Anti-CTLA-4 Antibody Might Be Effective Against Non-small Cell Lung Cancer With Large Size Tumor.

BACKGROUND/AIM: Immunotherapy using immune checkpoint inhibitors (ICIs) has revolutionized the treatment of advanced non-small cell lung cancer (NSCLC). Although several ICI options are available, the treatment regimen for NSCLC with large size tumors (large NSCLC) is controversial and the efficacy of anti-CTLA-4 antibody is unclear. This study thus investigated potential biomarkers for CTLA-4 blockade. PATIENTS AND METHODS: The correlation between tumor diameter and treatment duration was examined in patients with advanced NSCLC treated with anti-PD-1 antibody monotherapy in our institution. In addition, the ratio of tumor-infiltrating CD8+ T cells and regulatory T (Treg) cells in small and large size NSCLC was also evaluated using immunohistochemical staining. Finally, the efficacy of treatment with anti-CTLA-4 antibody against large NSCLC was investigated. RESULTS: A negative correlation was found between tumor diameter and treatment duration in patients treated with anti-PD-1 antibody monotherapy. Immuno-histochemical staining revealed that Treg cell infiltration was significantly higher in large NSCLC tumors than in small tumors. Among the patients with large NSCLC, the ICI regimen including anti-CTLA-4 antibody showed significant efficacies. CONCLUSION: Anti-PD-1 antibody monotherapy might be less effective against large NSCLC due to the infiltration of Treg cells. Therefore, it might be appropriate for large NSCLC to select a treatment including an anti-CTLA-4 antibody, which can target Treg cells.

Computed tomography-based centrilobular emphysema subtypes relate with pulmonary function.

INTRODUCTION: Centrilobular emphysema (CLE) is recognized as low attenuation areas (LAA) with centrilobular pattern on high-resolution computed tomography (CT). However, several shapes of LAA are observed. Our preliminary study showed three types of LAA in CLE by CT-pathologic correlations. This study was performed to investigate whether the morphological features of LAA affect pulmonary functions. MATERIALS AND METHODS: A total of 73 Japanese patients with stable CLE (63 males, 10 females) were evaluated visually by CT and classified into three subtypes based on the morphology of LAA including shape and sharpness of border; patients with CLE who shows round or oval LAA with well-defined border (Subtype A), polygonal or irregular-shaped LAA with ill-defined border (Subtype B), and irregular-shaped LAA with ill-defined border coalesced with each other (Subtype C). CT score, pulmonary function test and smoking index were compared among three subtypes. RESULTS: Twenty (27%), 45 (62%) and 8 cases (11%) of the patients were grouped into Subtype A, Subtype B and Subtype C, respectively. In CT score and smoking index, both Subtype B and Subtype C were significantly higher than Subtype A. In FEV1%, Subtype C was significantly lower than both Subtype A and Subtype B. In diffusing capacity of lung for carbon monoxide, Subtype B was significantly lower than Subtype A. CONCLUSION: The morphological differences of LAA may relate with an airflow limitation and alveolar diffusing capacity. To assess morphological features of LAA may be helpful for the expectation of respiratory function.

Classification of Centrilobular Emphysema Based on CT-Pathologic Correlations.

INTRODUCTION: Centrilobular emphysema (CLE) is recognized as low attenuation areas (LAA) with centrilobular distribution on high-resolution computed tomography. The LAA often exhibit a variety of shape or sharpness of border. This study was performed to elucidate the relationship between morphological features of LAA and pathological findings in CLE. MATERIALS AND METHODS: The inflated-fixed lungs from 50 patients with CLE (42 males, 8 females; 14 operated, 36 autopsied) were examined by a method of CT-pathologic correlations that consisted of three steps. The first, CT images of the sliced lungs of the inflated-fixed lung specimens were examined on the shape and the peripheral border of each LAA. The second, the sliced lungs were radiographed in contact with high magnification. The third, the surface of the sliced lungs was observed by using stereomicroscopy. The views at low magnification of stereomicroscope were compared with the radiographs and the CT images of the same sample. RESULTS: Using CT-pathologic correlations, LAAs of CLE were classified into three types as follows; round or oval shape with well-defined border (Type A), polygonal or irregular shape with ill-defined border and less than 5 mm in diameter (Type B), and irregular shape with ill-defined border and 5 mm or over in diameter (Type C). Type A, Type B and Type C LAA were mainly related to dilatation of bronchioles, destruction of proximal part of alveolar ducts, and destruction of distal part of alveolar ducts, respectively. Type A, Type B and Type C were dominant LAA in 5 (10%), 29 (58%) and 12 (24%) patients, respectively. However, remained 4 patients (8%) did not show dominant LAA type. CONCLUSION: Morphological features of LAA in CLE may depend on dilatation or destruction of certain parts of the secondary lobule. Type B LAA was the commonest type in CLE.

Secondary pulmonary alveolar proteinosis associated with myelodysplastic syndrome.

A 47-year-old man, who had been diagnosed as myelodysplastic syndrome (MDS), complained of a severe cough and a high-grade fever. Chest CT disclosed scattered small nodules and ground-glass opacities with interlobular septal thickening in both lung fields and a mass lesion in the right lower lobe. Pathological findings of the ground-glass opacities and the mass lesion obtained by video-assisted thoracoscopic surgery revealed the accumulation of eosinophilic amorphous material in the alveoli and confirmed the diagnosis of pulmonary alveolar proteinosis (PAP). Autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF) in sera were below sensitivity, while the GM-CSF level was elevated in bronchoalveolar lavage fluid. He was diagnosed as secondary PAP associated with MDS.

[Investigation of practical application of fluorescence in situ hybridization (FISH) analysis using microwave irradiation in formalin-fixed, paraffin-embedded tissue sections].

We investigated fluorescence in situ hybridization (FISH) analysis using microwave irradiation in formalin-fixed, paraffin-embedded tissue sections of breast fibroadenoma. Higher percentage of cells with 2 signal copies of chromosome 3 centromere could be obtained in the condition of 5 microns thick sections, when we counted cells of more than 4 microns of nuclei in thickness. This method showed about the same results as FISH using cells separated from the same tissues. Percentage of cells with 2 signal copies of chromosome 17 centromere in 14 cases was 80.6 +/- 4.0% (Mean +/- S.D.). This method is expected in the application of the prognosis estimation of the breast cancer.

Pulmonary MALT lymphoma with amyloid production in a patient with primary Sjögren's syndrome.

A 53-year-old woman was admitted to our hospital complaining of cough, low grade fever, chest pain and sicca symptoms. A chest radiograph showed an abnormal shadow and chest computed tomography revealed a tumor in left S6. She was diagnosed as Sjögren's syndrome by sialography and histological findings of labial biopsy. The surgically resected tumor specimen showed proliferation of lymphoid cells with lymphoepithelial lesions, which were positive for CD20 and kappa light chain. Kappa light chain-positive amyloid was found within the tumor. The tumor showed rearranged kappa light chain genes. The diagnosis was pulmonary mucosa associated lymphoid tissue lymphoma with amyloid production.