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We report a 60-year-old man with humidifier lung showing diffusely distributed centrilobular micronodules and branching opacities on chest computed tomography (CT). Fever and dyspnea occurred 2 months after using an ultrasonic humidifier. KL-6 and SP-D were within normal ranges. Bronchoalveolar lavage showed elevated lymphocytes (53 %) and histological findings of transbronchial lung biopsy demonstrated organizing pneumonia. His condition improved after cessation of the humidifier. A provocation test exhibited a positive response to the humidifier. Humidifier lung should be considered as a differential diagnosis in patients with these CT findings. Detailed clinical, pathological and microbiological examinations are needed to exclude other diseases.
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We report a 68-year-old woman with tracheobronchitis and laryngitis associated with Crohn's disease (CD), which was discovered during the evaluation of suspected lung cancer. She had no symptoms induced by these upper airway diseases (UADs). Bronchoscopy revealed swelling of the epiglottis with edematous change and a mass like epiglottis fold. There were nodular and edematous changes in the trachea and bilateral main bronchus. Histological findings demonstrated infiltration by numerous lymphocytes and plasma cells. Dexamethasone as the premedication for chemotherapy against lung cancer was efficacious for these extraintestinal manifestations of CD. Our case was rare in that bronchial lesion and UADs appeared concomitantly.
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Anti-melanoma differentiation-associated gene 5 (MDA5) and anti-aminoacyl-tRNA synthetase (ARS) antibodies are two major myositis-specific autoantibodies with distinct clinical features. However, the clinical course remains unclear in patients with clinically amyopathic dermatomyositis (CADM)-interstitial lung disease (ILD) who have co-existing anti-MDA5 and anti-ARS antibodies. Here, we describe the case of a 32-year-old woman with CADM-ILD who had anti-MDA5 and anti-PL12 antibodies. Her serum ferritin level was within the normal range. However, chest computed tomography revealed bilateral lower-lobe consolidation and ground-glass opacities. Treatment with prednisolone and immunosuppressants was successful in improving the skin lesion and ILD, but relapse occurred on reducing the dose of prednisolone. These clinical features match those of anti-ARS antibody-positive dermatomyositis-ILD. Because these two conditions show significantly different clinical features and require different intensities of treatment, clinicians should carefully follow-up these patients throughout the course of the disease.
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BACKGROUND: Clinical efficacy of immune checkpoint inhibitors (ICIs) for non-small cell lung cancer (NSCLC) with uncommon histology (uNSCLC) is unknown. METHODS: Patients with NSCLC treated with ICI monotherapy between January 2014 and December 2018 in 10 Japanese hospitals were retrospectively evaluated. The patients were divided into: (1) NSCLC with common histology (cNSCLC), defined as adenocarcinoma and squamous cell carcinoma; and (2) uNSCLC, defined as incompatibility with morphological and immunohistochemical criteria for adenocarcinoma or squamous cell carcinoma. Propensity score matching was performed to balance the two groups. RESULTS: Among a total of 175 patients included, 44 with uNSCLC (10 pleomorphic carcinomas, 9 large cell neuroendocrine carcinomas, 2 large cell carcinomas, and 23 not otherwise specified) and 44 with matched cNSCLC (32 adenocarcinomas and 12 squamous cell carcinomas) were selected for analyses. Median progression-free survival (PFS) (4.4 months, 95% confidence interval [CI] 1.8-7.7 months) and overall survival (OS) (11.4 months, 95% CI 7.4-27.4 months) in the uNSCLC patients were not significantly different from those in matched cNSCLC patients (5.4 months, 95% CI 3.1-7.6 months, p = 0.761; and 14.1 months, 95% CI 10.6-29.6 months, p = 0.381). In multivariate analysis, Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0-1 and programmed death ligand-1 (PD-L1) expression were predictive for PFS and OS in uNSCLC. CONCLUSIONS: ICIs had similar clinical efficacy for treatment of uNSCLC and cNSCLC. Good ECOG-PS and PD-L1 expression were predictive for efficacy of ICIs in uNSCLC.
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Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Japão , Modelos Logísticos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Intervalo Livre de Progressão , Pontuação de Propensão , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
A 41-year-old man presented with multiple superficial lymph nodes (LNs) swollen with elevated levels of serum immunoglobulin (Ig)G4 and C-reactive protein. Histological findings of his left inguinal LN revealed lymphoplasmacytic infiltration with numerous IgG4-positive plasma cells; IgG4+/IgG+ plasma cell ratio >40%. Chest computed tomography (CT) showed poorly defined centrilobular nodules, interlobular septal thickening, consolidations, and mediastinal LNs swelling. Bronchoalveolar lavage fluid (BALF) showed elevated eosinophils. A surgical lung biopsy showed focal dense eosinophil infiltration, in addition to lymphoplasmacytic infiltration, but few IgG4+ plasma cells. The diagnosis of multicentric Castleman disease (MCD) was made because of serum interleukin-6elevation. Treatment with prednisolone and tocilizumab improved his symptoms and lung lesions. This case shows that overlapping clinical and pathological features of MCD and IgG4-related disease may present in a single patient, showing the difficulty in distinguishing between these two diseases.
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BACKGROUND: Lung fibrosis is a serious life-threatening condition whose manifestation varies according to the localization and characteristics of fibroblasts, which are considered heterogeneous. Therefore, to better understand the pathology and improve diagnosis and treatment of this disease, it is necessary to elucidate the nature of this heterogeneity and identify markers for the accurate classification of human lung fibroblast subtypes. METHODS: We characterized distinct mouse lung fibroblast subpopulations isolated by fluorescence-activated cell sorting (FACS) and performed microarray analysis to identify molecular markers that could be useful for human lung fibroblast classification. Based on the expression of these markers, we evaluated the fibroblast-like cell subtype localization in normal human lung samples and lung samples from patients with idiopathic pulmonary fibrosis (IPF). RESULTS: Mouse lung fibroblasts were classified into Sca-1high fibroblasts and Sca-1low fibroblasts by in vitro biological analyses. Through microarray analysis, we demonstrated CD248 and integrin alpha-8 (ITGA8) as cell surface markers for Sca-1high fibroblasts and Sca-1low fibroblasts, respectively. In mouse lungs, Sca-1high fibroblasts and Sca-1low fibroblasts were localized in the collagen fiber-rich connective tissue and elastic fiber-rich connective tissue, respectively. In normal human lungs and IPF lungs, two corresponding major fibroblast-like cell subtypes were identified: CD248highITGA8low fibroblast-like cells and CD248lowITGA8high fibroblast-like cells, localized in the collagen fiber-rich connective tissue and in the elastic fiber-rich connective tissue, respectively. CONCLUSION: CD248highITGA8low fibroblast-like cells and CD248lowITGA8high fibroblast-like cells were localized in an almost exclusive manner in human lung specimens. This human lung fibroblast classification using two cell surface markers may be helpful for further detailed investigations of the functions of lung fibroblast subtypes, which can provide new insights into lung development and the pathological processes underlying fibrotic lung diseases.
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Antígenos CD/metabolismo , Antígenos de Neoplasias/metabolismo , Fibroblastos/metabolismo , Fibrose Pulmonar Idiopática/patologia , Cadeias alfa de Integrinas/metabolismo , Pulmão/citologia , Idoso , Animais , Antígenos Ly/metabolismo , Tecido Conjuntivo/patologia , Células do Tecido Conjuntivo , Tecido Elástico , Fibroblastos/classificação , Citometria de Fluxo , Humanos , Técnicas In Vitro , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Pessoa de Meia-Idade , Análise Serial de TecidosRESUMO
We herein report a 38-year-old woman with breast cancer who developed Pneumocystis jirovecii pneumonia (PCP) during neoadjuvant dose-dense chemotherapy combined with dexamethasone as antiemetic therapy. Chest computed tomography showed bilateral ground-glass opacities and consolidation. The serum ß-D-glucan levels were elevated, and P. jirovecii DNA was detected from the bronchoalveolar lavage fluid by polymerase chain reaction. Her clinical findings improved with trimethoprim/sulfamethoxazole and adjunctive steroid therapy. Clinicians must be mindful of the manifestations of PCP in non-human immunodeficiency virus (HIV)-infected immunocompromised patients and include the possibility of PCP in the differential diagnosis when confronted with breast cancer on dose-dense chemotherapy showing diffuse lung disease.
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Corticosteroides/uso terapêutico , Antibacterianos/uso terapêutico , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Pneumonia por Pneumocystis/induzido quimicamente , Pneumonia por Pneumocystis/tratamento farmacológico , Adulto , Feminino , Humanos , Terapia Neoadjuvante/efeitos adversos , Pneumocystis carinii/isolamento & purificação , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/fisiopatologia , Resultado do TratamentoRESUMO
Although differentiation of lung fibroblasts into α-smooth muscle actin (αSMA)-positive myofibroblasts is important in the progression of idiopathic pulmonary fibrosis (IPF), few biomarkers reflecting the fibrotic process have been discovered. We performed microarray analyses between FACS-sorted steady-state fibroblasts (lineage (CD45, TER-119, CD324, CD31, LYVE-1, and CD146)-negative and PDGFRα-positive cells) from untreated mouse lungs and myofibroblasts (lineage-negative, Sca-1-negative, and CD49e-positive cells) from bleomycin-treated mouse lungs. Amongst several genes up-regulated in the FACS-sorted myofibroblasts, we focussed on Ltbp2, the gene encoding latent transforming growth factor-ß (TGF-ß) binding protein-2 (LTBP2), because of the signal similarity to Acta2, which encodes αSMA, in the clustering analysis. The up-regulation was reproduced at the mRNA and protein levels in human lung myofibroblasts induced by TGF-ß1. LTBP2 staining in IPF lungs was broadly positive in the fibrotic interstitium, mainly as an extracellular matrix (ECM) protein; however, some of the αSMA-positive myofibroblasts were also stained. Serum LTBP2 concentrations, evaluated using ELISA, in IPF patients were significantly higher than those in healthy volunteers (mean: 21.4 compared with 12.4 ng/ml) and showed a negative correlation with % predicted forced vital capacity (r = -0.369). The Cox hazard model demonstrated that serum LTBP2 could predict the prognosis of IPF patients (hazard ratio for death by respiratory events: 1.040, 95% confidence interval: 1.026-1.054), which was validated using the bootstrap method with 1000-fold replication. LTBP2 is a potential prognostic blood biomarker that may reflect the level of differentiation of lung fibroblasts into myofibroblasts in IPF.
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Biomarcadores/metabolismo , Fibrose Pulmonar Idiopática/genética , Proteínas de Ligação a TGF-beta Latente/genética , Pulmão/metabolismo , Miofibroblastos/metabolismo , Idoso , Animais , Bleomicina/farmacologia , Células Cultivadas , Feminino , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Perfilação da Expressão Gênica/métodos , Humanos , Fibrose Pulmonar Idiopática/sangue , Fibrose Pulmonar Idiopática/metabolismo , Proteínas de Ligação a TGF-beta Latente/sangue , Proteínas de Ligação a TGF-beta Latente/metabolismo , Pulmão/citologia , Masculino , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Miofibroblastos/citologia , Miofibroblastos/efeitos dos fármacos , Fator de Crescimento Transformador beta1/farmacologiaRESUMO
Pathological differential diagnoses of pleuroparenchymal fibroelastosis (PPFE) include usual interstitial pneumonia (UIP) and pulmonary apical cap (PAC); however, there are no specific immunostaining makers to distinguish between these diseases. We performed immunohistochemistry using several pleural mesothelial cell-related markers, including cytokeratin-5/6, CAM5.2, WT-1, calretinin, desmin and podoplanin, for PPFE (n = 4), UIP (n = 10) and PAC (n = 3) lung sections. Among the examined markers, in PPFE and PAC lungs podoplanin commonly showed positivity for spindle cells both in thickened pleura and subpleural fibroelastosis lesions; these cells were also stained with α-smooth muscle actin, a marker of myofibroblasts. However, even in elastic fibre-rich cases, UIP lungs did not show such podoplanin-positive myofibroblasts in pleura/subpleura and fibroblastic foci. These findings were also verified using immunofluorescence. By contrast, immunohistochemically as well as morphologically, the difference between PPFE and PAC was not apparent. The presence of podoplanin-positive myofibroblasts could be a pathological hallmark of PPFE, suggesting a pathogenic process distinct from UIP but common to PAC.
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Fibrose Pulmonar Idiopática/diagnóstico , Doenças Pulmonares Intersticiais/diagnóstico , Miofibroblastos/metabolismo , Idoso , Bases de Dados Factuais , Diagnóstico Diferencial , Tecido Elástico/patologia , Feminino , Humanos , Fibrose Pulmonar Idiopática/metabolismo , Fibrose Pulmonar Idiopática/patologia , Doenças Pulmonares Intersticiais/metabolismo , Doenças Pulmonares Intersticiais/patologia , Masculino , Pessoa de Meia-Idade , Miofibroblastos/patologia , Pleura/patologiaRESUMO
We present an autopsy case of a "so-called adenosarcoma with ossification of the liver" in a 63-year-old man. Macroscopically, the well-circumscribed tumor with portal vein invasion was observed in the right lobe of the liver. The cut surface of the tumor had a solid and microcystic appearance. Microscopically, the tumor was characterized by a benign epithelial component and a malignant mesenchymal component. We believe the presence of biliary adenofibroma-like areas and the von Meyenburg complexes suggests that the tumor is possibly associated with a biliary adenofibroma. In addition, the present tumor was unique in that it showed scattered heterotopic ossification. Immunohistochemical study showed that the mesenchymal atypical spindle cells had characteristics of undifferentiated mesenchymal cells. This is the first report of a primary hepatic so-called adenosarcoma.
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Adenofibroma/patologia , Adenossarcoma/patologia , Doenças Biliares/patologia , Neoplasias Hepáticas/patologia , Ossificação Heterotópica/patologia , Autopsia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Radiologic pleuroparenchymal fibroelastosis (PPFE)-like lesion including pulmonary apical cap can be occasionally observed in clinical settings. However, the significance of radiologic PPFE-like lesion is unclear in connective tissue disease (CTD)-related interstitial lung disease (ILD). MATERIALS AND METHODS: A total of 113 patients with CTD-related ILD were enrolled and assessed for radiologic PPFE-like lesion, which was defined as bilateral, upper lobe, and subpleural dense consolidations with or without pleural thickening on chest high-resolution computed tomography. The clinical, radiologic, and pathologic characteristics were evaluated. RESULTS: Radiologic PPFE-like lesion was found in 21 patients (19%) and were relatively frequent in those with systemic sclerosis (6/14: 43%) and primary Sjögren's syndrome (4/14: 29%). Patients with PPFE-like lesion were significantly older, had lower body mass index, higher ratio of residual volume to total lung capacity, and higher complication rate of pneumothorax and/or pneumomediastinum than those without. Twelve of the 21 patients were diagnosed radiologically as usual interstitial pneumonia (UIP) or possible UIP pattern. Two of three patients who underwent surgical lung biopsy of the upper lobes showed UIP on histopathology. Another patient was confirmed to have upper lobe PPFE on autopsy. During the clinical course, progression of the radiologic PPFE-like lesions was observed in 13 of 21 patients. Six patients died (mortality rate: 29%) and their PPFE-like lesions were commonly progressive. In the total cohort, our multivariate analysis identified the presence of PPFE-like lesion as a significant risk factor for respiratory death (hazard ratio: 4.10, 95% confidence interval: 1.33-12.65, p = 0.01). CONCLUSION: In patients with CTD-related ILD, radiologic PPFE-like lesion, which may present as not only PPFE but also apical cap and upper lobe subpleural fibrosis commonly due to UIP, was not uncommon and was associated with poor prognosis. Clinicians should be cautious with this radiologic finding, particularly when it is progressive.
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Doenças do Tecido Conjuntivo/complicações , Doenças Pulmonares Intersticiais/complicações , Doenças Pleurais/complicações , Fibrose Pulmonar/complicações , Idoso , Doenças do Tecido Conjuntivo/diagnóstico por imagem , Doenças do Tecido Conjuntivo/patologia , Feminino , Humanos , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/patologia , Masculino , Pessoa de Meia-Idade , Doenças Pleurais/diagnóstico por imagem , Doenças Pleurais/patologia , Prognóstico , Fibrose Pulmonar/diagnóstico por imagem , Fibrose Pulmonar/patologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
Our aims were to identify pericyte-specific markers for the analysis of formalin-fixed, paraffin-embedded human tissue samples, and to characterize perivascular myoid cell neoplasms phenotypically. Previously identified pericyte markers failed to distinguish pericytes from other cellular types, such as vascular smooth muscle cells (vSMCs) and fibroblasts, in immunohistochemistry analysis. However, we compared gene expression profiles between pericytes, vSMCs, and fibroblasts, and performed human skin vasculature immunohistochemistry analysis, which led to the identification of myosin 1B (MYO1B) as a novel pericyte marker. Afterward, we investigated the expression levels of MYO1B and h-caldesmon (h-CD) in perivascular myoid cell neoplasms, angioleiomyomas (n=28), glomus tumors (n=23), and myopericytomas (n=3). Angioleiomyomas were shown to contain MYO1B-negative and h-CD-positive (MYO1B-hCD+) tumor cells, with vSMC features. Glomus tumors were predominantly composed of the MYO1B+hCD+ tumor cells, with the intermediate features between pericytes and vSMCs, whereas MYO1B+hCD- tumor cells with pericytic features and/or the MYO1B-hCD+ tumor cells with vSMC features were frequently found in these tumors. The perivascular concentric pattern of 2 myopericytoma cases was composed of MYO1B+hCD+ tumor cells, whereas that of one myopericytoma contained MYO1B-hCD+ tumor cells. These results indicate that the ability to distinguish between these cell types may allow us to understand the differentiation and origin of perivascular myoid cell neoplasms. This is the first study to identify cell properties of perivascular myoid cell neoplasms by using a pericyte-specific marker with considerably lower expression in vSMCs and fibroblasts.
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Angiomioma/química , Biomarcadores Tumorais/análise , Tumor Glômico/química , Miofibroma/química , Miosina Tipo I/análise , Pericitos/química , Neoplasias de Tecidos Moles/química , Adulto , Idoso , Angiomioma/genética , Angiomioma/patologia , Animais , Biomarcadores Tumorais/genética , Biópsia , Proteínas de Ligação a Calmodulina/análise , Diferenciação Celular , Linhagem da Célula , Feminino , Fibroblastos/química , Imunofluorescência , Perfilação da Expressão Gênica , Tumor Glômico/genética , Tumor Glômico/patologia , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Pessoa de Meia-Idade , Miócitos de Músculo Liso/química , Miócitos de Músculo Liso/patologia , Miofibroma/genética , Miofibroma/patologia , Miosina Tipo I/genética , Pericitos/patologia , Fenótipo , Pele/química , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/patologiaRESUMO
A 66-year-old man was found to have a very small ground-glass opacity in the apex of the left lung. Because the ground-glass opacity had slightly enlarged after 2 years, video-assisted thoracic surgery (VATS) biopsy was performed. The histological findings showed the alveolar spaces to be filled with PAS-positive granular materials, so pulmonary alveolar proteinosis was diagnosed. Although his bronchoalveolar lavage fluid (BALF) did not have a milky appearance, his serum and BALF GM-CSF autoantibody and serum KL-6 levels were elevated. Asymptomatic pulmonary alveolar proteinosis may appear as very small ground-grass opacities.
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Pulmão/diagnóstico por imagem , Proteinose Alveolar Pulmonar/diagnóstico por imagem , Idoso , Humanos , Masculino , Proteinose Alveolar Pulmonar/patologia , Tomografia Computadorizada por Raios XRESUMO
We report two cases of pneumonitis caused by Seishinrenshiin. A 54-year-old woman and a 80-year-old man had taken Seishinrenshiin for cystitis and benign prostatic hypertrophy. Their chest radiograph showed diffuse ground-glass shadows in the whole lung fields and chest CT showed diffuse ground-glass-opacities predominantly in the lower lung fields of both lungs. Biochemical tests revealed mild liver dysfunction and inflammatory reactions. Their abnormal chest shadows disappeared after discontinuation of Seishinrenshiin. We should be aware that Seishinrenshiin, as well as other Chinese herbal medicine, could be cause of drug-induced pneumonitis.
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Medicamentos de Ervas Chinesas/efeitos adversos , Pneumonia/induzido quimicamente , Idoso de 80 Anos ou mais , Cistite/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hiperplasia Prostática/tratamento farmacológicoRESUMO
A 54-year-old woman was found to have abnormal shadows on her chest radiograph taken on an annual medical examination. The chest radiograph showed multiple nodules in the bilateral middle and lower lung fields accompanied with bilateral hilar lymphadenopathy. A computed tomography of the neck and chest revealed nodules in her right middle lobe and bilateral lower lobes with an enlarged thyroid. A metastatic malignant disease involving both thyroid and lungs was suspected, therefore thyroid and lung biopsies were performed. The histological examination of the thyroid and the lung specimens revealed non-caseating epithelioid cell granulomas which were compatible with sarcoidosis. Although the thyroid involvement of sarcoidosis is rare, it should be included in the differential diagnosis with patients with thyroid swelling.