Intracellular levels of reactive oxygen species correlate with ABT-263 sensitivity in non-small-cell lung cancer cells.

ABT-263 (Navitoclax) is a BH3-mimetic drugs targeting anti-apoptotic B-cell lymphoma-2 (BCL-2) family proteins, including BCL-2, BCL-xL, and BCL-w, thereby inducing apoptosis. In small-cell lung cancer (SCLC) cells, the response to ABT-263 is associated with the expression of myeloid cell leukemia-1 (MCL-1) protein, however the efficacy of ABT-263 in non-small-cell lung cancer (NSCLC) has not been thoroughly evaluated. There are currently no established biomarkers for predicting the efficacy of ABT-263 treatment in NSCLC. We screened a panel of different NSCLC cell lines and found that ABT-263 inhibited cell proliferation and induced apoptosis in Calu-1, Calu-3, and BID007 cells. Inconsistent with previous reports on SCLC, low levels of MCL-1 did not predict the response to ABT-263 in NSCLC cells, however we found that intracellular levels of reactive oxygen species (ROS) in cancer cells were associated with sensitivity to ABT-263 in NSCLC cells. We also showed that increasing the level of intracellular ROS could enhance the sensitivity to ABT-263 in NSCLC cells. In summary, we propose that the intracellular levels of ROS could be used as a potential novel biomarker for predicting a response to ABT-263 in NSCLC. Furthermore, we show some evidence supporting the further assessment of ABT-263 as a new therapeutic strategy in patients with NSCLC combined with agents regulating ROS levels. We believe that our findings and follow-up studies on this matter would lead to novel diagnostic and treatment strategies in patients with NSCLC.

IgG4-related pleural disease in a patient with pulmonary adenocarcinoma under durvalumab treatment: a case report.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are the standard treatment for non-small cell lung cancer. The unique adverse events that can arise after treatment with ICIs are known as immune-related adverse events (irAE). As the number of cases under treatment with ICIs increases, new types of characteristics of irAE have emerged. This case report suggests that IgG4-related pleural disease could occur as an irAE. CASE PRESENTATION: A 64-year-old man was diagnosed with pulmonary adenocarcinoma stage IIIB. Following concurrent chemoradiotherapy, durvalumab was administered every two weeks. The patient complained of dyspnea on effort 4 months after the initiation of durvalumab therapy. Chest CT scans showed mild bilateral pleural effusion 4 months after the initiation of durvalumab therapy, and the amount of pleural effusion increased further at 7 months. Durvalumab was thought to be a potential cause of pleural effusion and was withdrawn after 13 courses of administration over 7 months. The level of serum IgG4 was 2750 mg/dL. The levels of IgG4 of the pleural fluids were 2790 mg/dL on the right side and 2890 mg/dL on the left side at 7 months. Microscopic examination of the pleural biopsy revealed lymphoplasmacytic infiltration with storiform fibrosis. Immunohistochemical examinations showed that the number of IgG4-positive cells was > 20/high power field and the percentage of IgG4-positive to IgG-positive plasma cells was > 50%. Oral prednisolone at a dose of 30 mg/day was initiated, and remarkable clinical improvements were achieved. After 4 months of prednisolone therapy, the level of serum IgG4 decreased to 370 mg/dL and chest CT revealed the disappearance of bilateral pleural effusion. CONCLUSION: This was a case of IgG4-related pleural disease in a patient with pulmonary adenocarcinoma under durvalumab treatment. To our knowledge, this is the first case report of IgG4-related pleural disease as an irAE. It is important to consider the possibility of IgG4-related pleural disease in cases of pleural effusion during the treatment with ICIs.

[A Patient with Small Cell Lung Cancer Presenting with Paralysis and Intramedullary Metastasis Successfully Treated with Chemotherapy].

A 77-year-old man was diagnosed with small cell lung cancer (SCLC: cT3N3M1b, Stage ⅣA)with bone metastases 1 year and 9 months ago. Although partial response was obtained after 6 courses of chemotherapy with carboplatin(CBDCA)and etoposide(VP-16), multiple brain metastases were observed 5 months after the completion of chemotherapy. The multiple brain metastases completely disappeared after whole brain irradiation. However, the patient experienced lower extremity weakness, predominantly in the left side, 5 months after irradiation. Contrast-enhanced magnetic resonance imaging(MRI) revealed an abnormal nodular lesion at the Th10 level, indicative of intramedullary spinal cord metastasis originating from the SCLC. After the patient was admitted to our hospital, his neurological symptoms progressed rapidly and he began to experience difficulty in standing, along with bowel and bladder dysfunction. Chemotherapy with CBDCA plus VP-16 improved the neurological symptoms, and MRI after 1 course of chemotherapy revealed a decrease in the size of the metastatic lesion in the spinal cord. Although neurological symptoms are common in patients with lung cancer, intramedullary metastases often promote irreversible neurological dysfunction. Herein, we report a patient with SCLC who developed intramedullary spinal cord metastasis and whose neurological symptoms dramatically improved after systemic chemotherapy.

Abscopal effect of radiation on multiple lung metastases of lung adenocarcinoma: a case report.

BACKGROUND: Abscopal effect is the out-of-field response to localized irradiation therapy that results in systemic antitumorigenic effects such as the regression of a tumor distant from the target site. CASE PRESENTATION: A 76-year-old woman was diagnosed with pulmonary adenocarcinoma (cT1bN0M0 stage IA), and right upper lobectomy was performed in November 2015. The pathological stage was pT1bN2M0 stage IIIA. Genomic analysis revealed an EGFR mutation. Immunohistochemical analysis revealed a programmed death-ligand 1 tumor proportion score of < 1%. The patient was under watchful observation without adjuvant chemotherapy. Multiple mediastinal and right hilar lymph node metastases were found in February 2018. Radiation therapy at a total dose of 60.0 Gy distributed in 30 fractions was performed over a period of 6 weeks. A computed tomography (CT) scan performed 6 weeks after irradiation therapy showed a reduction in lymph node metastases. However, left hilar and right supraclavicular lymph node metastases and multiple pulmonary metastases were newly observed outside of the irradiation field. A CT scan performed 6 weeks later showed a dramatic complete disappearance of the previously observed pulmonary metastases. No chemotherapy was administered during the period. CONCLUSION: This was a case of abscopal effect: irradiation of the mediastinum resulted in the disappearance of multiple pulmonary metastases in both lungs.

Effects of the common polymorphism in the human aldehyde dehydrogenase 2 (ALDH2) gene on the lung.

BACKGROUND: Aldehyde dehydrogenases (ALDHs) play a major role in detoxification of aldehydes. High expression of ALDHs is a marker for stem cells of many organs including the lungs. A common polymorphism in ALDH2 gene (ALDH2*2) results in inactivation of the enzyme and is associated with alcohol flushing syndrome and increased risk for cardiovascular and Alzheimer's diseases and some cancers. The effect of this ALDH2 polymorphism on the lung and its stem cells has not been thoroughly examined. METHODS: We examined the association between the ALDH2*2 allele and lung function parameters in a population of healthy individuals. We also examined its association with the incidence of asthma and COPD in patient cohorts. We used the in vitro colony forming assay to detect the effect of the polymorphism on lung epithelial stem cells from both primary human surgical samples and Aldh2*2 transgenic (Tg) and Aldh2 -/- mice. Response to acute and chronic lung injuries was compared between wild type (WT), Aldh2*2 Tg and Aldh2 -/- mice. RESULTS: In humans, the ALDH2*2 allele was associated with lower FEV1/FVC in the general population, but not with the development of asthma or COPD. Both the bronchial and lung epithelium carrying the ALDH2*2 allele showed a tendency for lower colony forming efficiency (CFE) compared to ALDH2 allele. In mice, the tracheal epithelial thickness, nuclear density, and number of basal stem cells were significantly lower in Aldh2 -/- and Aldh2*2 Tg adult mice than in WT. Electron microscopy showed significantly increased number of morphologically abnormal mitochondria in the trachea of Aldh2 -/- mice. Aldh2 -/- tracheal and lung cells showed higher ROS levels and fewer functional mitochondria than those from WT mice. No significant differences were detected when tracheal and lung epithelial stem cells were examined for their in vitro CFE. When exposed to chronic cigarette smoke, Aldh2*2 Tg mice were resistant to emphysema development, whereas influenza infection caused more epithelial damage in Aldh2 -/- mice than in WT mice. CONCLUSIONS: ALDH2 polymorphism has several subtle effects on the lungs, some of which are similar to changes observed during normal aging, suggesting a "premature lung aging" effect.

Characterization of the cell of origin and propagation potential of the fibroblast growth factor 9-induced mouse model of lung adenocarcinoma.

Fibroblast growth factor 9 (FGF9) is essential for lung development and is highly expressed in a subset of human lung adenocarcinomas. We recently described a mouse model in which FGF9 expression in the lung epithelium caused proliferation of the airway epithelium at the terminal bronchioles and led to rapid development of adenocarcinoma. Here, we used this model to characterize the effects of prolonged FGF9 induction on the proximal and distal lung epithelia, and examined the propagation potential of FGF9-induced lung tumours. We showed that prolonged FGF9 over-expression in the lung resulted in the development of adenocarcinomas arising from both alveolar type II and airway secretory cells in the lung parenchyma and airways, respectively. We found that tumour cells harboured tumour-propagating cells that were able to form secondary tumours in recipient mice, regardless of FGF9 expression. However, the highest degree of tumour propagation was observed when unfractionated tumour cells were co-administered with autologous, tumour-associated mesenchymal cells. Although the initiation of lung adenocarcinomas was dependent on activation of the FGF9-FGF receptor 3 (FGFR3) signalling axis, maintenance and propagation of the tumour was independent of this signalling. Activation of an alternative FGF-FGFR axis and the interaction with tumour stromal cells is likely to be responsible for the development of this independence. This study demonstrates the complex role of FGF-FGFR signalling in the initiation, growth and propagation of lung cancer. Our findings suggest that analysing the expressions of FGF-FGFRs in human lung cancer will be a useful tool for guiding customized therapy.

X -linked inheritance of primary ciliary dyskinesia and retinitis pigmentosa due to RPGR variant: A case report and literature review.

Bronchiectasis is a chronic respiratory condition characterized by irreversible bronchial dilation, often caused by infection or inflammation. It can be associated with primary ciliary dyskinesia (PCD), a hereditary disorder affecting cilia function in various organs and flagella. PCD's genetic heterogeneity leads to varying disease severity. PCD may be more prevalent in Asia, but its diagnosis is often delayed in Japan. This study reviewed a case of PCD and retinitis pigmentosa (RP) with the relevant literature. The patient had a persistent cough, sputum, and diffuse bronchiectasis. He was diagnosed with a combination of PCD and RP, with the presence of an X-linked retinitis pigmentosa GTPase regulator (RPGR) variant confirmed through electron microscopy, retinal scan, and genetic testing. Although co-occurrence of bronchiectasis and RP is rare, PCD should be considered in cases of persistent wet cough in childhood or unidentified bronchiectasis aetiology. Ophthalmologists should consider concomitant PCD in RP patients.

Delayed visit and treatment of lung cancer during the coronavirus disease 2019 pandemic in Japan: a retrospective study.

OBJECTIVE: The impact of the coronavirus disease 2019 (COVID-19) pandemic on cancer care remains a concern. We aimed to evaluate access to diagnosis and treatment for lung cancer during the pandemic. METHODS: Times (days) from lung cancer symptom onset or referral to visit (pre-visit time), from visit to diagnosis (pre-diagnosis time), and from diagnosis to treatment (pre-treatment time) during the pandemic were compared with the times during the pre-pandemic period. RESULTS: The number of patients diagnosed with lung cancer was 82 and 75 during the pandemic and pre-pandemic periods, respectively. The percentage of patients with advanced-stage cancer was higher (65.9% vs. 46.7%), the percentage of patients treated with surgery was lower and the percentage treated with medication was higher (24.4% vs. 41.3% and 57.3% vs. 40.0%, respectively), the pre-visit time was longer (28.2 vs. 11.4 days), and the pre-treatment time for surgery was longer (67.3 vs. 45.6 days) during the pandemic compared with the times during the pre-pandemic period, respectively. CONCLUSIONS: The COVID-19 pandemic resulted in delayed diagnoses, which could have led to patients being diagnosed with advanced disease. The pandemic also resulted in delayed therapy owing to the requirement for available intensive care unit beds for emergencies, including surgery.

Real-world clinical practice for advanced non-small-cell lung cancer in the very elderly: A retrospective multicenter analysis.

BACKGROUND: The optimal treatment for advanced non-small cell lung cancer (NSCLC) in very elderly patients is unclear. We aimed to evaluate their treatment in real-world clinical practice and identify suitable therapy that can improve their prognosis. MATERIALS AND METHODS: The medical records of 132 Japanese patients aged 80 years and older with advanced NSCLCs who were enrolled at a university hospital and its 9 affiliates were retrospectively analyzed. Clinical characteristics and overall survival (OS) were compared based on the Eastern Cooperative Oncology Group Performance Status (ECOG PS) and biomarker statuses. Patients were defined as biomarker-positive if programmed death-ligand 1 tumor proportion score (PD-L1 TPS) was ≥ 50% or activating mutations were present in epidermal growth factor receptor, anaplastic lymphoma kinase, or c-ros oncogene 1. Finally, the factors contributing to better prognosis were explored in both PS 0 - 2 and PS 3 - 4 patient groups. RESULTS: The PS 0 - 2 patients showed a longer median OS than the PS 3 - 4 patients (5.5 vs. 1.6 months). PS 0 - 2 patients with positive biomarkers who received chemotherapy showed a significantly longer median OS than those without (18.1 vs. 3.7 months). Among the biomarker-negative/unknown PS 0 - 2 patients, the median OS showed no significant difference between those who received chemotherapy and those who did not (4.5 vs. 3.1 months). The multivariate analysis showed that treatment with tyrosine kinase inhibitors or immune checkpoint inhibitors was related to better prognoses in the PS 0 - 2 group. CONCLUSION: Biomarker-matched therapy is effective even in very elderly patients. Meanwhile, the effectiveness of chemotherapy for biomarker-negative/unknown PS 0 - 2 patients is questionable.

Clinical Characteristics and Therapeutic Outcomes of Metastatic Peritoneal Carcinomatosis in Non-Small-Cell Lung Cancer.

BACKGROUND: Metastatic peritoneal carcinomatosis (MPC) is not common in patients with non-small cell lung cancer (NSCLC), and the clinical characteristics and treatment outcomes are still unclear. PATIENTS AND METHODS: We recruited 46 NSCLC patients with MPC at Keio University and affiliated hospitals (Keio Lung Oncology Group) between January 2011 and December 2017, then retrospectively investigated their clinical characteristics and the impact of treatment interventions on their survival. RESULTS: The profile of histological subtype was predominantly adenocarcinoma and 15 patients harbored driver oncogenes. Univariate and multivariate analysis demonstrated that performance status and the presence of a driver oncogene were significantly associated with the prolonged overall survival (OS). Regarding treatment, the median OS in the treatment group (9.3 months) was significantly longer than in the best supportive care group (1.3 months) (P < 0.0001). CONCLUSION: The prognosis of MPC in NSCLC patients who receive only the best supportive care is poor, but therapeutic intervention may improve prognosis.

Pulmonary Intravascular Large B-cell Lymphoma in a Patient Administered Methotrexate for Rheumatoid Arthritis.

A 70-year-old woman with rheumatoid arthritis undergoing methotrexate (MTX) treatment presented with dyspnea and a subfever. Computed tomography (CT) revealed a diffuse minimal ground-glass appearance in both lungs and splenomegaly. The gallium scintigram showed a diffuse, mild uptake in both lungs and the spleen. The lung biopsy specimen revealed the presence of CD20-positive atypical lymphocytes in the small pulmonary vessels. The patient was diagnosed with pulmonary intravascular diffuse large B-cell lymphoma (IVLBCL) and exhibited spontaneous regression after MTX was discontinued. This report describes a rare case of MTX-associated lymphoproliferative disorder expressing pulmonary IVLBCL.

A case report of metastatic lung adenocarcinoma with long-term survival for over 11 years.

RATIONALE: This is the first known report in the English literature to describe a case of metastatic non-small cell lung cancer that has been controlled for >11 years. PATIENT CONCERNS: A 71-year-old man visited our hospital because of dry cough. DIAGNOSIS: Chest computed tomography revealed a tumor on the left lower lobe with pleural effusion, and thoracic puncture cytology indicated lung adenocarcinoma. INTERVENTIONS: Four cycles of carboplatin and docetaxel chemotherapy reduced the size of the tumor; however, it increased in size after 8 months, and re-challenge chemotherapy (RC) with the same drugs was performed. Repeated RC controlled disease activity for 6 years. After the patient failed to respond to RC, erlotinib was administered for 3 years while repeating a treatment holiday to reduce side effects. The disease progressed, and epidermal growth factor receptor (EGFR) gene mutation analysis of cells from the pleural effusion detected the T790 M mutation. Therefore, osimertinib was administered, which has been effective for >1 year. OUTCOMES: The patient has survived for >11 years since the diagnosis of lung cancer. LESSONS: Long-term survival may be implemented by actively repeating cytotoxic chemotherapy and EGFR-tyrosine kinase inhibitor administration.

A Case of Influenza B and Mycoplasma pneumoniae Coinfection in an Adult.

A 19-year-old woman was referred to our hospital because of a persistent fever and cough that lasted for over a week. Influenza B virus infection was diagnosed using the rapid test kit. Initially, the patient was diagnosed with influenza B infection associated with lobar pneumonia and treated with an anti-influenza virus drug and sulbactam/ampicillin. The patient's fever persisted, and her respiratory condition worsened. On day 5, a computed tomography (CT) scan revealed an extension of the consolidation areas in the left lung and new opacities in the right lung. The antibiotic treatment was changed to meropenem and levofloxacin, and the patient's physical condition gradually improved. A sputum sample revealed the presence of Mycoplasma pneumoniae-specific DNA. Both influenza B virus and M. pneumoniae infections were confirmed serologically. This was a case of coinfection with influenza B virus and M. pneumoniae in a healthy young woman. The M. pneumoniae pneumonia diagnosis was delayed because the predominant feature observed in the CT scan was dense consolidation. M. pneumoniae should be considered as one of the causative pathogens in influenza coinfection cases with CT scan images presenting dense consolidation.

EGFR-mutant Non-small Cell Lung Cancer Accompanied by Transient Asymptomatic Pulmonary Opacities Successfully Treated with "Stop-And-Go" Osimertinib.

A 69-year-old man with post-operative recurrence of lung adenocarcinoma was treated with multiple chemotherapies, including epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors. A second biopsy revealed an EGFR T790M mutation. As 10th-line chemotherapy, osimertinib was initiated. After 24 weeks, chest computed tomography (CT) revealed asymptomatic ground-glass opacities in both lobes. After four weeks of osimertinib discontinuation, imaging revealed rapid lung cancer progression. Osimertinib was resumed. After 11 weeks, CT revealed decreased lung nodules with no exacerbation of interstitial lung disease. We describe a patient who experienced transient asymptomatic pulmonary opacities during treatment with osimertinib, which was successfully managed by a "stop-and-go" approach.

Erlotinib as second- or third-line treatment in elderly patients with advanced non-small cell lung cancer: Keio Lung Oncology Group Study 001 (KLOG001).

The aim of this study was to assess the efficacy and safety of erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), as second- or third-line treatment for elderly Japanese patients with non-small-cell lung cancer (NSCLC). The patients eligible for this phase II trial were aged ≥70 years, had stage III/IV or recurrent NSCLC, and had previously received 1 or 2 chemotherapy regimens that did not include EGFR-TKIs. The patients received erlotinib at a dose of 150 mg/day. The primary endpoint was overall response rate (ORR), and the secondary endpoints were progression-free survival (PFS), overall survival (OS) and toxicity. A total of 38 patients with a median age of 76 years were enrolled. The majority of the patients were men (66%), had an Eastern Cooperative Oncology Group performance status of 1 (58%), stage IV disease (66%) and adenocarcinoma (74%). Of the 35 patients, 13 (34%) had tumors with EGFR mutations. The ORR was 26.3% (95% confidence interval: 12.1-40.5%) and the disease control rate was 47.4%. The median PFS was 3.7 months and the median OS was 17.3 months. The grade 3 adverse events observed included rash (13%), diarrhea (5%), interstitial pneumonitis (5%), anorexia (3%) and gastrointestinal bleeding (3%). Grade 4 or 5 adverse events were not observed. The median OS did not differ significantly between patients aged <75 years (14.9 months) and those aged ≥75 years (19.0 months; P=0.226). Therefore, erlotinib was found to be effective and well-tolerated in elderly patients with previously treated NSCLC.

Using Micro-computed Tomography for the Assessment of Tumor Development and Follow-up of Response to Treatment in a Mouse Model of Lung Cancer.

Lung cancer is the most lethal cancer in the world. Intensive research is ongoing worldwide to identify new therapies for lung cancer. Several mouse models of lung cancer are being used to study the mechanism of cancer development and to experiment with various therapeutic strategies. However, the absence of a real-time technique to identify the development of tumor nodules in mice lungs and to monitor the changes in their size in response to various experimental and therapeutic interventions hampers the ability to obtain an accurate description of the course of the disease and its timely response to treatments. In this study, a method using a micro-computed tomography (CT) scanner for the detection of the development of lung tumors in a mouse model of lung adenocarcinoma is described. Next, we show that monthly follow-up with micro-CT can identify dynamic changes in the lung tumor, such as the appearance of additional nodules, increase in the size of previously detected nodules, and decrease in the size or complete resolution of nodules in response to treatment. Finally, the accuracy of this real-time assessment method was confirmed with end-point histological quantification. This technique paves the way for planning and conducting more complex experiments on lung cancer animal models, and it enables us to better understand the mechanisms of carcinogenesis and the effects of different treatment modalities while saving time and resources.

Activation of EGFR Bypass Signaling by TGFα Overexpression Induces Acquired Resistance to Alectinib in ALK-Translocated Lung Cancer Cells.

Alectinib is a highly selective ALK inhibitor and shows promising efficacy in non-small cell lung cancers (NSCLC) harboring the EML4-ALK gene rearrangement. The precise mechanism of acquired resistance to alectinib is not well defined. The purpose of this study was to clarify the mechanism of acquired resistance to alectinib in ALK-translocated lung cancer cells. We established alectinib-resistant cells (H3122-AR) from the H3122 NSCLC cell line, harboring the EML4-ALK gene rearrangement, by long-term exposure to alectinib. The mechanism of acquired resistance to alectinib in H3122-AR cells was evaluated by phospho-receptor tyrosine kinase (phospho-RTK) array screening and Western blotting. No mutation of the ALK-TK domain was found. Phospho-RTK array analysis revealed that the phosphorylation level of EGFR was increased in H3122-AR cells compared with H3122. Expression of TGFα, one of the EGFR ligands, was significantly increased and knockdown of TGFα restored the sensitivity to alectinib in H3122-AR cells. We found combination therapy targeting ALK and EGFR with alectinib and afatinib showed efficacy both in vitro and in a mouse xenograft model. We propose a preclinical rationale to use the combination therapy with alectinib and afatinib in NSCLC that acquired resistance to alectinib by the activation of EGFR bypass signaling.

Successful treatment of non-small-cell lung cancer with afatinib and a glucocorticoid following gefitinib- and erlotinib-induced interstitial lung disease: A case report.

Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)-induced interstitial lung disease (ILD) may be a life-threatening condition that may develop during treatment of lung cancer patients harboring EGFR mutations. We herein present the case of a 41-year-old female patient diagnosed with lung adenocarcinoma with an EGFR mutation (exon 19 deletion). The patient was treated with gefitinib followed by erlotinib and developed ILD induced by both EGFR-TKIs; furthermore, the patient acquired resistance to EGFR-TKI treatment. A repeat biopsy revealed a T790M mutation, which is associated with resistance to first-generation EGFR-TKIs, along with an exon 19 deletion identified by cytology of the pleural fluid. Treatment with afatinib and prednisolone resulted in tumor shrinkage, without worsening of the ILD. The present case demonstrated that combination treatment with afatinib and a glucocorticoid may be effective for the treatment of lung cancer patients who develop EGFR-TKI-induced ILD.

A Case of Disseminated Cryptococcal Infection and Concurrent Lung Tuberculosis in a Patient under Steroid Therapy for Interstitial Pneumonia.

Both disseminated cryptococcal infection and tuberculosis occur in hosts with impaired cell-mediated immunity, but there have been few reports about the concurrent infections in patients without human immunodeficiency virus infection. A 64-year-old man, who had been taking corticosteroids for interstitial pneumonia, was diagnosed with disseminated cryptococcal infection. While the patient was receiving anticryptococcal therapy, pulmonary tuberculosis also emerged. The patient developed acute exacerbation of interstitial pneumonia and passed away. Based on the patient's clinical course, serial computed tomography images, and autopsy results, we believe that the preceding several months of corticosteroid treatment might have contributed to these coinfections in the lungs already vulnerable due to underlying fibrosis.