Autoimmune Pulmonary Alveolar Proteinosis with Suspected Exacerbation after Osimertinib Administration for Lung Cancer.

A 46-year-old woman with lung cancer who received chemotherapy was admitted to our hospital for lower-lobe bilateral ground-glass opacity (GGO). GGO developed after the lung cancer diagnosis, deteriorated after the initiation of osimertinib, and incompletely decreased after interrupting osimertinib; therefore, flexible bronchoscopy was performed. Transbronchial lung biopsy histology and anti-granulocyte/macrophage colony-stimulating factor autoantibody positivity revealed autoimmune pulmonary alveolar proteinosis (aPAP) that did not require treatment. This rare case of aPAP comorbid with lung cancer suggested that using PAP findings to differentiate from drug-induced lung injury or lymphangitis is difficult and that osimertinib was suspected to exacerbate aPAP.

Novel Screening System of Virulent Strains for the Establishment of a Mycobacterium avium Complex Lung Disease Mouse Model Using Whole-Genome Sequencing.

The establishment of animal models reflecting human Mycobacterium avium complex (MAC) lung disease (LD) pathology has the potential to expand our understanding of the disease pathophysiology. However, inducing sustained infection in immunocompetent mice is difficult since MAC generally shows less virulence and higher genetic variability than M. tuberculosis. To overcome this hurdle, we developed a screening system for identifying virulent MAC strains using whole-genome sequencing (WGS). We obtained nine clinical strains from Mycobacterium avium complex lung disease (MAC-LD) patients and divided them into two groups to make the mixed strain inocula for infection. Intranasal infection with the strain mixture of both groups in BALB/c mice resulted in progressive infection and extensive granuloma formation in the lungs, suggesting the existence of highly pathogenic strains in each group. We hypothesized that the change in the abundance of strain-specific single-nucleotide variants (SNVs) reflects the change in bacterial number of each strain in infected lungs. Based on this hypothesis, we quantified individual strain-specific SNVs in bacterial DNA from infected lungs. Specific SNVs for four strains were detected, suggesting the pathogenicity of these four strains. Consistent with these results, individual infection with these four strains induced a high lung bacterial burden, forming extensive peribronchial granuloma, while the other strains showed a decreased lung bacterial burden. The current method combining mixed infection and WGS accurately identified virulent strains that induced sustained infection in mice. This method will contribute to the establishment of mouse models that reflect human MAC-LD and lead to antimycobacterial drug testing. IMPORTANCE To promote research on Mycobacterium avium complex (MAC) pathogenicity, animal models reflecting human progressive MAC lung disease (MAC-LD) are needed. Because there is high genetic and virulence diversity among clinical MAC strains, choosing a suitable strain is an important process for developing a mouse model. In this study, we developed a screening system for virulent strains in mice by combining mixed infection and whole-genome sequencing analysis. This approach is designed on the hypothesis that in vivo virulence of MAC strains can be examined simultaneously by comparing changes in the abundance of strain-specific single-nucleotide variants in the mouse lungs after infection with mixed strains. The identified strains were shown to induce high bacterial burdens and cause extensive peribronchial granuloma resembling the pulmonary pathology of human MAC-LD. The current method will help researchers develop mouse models that reflect human MAC-LD and will lead to further investigation of MAC pathogenicity.

Sjögren's Syndrome with Pleural Effusion: Difficult to Distinguish from Tuberculous Pleurisy Because of a High Adenosine Deaminase Level.

An 84-year-old woman visited our hospital for dyspnea due to right pleural effusion, with lymphocytic dominance and a high adenosine deaminase (ADA) level, that had been noted 1 month earlier. She was suspected of having tuberculosis pleurisy; however, anti-tuberculosis treatment yielded no improvements. She was diagnosed with pleural effusion due to primary Sjögren's syndrome (SjS) based on her dry eyes and mouth, positivity for anti-Sjögren's-syndrome-related antigen A/B, and histopathologic findings of a lip biopsy and thoracoscopic pleural biopsy. Her symptoms improved after starting steroid therapy. Cases of pleural effusion due to SjS with a high ADA level may be misdiagnosed as tuberculosis pleurisy.

An Autopsy Case of Pulmonary Veno-Occlusive Disease Complicated with Chronic Obstructive Pulmonary Disease and Severe Pulmonary Hypertension.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease with obstructed airflow and frequently causes secondary mild-moderate pulmonary hypertension (PH). However, a low proportion (1%-5%) of COPD patients develop severe therapy-resistant PH, and it is crucial to determine whether the patient has another disease capable of causing severe PH, including pulmonary arterial hypertension.Here, we describe a case of a 71-year-old male with COPD complicated by severe PH and right heart failure. He had a history of heavy smoking and developed progressive hypoxemia on exertion. He had severe airflow limitation (forced expiratory volume % in one second, FEV 1.0% = 42.8%) with a markedly reduced diffusing capacity of the lung (predicted diffusion capacity of carbon monoxide, %DLCO = 29%), and high-resolution computed tomography (CT) demonstrated significant lung parenchymal abnormalities such as diffuse interlobular septal thickening, ground-glass opacities, and enlarged mediastinal lymph nodes. He was diagnosed with group 3 PH caused by COPD but resistant to the treatment of COPD, diuretics, and oxygen therapy. Pathohistological analysis of autopsy specimens revealed the coexistence of interstitial fibrosis and partial occlusion of the small intrapulmonary veins, which led to a conclusive diagnosis of pulmonary veno-occlusive disease (PVOD).Because of its rarity and similarity with idiopathic pulmonary arterial hypertension, PVOD is difficult to diagnose antemortem and has a poor prognosis. High-resolution CT findings (septal thickening, ground glass, and enlarged lymph nodes) and severely reduced DLCO should be carefully evaluated for the early detection and treatment of PVOD in COPD patients with severe PH.

Chronic eosinophilic pneumonitis due to the inhalation of aerosolized face lotion: A case report.

RATIONALE: Inhalation of toxic agents can induce eosinophilic pneumonia. However, only a few case reports demonstrate that exposure to materials can induce chronic eosinophilic pneumonia (CEP). Here, we describe a rare case of CEP with mild alveolar hemorrhage due to the inhalation of aerosols from face lotion. This is the first report of eosinophilic pneumonia caused by face lotion exposure. PATIENT CONCERNS: A 39-year-old woman was admitted to our hospital with cough and dyspnea for 2 months, which coincided when she started to use a new aerosolized face lotion. Laboratory findings showed high blood eosinophil levels, and chest computed tomography (CT) scans revealed bilateral peripheral consolidation and ground-glass opacity mainly in the left upper lobe. She underwent flexible bronchoscopy. Eosinophils in bronchoalveolar lavage fluid (BALF) were slightly elevated, and the gross appearance of BALF was bloody. The histological examination of the transbronchial lung biopsy showed infiltration of eosinophils and macrophages in alveolar septa with edema and without vasculitis and granuloma formation; a small number of hemosiderin-laden macrophages were also observed. An inhalation challenge test involving the face lotion was performed. Six hours after the test, the blood test showed an increased white blood cell (WBC) count, and chest radiography showed slight exacerbation. Forced vital capacity decreased the following day. DIAGNOSIS: According to histological analysis and positive result of an inhalation challenge test, she was diagnosed with CEP with mild alveolar hemorrhage due to inhalation of aerosols from the face lotion. INTERVENTIONS AND OUTCOMES: She gradually improved without medication after stopping the use of face lotion. LESSONS: To the best of our knowledge, this is the first report of CEP with mild alveolar hemorrhage due to the inhalation of face lotion. Various inhaled agents, such as face lotion, can induce CEP in rare cases.

IgG4-related pleural effusion with high adenosine deaminase levels: A case report and literature review.

RATIONALE: Levels of pleural fluid adenosine deaminase (ADA), a useful marker for the diagnosis of tuberculous pleurisy, are elevated in some reports of immunoglobulin G4 (IgG4)-related pleural effusion. We describe a patient with IgG4-related pleural effusion who exhibited a high concentration of ADA. Furthermore, we reviewed the literature to compare patients with IgG4-related pleural effusion and tuberculous pleurisy. PATIENT CONCERNS: A 75-year-old male patient had dyspnea for 1 month with a left pleural effusion that was exudative, lymphocyte dominant. The pleural fluid test results revealed a total protein (TP) concentration of 6.60 g/dl, a lactate dehydrogenase (LDH) level of 383 IU/dl, and an ADA concentration of 54.5 U/L. An interferon gamma release assay showed a negative result. DIAGNOSES: Histological analysis of the thoracoscopic pleural biopsy revealed lymphoplasmacytic infiltration, with 80 IgG4-positive plasma cells/high-power field, and an IgG4/IgG ratio of approximately 40% to 50%. Other diseases were ruled out based on symptoms, negative autoimmune antigen results, and histopathologic findings. Thus, he was diagnosed with IgG4-related pleural effusion. INTERVENTIONS: He received 15 mg of prednisolone as therapy. OUTCOMES: His pleural effusion and symptoms improved gradually within several months, and prednisolone was tapered to 6 mg daily. LESSONS: It is important to distinguish between IgG4-related pleural effusion and tuberculous pleurisy. Therefore, we compared 22 patients with IgG4-related pleural effusion from PubMed and the Japan Medical Abstracts Society to 40 patients with tuberculous pleurisy at Fukujuji Hospital from January 2017 to May 2019. According to thoracentesis findings, 14 of 18 patients with IgG4-related pleural effusion had high ADA more than 40 U/L. The pleural effusion of patients with IgG4-related pleural effusion showed higher TP levels (P < .001) and lower LDH (P < .001) and ADA levels (P = .002) than those with tuberculous pleurisy. Moreover, the pleural fluid ADA/TP ratio was a good predictor for differentiating IgG4-related pleural effusion and tuberculous pleurisy (area under the receiver operating characteristic curve of 0.909; 95% confidence level: 0.824-0.994).

Late-onset myasthenia gravis successfully treated with local resection of cervical ectopic thymoma.

A 78-year-old woman was admitted complaining progressive respiratory failure, neck weakness and gait disturbance. She was diagnosed as acetylcholine receptor antibody-positive myasthenia gravis crisis with ectopic cervical thymoma. After she recovered from crisis by plasmapheresis and administration of prednisone, we did not choose extended thymectomy but chose local resection of ectopic thymoma considering her age and complications. After the operation, she got minimal manifestations and no relapse of thymoma. Although international and Japanese guidelines recommend extended thymectomy for myasthenia gravis with thymoma, isolated local resection of ectopic thymoma may be enough for controlling myasthenia gravis especially in elderly patients.

Pathological and Radiological Correlation in Prolonged Myeloperoxidase Anti-neutrophil Cytoplasmic Antibody-related Diffuse Alveolar Hemosiderosis.

A 60-year-old woman with a 20-year history of myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitis visited our hospital due to productive cough and a low-grade fever for several weeks. Thoracic computed tomography demonstrated scattered tiny nodules, patchy consolidation, ground glass opacities, and thickening interlobular septa. On video-assisted thoracic surgery, those abnormalities were found to correspond to the accumulation of hemosiderin-laden alveolar macrophages (AMs) in the alveolar spaces and alveolar septa due to MPO-ANCA vasculitis. The radiological findings persisted for a further two years, indicating the possibility of persistent vasculitis in the lung or evidence of incomplete clearance of hemosiderin-laden AMs.

A case of lung adenocarcinoma complicated by pulmonary talcosis occurring in a patient employed in the confectionery industry.

A 73-year-old Japanese man, who worked at a confectionery company for more than 20 years, was diagnosed with a 28 mm nodular lesion in the superior lobe of the right lung by whole-body computed tomography examination. A biopsy revealed the presence of adenocarcinoma. With a diagnosis of a primary lung cancer, a right upper lobectomy was performed. A nodular lesion, 25 × 23 mm in size, was observed in the upper right lobe lung field, and was diagnosed histopathologically as a papillary adenocarcinoma. In addition, fibrous scars in the central part of the tumor showed numerous Langhans and/or foreign body giant cells, and histiocytic cells that had phagocytized numerous small transparent crystals, together with coal powder deposition. The extracted crystals were observed with a scanning electron microscope, and although plate-like structures were observed, ferruginous bodies suggestive of asbestos were not found. The crystals were demonstrated to be talc by powder X-ray diffraction. Herein, we investigated a case of lung adenocarcinoma in a patient with talcosis, with discussions based on a literature search. This collision of talcosis and lung adenocarcinoma adds to an increasing body of knowledge on an apparent association between talc and cancer cases.

A 48-Year-Old Man With Multiple Pulmonary Nodular Opacities and Elevated KL-6 Level.

CASE PRESENTATION: A 48-year-old man was referred for evaluation of an abnormal chest shadow noted on a routine chest radiograph during physical examination. He was asymptomatic and had no significant medical history and occupational exposure. The patient lived in Tokyo and had no significant travel history. He had smoked approximately 20 cigarettes daily for 20 years. He had no illicit drug use and no animal-rearing history.

Quantitative correlation between cardiac MIBG uptake and remaining axons in the cardiac sympathetic nerve in Lewy body disease.

OBJECTIVES: Reduced cardiac meta-iodobenzylguanidine (MIBG) uptake and loss of cardiac sympathetic axons, as its possible anatomical substrate, were both recognised in Lewy body disease (LBD), while their direct correlation has so far remained speculative. Increasing availability of autopsy-confirmed cases of LBD prompted us to quantify residual cardiac sympathetic axons to establish their relationship to cardiac MIBG uptake. METHODS: We collected cardiac tissue samples from 23 patients with autopsy-confirmed LBD and two non-LBD control patients who underwent (123)I-MIBG cardiac scintigraphy in life. Samples of the left ventricular anterior wall were stained with anti-tyrosine hydroxylase (TH) and anti-neurofilament (NF) antibodies as markers of cardiac nerve axons. We quantified the immunolabelled areas and assessed their correlation to standardised heart to mediastinum (H/M) ratios of (123)I-MIBG cardiac scintigraphy. RESULTS: Cardiac MIBG uptake in the early and delayed phases was reduced in 90.9% and 95.7% of patients with LBD, respectively. The area of TH-immunoreactive axons correlated significantly with the H/M ratio in the early (p=0.036) as well as in the delayed (p=0.018) phases. The area of NF-immunoreactive axons also correlated with the H/M ratio in the early (p=0.003) as well as in the delayed (p=0.001) phases. CONCLUSIONS: Tight quantitative correlation between cardiac (123)I-MIBG uptake and corresponding loss of sympathetic axons in LBD, as established for the first time by this study, provides a scientific basis to confirm the reliability of MIBG cardiac scintigraphy as a powerful clinical tool to detect loss of these axons as a biomarker for the presence of Lewy body disease.

A case of pulmonary sarcoma with significant extension into the right lung.

A female patient in her 30s was referred to us with a mass approximately 8 centimeters in diameter in right lung segment 6. Bronchoscopy was done, and a tumorous lesion obstructing right B6 was found. Biopsy of this lesion supported suspicions of sarcoma or spindle cell carcinoma. Contrast-enhanced CT showed that the mass extended to and obstructed the right main pulmonary artery. A skip lesion was also suspected in the periphery of pulmonary artery trunk. The tumor was removed by right pneumonectomy accompanied by resection of the main and left pulmonary arteries under cardiopulmonary bypass. The pulmonary artery trunk and the left pulmonary artery were reconstructed with a vascular graft. Collectively, intimal sarcoma originating from the right main pulmonary artery with extension into the right lung was diagnosed. Significant extension of pulmonary artery sarcoma into the lung, as was observed in the present case, is considered to be rare, and to our knowledge this is the first report in which the primary lesion was biopsied by bronchoscopy.

High-grade lung adenocarcinoma with fetal lung-like morphology: clinicopathologic, immunohistochemical, and molecular analyses of 17 cases.

Low-grade lung adenocarcinoma of fetal lung type, which is well characterized by its unique clinicopathologic and molecular features, is recognized as a distinct variant of lung cancer. In contrast, high-grade lung adenocarcinoma with fetal lung-like morphology (HG-LAFM) has not been studied widely. To characterize this subset better, we analyzed 17 high-grade adenocarcinomas with at least focal component resembling a developing epithelium in the pseudoglandular phase of the fetal lung. These rare (ca. 0.4%) carcinomas occurred predominantly in elderly men with a heavy smoking history, who showed elevated serum α-fetoprotein in 4 of 5 cases tested. Histologic examination revealed a fetal lung-like component as a focal finding accounting for 5% to 60% of the total tumor volume. It was invariably admixed with tissues having a morphology not resembling that of a fetal lung. A coexisting non-fetal lung-like element was quite heterogenous in appearance, showing various growth patterns. However, clear-cell (88%), hepatoid (29%), and large cell neuroendocrine carcinoma (24%) histology seemed overrepresented. HG-LAFM was characterized immunohistochemically by frequent expression of α-fetoprotein (41%), glypican-3 (88%), SALL-4 (59%), neuroendocrine markers (82%), CDX-2 (35%), and p53 (65%). HG-LAFM was molecularly heterogenous in that EGFR or KRAS mutation was observed in 22% of cases tested for both. Our data indicate that HG-LAFMs might form a coherent subgroup of lung adenocarcinomas. However, the uniformly focal nature of the fetal lung-like element, widely diverse coexisting non-fetal lung-like histology, and inhomogenous molecular profiles lead us to believe that HG-LAFM is best regarded as a morphologic pattern showing characteristic association with several clinicopathologic parameters rather than a specific tumor entity.

Starch accumulation in the lungs of two infants following positive ventilation.

Two infants in different nurseries were found with cardiopulmonary arrest. Cardiopulmonary resuscitation was undertaken immediately in both cases, but was unsuccessful. The cause of death in both infants was diagnosed as sudden unexpected death, probably sudden infant death syndrome, at postmortem investigations. Microscopic examination at autopsy showed the presence of starch granules in the lungs. These were probably introduced during tracheal or nasotracheal intubation for cardiopulmonary resuscitation from gloves sterilized with powdered cornstarch. In both cases cellular staining of foreign bodies was weak and there were few starch granules within macrophages. Our findings suggest that the detection of cornstarch in the lungs can be an artifact arising from surgical gloves used in resuscitation. This artifact may easily occur in infants because of their immature lungs and short respiratory tract. Non-powdered gloves should be worn instead of powdered gloves during tracheal intubation, especially in infants.

A case of malignant peritoneal mesothelioma revealed with limitation of PET-CT in the diagnosis of thoracic metastasis.

A 47-year-old man was referred to our hospital because of a 2-month history of dry cough, 2-kg weight loss, and a feeling of abdominal fullness. The PET-CT scan depicts the intense standard uptake values (SUVs) of the anterior and subphrenic lymphnodes, and intraperitoneal cavity, especially in the omentum, while, no uptake was found in the pleural cavity. Based on the pathological findings of the open lung biopsy specimens, he was diagnosed with malignant peritoneal mesothelioma of epithelioid type with thoracic metastasis. The present case demonstrated the some of the limitations of PET-CT in the diagnosis of malignant mesothelioma, which failed to detect pleural involvement despite aggressive invasion by this tumor.