Tomonori Tanaka

Survival of Lung Adenocarcinoma Patients Predicted from Expression of PD-L1, Galectin-9, and XAGE1 (GAGED2a) on Tumor Cells and Tumor-Infiltrating T Cells.

The survival of lung adenocarcinoma patients could be predicted with the use of a discriminant function using as parameters tumor cell expression of PD-L1, Galectin-9, and XAGE1 (GAGED2a), and CD4 and CD8 T-cell infiltration. The immune status of tumors varies, and this may affect the overall survival (OS) of patients. We examined tumors from 120 patients with lung adenocarcinomas with a tissue microarray for T-cell infiltration and the expression of PD-L1 and Galectin-9 (both ligands for inhibitory receptors on T cells), and cancer/testis (CT) antigen XAGE1 (GAGED2a; a tumor antigen often found on lung tumors) expression, to determine their relevance to OS. Patients defined as pStage I–IIIA could be grouped, based on the expression profiles of PD-L1, Galectin-9, and XAGE1, into cluster A, who had prolonged survival, and cluster B, who had shorter survival. The difference in survival of the clusters was confirmed separately for pStage I and pStage II–IIIA patients. Cluster A patients who also had CD4 and CD8 T-cell infiltration showed even better survival, as expected. The findings were confirmed by examining an independent validation cohort of 68 pStage I lung adenocarcinoma patients. Our data showed that PD-L1 expression was a positive indicator, whereas Galectin-9 and XAGE1 expression was negative. In vitro analyses suggested that PD-L1 expression was upregulated by IFNγ secreted from activated T cells in the tumor and Galectin-9 expression was counteracting those T cells. Thus, use of these immune markers enables the creation of a discriminant function with which to classify tumors and predict survival. Cancer Immunol Res; 4(12); 1049–60. ©2016 AACR.

Rare idiopathic intestinal pneumonias (IIPs) and histologic patterns in new ATS/ERS multidisciplinary classification of the IIPs

The new American Thoracic Society/European Respiratory Society (ATS/ERS) update to the multidisciplinary classification of idiopathic interstitial pneumonias (IIPs) defines both rare IIPs and rare histologic patterns of IIPs. Although these diseases are rare, each has some distinguishing imaging and pathologic characteristics. Common findings for IIPs in computed tomography (CT) include cysts in lymphoid interstitial pneumonia (LIP), upper lobe subpleural consolidation in pleuropulmonary fibroelastosis (PPFE), symmetrical consolidation in acute fibrinous organizing pneumonia (AFOP), and peribronchovascular consolidation or centrilobular nodules in bronchiolocentric pattern of interstitial pneumonia.

Broader criteria of undifferentiated connective tissue disease in idiopathic interstitial pneumonias

BACKGROUND Kinder et al. proposed a broader definition of undifferentiated connective tissue disease (UCTD) and reported that the entity of nonspecific interstitial pneumonia (NSIP) is a lung manifestation of this more broadly defined UCTD. However, a retrospective study did not support their findings and its clinical significance remains unclear. METHODS We prospectively evaluated the significance of this broadly defined UCTD in idiopathic interstitial pneumonias (IIPs) in consecutive patients with surgical lung biopsy. Patients were evaluated with a symptoms check list and underwent comprehensive serologic testing as screening for UCTD. Clinical characteristics, high-resolution CT images, lung biopsy specimens, serial FVC change, and survival were analyzed. RESULTS Among 76 patients with IIPs, 24 patients (32%) fulfilled the UCTD criteria. Diagnosis of 24 patients with UCTD was usual interstitial pneumonia in 12 (50%), NSIP in 7 (29%), and unclassifiable interstitial lung disease (ILD) in 5 (21%). The diagnosis of 52 patients who did not have UCTD was idiopathic pulmonary fibrosis in 27 (52%), NSIP in 11 (21%), unclassifiable ILD in 13 (25%) and cryptogenic organizing pneumonia in 1 (2%). One-year and two-year FVC changes showed no significant difference between UCTD and non-UCTD, however, significant differences in FVC change were observed among histopathological diagnoses both in UCTD and in non-UCTD. In multivariate survival analysis, %FVC and histopathological UIP pattern were independent predictors for survival but UCTD diagnosis was not. CONCLUSIONS A diagnosis of UCTD was not useful in discriminating NSIP or in predicting disease progression and prognosis in our cohort of IIPs. Histopathological UIP pattern was an independent predictor for mortality irrespective of a diagnosis of UCTD.

Do you really know precise radiologic-pathologic correlation of usual interstitial pneumonia?

Although usual interstitial pneumonia (UIP) is the most common chronic interstitial pneumonia, understanding of pathologic backgrounds of CT findings has still not been enough. Since honeycombing on either scanning microgram or CT is essential for diagnosis of UIP in 2010 ATS-ERS-JRS-ALAT guide line, the role of radiologists has become much more important. We will summarize common and uncommon CT findings with radiologic-pathological correlation.

Anti-glycyl tRNA synthetase antibody associated interstitial lung disease without symptoms of polymyositis/dermatomyositis.

To the Editor: The anti-aminoacyl tRNA synthetase (ARS) antibody syndrome has large association with interstitial lung disease (ILD). The ARSs are a set of cellular enzymes, each of which catalyzes the formation of aminoacyl tRNA from a specific amino acid and its cognate tRNA. They can be found in; 25–35% of patients with chronic inflammatory muscle disorders, polymyositis (PM) and dermatomyositis (DM). Autoantibody to glycyl tRNA synthase (anti-EJ) is a form of eight anti-ARS antibodies identified in patients with PM/DM. Each of these anti-ARS antibodies has been reported to be associated with a similar syndrome, anti-synthetase syndrome, characterized by myositis with a high frequency of interstitial lung disease (ILD) (50–80%), arthritis (50–90%), and skin lesions of the fingers referred to as ‘mechanic’s hands’ (70%). Among those symptoms, ILD is the most serious life-threatening complication. Some cases of ILD with antiARS-antibody were reported to have no symptoms of myositis. The similarity of clinical features in patients with different anti-ARS antibodies is known, but some reports indicated that there are certain differences in clinical symptoms associated with each of the anti-ARS antibodies. Among eight anti-ARS antibodies, the most common antibody in all patients is anti-Jo-1 (35%). Anti-EJ positive patients are fewer (5–20%), but for the cases with ILD, anti-EJ is the most common antibody (20–35%). Although pulmonary manifestations and radiological findings of ILD in patients with anti-EJ have been reported, no reports have described the pathological features. In this report we describe the radiological and pathological features of an anti-EJ antibody positive patient with ILD, who had the no symptoms of PM/DM. A 56-year-old woman presented progressive nonproductive cough and dyspnea on exertion, with Medical Research Council dyspnea scale of grade 2, for 3 months. Her X-ray showed abnormal shadows. She was a neversmoker and had no significant medical history. She had no other environmental risk factors for respiratory disease except for the use of feather comforter. She was admitted to the hospital for a detailed assessment of her respiratory problem. On physical examination, fine crackles were heard on chest auscultation. Though Raynaud’s phenomena, arthralgia, morning stiffness and xerostomia were found, they didn’t fulfill the diagnostic criteria of any certain connective tissue disease. The blood gas analysis showed a mild hypoxia. The C-reactive protein level was elevated (2.90 mg/dL). The serum levels of Krabs von den Lungen-6 (KL-6) and surfactant protein-D (SP-D) were increased (1045 U/mL and 149.6 ng/mL, respectively). The patient’s serum were positive for anti EJ antibody, but negative for antinuclear antibody, other types of anti-ARS antibodies, and other autoantibodies suggesting autoimmune disorders. Pulmonary function test showed slight respiratory disability and diffusion function disorder. Bronchoalveolar lavage (BAL) fluid with differential cell counts were performed in left B5. The total cell number was 5.69 × 10/mL, and lymphocytes dominated at 45% in which the CD4/8 ratio was as low as 0.19. Sets of chest X-ray and high resolution computed tomography (HRCT) were obtained on admission and 2 months after the biopsy. Chest X-ray on admission revealed infiltrative shadows in the bilateral lung(Fig. 1a) and HRCT showed diffuse ground-glass opacities and areas of consolidation along the bronchovascular bundles predominantly in the lower lobes (Fig. 1c) After a video-assisted thoracic surgical (VATS) biopsy, due to rapid progression of the dyspnea, the patient was treated with methylprednisolone 1 g/day for 3 days followed by 40 mg/day of prednisolone with Cyclosporine A, 150 mg/day, for 22 days. Due to the significant improvement of respiratory symptoms and radiographic abnormality, the patient was discharged 70 days after her admission. No recurrent ILD was identified with 4 months’ follow up. Follow up radiograms after the therapy showed remarkable improvement for both bilateral lung fields (Fig. 1b,d). Video-assisted thoracic surgical (VATS) lung biopsy was performed to the left lower lobe superior segment, S6, and anterior basal segment, S8. Both specimens showed similar histological findings. Under the light microscope, the lesion was characterized by the pattern of nonspecific interstitial pneumonia (NSIP), showing moderate cellular inflammatory cell infiltration and mild increase of fibroblast in the alveolar septa. There was a slight centriacinar accentuation, but basically all areas of the lobule were diffusely affected. No area with complete normal lung was found. In addition to the findings typically seen in ordinary NSIP cases, acute inflammatory processes such as exudative edema in both airspace and alveolar septa, presence of a few organizing pneumonia (OP) foci of Masson body type, scattered airspace fibrin, denudation of the pneumocytes, and enlargement of alveolar Disclosure: None of the authors have any financial and personal relationships with other people or organizations that could inappropriately influence. Pathology International 2014; 64: 148–150 doi:10.1111/pin.12140 bs_bs_banner

Lung miliary micro-nodules in human T-cell leukemia virus type I carriers

Human T‐cell leukemia virus type 1 (HTLV‐1) carriers are rarely subject to inflammatory disorders in multiple organs, other than the well‐known complication, adult T‐cell leukemia/lymphoma (ATLL). HTLV‐1 associated bronchiolo‐alveolar disorder (HABA) has been proposed as an immune mediated pulmonary reaction seen rarely in HTLV‐1 carriers. The reported clinico‐pathological patterns of HABA are diffuse panbronchiolitis (DPB) and lymphoid interstitial pneumonia (LIP).

A Rare Case of Primary Pulmonary Glomus Tumor.

Glomus tumors are neoplasms originating from glomus bodies in the dermis or subcutis of the extremities. Extracutaneous presentations are rare, particularly in visceral organs where glomus bodies are sparse or even absent.1 Primary glomus tumors of the lung are extremely rare, and we have only been able to identify 12 reports from 1978 to 2008.1–4 We report a case of resected pulmonary glomus tumor and describe the clinicopathologic features with differential diagnoses on the basis of imaging findings.

IgG4-Related Disease With an Aortoduodenal Fistula After Abdominal Aortic Aneurysm Repair.

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