A combined immunohistochemical and histochemical approach on the differential diagnosis of giant cell epiphyseal neoplasms

The histological similarities and the common localization are the main causes of difficulties concerning the differential diagnosis between giant cell tumor of bone and chondroblastoma. The purpose of the present study was to detect whether histochemistry and/or immunohistochemistry could help to make the distinction between these two entities easier. The study was based on cases of chondroblastoma and giant cell tumor of bone from patients in the 2nd and 3rd decades of life. Histochemical detection of special intracellular and extracellular components (glycogen, glycosaminoglycans) as well as immunohistochemical investigation using various tumor markers (S-100, NSE, a-1-ACT, lysozyme, fibronectin) were performed on parallel paraffin sections. The presence of abundant intracytoplasmic glycogen granules and the immunoreactivity of the cells of chondroblastoma with S-100 and NSE, together with the presence of acidic sulfated glycosaminoglycans in the stroma, could help the differential diagnosis of this tumor from giant cell tumor of bone.     

Causes of attenuation of the sound waves in neoplasms of the breast. Histologic and echographic correlation study

The purpose of our study was to compare the ultrasound findings in malignant breast masses (which underwent biopsy) with their histological appearance. In our activity of breast sonography, we observed that the same histological type of breast cancer often shows a different ultrasonic image. The main difference concerns the sonic attenuation or increase through the neoplastic mass. The histological examination took into account the amount of stroma and cells and the architectural pattern of the lesion. Comparing these features with the ultrasonic image, it has been shown that sonic transmission is related more to the architectural pattern than to the fibrous content of the neoplastic tissue.     

Role of the laboratory in monitoring patients receiving dual antiplatelet therapy

Introduction: The increasing demand for therapeutic monitoring in patients receiving antiplatelet therapy has been paralleled by the development of instruments and tests whose clinical usefulness is still under debate. We devised a laboratory approach to detect patients with antiplatelet resistance at risk to develop thrombotic events. Methods: One hundred and eighty patients, under aspirin and clopidogrel after angioplasty and stent implantation, were studied by PFA100^® with collagen/epinephrine (CoEPI, cutoff 165s) cartridge and by Multiplate^® using arachidonic acid (ASPItest, pos < 862AUC), ADP (ADPtest, pos < 417AUC), and collagen (COLtest, pos < 607AUC). Results: Only 67 of 173 patients with ASPI < 862 displayed a prolonged CoEPI and up to 65 patients had normal CoEPI despite ASPI < 300. Patients with ASPI < 300 had significantly lower COL than patients with ASPI > 300. One hundred and thirty‐eight patients displaying ADP < 417 had significantly lower COL than those with ADP > 417. Association between COL and ADP remained after ASPI stratification: in patients with suboptimal (ASPI 300–892) or maximal (ASPI < 300) response to aspirin, having ADP < 417 (clopidogrel responsive) increased COL positivity, respectively, from 9.5 to 58.8% and from 47.6 to 82.7%. Conclusion: A combination of specific tests may be useful in identifying higher‐risk patients with poor compliance or drug resistance who potentially may benefit from therapy change.     

Interplay between oxidative stress and hepatic steatosis in the progression of chronic hepatitis C

BACKGROUND/AIMS: The contribution of oxidative stress to the pathogenesis of chronic hepatitis C (CHC) is still poorly elucidated. This study investigated the relationship between oxidative stress, insulin resistance, steatosis and fibrosis in CHC. METHODS: IgG against malondialdehyde-albumin adducts and HOMA-IR were measured as markers of oxidative stress and insulin resistance, respectively, in 107 consecutive CHC patients. RESULTS: Oxidative stress was present in 61% of the patients, irrespective of age, gender, viral load, BMI, aminotransferase level, histology activity index (HAI) and HCV genotype. Insulin resistance and steatosis were evident in 80% and 70% of the patients, respectively. In the patients infected by HCV genotype non-3, but not in those with genotype 3 infection HOMA-IR (p<0.03), steatosis (p=0.02) and fibrosis (p<0.05) were higher in the subjects with oxidative stress than in those without. Multiple regression analysis revealed that, HOMA-IR (p<0.01), fibrosis (p<0.01) and oxidative stress (p<0.05) were independently associated with steatosis, whereas steatosis was independently associated with oxidative stress (p<0.03) and HOMA-IR (p<0.02). Steatosis (p<0.02) and HAI (p=0.007) were also independent predictors of fibrosis. CONCLUSIONS: In patients infected by HCV genotype non-3, oxidative stress and insulin resistance contribute to steatosis, which in turn exacerbates both insulin resistance and oxidative stress and accelerates the progression of fibrosis.     

Genetic and epigenetic factors in autoimmune reactions toward cytochrome P4502E1 in alcoholic liver disease

Autoimmune reactions are often associated with alcoholic liver disease; however, the mechanisms responsible are largely unknown. This study investigates the potential role of the immune response against hydroxyethyl free radical (HER)-derived antigens and of polymorphisms in immunoregulatory genes in the development of anti-cytochrome P4502E1 (CYP2E1) autoantibodies in alcohol abusers. Immunoglobulin G (IgG) recognizing human CYP2E1 and HER-derived epitopes were measured by microplate immunosorbent assay in the sera of 90 patients with alcoholic fibrosis/cirrhosis (ALD), 37 heavy drinkers without liver disease or steatosis only (HD), and 59 healthy subjects. Single nucleotide polymorphisms in the interleukin 10 (IL-10) promoter and in exon 1 of the cytotoxic T-lymphocyte antigen-4 (CTLA-4) gene were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis. The titers and frequency of anti-CYP2E1 autoantibodies were significantly higher in ALD than in HD subjects or controls. ALD patients with anti-HER IgG had higher titers and a 4-fold increased risk (OR: 4.4 [1.8-10.9]) of developing anti-CYP2E1 autoantibodies than subjects without anti-HER antibodies. The mutant CTLA-4 G allele, but not the IL-10 polymorphism, was associated with an enhanced risk of developing anti-CYP2E1 IgG (OR: 3.8 [1.4-10.3]). CTLA-4 polymorphism did not influence antibody formation toward HER-antigens. ALD patients with concomitant anti-HER IgG and the CTLA-4 G allele had a 22-fold higher (OR: 22.9 [4.2-125.6]) risk of developing anti-CYP2E1 autoreactivity than subjects negative for these factors. In conclusion, antigenic stimulation by HER-modified CYP2E1 combined with an impaired control of T-cell proliferation by CTLA-4 mutation promotes the development of anti-CYP2E1 autoantibodies that might contribute to alcohol-induced liver injury.