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.

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.

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.

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.

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.

[Lung adenocarcinoma presented with reticular pattern in which both CA19-9 and carcinoembryonic antigen( CEA) were recognized as markers].

A 79-year-old male whose chest X-ray revealed a localized reticular shadow in health check was once treated medically with a diagnosis of interstitial pneumonia. Regardless of the treatment, the shadow increased in its size. Positron emission tomography (PET)-computed tomography(CT) was suggestive of a primary lung cancer in clinical stage IIIA. CA19-9 and CEA were 3,568.5 U/ml and 178.2 ng/ml respectively, and a left lower lobectomy was performed. The postoperative course was uneventful. Both tumor markers declined shortly after the surgery. But they increased in 8 months after the surgery associated with tumor recurrence. In spite of chemotherapy, the patient was expired 15 months following the surgery. Immunohistochemical staining showed the tumor was a well differentiated adenocarcinoma with positive findings of both CEA and CA19-9.

[Complete disappearance of pulmonary metastases in a case of rectal cancer treated with oral tegafur-uracil (UFT) and leucovorin (LV)].

We report a case of complete remission after treatment with tegafur-uracil (UFT)/Leucovorin (LV) therapy for pulumonary metastasis of rectal cancer. A 56-year-old male was admitted to our hospital with a diagnosis of rectal cancer (Ra, type2). Chest CT on admission demonstrated bilateral lung metastases (rt S2 and lt S4). After anterior resection of the primary tumor, oral UFT/LV was administered (UFT 400 mg/LV 75 mg, 4-week administration and 1-week no-administration period) on an outpatient basis. After 2 courses, chest CT revealed reduction of both metastases, and complete resection of the metastases by video assisted thoracic surgery (VATS) was planned. Pathological findings of a specimen revealed no residual cancer cells, indicating a complete response to UFT/LV therapy. After these treatments, combined therapy of UFT/LV was continued for 3 months, and the single administration of UFT was continued for 1 year. The patient experienced no adverse reactions, and has had no recurrent disease in 4 years. Oral UFT/LV therapy is considered to be a promising regimen for patients with resectable metastatic lesion from a standpoint of clinical efficacy and safety.

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.

[A case of multifocal micronodular pneumocyte hyperplasia without clinical findings of tuberous sclerosis].

A 30-year-old woman was referred because of multiple ground-glass opacities (GGOs) on chest CT examination. Lung biopsy was performed. Histologically, multifocal well-demarcated nodular lesions comprising proliferation of type II pneumocytes with mild fibrous thickening of the alveolar septa were observed in the lung tissue. We made a histopathologic diagnosis of multifocal micronodular pneumocyte hyperplasia (MMPH). Neither the clinical findings nor the family history of the patient suggested tuberous sclerosis (TSC). MMPH is a pulmonary manifestation of tuberous sclerosis, together with lymphangioleiomyomatosis (LAM). MMPH should be considered as a differential diagnosis of multiple GGOs in the lung even when findings of TSC and LAM are not recognized.

[A case of imatinib mesylate-induced pneumonitis based on the detection of epithelioid granulomas by video-assisted thoracoscopic surgery biopsy in a patient with chronic myeloid leukemia].

A 79-year-old man with chronic myeloid leukemia was referred to our department because of dry cough and low-grade fever, 272 days after commencing imatinib mesylate (Gleevec). High resolution computed tomography (HRCT) showed tiny scattered centrilobular nodules and ground-glass opacities throughout both lung fields, suggesting drug-induced pneumonitis. A thoracic video-assisted thoracoscopic surgery (VATS) biopsy specimen from the centrilobular nodules in the right upper lobe demonstrated patchy distribution of epithelioid cell granulomas and intra-alveolar organization. Most of those lesions were predominantly located in the alveolar spaces, which implicated non-transbronchial distribution. Following drug cessation alone, the patient's general condition and radiological abnormalities improved.

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).

Simple quantitative analysis of asbestos body using the sediment of formalin injected into surgically resected lung cancers.

A simple screening method for quantitatively analyzing asbestos bodies that can be carried out even in community hospitals, is needed in order for laborers and neighborhoods in the vicinity of asbestos factories to apply for compensation for asbestos-related injury. Eighty-eight consecutive cases of surgically resected primary lung cancer were analyzed for asbestos bodies using two methods, and the correlation between them was statistically examined. The first was the conventional technique using lung tissue digestion and phase-contrast scanning, and the second was the authors' method using light microscopy to scan the sediment of formalin-injected lung specimens. The overall correlation coefficient of the concentration of asbestos bodies between the authors' method (C(AB/SED)) and the conventional method (C(AB/DLT)) was 0.4576, a weak statistically significant correlation; in patients with occupational asbestos exposure, however, the correlation coefficient was 0.7341. Despite the cost, it may be prudent to use the conventional method under the present law for patients with C(AB/SED)>or=3.5/mL. C(AB/DLT) >3000/g dry lung tissue when C(AB/SED) is >or=3.5/mL suggests the potential for the accumulation of asbestos absorption by lung tissue.

[Kartagener syndrome with lung cancer and mediastinal tumor].

A 71-year-old man was admitted to Kanto Central Hospital with hemoptysis. He had had chronic sinusitis and deafness since childhood. Situs inversus, bronchiectasia, and diffuse panbronchiolitis had been also diagnosed at the age of 59. Chest computed tomography demonstrated a 5-cm mass in the anterior mediastinum as well as a 4-cm mass in the upper lobe of the right lung. A transbronchial lung biopsy of the right lung tumor revealed squamous cell carcinoma. Electron microscopic examination of the bronchial epithelial cilia revealed a total defect of both inner and outer dynein arms, leading to a diagnosis of primary ciliary dyskinesia. Biopsy of the mediastinal tumor was not performed. After concurrent chemoradiation therapy, the lung cancer decreased in size partial remission (PR) and the mediastinal tumor disappeared complete remission (CR). Later, a cavity formed in the tumor, where a Pseudomonas aeruginosa infection occurred. He died 1 year after the diagnosis of lung cancer was established. There have been 5 reported cases of Kartagener syndrome complicated with lung cancer, but to the best of our knowledge there have been no reports of Kartagener syndrome with mediastinal tumor.

[Case of sarcoidosis with myelodysplastic syndrome in an elderly woman].

An 85-year-old woman, who had been given a diagnosis of myelodysplastic syndrome with refractory anemia 2 years previously and required blood transfusion once a month, was admitted with complaints of fever, general fatigue, and dry cough. A chest X-ray film showed multiple small nodules in bilateral lung fields which were not observed 1 month previously. Although smear and culture tests for acid-fast bacilli in her bronchoalveolar lavage fluid, urine, and bone marrow aspiration fluid were all negative, miliary tuberculosis was strongly suspected. Antituberculosis drugs were administered, but neither her symptoms nor chest X-ray findings improved. Five months later, right oculomotor nerve palsy, followed by left abducens nerve paralysis occurred. Lumber puncture examination revealed lymphocytosis, and increased protein and ACE levels, suggesting neurosarcoidosis. A transbronchial lung biopsy specimen demonstrated non-caseating epithelioid granulomas. Oral administration of 30 mg/day prednisolone improved her symptoms as well as the chest X-ray findings.