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A 77-year-old man with Hansen's disease was referred to our hospital because of a small nodular lesion detected adjacent to the pleura in the right lower lobe (S10) on chest CT. He had lost all ten fingers due to Hansen's disease and was using a prosthetic limb after amputation of the right lower leg. Although the patient had an 11-year history of shoulder and back pain and was suspected of having interstitial pneumonia 6 years previously, no detailed examination had been conducted. Bronchoscopy did not yield a definitive diagnosis, and a lung biopsy was performed under thoracoscopic guidance. Histological examination of the resected nodule with colliquative necrosis revealed palisading granulomas with multinucleated giant cells and plasma cell infiltration with formation of lymphoid follicles. Since serum levels of both anti-MMP3 and anti CCP antibodies were elevated, rheumatoid arthritis (RA) with rheumatoid lung was diagnosed. Therefore, the nodule was considered a rheumatoid nodule. Since diagnosis of rheumatoid arthritis is difficult when lacking characteristic joint manifestations, it is important to include rheumatoid nodules as a differential diagnosis and to measure RA specific autoantibodies, to make a comprehensive diagnosis for non-specific necrotizing granulomas.

Objective This study assessed the diagnostic rate of pulmonary tuberculosis (PTB) using fiberoptic bronchoscopy (FBS) in patients with suspected PTB, and negative pre-bronchoscopy smear and polymerase-chain reaction (PCR) in sputum. Patients and Methods We retrospectively reviewed 201 culture-positive PTB patients that underwent FBS because both smear and PCR results in sputum were negative. The positive rates of smear for acid fast bacilli, PCR for Mycobacterium tuberculosis, the presence of granuloma in transbronchial biopsy (TBB), and culture of M. tuberculosis were analyzed. In addition, the radiographic features, contribution of FBS to rapid and/or definitive diagnosis of PTB, and drug susceptibility results of M. tuberculosis were also reviewed. Results There were 136 males and 102 patients under the age of 40 years; non-cavitary (156 cases) and minimal disease (119 cases) on radiographs predominated. The positive rates of FBS were: 44% (smear), 62% (PCR), 61% (TBB), and 87% (culture). These rates increased in smear and PCR examinations when taken from wider spread shadows on radiographs. The combination of the various bronchoscopy samples increased the diagnostic rate to 92% when all examinations were combined. Positive culture results depended on FBS procedures in 80 cases. Twenty-one cases showed resistance to at least one of the major anti-tuberculous agents. Conclusion This analysis revealed high positive rates of PTB from bronchoscopy samples, providing rapid and definitive ability for PTB diagnosis, and details of drug susceptibility. Therefore, FBS is an important diagnostic procedure in patients with suspected PTB whose sputum specimens were negative both for smear and PCR analyses.

A 34-year-old Japanese man working in Mexico City since April 2004, was referred to our hospital in December 2005 because of a nodule in the left lingular bronchus, first pointed out in September 2005. Transbronchial lung biopsy (TBLB) revealed coagulation necrosis, which contained yeast-like cells stained with fungiflora Y stain. We diagnosed pulmonary histoplasmosis (histoplasmoma type) based on the shape of the fungi and on his residential history. The nodule, resected in January, presented histological findings in concordance with the TBLB specimen. We later confirmed his serum was positive for an anti-histoplasma antibody. The pathogen was identified as Histoplasma capsulatum by PCR using lung tissue. This is apparently the first report of Histoplasmosis diagnosed by TBLB. Since imported mycosis is increasing, we should accumulate cases to make guidelines for diagnosis and treatment.

We investigated the incidence of tuberculous pleurisy among patients with adenosine deaminase (ADA) levels of 50 IU/L or less in a pleural effusion, and without a previous diagnosis of carcinomatous pleurisy or Mycobacterium tuberculosis.Subjects were selected from patients who had undergone pleural biopsy by thoracoscopy at National Hospital Organization Tokyo Hospital from January 1995 to November 2004, and who had ADA levels of less than 50 IU/L in pleural fluid obtained preoperatively by thoracentesis. In all subjects, smear, culture, and polymerase chain reaction for Mycobacterium tuberculosis were negative.Of 138 patients who underwent thoracoscopic pleural biopsy, a total of 50 had effusions with ADA levels of less than 50 IU/L. Six (12%) of these patients were diagnosed with tuberculous pleurisy after biopsy. Three patients with an effusion ADA level of 35 IU/L or less were diagnosed with tuberculous pleurisy.Occult tuberculous pleurisy is significantly common in patients with pleural effusion ADA levels of 50 IU/L or less and who may otherwise be diagnosed with nonspecific pleurisy.

To clarify clinico-pathological features of tuberculosis found at autopsy.This study investigates 18 (3.7%) of active pulmonary tuberculosis out of 489 autopsy in Tachikawa Sougo Hospital during the period from 1992 to 2005.There were 11 men and 7 women, with a median age of 69.5 years. Tubercle bacilli were proved from sputum in 6, which consisted of 3 with positivity on sputum smear microscopy and culture, and 3 with positivity only on sputum culture. Two were examined, but not diagnosed before death. Three didn't show any positive result despite of repeated sputum tests. The features of the chest radiological findings were: (1) Shadows that present prior tuberculosis (ex: nodules, fibrotic lesion) were found in 9 and ground-glass-opacity in 5. (2) In 6, radiological findings consistent with tuberculosis were not pointed out because shadows such as fibrosis, pleural effusion, or cancer were mixed in the same lung. (3) In 11, main radiological findings were found in atypical segments, when there were some underlying conditions such as the use of corticosteroidal therapy or diabetes mellitus. Four were diagnosed correctly, and treated with anti-tuberculosis drugs. Other 14 were not diagnosed before death and diagnosed wrongly as pneumonia, cancer, or other diseases. Encapsulated caseous nodules were seen in 7, and autopsy confirmed that 12 including these 7 were caused by endogenous reactivation. Miliary tuberculosis was found in 5, caseous pneumonia/bronchitis in 6. One had tuberculous empyema. As to underlying diseases, 8 had malignant disease, 6 had diabetes mellitus and 6 were treated with corticosteroids.This study suggests that sputum culture or radiological findings are not sufficient enough to diagnose tuberculosis, especially in compromised host. We emphasize the vital role of treatment for latent tuberculosis for cases with high risk of endogenous reactivation, and it's necessary to make the guideline for the treatment of such latent tuberculosis.

A 71-year-old previously healthy woman, presented with respiratory failure several days after initiation of cough and fever. A chest X-ray revealed multiple infiltrative shadows with airbronchograms in bilateral middle and lower lung fields. Transbronchial lung biopsy, performed after steroid pulse therapy which induced transient improvement, demonstrated exudative lesions with massive aggregation of histiocytes containing yeast-like fungi in their cytoplasm. Since the test for cryptococcal antigens was positive, a diagnosis of primary pulmonary cryptococcosis was made. Despite intravenous fluconazole injection for aweek, the severity of fungus infiltration increased. The treatment was therefore changed to a combination of intravenous amphotericin B and oral prednisolone, which achieved clinical improvement. In conclusion, in the case of rapidly progressive pulmonary cryptococcosis with widespread exudative lesions, addition of steroid therapy should be considered when antifungal agents alone prove ineffective.

The aim of this study was to evaluate the usefulness of bronchofiberscopy (BFS) in the diagnosis of pulmonary non-tuberculous mycobacteriosis (PNTM).Among 909 PNTM patients admitted to our hospital during the period from 1995 to 2006, BFS was performed for the diagnosis of PNTM in 107 patients (12%) who had either a negative sputum-smear for acid-fast bacilli (AFB) (n = 100) or from whom it had been impossible to collect sputum (n =7). For these 107 cases, we retrospectively compared and analyzed the findings from specimens obtained by BFS, such as smears, cultures, polymerase-chain reaction (PCR), and transbronchial lung biopsy (TBLB), with clinical, radiological, and sputum examination disease, was also seen in the positive ratios of other nontuberculous mycobacteriosis cases. Type and/or spread of MAC disease on chest radiographs did not relate to positive ratios of BFS obtained specimens. Based on overall BFS findings, including the examination of sputum immediately after BFS, 68 of 92 (74%) patients met the diagnostic criteria of MAC disease. Furthermore, through a combination of positive-TBLB findings and positive-PCR findings of BFS specimens, we were able to obtain an early and strong indication of MAC disease in 17 of 36 (47%) patients.Using BFS to obtain various kinds of specimens is a useful tool for the early and definite diagnosis of PNTM/pulmonary MAC disease.

胸部X線上で結節性陰影および両側肺門リンパ節腫脹を呈し, 鋭匙細胞診所見からサルコイドーシス (以下, サ症) がつよく示唆され, ほかの検査所見から確診しえた症例を報告する.症例は55歳女性.検診にて胸部異常陰影を指摘され旭中央病院受診.両肺に多発性異常陰影があり, 鋭匙細胞診・経気管支肺生検 (以下TBLB) を行った.鋭匙細胞診では, 類上皮細胞の集塊が多数観察され, 多核巨細胞もわずかながらみられた.壊死背景をまったく欠き, 異物・真菌などもみられなかったことから, 細胞診の段階でサ症をつよく疑った.TBLBで気管支壁内に非乾酪壊死性類上皮細胞性肉芽種がみられた.以上の所見およびほかの検査所見からサ症と確診した.剥離細胞診はサ症の診断にほぼ無力であるが, 直接採取法による細胞診は結節性病変をともなうサ症診断に有力な手段になりうることが確認された.

A 72-year-old woman who had been treated for coxotuberculosis was examined because of persistent hemoptysis. Chest X-ray films and CT scans revealed atelectasis of the right middle lobe and bronchial calcification. Bronchoscopy showed a yellow broncholith with pus 1 cm from the orifice of the right B4 bronchus. Actinomyces israelii was isolated by anaerobic culture of bronchial lavage fluid. Since the broncholith occluded the right middle lobe bronchus and had caused repeated episodes of infection the right middle lobe was resected by video-assisted thoracoscopic surgery. Histological examination revealed broncholiths due to calcification of peripheral caseating nodules of tuberculosis, which is a rarely finding.

Background and objective: The aim of this study was to describe the features of lung cancers associated with chronic tuberculous pyothorax. Methods: Clinicopathological data from patients with coexisting lung cancer and chronic latent pyothorax caused by tuberculosis (TB) were analysed, and cancer tissue samples were investigated for the presence of Epstein–Barr virus. Results: Twelve patients were identified, and all had a history of tuberculous pleuritis or surgical intervention for TB. The interval between the onset of TB and lung cancer was more than 30 years in nine patients and the most frequent symptom was chest pain (six patients). All cancers were in the ipsilateral lung to the pyothorax, and in nine of the 12 patients the cancers were located adjacent to the pyothorax. In situ hybridization analysis for Epstein–Barr virus-encoded small RNA failed to show positive signals in any of the six cancer tissues examined. Conclusions: Lung cancer associated with chronic pyothorax always developed in the ipsilateral lung to the pyothorax, and there was no evidence for the presence of Epstein–Barr virus in the cancer tissues examined.

Desquamative interstitial pneumonia (DIP) is a rare pattern of diffuse parenchymal lung disease known to overlap with respiratory bronchiolitis-interstitial lung disease (RB-ILD). The aim was to review biopsy-proven cases of DIP to investigate further the clinical, imaging and histological features of this disease.Twenty patients fulfilled the pathological criteria: 19 men and one woman with a mean age of 54 years. Clinical features, bronchoalveolar lavage (BAL) data, radiological findings, pathological findings other than criteria, effect of therapy and outcome were examined. The BAL data for 17 cases revealed marked eosinophilia (mean 18%) and moderate neutrophilia (mean 11%). Computed tomography in 17 patients showed peripheral involvement in all cases with a clear margin in 64% and thin-walled cysts in 35% of cases. Additional pathological features were a distinct lobular distribution (70%) and architectural destruction (70%) with cyst formation (55%). Eighteen of the 19 patients (95%) improved under steroid pulse and/or oral therapy. Sixteen subjects (80%) are alive, three died of other diseases and one died of DIP 74 months after the diagnosis. Percent vital capacity increased significantly and new thin-walled cysts appeared in one case.BAL eosinophilia, lobular distribution and architectural destruction with cyst formation are characteristic features of DIP.

The aim of this study is to clarify the features of bronchial tuberculosis.We analyzed the clinicopathological data from 103 out of 4467 (2.3%) cases of culture positive tuberculosis admitted to the National Hospital Organization Tokyo National Hospital in the period from 1993 to 2004 in which bronchial tuberculosis was confirmed by bronchofiberscopy.There were 62 women and 41 men, and 53 cases were less than 50 years old. The most common symptom, namely cough was observed in 70 cases, while 79 cases showed III1 to III2 on roentgenographic examination, and 81 cases were smear-positive for acid-fast bacilli in the sputum. Regarding the bronchofiberscopic findings, ulcers were detected in 60 cases, and the major site of bronchial tuberculosis was in the left main bronchus (35 cases). The number of the cases in which the time span from the onset of symptoms to diagnosis took over 3 months was 29, and 26 of them were "doctor's delay" cases which had a history of medical consultation resulting in diagnosis and treatment of other diseases, such as bronchial asthma (7 cases). There were 41 cases in which the second bronchofiberscopic findings have been reviewed, and regardless of the length of the span from the onset to diagnosis, the first bronchofiberscopy mostly revealed ulcer within 1 month after the start of treatment for tuberculosis, and 3 months after the start of treatment, many patients developed fibrous scars. Between 1999 to 2004, the first bronchofiberscopies were usually performed within 2 weeks to 1 month after the start of the treatment in contrast to the cases admitted between 1993 to 1998 in which bronchofribroscopy was mainly performed before the start of the treatment. However, there were no differences in the findings due to the timing of bronchofiberscopy.The clinical characteristics of bronchial tuberculosis have not changed, and the delay of diagnosis of bronchial tuberculosis due to doctor's delay also continues to be an important issue today. In patients showing positive sputum smear for mycobacteria, the timing of bronchofiberscopy, although required upon medical examination, is considered to be more appropriately performed from 2 weeks to 1 month after the start of treatment from the view point of nosocomial tuberculosis infection control strategy.

We reviewed 72 patients with coexisting lung cancer and pulmonary mycobacteriosis, and discuss the features and transition of these coexistent cases. There were 56 pulmonary tuberculosis (PTB) cases and 16 non-tuberculous mycobacteriosis (PNTM) cases, 62 men and 10 women, with a mean age of 69 years. In 43 cases, both diseases were concurrently detected, lung cancer was first detected in 19 cases, and mycobacteriosis was first detected in 10 cases. The frequency of lung cancer in cases with active pulmonary mycobacteriosis was 1.2%. Pulmonary mycobacteriosis was characterized by Type II (40 cases) and Spread 2 (42 cases) on chest X-rays; the most frequent histologic type of lung cancer was squamous cell carcinoma (32 cases) and most were stage III-IV cases (57 cases). After PTB treatment, the negative conversion rate of sputum cultures in both the concurrently detected group and the group in which lung cancer was initially detected was 56% within one month and 94% within 2 months. For the treatment of lung cancer, 33 cases received supportive care, 13 patients underwent resection and 17 received chemotherapy or chemoradiotherapy. In PNTM cases, both lung cancer and pulmonary mycobacteriosis showed a slight state compared to those in PTB cases, and in the group in which lung cancer was initially detected, both diseases were more advanced or severe than those in the concurrently detected group or in the group in which mycobacteriosis was initially detected. The rate of coexisting lung cancer and pulmonary mycobacteriosis was unchanged at 1-2%, and the incidence of stage IV lung cancer cases has increased recently. Coexisting lung cancer and pulmonary mycobacteriosis is an important condition in respiratory disease in Japan. Physicians should be aware of the possibility of PTB coexisting with lung cancer.

We directly examined the thoracic cavity by thoracoscopy under local anesthesia, performed pleural biopsy, and made a definitive pathological diagnosis in tuberculous pleurisy.We performed a retrospective study of 32 patients who had been bacteriologically and pathologically diagnosed with tuberculous pleurisy by thoracoscopy under local anesthesia in our hospital between January 1995 and November 2004.Bacteriological examination of pleural fluids obtained by thoracentesis before examination showed that one sample was polymerase chain reaction (PCR)-positive, and 5 samples were culture-positive. Bacteriological examination of pleural fluids obtained by thoracoscopy revealed that 2 samples were PCR-positive, and 5 samples culture-positive, including 2 preoperatively positive samples. The adenosine deaminase (ADA) levels ranged from 18.3 to 279.0 U/L, with a mean of 72.9 U/L, including 50 U/L or less in 5 patients and 35 U/L or less in 3 patients. Thirty patients (93.8%) were successfully diagnosed by pleural biopsy with pathological examination, and 21 (65.6%) of them by pathological examination alone.In patients with suspected tuberculous pleurisy, thoracoscopic pleural biopsy under local anesthesia should be actively performed, because the technique has a high diagnostic rate, and can be easily and safely performed.

We reviewed an autopsied 27-year-old female with obliterative bronchiolitis associated with Stevens-Johnson syndrome. She had a history of Stevens-Johnson syndrome at age 10 years old and was treated with corticosteroids. Two months after the onset of dermatitis, the patient complained of dyspnea on exertion. The chest radiograph showed hyperinflation, and pulmonary function tests revealed obstructive impairment. The respiratory failure progressed due to respiratory tract infection and pneumothorax. She underwent thoracoscopic cyst surgery for right pneumothorax. Although the patient was clinically diagnosed as having obliterative bronchiolitis and received corticosteroids therapy and mechanical ventilation, she died of progressive respiratory failure 17 years after the onset of Stevens-Johnson syndrome. On autopsy, the macroscopic appearance of both lungs showed multiple white nodules in the centrilobular lesion corresponding to the obliteration of the small bronchioli. The microscopic appearance revealed constrictive bronchiolitis in the membranous bronchioli of both lungs associated with secondary bronchiectasis caused by superimposed infection.

We observed a rare case of lung carcinoma accompanied by active pulmonary tuberculosis in the same lobe. The chest x-ray of a 49-year-old man revealed an abnormal shadow in the right upper field and a giant bulla in the left upper field. Chest computed tomography (CT) revealed a nodule with consolidation, which was not continuous in the right S3. Bronchoscopically, epidermoid carcinoma existed in the proximal right upper bronchus. In the sputum specimens, the smear was negative, but the polymerase chain reaction of Mycobacterium tuberculosis and culture was positive. Anti-tuberculosis treatments were administered for approximately 4 weeks, but the chest x-ray remained unchanged. Right upper lobectomy with bronchoplasty (wedge resection of the right upper bronchus) was performed, and the anastomosis was covered with an intercostal muscle flap. Lymphadenectomy of the right hilum and mediastum was also performed. Microscopy revealed epidermoid carcinoma in the proximal tumor (pT3N0M0-stage IIB) and epithelioid granuloma with caseous necrosis, granulomatous pneumonia, exudative lesions, and fibrocaseous nodules in the distal lung. After surgery, anti-tuberculosis treatment was resumed.

A 67-year-old man with a past history of pulmonary tuberculosis had been referred to our department complaining of bloody sputum. The chest radiograph on admission showed a cavity in the left upper lung field. Chest CT showed a mass-like fungus ball in the cavity. Pulmonary aspergillosis was diagnosed from the sputum mycology, serum Aspergillus antigen and antibody. Even though 150 mg per day Funguard (micafungin sodium) was given intravenously for 4 weeks, the pulmonary aspergillosis did not improve. Dynamic MRI obtained 20 seconds after intravenous injection of contrast material revealed penetrating vessels in the wall of the cavity, and dilated and proliferative vessels surrounding the cavitary lesion. On the basis of the MRI findings which suggested the risk of massive hemoptysis, we performed left upper lobectomy. The histological specimen revealed dilated pulmonary arteries in the wall of the cavity, corresponding to the penetrating vessels on MRI. This is the first report of radiologic-pathologic correlation using dynamic MRI for pulmonary aspergillosis, to the best of our knowledge.

A 59-year-old man who had just completed therapy for tuberculosis, fell down in sauna and was admitted to a hospital. As acid-fast bacilli were positive (Gaffky 2) in sputum and residual cavity was shown in the right upper lobe on chest X-ray, he was transferred to our hospital. In spite of starting antituberculous chemotherapy, small nodular shadows appeared diffusely and were changed into ground-glass appearance on chest X-ray. The trans-bronchial-lung-biopsy revealed alveolitis mainly composed of lymphocyte infiltration with non-caseous epithelioid cell granulomas and organization which are likely to appear in hypersensitivity pneumonitis. As the acid-fast bacilli were identified as Mycobacterium avium, clarithromycin and kanamycin were added to the chemotherapy, but no improvement was observed in clinical feature. Corticosteroid therapy was further added and clinical feature improved immediately. Although we did not examine the presence of Mycobacterium avium in the water of sauna bath, we suspected this case as Hot Tub Lung based on clinical features and the response to treatment.

Lymphangioleiomyomatosis (LAM) affects exclusively women of reproductive age, involves the lungs and axial lymphatic system, and is frequently complicated with renal angiomyolipomas. LAM lesions are generated by the proliferation of LAM cells with mutations of one of the tuberous sclerosis complex (TSC) genes. Recent studies indicate that LAM cells can migrate or metastasize to form new lesions in multiple organs, although they show a morphol- ogically benign appearance. In the previous study, we reported LAM- associated lymphangiogenesis and implicated its role in the progres- sion of LAM. In this study, we further focused on the lymphatic abnormalities in LAM: LAM-associated chylous fluid (5 pleural effusion and 2 ascites), surgically resected diaphragm (1 patient), and axial lymphatic system including the thoracic duct, lymph nodes at various regions, and diaphragmatic lymphatic system (5 autopsy cases). We demonstrated that LAM cell clusters enveloped by lym- phatic endothelial cells (LCC) in all chylous fluid examined. We identified LAM lesion in the diaphragm (2 of 5 autopy cases and one surgical specimen), thoracic duct (5 of 5), and lymph nodes (retro- peritoneal (5 of 5), mediastinal (4 of 5), left venous angle (5 of 5) with total positive rate of 68% to 88% at each region of the lymph node, but less frequent or none at remote lymph nodes located away from the axial lymph trunk (cervical (1 of 5) and axillary (0 of 5)). LCCs were identified in intra-LAM lesional lymphatic channels where LAM cells proliferate along lymphatic system. In in vitro culture system, LCC can fragment into each proliferating LAM cell. These findings suggest that LAM-associated lymphangiogenesis demarcates LAM lesion into bundle- or fascicle-like structure and eventually shed LCC into the lymphatic circulation and that LCCs play a central role in the dissemination of LAM lesion.

The aim of this study is to clarify the clinical and pathological anatomical picture of cases in which lung cancer and active pulmonary mycobacteriosis are intermingled in the same lobe of the lung.We analyzed clinicopathological data on 11 cases in which lung cancer and active pulmonary mycobacteriosis are intermingled in the same lung lobe out of 61 admitted cases of coexisting lung cancer and active pulmonary mycobacteriosis, encountered at National Hospital Organization Tokyo National Hospital during the period from 1991 to 2003.The subjects were 10 men and 1 woman, with a mean age of 68 years. The species of mycobacteriosis were M. tuberculosis in 6 and nontuberculous mycobacteriosis in 5 (M. avium disease and M. abscessus disease in 2 each, and M. kansasii disease in 1). The frequency of the mixture was 13% (6/45) in patients with lung cancer and tuberculosis and was 31% (5/16) in patients with lung cancer and nontuberculous mycobacteriosis. Radiographic findings revealed that both cancer shadows and mycobacteriosis shadows are identified in 8 of the 11 patients, whereas cancer shadows were recognized but mycobacteriosis shadows could not be pointed out in the remaining 3 patients. We divided 7 cases (5 resection scases and 2 autopsy cases) with the mixture of cancer and mycobacteriosis into 2 types from the macroscopic images: (1) type A (4 cases, the foci of lung cancer and tuberculosis, which were separated originally, progressed mutually, and has adjoined), and (2) type B (2 cases, the foci of mycobacteriosis existed within or in the edge of the foci of lung cancer). There were 3 nontuberculous mycobacteriosis cases and 1 tuberculosis case in type A, and 2 tuberculosis cases and 1 nontuberculous mycobacteriosis in type B. In nontuberculous mycobacteriosis cases, cancer and mycobacteriosis had often adjoined under the conditions of preexisting lung disease, such as a lung cyst, whereas in tuberculosis cases, it was characteristically shown that the wall of encapsulated caseous nodules was destroyed by cancer invasion, and that the tuberculous nodules were reactivated. These findings seemed to be related to exogenous infection of nontuberculous mycobacteriosis to the injured lungs and to endogenous reactivation of tuberculosis from inactive tuberculous lesions.Lung cancer and active pulmonary mycobacteriosis are often seen intermingled in the same lung lobe, and the mixture pictures of the two diseases are variable. The physicians should carefully note about the mixture of lung cancer and mycobacteriosis, though the findings are not clear on the chest plain radiographs.

A 57-year-old man with massive right pleural effusion was admitted to our hospital. Thoracoscopy revealed, fine granulations and small nodules scattered on the parietal pleura. Biopsy specimens suggested malignant mesothelioma. We performed thoracoscopy again one month later under general anesthesia to make a definitive diagnosis. At that time, the parietal pleura was covered with a large tumor and malignant mesothelioma was diagnosed by biopsy. We could find early pleural lesions of malignant mesothelioma in thoracoscopy. While we managed to make a definitive diagnosis, the tumor progressed rapidly during one month. If malignant pleural mesothelioma is suspected, it is necessary to make all efforts, including surgical biopsy, to diagnose during the early stage of disease.

We report a rare case of invasive thymoma with endobronchial growth in a 69- year-old woman. Chest CT revealed an ill-defined mass with a calcified lesion in the anterior mediastinum and coin lesion in the bilateral lung fields. An endobronchial polypoid tumor in the right B3 bronchus was found by bronchoscopic examination. A biopsy specimen obtained from the polypoid tumor suggested thymoma. After radiotherapy combined with chemotherapy, thymothymectomy combined with right upper lobectomy through median sternotomy was performed. The surgical specimen revealed that the tumor extended nodularly, not only into the pulmonary parenchyma but also into the bronchial lumen. We performed an added chemotherapy for lung metastasis, and partial resection of lung with video-assisted thoracoscopic surgery (VATS) was done. Now she is alive and disease-free.

HIV-1 infection is a major cause of worldwide epidemic of tuberculosis. There is increasing clinical evidence that coinfection with M. tuberculosis accelerates progression of AIDS. We found that, in vivo, HIV-1 load and mutation increase in involved lung segments in patients with pulmonary tuberculosis. We also reported that Mycobacterium tuberculosis stimulates HIV-1 replication by enhancing transcription on the 5' LTR in a macrophage cell line, THP-1, in vitro. In contrast, HIV-1 replication is suppressed by M. tuberculosis infection of monocytes derived macrophages (MDM) or differentiated monocytic THP-1 cells. We observed that HIV-1 5' LTR function was repressed in PMA differentiated THP-1 cells after co-infection with M. tuberculosis. Point mutations in C/EBP beta binding domains of the HIV-1 LTR negative regulatory element (NRE) abolished promoter repression. Monocyte-derived macrophages and differentiated THP-1 cells increased expression of the 16kDa inhibitory form of C/EBP after M. tuberculosis co-infection. Bronchoalveolar lavage cells obtained from normal controls and alveolar macrophages from uninflamed lung of tuberculosis patients also expressed the 16kDa inhibitory form of C/EBP. However, alveolar macrophages from lung segments involved with pulmonary tuberculosis had markedly reduced C/EBP expression. These data suggest that 16kDa isoform of C/EBP plays an important role for the control of HIV-1 replication in macrophages. We propose derepression of HIV-1 LTR mediated transcription as one mechanism for enhanced HIV-1 replication observed in pulmonary tuberculosis. Since the cellular immune response in pulmonary tuberculosis requires lymphocyte/macrophage interaction, a model system was developed in which lymphocytes were added to AM. Contact between lymphocytes and AM reduced inhibitory C/EBP beta, activated NF-kappaB and enhanced HIV-1 replication. If contact between lymphocytes and macrophages was prevented, inhibitory C/EBP beta expression was maintained and the HIV-1 long terminal repeat (LTR) was not maximally stimulated although NF-kappaB was activated. Antibodies which cross-linked macrophage expressed B-7, VCAM and CD-40 were used mimic lymphocyte contact. Cross-linking antibodies abolished inhibitory C/EBP beta expression; however, the HIV-1 LTR was not maximally stimulated and NF-kappaB was not activated. Maximal HIV-1 LTR stimulation required both lymphocyte derived soluble factors and cross-linking of macrophage expressed co-stimulatory molecules. These results demonstrate that neither contact nor soluble factor(s) are sufficient to maximally enhance HIV-1 LTR activity in macrophages. Contact between activated lymphocytes and macrophages is necessary to downregulate inhibitory C/EBP beta, thereby derepressing the HIV-1 LTR. Lymphocyte derived soluble factor(s) activate NF-kappaB, further enhancing the HIV-1 LTR.

We experienced a rare case of primary malignant lymphoma of the rib. The case was a 67-year-old female. An abnormal shadow of the chest X-ray was pointed out. Preoperative diagnosis was extrapulmonary lesion on the chest computed tomography (CT) and magnetic resonance imaging (MRI). The tumor accompanied with chest wall resection was done. The tumor cell was appeared in the bone marrow diffusely. The tumor invaded the canal of bone cortex and expanded the neighbor tissue. Histologically tumor was diagnosis of the malignant lymphoma, diffuse large B-cell type, stained by negative in L 26, positive in CD 43, positive in CD 79 a, negative in UCHL-1, and negative in CD 3. EBV-encoded small RNAs (EBERs) and EBV-EBNA 2 was negative. This tumor was not able to proved to Epstein-Bar virus.

A 59-year-old HIV-infected man who had been treated for pulmonary cryptococcosis in another hospital was suffering from pulmonary tuberculosis. He was admitted to our hospital for treatment of tuberculosis. The chest radiograph on admission showed a large cavity in the left lower lung field. Chest CT showed a mass like a fungus ball in the cavity. Pulmonary aspergillosis was diagnosed from the sputum mycology and serum immunoprecipitins. During the treatment of pulmonary tuberculosis and cryptococcosis, thickening of the wall of the cavity was seen together with adjacent bone destruction. In an autopsy, Aspergillus spp. Were found to have invaded the bone tissue and caused bone destruction. Pulmonary aspergillosis in an AIDS patient is infrequent, and is rare in additional association with bone invasion and destruction.

To clarify the clinical features of the coexisting lung cancer and nontuberculous mycobacteriosis of the lung.We analyzed clinical data on 11 admitted cases of coexisting lung cancer and pulmonary non-tuberculous mycobacteriosis at National Organization Tokyo Hospital during the period from 1997 to 2002.There were 10 men and 1 woman, with a mean age of 66 years. Five of 11 patients had underlying pulmonary disorders, such as healed tuberculosis and lung cyst. Histological types of lung cancer were squamous cell carcinoma in 4, adenocarcinoma and small cell carcinoma in 3 each, and 8 out of 11 cases were in stages III to IV. We classified the 11 cases into 2 groups: (1) lung cancer concurrently detected with mycobacteriosis (8 cases) and (2) lung cancer sequentially detected during the follow-up of mycobacteriosis (3 cases). Lung cancers in the latter group were in relatively early stages and all patients of this group received resection of the cancer, while most of lung cancers in the concurrent group were in far-advanced, and palliative and/or supportive treatment for lung cancer were frequently selected. The strains of mycobacteria were as follows: M. avium complex (6 cases) and M. kansasii (5 cases). The incidence of lung cancer among patients with nontuberculous mycobacteriosis was 2.5 percent (2 percent of M. avium complex diseases patients and 8.2 percent of M. kansasii disease patients), while the incidence of nontuberculous mycobacteriosis in untreated lung cancer patients was 1.4 percent. Analysis of anatomical relationship between lung cancer and non-tuberculous mycobacteriosis revealed that the two diseases located in the same lung in 8 cases, and also in the same lobe in 4 out of the 8 cases. Outcome of treatment for nontuberculous mycobacteriosis was good especially in patients with M. kansasii disease, and it seemed that coexisting nontuberculous mycobacteriosis did not influence on the prognosis of lung cancer patients.In the management of lung cancer, physicians should consider the possibility of coexisting pulmonary non-tuberculous mycobacteriosis, as well as coexisting pulmonary tuberculosis.

To clarify features of thoracic malignancies occurred in patients with chronic tuberculous empyema.We analyzed clinicopathological data of 15 patients with thoracic malignancies who had chronic tuberculous empyema, encountered at Tokyo National Hospital during the period from 1977 to 2002.There were 13 men and 2 women, with a mean age of 67 years. Most of all (13/15) patients had history of surgery for tuberculosis including artificial pneumothorax (9 cases). Malignancies consisted of pyothorax-associated lymphoma (PAL; 9 cases), lung cancer (4 cases), malignant fibrous histiocytoma (1 case), and angiosarcoma (1 case). There were no differences in background factors between PAL patients and the other patients. Common symptoms were chest pain (10 cases), fever (7 cases), and bloody sputum (4 cases) and it seemed that these symptoms were more evident in patients with PAL than in patients with other diseases. Plain chest X-ray films often failed to detect the tumor, and the diagnosis was often obtained by sputum cytology, bronchofiberscopy, transcutaneous biopsy, and resection with support of CT and/or MRI films. On radiographs, all tumors located in empyema cavities or around empyema walls, and a pulmonary mass adjacent to the empyema wall was characteristic of lung cancer. PAL showed certainly good outcome; 40% 5-year survival rate with resection or chemoradiotherapy. On the other hand, all of lung cancer cases were diagnosed at stage III, and had poor outcome, and the remaining patients with the other malignancies also had poor outcome.Clinicians should keep in mind occurrence of several thoracic malignancies during the follow-up of patients with chronic tuberculous empyema.

We reported a 69-year-old woman with multiple system atrophy (MSA), who had a heteroallelic missense mutation (G1874A, Gly--Glu) in the exon 11 of the ceruloplasmin (Cp) gene. At the age of 64, she began to complain of progressive gait disturbance, which was resistant to anti-Parkinsonian drug treatment. Neurological examination revealed parkinsonism such as rigidity, akinesia, mild tremor and postural instability, accompanying saccadic eye movement, dysarthria, dysphagia, orthostatic hypotension and bladder disturbance. She showed neither cerebellar signs nor dementia. Serum Cp and copper concentrations were 13-18 mg/dl and 38-56 micrograms/dl, respectively, which were decreased to about a half of normal values. Brain MRIs revealed high intensity areas in the bilateral putamens in the T2-weighted image, and mild pontine base atrophy. She died of respiratory failure due to laryngeal paresis after five years from the onset. Neuropathological examination revealed brown-colored putamens, where there was severe neuronal cell loss with gliosis. Though atrophy of the pontine base was mild, transverse myelinated fibers were pale in Klüver-Barrera stain. There were Purkinje cell loss of moderate degree and appearance of torpedos in the cerebellum. Both silver staining and immunohistochemical staining to alpha-synuclein showed glial cytoplasmic inclusions, which were found predominantly in the putamens. These clinical features and neuropathological findings were compatible with multiple system atrophy (MSA). Iron staining of the brain revealed iron deposition in the putamens and the substantia nigra, but not in the pontine base nor in the cerebellum. Furthermore, we failed to reveal it in both the liver and the pancreas as well as the thalamus and the caudate nucleus, which were common sites of iron deposition in the previous cases of Cp gene mutation. We have already reported three other MSA cases with a- or hypo-ceruloplasminemia with similar clinical and pathological features to this case. One of them, in which gene analysis was also available, did not have any mutations in its Cp gene. Therefore, the gene mutation of this case may not be a direct cause to MSA, but the fact that the most cases of MSA with hypoceruloplasminemia showed striatonigral degeneration (SND) type implies some relationship between hypoceruloplasminemia and SND.

Interstitial pneumonia (IP) is a serious adverse event of interferon alpha (IFNalpha) treatment for chronic hepatitis C (CH-C). Among 558 CH-C patients who received IFNalpha treatment with or without ribavirin between January 1992 and June 2002, six patients (1.1%) developed IP, including one patient who developed IP in 1993 and again in 2002. Among the seven cases who contracted IP, at the onset of IP, seven (100%), five (71%), and two cases (29%) had elevated serum levels of KL-6, surfactant protein A (SP-A), and surfactant protein D (SP-D), respectively. Prior to starting IFN treatment (baseline), the serum SP-A and SP-D levels were within the normal range in all seven cases, but the serum KL-6 level was elevated in five of the seven cases, contrasting with that in three of 48 age-adjusted CH-C patients who did not develop IP during IFN treatment (71 vs. 6%; P=0.0003). Furthermore, the circulating KL-6 level at baseline was significantly higher among the seven cases than among the controls (543+/-105 vs. 304+/-98 U/ml, P=0.0001). These results indicate that measurement of the circulating KL-6 level in CH-C patients before IFN treatment may be useful for predicting the occurrence of IP during IFN treatment.

A 64-year-old man was admitted to our hospital because of productive cough and fever. Chest radiography on admission revealed air space consolidation in the right middle and lower lung fields and ground-glass opacity in the left middle lung field. He had been constipated for several years and had taken mineral oil for about a year. Sputum smears demonstrated acid bacilli, and cultures disclosed Mycobacterium abscessus. The transbronchial lung biopsy specimen showed granulomatous inflammation and numerous lipoid-laden macrophages in the alveolar spaces. Mycobacteria were present within the mineral oil and lipid-laden macrophages. It is likely that the mineral oil increased the pathogenicity of the mycobacteria.

A 30-year old man of Myanmar origin was admitted to our hospital because of productive cough, anorexia, weight loss and fever. Sputum smear was strongly positive for M. tuberculosis (Gaffky 6) and sputum culture proved M. tuberculosis. Caseous necrosis with Langhans giant cells was observed in the biopsied specimens of the liver and bone marrow. He was diagnosed as miliary tuberculosis. Treatment with combined use of isoniazid, rifampicin, ethambutol and streptomycin was started. After one month, his cough resolved, fever subsided and chest X-ray findings improved. Two months later, non-productive cough and fever recurred. Chest radiograph and computed tomographic scan of the chest revealed diffuse ground-glass opacity. Specimens taken by transbronchial biopsy showed pneumocystis carinii in alveoli. Pulsed use of methyprednisolone with Trimethoprim-sulfamethoxazole was started. The symptoms and chest X-ray findings disappeared and he recovered uneventfully. Tests for HIV infection were negative. Anti-HTLV antibody was negative. There were no other suggestive evidences of immune suppression. CD4+T cell count was low, when Pneumocystis carinii pneumonia occurred. The relation between miliary tuberculosis, Pneumocystis carinii pneumonia and CD4-T lymphocytopenia has remained unelucidated.

We presented first two cases of multiple system atrophy (MSA) with a-/hypo-ceruloplasminemia (hypo-Cp). To know whether hypo-Cp was a cause of MSA, we investigated distribution of iron in brains.Investigating history, neurological sings and symptoms, neuroimagings, and neuropathological findings of the 2 cases, we demonstrate that these 2 cases were typical MSA. Serum ceruloplasmin (Cp) values of two cases were investigated, as well as those of 14 MSA patients diagnosed after the 2 cases. In the 2 cases, we compared distribution of lesions and distribution of iron depositions revealed by Berlin blue stain (iron stain). Further, we compared depositions of iron in substantia nigra, putamen, and dentate nucleus of the 2 cases with those of 4 control MSA, 2 Parkinson's disease (PD), 2 amyotrophic lateral sclerosis (ALS), and 3 controls.Case 1 was 68-year-old man who developed gait disturbance, and had anti-Parkinson disease drugs after diagnosis of PD. Parkinsonism was progressed, and became bed-ridden after 6 years when he died. Neuropathological finding was typical MSA from distribution of lesions, as well as existence of GCIs and NCIs. Case 2 was 61-year-old man who developed parkinsonism. After 9 years, he had tracheostomy, and after 11 years died of renal failure. Neuropathological finding was typical MSA. With an investigation of serum Cp values of clinically diagnosed 14 MSA patients, we found 2 other cases of MSA with hypo-Cp. Iron stain of the 2 brains revealed that iron depositions were found in substantia nigra and putamen, but were not found neither in pontine base, cerebellum, nor inferior olive. Iron depositions were also seen in substantia nigra and putamen of control MSA cases as same degree as MSA with hypo-Cp, but iron depositions were fewer in PD, ALS and controls.Clinico-pathological findings of the the 2 cases were those of typical MSA, but were not same as those of previously reported hypo-Cp. Previous reports suggested iron depositions as a cause of brain lesions, but, we concluded that, in the 2 cases, iron depositions were not a direct cause of MSA lesions. However, high incidence of association of hypo-Cp and MSA shown in our study suggests a relation between hypo-Cp and MSA.

HIV-1 replication is remarkably augmented in macrophages at the site of inflammation due to tuberculosis. Reduction of expression of an inhibitory C/EBP beta transcription factor and activation of NF-kappa B are observed at the site of inflammation. Of 18 paraffin embedded tissue sections of HIV-tuberculosis coinfected autopsy or biopsy samples, 9 samples were positive for HIV-p24 staining, which were all derived from patients with blood CD4 cell counts more than 50/mm3. Moreover, the P24 positive cells were morphologically macrophages or epithelioid cells. CD4 positive lymphocytes consistently located near the P24 positive macrophages. Therefore, we hypothesized that lymphocyte-macrophage contact is important for maximal HIV production from macrophages. In vitro experiments showed that contact between lymphocytes and macrophages reduced inhibitory C/EBP beta, activated NF-kappa B and enhanced HIV-1 replication. If contact between lymphocytes and macrophages was prevented, inhibitory C/EBP beta expression was maintained and the HIV-1 long terminal repeat (LTR) was not maximally stimulated although NF-kappa B was activated. Antibodies which cross-linked macrophage expressed B-7, VCAM and CD40 were used mimic lymphocyte contact. Cross-linking antibodies abolished inhibitory C/EBP beta expression; however, the HIV-1 LTR was not maximally stimulated and NF-kappa B was not activated. Maximal HIV-1 LTR stimulation required both lymphocyte derived soluble factors and cross-linking of macrophage expressed costimulatory molecules. These results demonstrate that neither contact nor soluble factor(s) are sufficient to maximally enhance HIV-1 LTR activity in macrophages. Contact between activated lymphocytes and macrophages is necessary to down-regulate inhibitory C/EBP beta, thereby derepressing the HIV-1 LTR. Lymphocyte derived soluble factor(s) activate NF-kappa B, further enhancing the HIV-LTR.

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The patients with active tuberculosis in whom respiratory failure requiring mechanical ventilation developed were studied retrospectively. Nine patients (M 8, F 1) were identified at the National Tokyo Hospital during 5 years from January, 1993 to December, 1997. Seven of 9 patients were single men, and the duration of symptoms before admission was over 1 month in all patients, while the time from first visit to diagnosis was less than 7 days. All patients were identified as malnourished, and 7 patients suffered from another underlying diseases. The patients were classified into two groups. Six of 9 patients had pulmonary tuberculosis and the other three had miliary disease. The proportion of cases requiring mechanical ventilation was 0.3% and 8.6%, respectively, in pulmonary tuberculosis and miliary tuberculosis. At the start of mechanical ventilation, PaO2/FIO2 was lower than 200 in all 9 patients, and 6 patients were probably ARDS. Steroids (methylprednisolone 250-1000 mg/day) were used in all 9 patients. Despite the use of mechanical ventilation and antituberculous therapy, 8 out of 9 patients died. Only one patient with miliary tuberculosis survived. The establishment of the therapy for acute respiratory failure is needed so as to improve prognosis of such cases. At the same time, the delay in consulting a doctor led to acute respiratory failure in most cases, so it is also important to encourage tuberculosis patients to visit a doctor as soon as possible, after the appearance of symptoms.

The resistance of tumor cells to chemotherapeutic drugs is a major obstacle to successful cancer chemotherapy. Expression of the MDR 1 gene, which encodes for a transmembrane efflux pump (P-glycoprotein), leads to decreased intracellular accumulation and resistance to a variety of anticancer drugs. Recently, one mutant p 53 form was shown to stimulate the MDR 1 gene promoter in vitro, whereas wild-type p 53 repressed this activity. We examined the relationship between p 53 gene mutation and MDR 1 gene expression in specimens from non-small cell lung cancer patients. Tumor samples were obtained from 21 patients during surgery. Mutations of exon 5 through exon 8 of the p 53 gene were detected by the polymerase chain reaction single strand conformation polymorphism method. MDR 1 expression was semi-quantified by the reverse transcriptase polymerase chain reaction method. We identified p 53 gene mutation in samples from 7 patients. MDR 1 gene expression was observed in samples from 20 patients. The expressivity of the MDR 1 gene tended to be higher in patients with adenocarcinoma. No significant relationship between p 53 mutation and MDR 1 expressivity was observed in our study.

To clarify the features of the coexistence of active pulmonary tuberculosis in patients with lung cancer, we analyzed clinical data on 25 cases with coexisting lung cancer and active pulmonary tuberculosis encountered at Tokyo National Chest Hospital during the period from 1991 to 1998. There were 23 men and 2 women, with a mean age of 70 years. The incidence of lung cancer among patients with active pulmonary tuberculosis at our hospital was 0.7 per cent, while the incidence of active pulmonary tuberculosis in untreated lung cancer patients at our hospital was 1.9 per cent. We classified the 25 cases into 2 groups as follows: (1) tuberculosis sequential to lung cancer (11 cases) and (2) tuberculosis concurrently detected with lung cancer (14 cases). All patients in the former group were transferred from other hospitals after diagnosing the coexistence of pulmonary tuberculosis during the management of lung cancer. Histological types of lung cancer were squamous cell carcinoma in 12, adenocarcinoma in 9, and small cell carcinoma in 4, and as to the disease stage, stages III to IV were predominant. Analysis on relationship of chest X-ray findings between lung cancer and pulmonary tuberculosis revealed that in general, the location of lung cancer and tuberculosis seemed to be independent. Tuberculosis in the sequential group was more extensive and severer than in the concurrent group. In the concurrent group, treatment for tuberculosis was successful except for one case, and coexisting tuberculosis did not seem to affect the course of lung cancer among this group. However, in the sequential group, 5 patients died within 3 months, 2 of them died of tuberculosis. We consider that in the management of lung cancer, physicians should consider the possibility of coexistent active pulmonary tuberculosis and should not make delay in the diagnosis of active pulmonary tuberculosis.

To clarify features of lung cancer in patients with tuberculosis sequelae, we analyzed data on 15 cases (5.1%) who were diagnosed with lung cancer before death among 294 deceased cases with tuberculosis sequelae at our hospital. There were 12 men and 3 women, with a mean age of 64 years. Most of the 15 patients had pulmonary dysfunction, and 4 had received home oxygen therapy. All 12 men had a history of smoking, and 10 of them had squamous cell carcinoma of the lung. There was no definite correlation between the locations of the tuberculosis lesion and those of lung cancer lesion on chest X-rays. Twelve patients had had thoracoplasty for tuberculosis, and in 6 of these patients the lung cancer occurred in the same lung. Lung cancer was apt to be diagnosed in an advanced stage. However, in patients who received home oxygen therapy, diagnosis had been made at an early stage because of the frequent chest X-ray follow-up. We conclude that lung cancer is an important complication in patients with tuberculosis sequelae, and early diagnosis of lung cancer by careful follow-up is essential in the care of cases with tuberculosis sequelae who have poor pulmonary function and/or systemic conditions.

Seventy-four cases of miliary tuberculosis were studied retrospectively. The mean age of the patients was 45.3 years. Twenty-two patients suffered from another underlying diseases. Six were infected with human immunodeficiency virus. Twelve had been treated with corticosteroids. Fever was present in 97.3 per cent of patients. Elevation of serum alkaline phosphatase was found in 67.6 per cent of cases. The skin reaction to tuberculin was positive in 61.2 per cent. Nodular shadows were found in the chest X-ray in 98.6 per cent of cases. The nodules were smaller than 2 mm in diameter in 52.7 per cent of cases. Other findings were enlargement of mediastinal lymph node (17.6%), cavities (23.0%), pleural effusion (27.0%), and consolidation (35.1%). Sputum cultures and urine cultures were positive for Mycobacterium tuberculosis in 76.8 per cent and 58.6 per cent of cases respectively. The diagnosis was confirmed by histopathological findings in some cases. The rate of positive biopsies was 61.5 per cent by bone marrow aspiration, 83.3 per cent by lymph node biopsy, 100 per cent by liver and lung biopsy. Antituberculosis therapy was successful in most of the patients. Seven patients died of miliary tuberculosis, 4 of them had adult respiratory distress syndrome.