A case of angioimmunoblastic T-cell lymphoma presenting with migration of lung shadows.

A 62-year-old woman presented with chronic cough. Chest CT showed multiple nodules and consolidation. Bronchoscopy could not confirm a specific diagnosis. Because her symptoms and lung opacities improved spontaneously, she was followed without treatment. Seven months later, chest radiography showed worsening of consolidation and a tumorous shadow. After performing cervical lymph node and lung tissue biopsies, we diagnosed her as having angioimmunoblastic T-cell lymphoma (AITL). Cases of AITL showing migration of lung shadows have not been reported. AITL development is influenced by immunodeficiency and reactivation of EBV, and migration of lung opacities may be related to the patient's immune status.

Prognostic factors of virus-associated pneumonia other than COVID-19 in adults.

OBJECTIVE: To determine prognostic factors of virus-associated pneumonia other than coronavirus disease 2019. METHODS: We retrospectively studied patients suffering from virus-associated community-acquired pneumonia, and who were admitted to Saitama Cardiovascular and Respiratory Center from 2002 to 2020. Prognostic factors were analyzed by univariable and multivariable regression analysis of patient demographics, laboratory data, chest imaging, severity on admission, and initial treatment. PATIENTS: HIV-positive patients, those with non-resected lung cancer or receiving chemotherapy, and those with COVID-19 were excluded. Included were 363 patients diagnosed by nucleic acid amplification method, paired sera, and rapid diagnostic tests. RESULTS: A CURB-65 score of ≥3 was significant by univariable analysis for 60-day mortality but was nonsignificant by multivariable analysis. The poor prognostic factors that were significant by multivariable analysis (p < 0.05) included immunosuppressive state due to systemic corticosteroid or immunosuppressant administration, acute kidney injury on admission, and corticosteroid administration initiated within 5 days or 5 days to 2 weeks from onset. CONCLUSION: A CURB-65 score of ≥3, which is considered to indicate severe pneumonia, was of limited value for predicting mortality of virus-associated pneumonia. We showed patients' underlying diseases and complications to be independent factors of poor prognosis for 60-day mortality. Timing of the initiation of corticosteroid administration remains to be elucidated.

Drug-induced lung disease due to topical minoxidil.

A 55-year-old man presented to our institution with abnormal chest X-ray shadows. Chest computed tomography (CT) showed left-sided interlobular septal thickening; thus, we suspected lymphangitis carcinomatosis and other disorders that show similar CT findings. Bronchoscopy and laboratory and imaging studies yielded no diagnostic findings. Pulmonary shadows during follow-up spontaneously improved then worsened. Thoracoscopic lung biopsy samples showed interstitial pneumonia and granulomas but the etiology of the pulmonary lesion could not be determined. At seven years after presentation, the patient's pulmonary shadows had gradually deteriorated, and he reported using topical minoxidil. His history of minoxidil use was linked to changes in the pulmonary shadows. The diagnostic delay was due to the patient's hesitancy to report drugs obtained online and the difficulty in obtaining such a history.

Histologic Characteristics and Clinical Courses of Primary Viral Pneumonia Other than COVID-19.

Objective To clarify both the histologic changes in primary viral pneumonia other than COVID-19 and whether patients with severe lung injury (SLI) on biopsy specimens progress to severe respiratory insufficiency. Methods Patients with primary viral pneumonia other than COVID-19, who underwent lung tissue biopsy, were retrospectively studied. Patients Forty-three patients (41 living patients and 2 autopsied cases) were included in the study. Results Nine patients had SLI, whereas most of patients who recovered from primary viral pneumonia showed a nonspecific epithelial injury pattern. One patient underwent a biopsy under mechanical ventilation. Two of 8 (25.0%) patients on ambient air or low-flow oxygen therapy progressed to a severe respiratory condition and then to death, while only 1 (3.1%) of 32 patients without SLI progressed to a severe respiratory condition and death (p=0.096). The proportion of patients who required O2 treatment for ≥2 weeks was higher in patients with SLI than in those without SLI (p=0.033). The 2 autopsy cases showed a typical pattern of diffuse alveolar damage, with both showing hyaline membranes. Non-specific histologic findings were present in 32 patients without SLI. Conclusion Some patients with SLI progressed to severe respiratory insufficiency, whereas those without SLI rarely progressed to severe respiratory insufficiency or death. The frequency of patients progressing to a severe respiratory condition or death did not differ significantly between those with and without SLI. The proportion of patients who required longer O2 treatment was higher in SLI group than in those without SLI.

Loop-Mediated Isothermal Amplification as Point-of-Care Testing for EGFR-Mutated Lung Adenocarcinoma.

Liquid biopsy has been adapted as a diagnostic test for EGFR mutations in patients with advanced or metastatic non-small cell lung cancer (NSCLC). Loop-mediated isothermal amplification (LAMP) has been widely used for the rapid detection of pathogens through DNA amplification. This study investigated the efficacy of an EGFR-LAMP assay using plasma samples of patients with resected NSCLC tumors. The EGFR status was investigated using both LAMP and next-generation sequencing (NGS) assays in cases that met the following criteria: (1) pulmonary adenocarcinoma with EGFR mutation detected by the Therascreen EGFR PCR Kit and (2) preoperative plasma samples contained enough DNA for the LAMP and NGS experiments. Among 51 specimens from patients with EGFR-mutated tumors or metastatic lymph nodes, the LAMP assay detected 1 EGFR mutation that was also detected in the NGS assay. However, a plasma sample that demonstrated EGFR wild type in the LAMP assay showed an EGFR mutant status in NGS. The detection rates (1.9% in LAMP and 3.9% in NGS) were very low in both assays, demonstrating a similar performance in detecting EGFR mutations in NSCLC tumors; therefore, it could be a more suitable test for the advanced stage, not the early stage. Notably, the LAMP assay was more time-saving, cost-effective, and straightforward. However, further investigation is required to develop a more sensitive assay.

Slowly progressive interstitial lung disease preceding typical dermatomyositis symptoms in anti-melanoma differentiation-associated gene 5 antibody-positive clinically amyopathic dermatomyositis.

A 73-year-old woman who visited our hospital complaining of dry cough for three months was refractory to antimicrobial therapy. Chest computed tomography revealed subpleural consolidation. Specimens obtained from surgical lung biopsy revealed subpleural perilobular airspace organization and fibrosis. After the biopsy, mechanic's hand and Gottron's papules appeared, and anti-melanoma differentiation-associated gene 5 (MDA5) antibody was found to be positive. Subsequently, anti-MDA5 antibody measured in cryopreserved serum from her first admission proved to be positive. It is difficult to suspect the presence of anti-MDA-5 antibody in patients with interstitial lung disease without typical dermatomyositis symptoms or slow disease progression.

Rheumatoid Arthritis Accompanying Diffuse Panbronchiolitis.

A 58-year-old woman with rheumatoid arthritis (RA) visited our hospital complaining of a persistent cough and sputum for the past year. She had a high cold hemagglutinin titer and chronic sinusitis. Chest computed tomography revealed bilateral diffuse centrilobular nodules, bronchiectasis, and bronchial wall thickening. A surgical lung biopsy was performed that confirmed diffuse panbronchiolitis (DPB) because of the lymphocytic and plasmacytic infiltrates in the respiratory bronchioles. Her condition improved after the administration of clarithromycin. Several cases of RA complicating DPB have previously been reported, but only in Japan. We need to consider DPB as a bronchiolitis types accompanying RA among Japanese patients.

Comparative study of the loop-mediated isothermal amplification method and the QIAGEN therascreen PCR kit for the detection of EGFR mutations in non-small cell lung cancer.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutations are important biomarkers in the treatment of patients with advanced or metastatic diseases. The therascreen EGFR Rotor-Gene Q (RGQ) PCR Kit® (Qiagen, Inc.) is an approved diagnostic test for EGFR mutations in non-small cell lung cancer (NSCLC). This study aims to investigate the diagnostic capability of a loop-mediated isothermal amplification (LAMP) assay as an accurate, efficient, and cost-effective alternative to the therascreen assay. METHODS: EGFR mutations were investigated by LAMP and therascreen assays using tissue samples that were surgically resected or biopsied from 117 consecutive patients with NSCLC tumors. The EGFR status from the LAMP assay was compared with that of the therascreen assay. Next-generation sequencing (NGS) was performed to confirm EGFR status of tumors that did not match in both assays. To establish an optimal LAMP AUC value, receiver operating characteristics (ROC) curve analysis was performed within tumors with exon 19 deletion or L858R point mutation. RESULTS: Of the 117 tumors assayed, 45 tumors with EGFR mutations and 68 tumors with EGFR wild type were matched in both assays, four tumors having mismatched EGFR statuses. NGS further confirmed that two of the four discordant tumors had the same EGFR status that was determined by the LAMP assay. The AUC values were 0.973 (95% CI: 0.929-1.00) in exon 19 deletion, and 0.952 (95% CI: 0.885-1.00) in L858R point mutation. In exon 19 deletion, sensitivity, specificity, and accuracy were 89.3%, 98.9%, and 96.6%, respectively, and 94.7%, 95.9%, and 95.7%, respectively, in L858R using AUC value of 0.222. CONCLUSIONS: The LAMP assay compared favorably with the therascreen assay and has potential as an effective, simple, rapid, and low-cost diagnostic alternative. Based on these results, a liquid biopsy LAMP system should be developed for point-of-care testing of oncogenes in the near future.

Two Cases of Primary Rhinovirus Pneumonia with Multiple Pulmonary Nodules.

Two patients, a 60-year-old man and 43-year-old woman, presented to our hospital with symptoms of respiratory tract infection. These patients showed imaging findings of multiple small nodules, ground-glass opacities, and consolidations. In case 1, although antibiotics were started, bilateral shadows spread widely, which made us suspect interstitial pneumonia. The condition improved after steroid administration, and there has been no recurrence since completing this treatment. In case 2, the patient recovered rapidly with antibiotics only. In both cases, we performed bronchoalveolar lavage, in which only human rhinovirus infection was detected by multiplex polymerase chain reaction testing, and primary rhinovirus pneumonia was diagnosed.

High incidence of false-positive results of IgG antibody against SARS-CoV-2 with rapid immunochromatographic antibody test due to human common cold coronavirus infection.

We experienced a 72-year-old man who developed laboratory-confirmed human coronavirus HKU1 pneumonia. PCR testing for SARS-CoV-2 from a nasopharyngeal specimen was negative twice, and rapid immunochromatographic antibody test (RIAT) using a commercially available kit for IgM and IgG against SARS-CoV-2 showed him turning positive for IgG against SARS-CoV-2. We then performed RIAT in stored serum samples from other patients who suffered laboratory-confirmed human common cold coronaviruses (n = 6) and viruses other than coronavirus (influenza virus, n = 3; rhinovirus, n = 3; metapneumovirus, n = 1; adenovirus, n = 1) admitted until January 2019. Including the present case, four of 7 (57%) showed false-positive RIAT results due to human common cold coronaviruses infection. Two of the 4 patients showed initial negative to subsequent positive RIAT results, indicating seroconversion. RIAT was positive for IgG and IgM in viruses other than coronavirus in 2 (25.0%) and 1 (12.5%) patient. Because of high incidence of false positive RIAT results, cross antigenicity between human common cold coronaviruses and SARS-CoV-2 can be considered. Results of RIAT should be interpreted in light of epidemics of human common cold coronaviruses infection. Prevalence of past SARS-CoV-2 infection may be overestimated due to high incidence of false-positive RIAT results.

Amyloidosis of the respiratory system: 16 patients with amyloidosis initially diagnosed ante mortem by pulmonologists.

BACKGROUND: Ante mortem diagnosis of amyloidosis of the respiratory system is rare. Few data are available regarding clinical presentation, precursor proteins, diagnostic procedures, comorbidities, complications, and outcome. We assessed clinical features of a series of patients with amyloidosis of the respiratory system in two Japanese centres. METHODS: Medical records of 16 patients with amyloidosis of the respiratory system were retrospectively analysed. Amyloid was diagnosed by polarisation microscopy using Congo red-stained tissue specimens and classified immunohistochemically. RESULTS: Median patient age was 71 years, and median follow-up period was 5 years. Immunoglobulin light-chain (AL)-λ amyloidosis was found in eight and AL-κ in five patients. Two patients harboured wild-type transthyretin and one harboured serum amyloid A-derived amyloid. Five different forms of amyloidosis of the respiratory system were observed: nodular pulmonary amyloidosis (seven patients), diffuse alveolar-septal amyloidosis (five), mediastinal lymph node amyloidosis (three), tracheobronchial amyloidosis (one), and pleural amyloidosis (one). One patient had diffuse alveolar-septal amyloidosis and mediastinal lymph node amyloidosis. Three of five patients with diffuse alveolar-septal amyloidosis were diagnosed by transbronchial lung biopsy as having concurrent diffuse alveolar haemorrhage or pneumocystis pneumonia. Two of three patients with mediastinal lymph node amyloidosis were diagnosed by endobronchial ultrasound-guided transbronchial needle aspiration. CONCLUSIONS: Not only nodular pulmonary amyloidosis, diffuse alveolar-septal amyloidosis, and tracheobronchial amyloidosis but also mediastinal lymph node amyloidosis and pleural amyloidosis should be considered in the differential diagnosis of amyloidosis of the respiratory system. Useful diagnostic methods include transbronchial lung biopsy for diffuse alveolar-septal amyloidosis and endobronchial ultrasound-guided transbronchial needle aspiration for mediastinal lymph node amyloidosis.

A 72-Year-Old Woman With Respiratory Failure and Bilateral Ground-Glass Opacities.

A 72-year-old woman with diabetes mellitus was admitted to our hospital because of dyspnea on exertion. Sputum cytologic evaluation revealed intranuclear inclusion bodies in the cells; we therefore considered viral pneumonia and performed a bronchoscopy. The bronchial washing fluid was positive for immunoperoxidase staining of herpes simplex virus type 1 (HSV1) and HSV1 polymerase chain reaction. The patient was diagnosed as having pneumonia due to HSV1 and was successfully treated with acyclovir.

Pulmonary high-grade fetal adenocarcinoma associated with cystic airspace: A case report.

Lung cancers associated with cystic airspaces have a life-threatening risk of a missed or delayed diagnosis. Here, we report a case of pulmonary high-grade fetal adenocarcinoma, a rare lung carcinoma associated with cystic airspaces, as confirmed by computed tomography (CT) scan. A 73-year-old asymptomatic male with a 52-pack a year smoking habit was referred to our hospital. Lung CT showed a thin-walled cystic space with exophytic and endophytic solid nodules along the cyst wall. After surgery, histological analysis of a resected lung specimen revealed a pure high-grade fetal adenocarcinoma probably associated with emphysematous bullae in pulmonary emphysema, suggesting smoking contributed to this pure form, as well as the emphysema. In conclusion, when treating elderly men with a smoking history, physicians need to carefully examine the walls of cystic airspaces on CT for fetal adenocarcinoma. KEY POINTS: Significant findings of the study •Pulmonary high-grade fetal adenocarcinoma may be associated with emphysematous bullae manifesting as cystic air spaces as shown by computed tomography. What this study adds •When scanning by computed tomography, physicians should carefully examine the pulmonary cystic airspace walls in elderly men with a smoking history.

A novel loop­mediated isothermal amplification method for efficient and robust detection of EGFR mutations.

The activation of somatic mutations conferring sensitivity to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors has been widely used in the development of advanced or metastatic primary lung cancer therapy. Therefore, identification of EGFR mutations is essential. In the present study, a loop­mediated isothermal amplification (LAMP) method was used to identify EGFR mutations, and its efficiency was compared with the Therascreen quantitative PCR assay. Using LAMP and Therascreen to analyze surgically resected tissue samples from patients with pulmonary adenocarcinoma, EGFR mutations were observed in 32/59 tumor samples (LAMP) and 33/59 tumor samples (Therascreen). Notably, the LAMP assay identified one tumor as wild­type, which had previously been identified as a deletion mutation in exon 19 via the Therascreen assay (Case X). However, the direct sequencing to confirm the EGFR status of the Case X adhered to the results of the LAMP assay. Further experiments using Case X DNA identified this exon 19 deletion mutation using both methods. In addition, a novel deletion mutation in exon 19 of the EGFR was identified. Overall, the present study shows that the LAMP method may serve as a valuable alternative for the identification oncogene mutations.

Viral Pneumonia Requiring Differentiation from Acute and Progressive Diffuse Interstitial Lung Diseases.

Objective The clinical characteristics and chest imaging findings of viral pneumonia and several interstitial lung diseases (ILDs) overlap, and viral pneumonia may be underrecognized and misdiagnosed as certain ILDs. To clarify the frequency of viral pneumonia among patients with acute progressive clinical courses that required a differential diagnosis between ILDs and pneumonia, and to determine the most frequent ILDs misdiagnosed in cases of viral pneumonia. Patients and Methods We retrospectively analyzed patients hospitalized from 2010 to 2017 with an acute clinical course (≤30 days) who underwent bronchoalveolar lavage (BAL) for the differential diagnosis of infection and ILDs. We performed a multiplex PCR for respiratory viruses using the patients' preserved BAL fluid. The final diagnosis was made by a multidisciplinary approach and after considering the PCR results. The diagnosis at discharge was compared to the final diagnosis. Results Among the 109 patients, 53 were diagnosed with viral pneumonia. Viral pneumonia and other diseases showed some differences in symptoms and laboratory data; however, the differences were small or overlapped. Viral pneumonia was misdiagnosed on discharge as acute fibrinous organizing pneumonia, cryptogenic organizing pneumonia, or chronic eosinophilic pneumonia (AFOP/COP/CEP) (n=22), acute interstitial pneumonia (n=5), connective tissue disease-related ILDs (n=3), unclassifiable interstitial pneumonia (n=2), drug-induced ILD (n=1), and pneumonia (n=20). Conclusion Approximately half of the patients who underwent BAL had viral pneumonia. The most common ILD-related misdiagnoses were AFOP/COP/CEP. Differences in symptoms and laboratory findings between viral pneumonia and other diseases were small, and viral pneumonia should be included in the differential diagnosis when physicians encounter cases in which the abovementioned ILDs are suspected.

Diffuse alveolar hemorrhage caused by IgA deposition associated with multiple myeloma.

We report a man with diffuse alveolar hemorrhage caused by multiple myeloma who was diagnosed with the aid of bronchoalveolar lavage and transbronchial lung biopsy. Multiple myeloma should be considered as an important differential diagnosis in patients with diffuse alveolar hemorrhage, and bronchoscopy may help to differentiate the cause.

Nivolumab-induced Myocarditis Successfully Treated with Corticosteroid Therapy: A Case Report and Review of the Literature.

A 62-year-old man presented to our hospital for the further evaluation and treatment of his back pain, general fatigue, and dyspnea, which had developed 4 days after the 29th administration of nivolumab to treat his lung cancer. Based on his clinical history, elevated serum cardiac enzyme values, and cardiac magnetic resonance (CMR) imaging and myocardial biopsy findings, he was diagnosed with myocarditis induced by nivolumab. Corticosteroid therapy improved his condition, and CMR performed on hospital day 11 also showed remarkable improvement. Although nivolumab-induced myocarditis is rare, cardiologists should consider it when encountering patients treated with such a drug for malignant disease.

Spontaneous regression of primary endobronchial extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue.

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) of pulmonary origin is a relatively rare disease. In particular, reports of MALT lymphoma occurring and localized in the trachea or bronchus have been limited. Pulmonary MALT lymphoma has been reported to demonstrate spontaneous regression, whereas there is only one reported case of spontaneous regression of primary endobronchial MALT lymphoma. We herein report the case of a 70-year-old man with primary endobronchial MALT lymphoma who showed spontaneous regression with an interest of endobronchial findings.