Histological analysis of vasculopathy associated with pulmonary hypertension in combined pulmonary fibrosis and emphysema: comparison with idiopathic pulmonary fibrosis or emphysema alone.

AIMS: To evaluate pulmonary vasculopathy in an autopsy series of patients with combined pulmonary fibrosis and emphysema (CPFE), and compare these findings with those of patients with idiopathic pulmonary fibrosis (IPF) alone and emphysema alone. METHODS AND RESULTS: We retrospectively analysed the clinical, radiological and pathological features of 26 patients with CPFE, 11 with IPF, and 23 with emphysema. We evaluated pulmonary vascular, venous-venular and arteriolar tissue changes in the fibrotic, emphysematous and relatively unaffected (preserved) areas by using the Heath-Edwards scoring system. We found moderate-to-severe vasculopathy in the CPFE group, but no significant differences in the fibrotic and emphysematous areas among the three groups. However, in the preserved area, the grading was significantly different among the three groups (P < 0.001), and vasculopathy in the CPFE group was the most severe. Although venous-venular and arteriolar changes in almost all fibrotic and emphysematous areas in the three groups showed no significant differences, there were significant differences in venous-venular (P = 0.004) and arteriolar (P < 0.001) changes in the preserved area among the three groups, which were most prevalent in the CPFE group. In the CPFE group, venous-venular changes and vasculopathy by Heath-Edwards grading were highest in the fibrotic area and lowest in the preserved area. CONCLUSIONS: These results imply that pulmonary vasculopathy in patients with CPFE could occur in the whole lung tissue. This may explain the tendency for it to lead to the development of pulmonary hypertension in CPFE cases.

Comparison of clinical and pathological features of lung lesions of systemic IgG4-related disease and idiopathic multicentric Castleman's disease.

AIMS: The lung lesion [immunoglobulin (Ig)G4-L] of IgG4-related disease (IgG4-RD) is a condition that occurs together with IgG4-RD and often mimics the lung lesion [idiopathic multicentric Castleman's disease (iMCD-L)] of idiopathic multicentric Castleman's disease (iMCD). Because no clinical and pathological studies had previously compared features of these diseases, we undertook this comparison with clinical and histological data. METHODS AND RESULTS: Nine patients had IgG4-L (high levels of serum IgG4 and of IgG4+ cells in lung specimens; typical extrapulmonary manifestations). Fifteen patients had iMCD-L (polyclonal hyperimmunoglobulinaemia, elevated serum interleukin-6 levels and polylymphadenopathy with typical lymphadenopathic lesions). Mean values for age, serum haemoglobin levels and IgG4/IgG ratios were higher in the IgG4-L group and C-reactive protein levels were higher in the iMCD-L group. All IgG4-RD lung lesions showed myxomatous granulation-like fibrosis (active fibrosis), with infiltration of lymphoplasmacytes and scattered eosinophils within the perilymphatic stromal area, such as interlobular septa and pleura with obstructive vasculitis. All 15 lung lesions of iMCD, however, had marked accumulation of polyclonal lymphoplasmacytes in lesions with lymphoid follicles and dense fibrosis, mainly in the alveolar area adjacent to interlobular septa and pleura without obstructive vasculitis. CONCLUSIONS: Although both lesions had lymphoplasmacytic infiltration, lung lesions of IgG4-RD were characterized by active fibrosis with eosinophilic infiltration within the perilymphatic stromal area with obstructive vasculitis, whereas lung lesions of iMCD had lymphoplasmacyte proliferating lesions mainly in the alveolar area adjacent to the perilymphatic stromal area. These clinicopathological features may help to differentiate the two diseases.

Efficacy and safety of stereotactic body radiotherapy using CyberKnife in Stage I primary lung tumor.

BACKGROUND: CyberKnife® (CK) is a new, advanced radiotherapy technique. This study aimed to evaluate its efficacy and toxicity in Japanese patients with early-stage primary lung tumor who were medically unfit and inoperable. METHODS: This retrospective study investigated patients who received CK treatment for medically inoperable Stage І primary lung tumor at the Japanese Red Cross Medical Center between June 2011 and September 2016. Each patient received a total of 36-48 Gy (median, 43 Gy) administered by CK in 4-5 fractions. RESULTS: Totally, 40 patients (T1a, n = 19; T1b, n = 15; T2a, n = 6) were included. Their median age was 86 (range, 56-95) years. Tracking required the use of fiducial markers in 28 patients and the Xsight Spine Tracking System in 12. The median follow-up was 14.5 (range, 1-51) months. Local recurrence occurred in seven (17.5%) patients. The local progression-free survival rates at 1 and 2 years were 83.9% and 74.0%, respectively. Distant recurrence occurred in regional lymph nodes (n = 5), the lung outside the radiation field (n = 3), and the bone (n = 1). Seven patients died. Overall survival rates at 1 and 2 years were 93.6% and 73.1%, respectively. Radiation pneumonitis was identified in 28 (70%) patients (Grade 1, n = 25; Grade 2, n = 2; Grade 5, n = 1). CONCLUSIONS: CK showed good local control with limited toxicity and could be an alternative treatment modality in medically inoperable patients with Stage І primary lung tumor.

Trousseau's syndrome: cancer-associated thrombosis.

Trousseau's syndrome (cancer-associated thrombosis) is the second leading cause of death in cancer patients, after death from cancer itself. The risk of a venous thromboembolism is 4- to 7-fold higher in patients with cancer than in those without cancer. The causes of this impaired coagulation are associated with general patient-related risk factors, and other factors that are specific to the particular cancer or treatment. It is important to assess the risk of thrombotic events in cancer patients and administer effective prophylaxis and treatment. Effective prophylaxis and treatment of venous thromboembolism reduces morbidity and mortality, and improves patients' quality of life. Low molecular weight heparin is the first-line treatment for venous thromboembolism, as an effective and safe means for prophylaxis and treatment, according to guidelines released by international scientific societies. Oral anticoagulation therapy with warfarin is preferable to no therapy. However, warfarin has low efficacy and is associated with high rates of recurrence. If low molecular weight heparin is unavailable, some guidelines recommend the use of vitamin K antagonists that have a target international normalized ratio in the range of 2-3, as acceptable alternatives. Novel oral anticoagulants that directly inhibit factor Xa or thrombin are promising for the prophylaxis of high-risk cancer patients and in the long-term treatment of venous thromboembolism. However, to date, there is insufficient evidence to support the use of these new anticoagulants.

Transformation to small-cell lung cancer as a mechanism of acquired resistance to crizotinib and alectinib.

A 56-year-old woman, a never-smoker, had postoperative recurrence of anaplastic lymphoma kinase rearranged lung cancer. She achieved a partial response to treatment with an anaplastic lymphoma kinase tyrosine kinase inhibitor, crizotinib. After the tumor regrowth, crizotinib was switched to alectinib; once again a partial response was observed. At the second recurrence, transbronchial needle aspiration of the right paratracheal node was performed, which revealed cytological findings of small-cell carcinoma. While treatment with cisplatin-irinotecan chemotherapy made reduction of some tumor shadows, including the biopsied mediastinal lymph nodes, new, small, nodular shadows, highly suggestive of pulmonary metastases, were detected in both lung fields. This case may show proof of the transformation to small-cell lung cancer as a mechanism of resistance to anaplastic lymphoma kinase tyrosine kinase inhibitors in anaplastic lymphoma kinase rearranged tumor. However, this transformation may also be only one part of the resistance mechanism of the heterogeneous tumor.

An autopsy study of combined pulmonary fibrosis and emphysema: correlations among clinical, radiological, and pathological features.

BACKGROUND: Clinical evaluation to differentiate the characteristic features of pulmonary fibrosis and emphysema is often difficult in patients with combined pulmonary fibrosis and emphysema (CPFE), but diagnosis of pulmonary fibrosis is important for evaluating treatment options and the risk of acute exacerbation of interstitial pneumonia of such patients. As far as we know, it is the first report describing a correlation among clinical, radiological, and whole-lung pathological features in an autopsy cases of CPFE patients. METHODS: Experts retrospectively reviewed the clinical charts and examined chest computed tomography (CT) images and pathological findings of an autopsy series of 22 CPFE patients, and compared these with findings from 8 idiopathic pulmonary fibrosis (IPF) patients and 17 emphysema-alone patients. RESULTS: All patients had a history of heavy smoking. Forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC%) was significantly lower in the emphysema-alone group than the CPFE and IPF-alone groups. The percent predicted diffusing capacity of the lung for carbon monoxide (DLCO%) was significantly lower in the CPFE group than the IPF- and emphysema-alone groups. Usual interstitial pneumonia (UIP) pattern was observed radiologically in 15 (68.2%) CPFE and 8 (100%) IPF-alone patients and was pathologically observed in all patients from both groups. Pathologically thick-cystic lesions involving one or more acini with dense wall fibrosis and occasional fibroblastic foci surrounded by honeycombing and normal alveoli were confirmed by post-mortem observation as thick-walled cystic lesions (TWCLs). Emphysematous destruction and enlargement of membranous and respiratory bronchioles with fibrosis were observed in the TWCLs. The cystic lesions were always larger than the cysts of honeycombing. The prevalence of both radiological and pathological TWCLs was 72.7% among CPFE patients, but no such lesions were observed in patients with IPF or emphysema alone (p=0.001). The extent of emphysema in CPFE patients with TWCLs was greater than that in patients without such lesions. Honeycombing with emphysema was also observed in 11 CPFE patients. CONCLUSIONS: TWCLs were only observed in the CPFE patients. They were classified as lesions with coexistent fibrosing interstitial pneumonia and emphysema, and should be considered an important pathological and radiological feature of CPFE.

Diagnostic performance of interferon-gamma release assays in elderly populations in comparison with younger populations.

An understanding of the diagnostic performance of interferon-gamma release assays (in terms of parameters such as specificity, positive predictive value, and likelihood ratio) is important in the diagnosis of active tuberculosis in elderly Japanese patients because the high proportion of a prior history of tuberculosis among these patients can lead to misleading results. To elucidate the diagnostic performance of such assays, we examined the results of the QuantiFERON-TB Gold In-Tube test (QFT-GIT) in 65 patients in a younger group, and 52 patients in an elderly group who were suspected of having active tuberculosis and who had received the QFT-GIT. The median ages of the younger patients and elderly patients were 54 and 78 years, respectively. Among patients with active tuberculosis, the number of those with positive results on the QFT-GIT was similar in the two age groups [15 out of 17 (88.2 %) in the younger patients compared with 7 out of 8 (87.5 %) in the elderly patients]. However, in the patients with other diseases the number of those with positive QFT-GIT results was significantly different in the younger and elderly groups, being 6.3 and 27.3 %, respectively (P = 0.01). Although the sensitivity, negative predictive value, and negative likelihood ratio were similar in the two groups, the specificity, positive predictive value, and positive likelihood ratio were significantly lower in the elderly patients, being 72.7% (95 % confidence interval [CI], 57.2-85.0) compared with 93.8% (95 % CI, 82.8-98.7), 36.8% (95 % CI, 16.3-61.6) compared with 83.8% (95 % CI, 58.6-96.4), and 3.21 (95 % CI, 1.85-5.56) compared with 14.12 (95 % CI, 4.66-42.81), respectively. In the elderly patients with positive results on the test, a comparison of clinical data between those with active tuberculosis and those with other diseases demonstrated that the only clinical parameter showing a significant difference between these two groups was the radiological finding of small nodules in the patients with active tuberculosis (P < 0.01). The QFT-GIT may be less accurate in elderly patients, and radiological findings can be helpful in the clinical evaluation of patients with positive results on the test.

[Emergency oncology cases for whom stereotactic radiotherapy by cyberknife proved effective for cerebellar metastasis of lung cancer].

BACKGROUND: Cerebellar metastasis sometimes causes symptoms such as ataxia and dizziness, or hydrocephalus by compression of the fourth ventricle, making emergency treatment necessary. We report two cases for whom we performed emergency stereotactic radiotherapy, and whose tumors decreased and symptoms improved. Case 1: A 58-year-old male was diagnosed with small cell lung cancer in December 2008, and received chemotherapy and conventional radiotherapy at another hospital. He developed difficulty in walking and experienced nausea from March 2010 on. Because neoplastic lesions had been found in the cerebellar vermis on computed tomography(CT)scan, he was referred to our hospital. We urgently performed stereotactic radiotherapy by CyberKnife, and his symptoms then improved. As a chest CT scan revealed a mass lesion in his right upper lobe, the diagnosis of recurrent small cell lung cancer was made, and we performed chemotherapy sequentially. Case 2: A 73-year-old female experienced severe headache and dizziness and noticed difficulty in walking in July 2010. Because neoplastic lesions had been found in the left cerebellar hemisphere on CT scan at another hospital, she was referred to our hospital. Chest X-ray films showed a mass lesion in the left middle lung field and cytologic examination of sputum showed squamous cell carcinoma. We urgently performed stereotactic radiotherapy by CyberKnife, and her symptoms then improved. Therefore, we performed chemotherapy sequentially. CONCLUSION: Stereotactic radiotherapy by CyberKnife is less invasive, and is one good treatment option in the event of an emergency.

Pathological differentiation of chronic hypersensitivity pneumonitis from idiopathic pulmonary fibrosis/usual interstitial pneumonia.

AIMS: To evaluate the histological characteristics differentiating chronic hypersensitivity pneumonitis (chronic HP) with a usual interstitial pneumonia (UIP)-like pattern from idiopathic pulmonary fibrosis (IPF)/UIP. METHODS AND RESULTS: Surgical lung biopsy specimens from 22 patients with chronic HP diagnosed as having a UIP-like pattern upon histological examination and 13 patients with IPF/UIP were examined and the incidences of bronchiolitis, perilobular fibrosis, centrilobular fibrosis, bridging fibrosis, organizing pneumonia, fibroblastic foci, honeycombing, granulomas, giant cells, lymphocytic alveolitis and lymphoid follicles were compared. Bronchiolitis, centrilobular fibrosis, bridging fibrosis, organizing pneumonia, granulomas, giant cells and lymphocytic alveolitis were significantly more frequent among patients with chronic HP than among patients with IPF (all P<0.01). CONCLUSIONS: Centrilobular fibrosis, bridging fibrosis and organizing pneumonia, in addition to bronchiolitis, granulomas and giant cells, are characteristic features of chronic HP with a UIP-like pattern. These features are therefore important in differentiating chronic HP from IPF/UIP, as management strategies differ for the two disorders.

[Three cases of allergic bronchopulmonary mycosis due to Schizophyllum commune].

We report 3 cases of allergic bronchopulmonary mycosis (ABPM) due to Schizophyllum commune. The first patient, an 82-year-old woman, presented with atelectasis of the left upper lobe with mucoid impaction due to Schizophyllum commune. The second patient, a 53-year-old woman, presented with atelectasis of the right middle lobe with mucoid impaction due to Schizophyllum commune. The last patient, a 49-year-old woman, underwent a left lingular lobectomy with a diagnosis of lung abscess, but the diagnosis was retrospectively changed to ABPM in a later review of the findings of the surgical specimens. The diagnosis and treatment of ABPM are not well defined, and this considerably delayed our diagnosis in these three cases. We hope to establish a more definitive diagnosis and treatment for ABPM through ongoing encounters with patients.

[Two cases of microscopic polyangitis with preceding interstitial pneumonia diagnosed by surgical lung biopsy].

We encountered 2 cases of microscopic polyangitis (MPA) with preceding interstitial pneumonia. The patients were elderly men, and radiological findings showed a UIP pattern in both cases. Furthermore, ANCA-associated vasculitis had been suspected since the first admission in case 1, because MPO-ANCA tests were positive, and the surgical lung biopsy revealed vasculitis in a honeycomb lesion. A diagnosis of idiopathic pulmonary fibrosis was made in case 2 because no findings of vasculitis were pathologically confirmed, and MPO-ANCA was not examined. Both patients were followed up without any treatment, but steroid therapy with immunosuppressants was initiated after a diagnosis of MPA was made from a renal failure complication. Remission continued in case 1, but patient 2 died due to a pulmonary hemorrhage complication, despite some temporary improvements. An autopsy revealed massive alveolar hemorrhage and neutrophil infiltration in the alveolar walls that suggested pulmonary capillaritis, in spite of the absence of pathological evidence, which was not detected in the honeycomb lesions. These 2 cases indicate that MPO-ANCA should be examined in the follow-up of chronic interstitial pneumonia. Furthermore, it should be assumed that the size of involved blood vessels, their distribution and the timing of occurrence may be different in individual case of ANCA-associated interstitial pneumonia.

Microangiopathy in Ocular Sarcoidosis Using Fluorescein Gonio and Fundus Angiography from Diagnostic and Therapeutic Aspects.

In this retrospective study, we investigated vascular abnormalities in sarcoidosis using fluorescein gonioangiography (FGA) to detect angle neovascularization (ANV), fundus fluorescein angiography (FFA), and pathological specimens from the aspects of microangiopathy. In 57 sarcoidosis patients, clinical data was reviewed by dividing the cases into three groups (Group I: histologically diagnosed; Group II: positive bilateral hilar lymphadenopathy (BHL); Group III: negative BHL). The FFA, FGA, and pathological examination data in the autopsy eyes and trabeculectomy specimens were investigated. FGA and FFA detected ANV (91%) and nodule-associated abnormalities (87%), respectively. No intraocular pressure (IOP) elevation was observed after continuous topical betamethasone, except in the steroid responder group. Maximum IOP had significant correlation with nodules in the angle (p = 0.02696) and visual field defect (p = 0.0151). Granulomas adjacent to blood vessels, including the Schlemm's canal, and thickening of the retinal blood vessel wall caused occlusion of those vessels. Photocoagulation was required for retinal tears (14%) and the retinal blood vessel occlusion (7%). Suppression of IOP elevation via continuous topical betamethasone may be important to avoid irreversible outflow-route changes and optic-nerve damage, and the concept of microangiopathy in ocular sarcoidosis may be important for understanding the proper treatment of serious complications.

Genetic control of CCL24, POR, and IL23R contributes to the pathogenesis of sarcoidosis.

Sarcoidosis is a genetically complex systemic inflammatory disease that affects multiple organs. We present a GWAS of a Japanese cohort (700 sarcoidosis cases and 886 controls) with replication in independent samples from Japan (931 cases and 1,042 controls) and the Czech Republic (265 cases and 264 controls). We identified three loci outside the HLA complex, CCL24, STYXL1-SRRM3, and C1orf141-IL23R, which showed genome-wide significant associations (P < 5.0 × 10-8) with sarcoidosis; CCL24 and STYXL1-SRRM3 were novel. The disease-risk alleles in CCL24 and IL23R were associated with reduced CCL24 and IL23R expression, respectively. The disease-risk allele in STYXL1-SRRM3 was associated with elevated POR expression. These results suggest that genetic control of CCL24, POR, and IL23R expression contribute to the pathogenesis of sarcoidosis. We speculate that the CCL24 risk allele might be involved in a polarized Th1 response in sarcoidosis, and that POR and IL23R risk alleles may lead to diminished host defense against sarcoidosis pathogens.

[A study on clinical features of Mycobacterium kansasii pulmonary disease in women].

OBJECTIVES: To clarify clinical features of M. kansasii pulmonary disease in women. METHODS: We performed a retrospective analysis of M. kansasii pulmonary disease in women compairing with that in men. We focused on 8 female cases of M. kansasii pulmonary disease during the past 7 years from June 1998 to August 2005. RESULTS: The cases of M. kansasii pulmonary disease in women have increased in the latter few years. The mean age of female cases was higher than that of male cases, 65.6 and 53.1 years old, respectively. The number of female cases with smoking history was lower than that of male cases, 37.5% and 90.0%, respectively. Two female cases had underlying pulmonary diseases, as compared with 10 male cases, 25.0% and 33.3%, respectively. The radiological findings in female cases included 2 cavitary opacities, 1 infiltrative opacity and 5 nodular, bronchiectatic opacities, as compared with 27 cavitary opacities, 1 infiltrative opacity, 1 solitary nodular opacity and 1 nodular, bronchiectatic opacity in male cases. MAC was also detected in 2 female cases, who presented with nodular, bronchiectatic opacities. On the other hand, there were 6 female cases, in which no other NTM was detected. 3 cases showed cavitary or infiltrative opacities, which improved with the following 3 tuberculous drugs INH, RFP, and EB (HRE), while others showed nodular, bronchiectatic opacities, in which 2 cases showed radiological exacerbations without any treatment and another one revealed an improvement with HRE. CONCLUSIONS: M. kansasii pulmonary disease in women tends to be identified in elderly who smoke less and have no underlying pulmonary diseases, and most of radiological findings in female cases revealed nodular, bronchiectatic opacities. Summing up all these findings, clinical features of M. kansasii pulmonary disease in women was considered to resemble that of MAC infection, and it was speculated that the increase of M. kansasii pulmonary disease in women has some relationship with that of MAC infection in middle or lingular lobe. However, it was confirmed that some cases of M. kansasii pulmonary disease in women might primarily present with nodular, bronchiectatic lesions, regardless of MAC infection.

Is hypothyroidism in idiopathic pleuroparenchymal fibroelastosis a novel lung-thyroid syndrome?

BACKGROUND: Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a rare type of interstitial pneumonia characterized by fibroelastosis. Patients with IPPFE as well as idiopathic interstitial pneumonia often have autoimmune diseases, which sometimes coincide with hypothyroidism (HypoT). However, there have been no reports on the association between IPPFE and HypoT. The purpose of this study was to evaluate the correlation between IPPFE and HypoT. We also examined the pathological features of the thyroid glands from autopsied cases. METHODS: Thirteen patients diagnosed with IPPFE from among 255 consecutive cases of idiopathic interstitial pneumonia were included in this study; pertinent data were obtained from our hospital's clinical library. We examined the prevalence of HypoT and compared the clinical, radiological, and pathological features between the patients with and those without HypoT. Histological analyses of the lungs and thyroid glands were performed in 4 and 3 cases, respectively. RESULTS: HypoT was identified in 7 of 13 patients (53.8%). Sex, body mass index, survival time, and laboratory test results were not significantly different between patients with and those without HypoT. Radiological and pathological lung findings were similar between both groups of patients. Thyroid gland histology demonstrated perifollicular or interlobular fibrosis without inflammation in all three cases, including a euthyroid case. CONCLUSIONS: Although we only analyzed a small number of IPPFE cases, HypoT was prevalent among all of them. Characteristic fibrosis in the thyroid gland was observed even in a euthyroid case. Therefore, patients with IPPFE may potentially have thyroid gland dysfunction through a common pathogenesis in both organs.

The Significant Antitumor Activity of Nivolumab in Lung Adenocarcinoma with Choriocarcinomatous Features.

We report the case of a 60-year-old Japanese man with a metastatic brain tumor that caused ataxia. As a consequence of resection of a cerebellar tumor, the tumor was diagnosed as a poorly differentiated adenocarcinoma with choriocarcinomatous features. The patient underwent bronchoscopy, leading to a diagnosis of the same histology as the brain tumor. After the administration of first-line chemotherapy and maintenance therapy due to progressive disease, he was given nivolumab and obtained a partial response; however, 11-months later, computed tomography showed tumor progression. Our experience suggests that nivolumab has strong activity, even in patients with a rare form of lung cancer.

Sarcoidosis and NOD1 variation with impaired recognition of intracellular Propionibacterium acnes.

Sarcoidosis is a systemic granulomatous disease of unknown etiology. NOD2 mutations have been shown to predispose to granulomatous diseases, including Crohn's disease, Blau syndrome, and early-onset sarcoidosis, but not to adult sarcoidosis. We found that intracellular Propionibacterium acnes, a possible causative agent of sarcoidosis, activated NF-kappaB in both NOD1- and NOD2-dependent manners. Systematic search for NOD1 gene polymorphisms in Japanese sarcoidosis patients identified two alleles, 796G-haplotype (156C, 483C, 796G, 1722G) and 796A-haplotype (156G, 483T, 796A, 1722A). Allelic discrimination of 73 sarcoidosis patients and 215 healthy individuals showed that the frequency of 796A-type allele was significantly higher in sarcoidosis patients and the ORs were significantly elevated in NOD1-796G/A and 796A/A genotypes (OR [95% CI]=2.250 [1.084, 4.670] and 3.243 [1.402, 7.502], respectively) as compared to G/G genotype, showing an increasing trend across the 3 genotypes (P=0.006 for trend). A similar association was found when 52 interstitial pneumonia patients were used as disease controls. Functional studies showed that the NOD1 796A-allele was associated with reduced expression leading to diminished NF-kappaB activation in response to intracellular P. acnes. The results indicate that impaired recognition of intracellular P. acnes through NOD1 affects the susceptibility to sarcoidosis in the Japanese population.

[A case of volcanic ash lung: report of a case].

A 57-year-old woman inhaled much volcanic ash without using a mask every day during the eruption of the Miyake Volcano in August 2000. An abnormal shadow was pointed out on her chest radiography by chance, after she sought refuge in Higashimurayama city in September. She had no respiratory symptoms and her chest radiography in an annual health check in July 2000 had showed no abnormality. She was admitted to our hospital and thoracoscopic lung biopsy was performed. We diagnosed it as lung inflammation caused by volcanic ash. The reasons for diagnosis were because the abnormal shadow appeared after the inhalation of volcanic ash, chest computed tomography showed diffuse irregular shadows with air bronchogram, thoracoscopic lung biopsy showed cellular-bronchiolitis around crystals, and the results of mineralogical analysis of the particles in alveolar macrophages detected in the biopsy specimen by scanning electron microscopy (SEM) were very similar to those of volcanic ash. The shadow on her chest radiography disappeared gradually without any treatment, but she avoided further exposure to volcanic ash. It is necessary to consider volcanic ash capable of causing lung inflammation.

Pathophysiological Implication of Computed Tomography Images of Chronic Pulmonary Aspergillosis.

Chronic pulmonary aspergillosis (CPA) is a refractory disorder that needs long-term antifungal treatment and occasionally results in fatal respiratory failure and hemoptysis. However, the pathological features of the disorder have not been thoroughly delineated. Thirty cases were therefore analyzed clinically and histologically to elucidate the pathophysiology of CPA. The subjects comprised 14 individuals who underwent surgical removal and 16 patients who died. No subject exhibited a severely immunocompromised state. The main symptoms included cough, hemosputum, and dyspnea. Chest computed tomography (CT) findings revealed a cavity, fungus ball, and consolidation and/or ground glass opacity (GGO); 27 serial CT scans showed enlarged consolidation and/or GGO (70%), dilatation of the cavity (26%), and extension to the opposite lung (22%). Histopathological findings revealed a cavity with ulceration, bronchitis, and various degrees of organizing pneumonia (OP) that were correlated with the area of consolidation and GGO on the CT scan. The essential pathophysiology of CPA can be understood as an active state of ulceration of the cavity and/or erosive bronchitis caused by contact with the fungus ball, which may play a significant role in the development of OP. Consequently, OP is thought to reflect respiratory failure that relates to the prognosis of CPA.

Sarcoid Myositis with Anti-Ku Antibody Consistent with both Sarcoidosis and Polymyositis.

We herein describe a case of sarcoid myositis with anti-Ku antibody positivity. Pathological findings of the muscle were compatible with sarcoidosis, but could not be completely distinguished from myositis diseases that arise from other causes. According to a physical examination, pathological findings, the detection of anti-Ku antibody and the human leukocyte antigen (HLA)-DPB1 allele, we strongly suspected that the patient developed both sarcoidosis and polymyositis. Sarcoidosis is often complicated by autoimmune diseases. This case suggests the possibility that sarcoidosis and other autoimmune diseases may have common causal genetic factors.