Periostin-related progression of different types of experimental pulmonary hypertension: A role for M2 macrophage and FGF-2 signalling.

BACKGROUND AND OBJECTIVE: Remodelling of pulmonary arteries (PA) contributes to the progression of pulmonary hypertension (PH). Periostin, a matricellular protein, has been reported to be involved in the development of PH. We examined the role of periostin in the pathogenesis of PH using different types of experimental PH. METHODS: PH was induced by vascular endothelial growth factor receptor antagonist (Sugen5416) plus hypoxic exposure (SuHx) and venous injection of monocrotaline-pyrrole (MCT-P) in wild-type (WT) and periostin-/- mice. Pulmonary haemodynamics, PA remodelling, expression of chemokines and fibroblast growth factor (FGF)-2, accumulation of macrophages to small PA and the right ventricle (RV) were examined in PH-induced WT and periostin-/- mice. Additionally, the role of periostin in the migration of macrophages, human PA smooth muscle (HPASMCs) and endothelial cells (HPMVECs) was investigated. RESULTS: In PH induced by SuHx and MCT-P, PH and accumulation of M2 macrophage to small PA were attenuated in periostin-/- mice. PA remodelling post-SuHx treatment was also mild in periostin-/- mice compared to WT mice. Expression of macrophage-associated chemokines and FGF-2 in lung tissue, and accumulation of CD68-positive cells in the RV were less in SuHx periostin-/- than in SuHx WT mice. Periostin secretion in HPASMCs and HPMVECs was enhanced by transforming growth factor-ß. Periostin also augmented macrophage, HPASMCs and HPMVECs migration. Separately, serum periostin levels were significantly elevated in patients with PH compared to healthy controls. CONCLUSION: Periostin is involved in the development of different types of experimental PH, and may also contribute to the pathogenesis of human PH.

Idiopathic dendriform pulmonary ossification diagnosed by bronchoscopic lung cryobiopsy: A case report.

Dendriform pulmonary ossification (DPO) is a rare condition characterized by heterotopic bone production of unknown origin within the pulmonary tissue. Many cases are asymptomatic with slow progression and are often diagnosed incidentally during autopsy. Thus, only few cases are diagnosed while the patient is still alive since surgical lung biopsy is often needed for pathological diagnosis. This is the case of a 37-year-old man treated at our hospital due to abnormal findings on chest x-ray without any symptoms. His high-resolution computed tomography revealed diffuse reticular shadows and micronodules, consistent with calcification. He underwent transbronchial lung cryobiopsy (TBLC) and was diagnosed with idiopathic DPO based on pathological findings. To our knowledge, this is the first reported case of DPO diagnosed using TBLC. TBLC can be a useful yet minimally invasive diagnostic tool to diagnose DPO and other interstitial lung diseases.

Disseminated nontuberculous mycobacteriosis and fungemia after second delivery in a patient with MonoMAC syndrome/GATA2 mutation: a case report.

BACKGROUND: Heterozygous mutations in the transcription factor GATA2 result in a wide spectrum of clinical phenotypes, including monocytopenia and Mycobacterium avium complex (MAC) infection (MonoMAC) syndrome. Patients with MonoMAC syndrome typically are infected by disseminated nontuberculous mycobacteria, fungi, and human papillomavirus, exhibit pulmonary alveolar proteinosis during late adolescence or early adulthood, and manifest with decreased content of dendritic cells (DCs), monocytes, and B and natural killer (NK) cells. CASE PRESENTATION: A 39-year-old woman was diagnosed with MonoMAC syndrome postmortem. Although she was followed up based on the symptoms associated with leukocytopenia that was disguised as sarcoidosis with bone marrow involvement, she developed disseminated nontuberculous mycobacterial infection, fungemia, and MonoMAC syndrome after childbirth. Genetic testing revealed a heterozygous missense mutation in GATA2 (c.1114G > A, p.A372T). Immunohistochemistry and flow cytometry showed the disappearance of DCs and decreased frequency of NK cells in the bone marrow, respectively, after childbirth. CONCLUSIONS: To the best of our knowledge, this is the first study reporting that MonoMAC syndrome can be exacerbated after childbirth, and that immunohistochemistry of bone marrow sections to detect decreased DC content is useful to suspect MonoMAC syndrome.

Atezolizumab-induced fulminant type 1 diabetes mellitus occurring four months after treatment cessation.

Atezolizumab is an immune checkpoint inhibitor (ICI) that is often associated with the development of several immune-related adverse events, including fulminant type 1 diabetes mellitus (F1DM). Here, we present the case of a 73-year-old woman who was diagnosed with lung adenocarcinoma after surgical lung lobectomy. Two years later, she developed pulmonary metastasis, and atezolizumab treatment was initiated after seven years. However, she only completed two cycles of atezolizumab treatment because of disease progression. Four months after the interruption of atezolizumab treatment, she presented to the emergency department with fatigue and vomiting. On admission, she had a serum glucose level of 962 mg/dL, metabolic acidosis, and elevated ketone body levels. She was diagnosed with diabetic ketoacidosis induced by atezolizumab treatment. Her symptoms improved by insulin therapy. When ICIs are administered, care should be taken regarding the development of F1DM.

Transbronchial lung biopsy for the diagnosis of lymphangioleiomyomatosis: the severity of cystic lung destruction assessed by the modified Goddard scoring system as a predictor for establishing the diagnosis.

BACKGROUND: A guide of patient selection for establishing the diagnosis of lymphangioleiomyomatosis (LAM) by transbronchial lung biopsy (TBLB) has not been established, although the pathological confirmation of LAM by lung biopsy is desirable, particularly when patients have no additional test results except typical findings of computed tomography (CT) of the chest. METHODS: We retrospectively reviewed the medical records of LAM patients who visited at our hospital from January 2010 to September 2018. We found 19 patients who underwent TBLB and collected the following data to investigate which parameters could predict the TBLB diagnostic positivity for LAM: age, degree of exertional dyspnea, pulmonary function test, cystic lung destruction visually assessed by the modified Goddard scoring system (MGS), serum level of vascular endothelial growth factor-D, and TBLB-related data. RESULTS: The diagnosis of LAM was established by TBLB in 15 of 19 patients (78.9%) and no serious complications occurred. MGS was significantly higher in the TBLB-positive group than the TBLB-negative group. In LAM patients without pulmonary lymphatic congestion on CT (N = 16), multivariable logistic regression analysis revealed that MGS and FEV1/FVC were independent contributing parameters for TBLB diagnostic positivity. However, the analysis of Bayesian inference demonstrated that MGS is a better predictor than FEV1/FVC; the probability of establishing diagnosis exceeds 80% if MGS is > 2 (i.e., area of cystic destruction occupies > 25% of lung parenchyma on CT). CONCLUSIONS: MGS may be a helpful and convenient tool to select candidates for TBLB to establish the diagnosis of LAM pathologically.

Clinical features of squamous cell lung cancer with anaplastic lymphoma kinase (ALK)-rearrangement: a retrospective analysis and review.

Anti-anaplastic lymphoma kinase (ALK)-targeted therapy dramatically improves therapeutic responses in patients with ALK-rearranged lung adenocarcinoma (Ad-LC). A few cases of squamous cell lung carcinoma (Sq-LC) with ALK rearrangement have been reported; however, the clinicopathological features and clinical outcomes following treatment with ALK inhibitors are unknown. We addressed this in the present study by retrospectively comparing the clinical characteristics of five patients with ALK-rearranged Sq-LC with those of patients with ALK-rearranged Ad-LC and by evaluating representative cases of ALK inhibitor responders and non-responders. The prevalence of ALK rearrangement in Sq-LCs was 1.36%. Progression-free survival (PFS) after initial treatment with crizotinib was significantly shorter in Sq-LC than in Ad-LC with ALK rearrangement (p = 0.033). Two ALK rearrangements assayed by fluorescence in situ hybridization (FISH)-positive/immunohistochemistry-negative cases did not respond to crizotinb, and PFS decreased following alectinib treatment of ALK-rearranged Sq-LC (p = 0.045). A rebiopsy revealed that responders to ceritinib harbored the L1196M mutation, which causes resistance to other ALK inhibitors. However, non-responders were resistant to all ALK inhibitors, despite the presence of ALK rearrangement in FISH-positive circulating tumor cells and circulating free DNA and absence of the ALK inhibitor resistance mutation. These results indicate that ALK inhibitors remain a reasonable therapeutic option for ALK-rearranged Sq-LC patients who have worse outcomes than ALK-rearranged Ad-LC patients and that resistance mechanisms are heterogeneous. Additionally, oncologists should be aware of the possibility of ALK-rearranged Sq-LC based on clinicopathological features, and plan second-line therapeutic strategies based on rebiopsy results in order to improve patient outcome.

Autofluorescence imaging bronchoscopy as a novel approach to the management of tracheobronchopathia osteochondroplastica: a case report.

Tracheobronchopathia osteochondroplastica (TO) is not only rare but also presents highly varied and unpredictable clinical manifestations. Consequently, the management and treatment strategies remain unclear. An accurate evaluation tool is important for the management of individual patients in the absence of standard guidelines. Although bronchoscopy is the gold standard for diagnosis, it cannot satisfactorily detect the treatment response and disease progression because subtle mucosal changes can go undetected. Therefore, improved techniques that can detect subtle mucosal changes associated with TO are desirable. Autofluorescence imaging bronchoscopy (AFI) is a recently introduced advanced endoscopic technology that can detect subtle mucosal changes with the aid of different colors. Here we report the first case, to the best of our knowledge, involving a 42-year-old man with TO in whom tracheal involvement was evaluated by AFI and detected as the appearance of a magenta color.

Bevacizumab-induced chronic interstitial pneumonia during maintenance therapy in non-small cell lung cancer.

Bevacizumab is a monoclonal antibody targeting the vascular endothelial growth factor receptor and a key drug for advanced non-small cell lung cancer. There are few reports describing bevacizumab-induced chronic interstitial pneumonia. A 62-year-old man with advanced non-small cell lung cancer was admitted to our hospital with dyspnea. He previously received four courses of carboplatin plus paclitaxel with bevacizumab combination therapy and thereafter received four courses of maintenance bevacizumab monotherapy. A chest-computed tomography scan on admission revealed diffuse ground glass opacity. He had not received any other drugs and did not have pneumonia. Thus, he was diagnosed with bevacizumab-induced chronic interstitial pneumonia and was treated with a high dose of corticosteroids. After steroid treatment, his dyspnea and radiological findings improved. This case report is the first description of bevacizumab-induced chronic interstitial pneumonia during maintenance therapy in a patient with non-small cell lung cancer.

Potential Role of CT Metrics in Chronic Obstructive Pulmonary Disease with Pulmonary Hypertension.

PURPOSE: Recent imaging studies demonstrated the usefulness of quantitative computed tomographic (CT) analysis assessing pulmonary hypertension (PH) in patients with chronic obstructive lung disease (COPD-PH). The aim of this study was to investigate whether it would be also valuable for predicting and evaluating the effect of pulmonary vasodilators in patients with COPD-PH. METHODS: We analyzed a correlation between the extent of cystic destruction (LAA%) and total cross-sectional areas of small pulmonary vessels less than 5 mm(2) (%CSA <5) in many CT slices from each of four COPD-PH patients before and after the initiation of pulmonary vasodilator. To evaluate those generalized data from patients with COPD, we evaluated multiple slices from 42 patients whose PH was not clinically suspicious. We also selected five PH patients with idiopathic interstitial pneumonia (IIP-PH) and analyzed serial changes of pulmonary artery enlargement (PA:A ratio). RESULTS: In 42 COPD patients without PH, LAA% had a statistically significant negative correlation with %CSA <5. However, three of four COPD-PH patients manifested no such correlation. In two patients, clinical findings were dramatically improved after the initiation of pulmonary vasodilator. Notably, LAA% and %CSA <5 in those patients correlated significantly after its treatment. In COPD-PH, the PA:A ratio was significantly decreased after the initiation of pulmonary vasodilator therapy (1.25 ± 0.13 vs. 1.13 ± 0.11, p = 0.019), but not in IIP-PH. CONCLUSIONS: Our study demonstrates that the use of quantitative CT analysis is a plausible and beneficial tool for predicting and evaluating the effect of pulmonary vasodilators in patients with COPD-PH.

Genistein attenuates hypoxic pulmonary hypertension via enhanced nitric oxide signaling and the erythropoietin system.

Upregulation of the erythropoietin (EPO)/EPO receptor (EPOR) system plays a protective role against chronic hypoxia-induced pulmonary hypertension (hypoxic PH) through enhancement of endothelial nitric oxide (NO)-mediated signaling. Genistein (Gen), a phytoestrogen, is considered to ameliorate NO-mediated signaling. We hypothesized that Gen attenuates and prevents hypoxic PH. In vivo, Sprague-Dawley rats raised in a hypobaric chamber were treated with Gen (60 mkg/kg) for 21 days. Pulmonary hemodynamics and vascular remodeling were ameliorated in Gen-treated hypoxic PH rats. Gen also restored cGMP levels and phosphorylated endothelial NO synthase (p-eNOS) at Ser(1177) and p-Akt at Ser(473) expression in the lungs. Additionally, Gen potentiated plasma EPO concentration and EPOR-positive endothelial cell counts. In experiments with hypoxic PH rats' isolated perfused lungs, Gen caused NO- and phosphatidylinositol 3-kinase (PI3K)/Akt-dependent vasodilation that reversed abnormal vasoconstriction. In vitro, a combination of EPO and Gen increased the p-eNOS and the EPOR expression in human umbilical vein endothelial cells under a hypoxic environment. Moreover, Gen potentiated the hypoxic increase in EPO production from human hepatoma cells. We conclude that Gen may be effective for the prevention of hypoxic PH through the improvement of PI3K/Akt-dependent, NO-mediated signaling in association with enhancement of the EPO/EPOR system.

Breakthrough lung Scedosporium prolificans infection with multiple cavity lesions in a patient receiving voriconazole for probable invasive aspergillosis associated with monoclonal gammopathy of undetermined significance (MGUS).

Breakthrough non- Aspergillus mold infections among patients receiving the anti-mold azole antifungal agents like voriconazole or posaconazole have been increasingly reported. We report a case of lung Scedosporium prolificans infection with multiple cavities in a 58-year-old man with monoclonal gammopathy of undetermined significance (MGUS) during voriconazole treatment for probable invasive aspergillosis. Cultures of repeated sputum specimens yielded the same fungus until his death 83 days after diagnosis. S. prolificans should be considered in patients with breakthrough infections receiving voriconazole.

Osteopontin expression in pulmonary tumor thrombotic microangiopathy caused by gastric carcinoma.

Pulmonary tumor thrombotic microangiopathy (PTTM) is characterized by fibrocellular intimal proliferation and thrombus formation in small pulmonary arteries and arterioles in patients with metastatic carcinoma. Osteopontin (OPN) is a multifunctional cytokine and adhesive protein, and has been demonstrated to be implicated in fibrosis, neointima formation, arterial occlusion by thrombus, and tumor metastases in cooperation with platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF). Herein is described an autopsy case of gastric adenocarcinoma with severe pulmonary hypertension due to PTTM. Histologically, tumor cell emboli markedly induced both fibromuscular intimal thickening and thrombosis, resulting in luminal stenosis and occlusion of small pulmonary arteries and arterioles. Tumor cells, both in the PTTM lesions and primary gastric carcinoma, had positive immunoreactivity for OPN, PDGF, and VEGF. In addition, proliferating fibromuscular intimal cells also showed expression of OPN, PDGF, and VEGF. These findings suggest that OPN may be involved in fibrocellular intimal proliferation and thrombus formation in PTTM together with PDGF and VEGF. To the best of the authors' knowledge this is the first report to demonstrate the possible involvement of OPN in PTTM. It is postulated that OPN is one of the candidate molecules for the development of PTTM.

Malignant pleurisy associated with primary lung cancer well controlled by pleurodesis using distilled water.

The patient was an 84-year-old man patient diagnosed as malignant pleurisy associated with lung cancer. After drainage of the right pleural effusion, pleurodesis with distilled water was performed. Despite the enlargement of the primary lesion of the lung cancer during the follow-up period, the amount of pleural effusion did not increase for more than one year. No adverse effects associated with pleurodesis were noted. Pleurodesis with distilled water should be considered as one of the choices for treatment in the management of malignant pleurisy especially in elderly.

Involvement of RhoA/Rho kinase signaling in protection against monocrotaline-induced pulmonary hypertension in pneumonectomized rats by dehydroepiandrosterone.

RhoA/Rho kinase (ROCK) signaling plays a key role in the pathogenesis of experimental pulmonary hypertension (PH). Dehydroepiandrosterone (DHEA), a naturally occurring steroid hormone, effectively inhibits chronic hypoxic PH, but the responsible mechanisms are unclear. This study tested whether DHEA was also effective in treating monocrotaline (MCT)-induced PH in left pneumonectomized rats and whether inhibition of RhoA/ROCK signaling was involved in the protective effect of DHEA. Three weeks after MCT injection, pneumonectomized rats developed PH with severe vascular remodeling, including occlusive neointimal lesions in pulmonary arterioles. In lungs from these animals, we detected cleaved (constitutively active) ROCK I as well as increases in activities of RhoA and ROCK and increases in ROCK II protein expression. Chronic DHEA treatment (1%, by food for 3 wk) markedly inhibited the MCT-induced PH (mean pulmonary artery pressures after treatment with 0% and 1% DHEA were 33+/-5 and 16+/-1 mmHg, respectively) and severe pulmonary vascular remodeling in pneumonectomized rats. The MCT-induced changes in RhoA/ROCK-related protein expression were nearly normalized by DHEA. A 3-wk DHEA treatment (1%) started 3 wk after MCT injection completely inhibited the progression of PH (mean pulmonary artery pressures after treatment with 0% and 1% DHEA were 47+/-3 and 30+/-3 mmHg, respectively), and this treatment also resulted in 100% survival in contrast to 30% in DHEA-untreated rats. These results suggest that inhibition of RhoA/ROCK signaling, including the cleavage and constitutive activation of ROCK I, is an important component of the impressive protection of DHEA against MCT-induced PH in pneumonectomized rats.

Successful resection of dermatomyositis associated with thymic carcinoma: report of a case.

We report a case of thymic carcinoma associated with dermatomyositis (DM) in a 53-year-old man. The patient presented with the characteristic features of a skin rash with Gottron's papules, proximal muscle weakness, and increased serum levels of the muscle-associated enzymes. Comprehensive clinical examinations revealed an anterior mediastinal tumor. We resected the tumor and histological examination confirmed squamous cell carcinoma of the thymus. Thereafter, his clinical symptoms improved dramatically and his serum levels of muscle-associated enzymes dropped, indicating that the DM was a paraneoplastic phenomenon. Our search of the literature found only one other case report of DM accompanied by thymic carcinoma, and to our knowledge, this is the fi rst documented case of dramatic improvement of DM after resection of thymic carcinoma. We propose that thymic carcinoma should be added to the list of malignancies that can complicate DM as a paraneoplastic disease.

Dehydroepiandrosterone upregulates soluble guanylate cyclase and inhibits hypoxic pulmonary hypertension.

OBJECTIVE: It has been reported that dehydroepiandrosterone is a pulmonary vasodilator and inhibits chronic hypoxia-induced pulmonary hypertension. Additionally, dehydroepiandrosterone has been shown to improve systemic vascular endothelial function. Thus, we hypothesized that chronic treatment with dehydroepiandrosterone would attenuate hypoxic pulmonary hypertension by enhancing pulmonary artery endothelial function. METHODS AND RESULTS: Rats were randomly assigned to five groups. Three groups received food containing 0, 0.3, or 1% dehydroepiandrosterone during a 3-wk-exposure to simulated high altitude (HA). The other 2 groups were kept at Denver's low altitude (LA) and received food containing 0 or 1% dehydroepiandrosterone. Dehydroepiandrosterone dose-dependently inhibited hypoxic pulmonary hypertension (mean pulmonary artery pressures after treatment with 0, 0.3, and 1% dehydroepiandrosterone=45+/-5, 33+/-2*, and 25+/-1*# mmHg, respectively. *P<0.05 vs. 0% and # vs. 0.3%). Dehydroepiandrosterone (1%, 3 wks) treatment started after rats had been exposed to 3-wk hypoxia also effectively reversed established hypoxic pulmonary hypertension. Pulmonary artery rings isolated from both LA and HA rats treated with 1% dehydroepiandrosterone showed enhanced relaxations to acetylcholine and sodium nitroprusside, but not to 8-bromo-cGMP. In the pulmonary artery tissue from dehydroepiandrosterone-treated LA and HA rats, soluble guanylate cyclase, but not endothelial nitric oxide synthase, protein levels were increased. CONCLUSION: These results indicate that the protective effect of dehydroepiandrosterone against hypoxic pulmonary hypertension may involve upregulation of pulmonary artery soluble guanylate cyclase protein expression and augmented pulmonary artery vasodilator responsiveness to nitric oxide.

Involvement of RhoA/Rho kinase signaling in pulmonary hypertension of the fawn-hooded rat.

The fawn-hooded rat (FHR) develops severe pulmonary hypertension (PH) when raised for the first 3-4 wk of life in the mild hypoxia of Denver's altitude (5,280 ft.). The PH is associated with sustained pulmonary vasoconstriction and pulmonary artery remodeling. Furthermore, lung alveolarization and vascularization are reduced in the Denver FHR. We have recently shown that RhoA/Rho kinase signaling is involved in both vasoconstriction and vascular remodeling in animal models of hypoxic PH. In this study, we investigated the role of RhoA/Rho kinase signaling in the PH of Denver FHR. In alpha-toxin permeabilized pulmonary arteries from Denver FHR, the contractile sensitivity to Ca2+ was increased compared with those from sea-level FHR. RhoA activity and Rho kinase I protein expression in pulmonary arteries of Denver FHR (10-wk-old) were higher than in those of sea-level FHR. Acute inhalation of the Rho kinase inhibitor fasudil selectively reduced the elevated pulmonary arterial pressure in Denver FHR in vivo. Chronic fasudil treatment (30 mg.kg-1.day-1, from birth to 10 wk old) markedly reduced the development of PH and improved lung alveolarization and vascularization in Denver FHR. These results suggest that Rho kinase-mediated sustained vasoconstriction, through increased Ca2+ sensitivity, plays an important role in the established PH and that RhoA/Rho kinase signaling contributes significantly to the development of PH and lung dysplasia in mild hypoxia-exposed FHR.

Hypoxia and Rho/Rho-kinase signaling. Lung development versus hypoxic pulmonary hypertension.

Intracellular signaling via the small GTP-binding protein RhoA and its downstream effector Rho-kinase plays a role in regulating diverse cellular functions, including cell contraction, migration, gene expression, proliferation, and differentiation. Rho/Rho-kinase signaling has an obligatory role in embryonic cardiac development, and low-level chemical activation of Rho promotes branching morphogenesis in fetal lung explants. Gebb has found that hypoxia markedly augments branching morphogenesis in fetal rat lung explants, and our preliminary results suggest this is associated with activation of RhoA. Whereas hypoxia-induced activation of Rho/Rho-kinase may promote fetal lung development, other evidence indicates it has adverse effects in the lungs of neonates and adults. When exposed at birth to the mild hypoxia of Denver's altitude (5,280 ft), the neonatal fawn-hooded rat (FHR) develops severe pulmonary hypertension (PH) associated with impaired lung alveolarization and vascularization. We have observed that administration via the drinking water of the Rho-kinase inhibitor fasudil to the nursing, Denver FHR mother for the first 2 to 3 weeks, and then directly to the Denver FHR pups for the next 7 to 8 weeks, ameliorates the lung dysplasia and PH. The adult Sprague-Dawley rat develops PH when exposed for 3 to 4 wk to a simulated altitude of 17,000 ft. We have found that this hypoxic PH is associated with activation of pulmonary artery Rho/Rho-kinase and is almost completely reversed by acute intravenous administration of the Rho-kinase inhibitor Y-27632. In addition, chronic in vivo treatment with Y-27632 reduces development of the hypoxic PH. In summary, hypoxic activation of Rho/Rho-kinase signaling may be important for fetal lung morphogenesis, but continued activation of this pathway in the neonate impairs postnatal lung development and re-activation in the adult contributes to development of PH.

[A case of pulmonary squamous cell carcinoma coexisting with pulmonary actinomycosis].

A 71-year-old man was referred to our hospital complaining of cough. Chest radiography revealed a mass opacity in the right upper lung field. A transbronchial biopsy specimen revealed non-specific inflammatory changes. Percutaneous lung aspiration biopsy under ultrasound guidance demonstrated gram-positive rods, suggesting actinomyces. On the diagnosis of pulmonary actinomycosis, the patient was treated with penicillin-G and his symptoms were relieved. In a three-month follow-up, the mass shadow in the right upper lung field was found to have increased in size. Squamous cell lung cancer was diagnosed on the basis of repeated transbronchial tumor biopsies, and right upper lobectomy was performed. Most cases of pulmonary actinomycosis have been diagnosed from post-surgical tumor specimens taken on suspicion of the presence of lung cancer. However, the lung cancer in this case was difficult to diagnose because the lung cancer was co-existent with pulmonary actinomycosis.