parenchymal cryo biopsy revealed nodular deposits of extramedullary hematopoiesis in lung parenchyma and moderate to severe vascular medial and intimal thickening of pulmonary vasculature consistent with pulmonary parenchymal extramedullary hematopoiesis associated with pulmonary hypertension (a rare compensatory mechanism in myeloproliferative disorders). In this report, we explore the manifestations, pathogenesis, treatment, and prognosis of pulmonary extramedullary hematopoiesis reported in the literature.

Connective tissue disease-related interstitial lung disease (CTD-ILD) and interstitial lung abnormality (ILA): Evolving concept of CT findings, pathology and management.

Connective tissue diseases (CTDs) demonstrating features of interstitial lung disease (ILD) include systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), dermatomyositis (DM) and polymyositis (PM), ankylosing spondylitis (AS), Sjogren syndrome (SS), and mixed connective tissue disease (MCTD). On histopathology of lung biopsy in CTD-related ILDs (CTD-ILDs), multi-compartment involvement is an important clue, and when present, should bring CTD to the top of the list of etiologic differential diagnoses. Diverse histologic patterns including nonspecific interstitial pneumonia (NSIP), usual interstitial pneumonia (UIP), organizing pneumonia, apical fibrosis, diffuse alveolar damage, and lymphoid interstitial pneumonia can be seen on histology in patients with CTD-ILDs. Although proportions of ILDs vary, the NSIP pattern accounts for a large proportion, especially in SSc, DM and/or PM and MCTD, followed by the UIP pattern. In RA patients, interstitial lung abnormality (ILA) is reported to occur in approximately 20-60% of individuals of which 35-45% will have progression of the CT abnormality. Subpleural distribution and greater baseline ILA involvement are risk factors associated with disease progression. Asymptomatic CTD-ILDs or ILA patients with normal lung function and without evidence of disease progression can be followed without treatment. Immunosuppressive or antifibrotic agents for symptomatic and/or fibrosing CTD-ILDs can be used in patients who require treatment.

Interstitial lung abnormality (ILA) and nonspecific interstitial pneumonia (NSIP).

This review article aims to address mysteries existing between Interstitial Lung Abnormality (ILA) and Nonspecific Interstitial Pneumonia (NSIP). The concept and definition of ILA are based upon CT scans from multiple large-scale cohort studies, whereas the concept and definition of NSIP originally derived from pathology with evolution to multi-disciplinary diagnosis. NSIP is the diagnosis as Interstitial Lung Disease (ILD) with clinical significance, whereas only a part of subjects with ILA have clinically significant ILD. Eventually, both ILA and NSIP must be understood in the context of chronic fibrosing ILD and progressive ILD, which remains to be further investigated.

Connective tissue disease-related interstitial lung disease (CTD-ILD) and interstitial lung abnormality (ILA): Evolving concept of CT findings, pathology and management.

The connective tissue diseases (CTDs) demonstrating features of interstitial lung disease (ILD) include systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), progressive systemic sclerosis (PSS), dermatomyositis (DM) and polymyositis (PM), ankylosing spondylitis (AS), Sjogren's syndrome (SS), and mixed connective tissue disease (MCTD). In RA patients in particular, interstitial lung abnormality (ILA) (of varying degrees; severe vs. mild) is reported to occur in approximately 20-60 % of individuals and CT disease progression occurs in approximately 35-45 % of them. The ILAs have been associated with a spectrum of functional and physiologic decrement. The identification of progressive ILA may enable appropriate surveillance and the commencement of treatment with the goal of improving morbidity and mortality rates of established RA-ILD. Subpleural distribution and higher baseline ILA/ILD extent were risk factors associated with disease progression. At histopathologic analysis, connective tissue disease-related interstitial lung diseases (CTD-ILDs) are diverse and include nonspecific interstitial pneumonia (NSIP), usual interstitial pneumonia (UIP), organizing pneumonia (OP), apical fibrosis, diffuse alveolar damage (DAD), and lymphoid interstitial pneumonia (LIP). Even though proportions of ILDs vary, NSIP pattern accounts for a large proportion, especially in PSS, DM/PM and MCTD, followed by UIP pattern. Evidence has been published that treatment of subclinical CT lung abnormalities showing a tendency to progress to ILD may stabilize the CT alterations. The identification of subclinical lung abnormalities can be appropriate in the management of the disease and CT appears to be the gold standard for the evaluation of lung parenchyma.

Pleuroparenchymal fibroelastosis-like lesions in patients with interstitial pneumonia diagnosed by multidisciplinary discussion with surgical lung biopsy.

PURPOSE: The present study aimed to evaluate the significance of Pleuroparenchymal fibroelastosis (PPFE)-like lesions in predicting prognosis in patients with chronic interstitial pneumonia (IP). METHOD: The present study enrolled 207 patients with IP in whom surgical lung biopsy was performed. Among the patients enrolled in the present study, 77 had idiopathic pulmonary fibrosis (IPF), 15 had nonspecific interstitial pneumonia (NSIP), 13 had chronic hypersensitivity pneumonitis (CHP), 41 had connective tissue disease (CTD), three had PPFE, and 58 had unclassifiable diagnosis. The incidence, characteristics, and thickness of PPFE-like lesions were evaluated in each patient with IP. Additionally, the influence of PPFE-like lesions on the prognosis was also determined. RESULTS: Of 207 patients, 160 (77.3 %) showed PPFE-like lesions. The frequency of PPFE-like lesions was similar in patients with IPF, NSIP, CHP, CTD, and unclassifiable diagnosis (79.5 %, 79.5 %, 73.2 %, 65.9 %, and 81 %, respectively); however, PPFE-like lesions were present in all patients with PPFE (p = 0.42). Consequently, there was no significant difference in the characteristics of PPFE-like lesions among patients with all forms of IP, except PPFE. PPFE-like lesions were not a significant predictor of prognosis (hazard ratio [HR], 1.16; 95 % confidence interval [CI], 0.64-2.10, p = 0.62); however, patients with PPFE-like lesions under the aortic arch had significantly poorer prognoses (HR, 2.70; 95 % CI, 1.66-4.39, p < 0.001). For craniocaudal extent comparison, patients with IPF with PPFE-like lesions below the level of the carina had significantly poorer prognoses than those without PPFE-like lesions (p = 0.001, overall survival 53.1 and 80.6, respectively). CONCLUSION: PPFE-like lesions are common in patients with IP, and their characteristics were not significantly different among all forms of IP, except idiopathic PPFE. The broad extent of PPFE-like lesions is an important predictor of prognosis in patients with IPF.

A case of acute progressive diffuse interstitial lung disease preceding idiopathic multicentric Castleman disease.

It has been considered that idiopathic multicentric Castleman disease often involves pulmonary complications recognized as lymphocytic interstitial pneumonia. On the other hand, recent reports show that the computed tomography often show diffuse interstitial lung disease inconsistence with lymphocytic interstitial pneumonia. Pulmonary diseases with idiopathic multicentric Castleman disease are still rare and poorly understood. Here, we report a case of acute progressive diffuse interstitial lung disease, diagnosed as non-specific interstitial pneumonia, preceding idiopathic multicentric Castleman disease. A 65-year-old male visited our outpatient clinic for dyspnea on exertion. Imaging tests revealed interstitial lung disease showing non-specific interstitial pneumonia pattern, pulmonary function test proved the decline of vital capacity and laboratory tests showed increased fibrosis biomarkers; therefore, initially, he had been diagnosed as non-specific interstitial pneumonia. However, imaging tests also showed mediastinum lymphadenopathy, and laboratory tests revealed increased interleukin-6. Idiopathic multicentric Castleman disease was suspected. The lung and mediastinum lymph node biopsies were performed, and pathological findings of the lymph nodes were compatible with multicentric Castleman disease. Pathological findings of the lung showed that the fibrous thickening of interstitium and the collapse of alveoli. We diagnosed this case as idiopathic multicentric Castleman disease preceded by diffuse interstitial lung disease. Treatment with prednisolone improved the dyspnea, and the pulmonary lesions disappeared. The presented case suggests that interstitial lung disease could precede idiopathic multicentric Castleman disease. Chest physicians should be aware that idiopathic multicentric Castleman disease is one of the causative diseases of diffuse interstitial lung disease like non-specific interstitial pneumonia on the chest images.

IgG4-related disease presenting with combined pulmonary fibrosis and emphysema (CPFE).

A 64-year-old man was admitted to our hospital with an abnormal chest shadow. The patient was a current-smoker and had a past illness of autoimmune pancreatitis with a high serum level of IgG4, 348 mg/dL. Chest CT showed upper-lobe emphysema, and lower-lobe reticulation with honeycombing, suggestive of combined pulmonary fibrosis with emphysema (CPFE). Surgical lung biopsy was revealed a usual interstitial pneumonia pattern with marked infiltration of IgG4-positive plasma cells. The patient was diagnosed with IgG4 related disease (IgG4-RD) presenting with CPFE. Pulmonary manifestation was improved by corticosteroid therapy. IgG4-RD may be an underlying condition in patient with CPFE.

An autopsy case of bird-related chronic hypersensitivity pneumonitis presenting with repeated acute exacerbation.

A 68-year-old woman was admitted to our hospital with a dry cough in 2010. Chest computed tomography showed the appearance of a nonspecific interstitial pneumonia (NSIP) pattern. Video-assisted thoracoscopic surgery (VATS) was performed, and the specimens prominently showed a usual interstitial pneumonia (UIP) pattern. She was diagnosed with bird-related chronic hypersensitivity pneumonitis (BRCHP) on the basis of the detection of antibodies to pigeon dropping extract in her serum and a history of using feather-filled duvets and indirect exposure to birds in her living environment. Even though she was treated with corticosteroids and immunosuppressants and recommended to avoid bird-related antigens, she had a progressive course with repeated acute exacerbation episodes and died of respiratory failure. The autopsy findings showed diffuse alveolar damage superimposed on UIP. Clinicians should be aware that BRCHP patients especially with histopathologically UIP pattern may experience acute exacerbation.

Lymphocytic interstitial pneumonia in a patient with mixed connective tissue disease - A case report.

Lymphocytic interstitial pneumonia (LIP) is an uncommon interstitial lung disease that is characterized by an interstitial infiltrate of lymphoplasmacytic cells. While idiopathic LIP appears to be extremely rare, most reported cases of LIP have been associated with coexisting immune derangements, particularly autoimmune diseases such as Sjögren's syndrome. In this report, we describe the presentation of LIP in a patient with underlying mixed connective tissue disease.

Interstitial pneumonia caused by dabigatran.

We describe the case of a 73-year-old man who experienced dry cough and exertional dyspnea after dabigatran administration. Chest radiographs revealed the development of bilateral consolidative and ground glass opacity, and transbronchial lung biopsy showed organized materials in the alveolar spaces with moderate inflammatory infiltrate and focal fibrosis. Lung opacity gradually disappeared after discontinuing dabigatran. To date, there has been only one report regarding dabigatran-induced lung injury, except for alveolar hemorrhage and eosinophilic pneumonia. Therefore, we should consider that any drug can cause various types of lung injuries.

Lung histopathological pattern in a survivor with rapidly progressive interstitial lung disease and anti-melanoma differentiation-associated gene 5 antibody-positive clinically amyopathic dermatomyositis.

Anti-melanoma differentiation-associated gene 5 (MDA5) antibodies are specific indicators of patients with dermatomyositis, particularly clinically amyopathic dermatomyositis (CADM). CADM is occasionally accompanied by fatal, treatment-resistant, rapidly-progressive interstitial lung disease (RP-ILD). All previous reports showed that histopathological findings in RP-ILD with anti-MDA5 antibody-positive CADM indicated diffuse alveolar damage (DAD). This is the first report describing a non-DAD pattern in RP-ILD with anti-MDA5 antibody-positive CADM, which was improved by immunosuppressive therapy. This case may be a milder clinical phenotype than a typical DAD pattern in RP-ILD with anti-MDA5 antibody-positive CADM.