The impact of IL-6 and IL-28B gene polymorphisms on treatment outcome of chronic hepatitis C infection among intravenous drug users in Croatia.

BACKGROUND: Several genes and their single nucleotide polymorphisms (SNPs) are associated with either spontaneous resolution of hepatitis C infection or better treatment-induced viral clearance. We tested a cohort of intravenous drug users (IVDU) diagnosed with chronic hepatitis C virus (HCV) for treatment response and its association with the SNPs in the interleukin-6 (rs1800795-IL6) and the interleukin-28B (rs12979860-IL28B) genes. METHODS: The study included 110 Croatian IVDU positive for anti-HCV antibody. Genotyping was performed by polymerase chain reaction (PCR) based approach. Patients were treated by standard pegylated-interferon/ribavirin and followed throughout a period of four years, during which sustained virological response (SVR) was determined. All data were analysed with statistical package SPSS 19.0 (IBM Corp, Armonk, NY, USA) and PLINK v1.07 software. RESULTS: Patients showed a significantly better response to treatment according to the number of copies of the C allele carried at rs1800795-IL6 (P = 0.034). All but one of the patients with CC genotype achieved SVR (93%), whereas the response rate of patients with GG genotype was 64%. The association of rs1800795-IL6 with SVR status remained significant after further adjustment for patients' age, fibrosis staging, and viral genotype (OR 2.15, 95% CI 1.16-4.68, P = 0.019). Distributions of allele frequencies at the locus rs12979860-IL28B among the study cohort and the underlying general population were suggestive of a protective effect of CC genotype in acquiring chronic hepatitis C in the Croatian IVDU population. DISCUSSION: The rs1800795-IL6 polymorphism is associated with positive response to treatment in IVDU patients positive for HCV infection. A protective role of rs12979860-IL28B CC genotype in acquiring chronic hepatitis C is suggested for Croatian IVDU population.

The significance of immunohistochemical expression of merlin, Ki-67, and p53 in meningiomas.

Meningiomas are one of the most common CNS tumors whose appearance is closely linked to NF2 gene product merlin. Tumor markers Ki-67 and p53 play established role in tumor progression which should be analyzed in close association with merlin expression. The aim of this study was to investigate the immunohistochemical expression of merlin in meningiomas, correlation with Ki-67 and p53, and to determine the association of these results with histologic grade and subtype. The histologic sections of 170 patients with totally resected meningiomas, between January 2000 and December 2010, were classified according to WHO, immunohistochemically stained for Ki-67, p53, and merlin, and analyzed using light microscope. Ki-67 median was 5.6 times higher in group of patients with negative merlin than in those with positive merlin (P=0.05). Statistically significant correlation of merlin with p53 was found (P<0.001). Merlin expression between 2 combined groups (meningothelial/secretory and fibroblastic/transitional) was statistically significant (P=0.002). By comparing merlin expression and p53 levels, statistically significant difference was found (P=0.017). In the group with positive merlin and negative p53 as well as positive merlin and low p53, meningothelial/secretory subtypes of meningiomas were more common. In combination of negative merlin and negative p53 as well as negative merlin and high p53, there were more meningiomas of fibroblastic/transitional subtype. There was no statistically significant correlation between merlin and tumor grade (P=0.420). There is undeniable influence of merlin on the development and the proliferative ability of meningioma subtypes. Significant role of p53 pathway was confirmed.

Polypoid angiomyofibroblastoma tumor of nasal cavity: case report.

We report an extremely rare case and localization of polypoid angiomiofibroblastoma tumour, a case report and review of the world literature concerning angiomiofibroblastoma tumour. We present the case of a 74-year-old man who underwent left anterior and posterior ethmoidectomy with extirpation of tumour mass from left nasal cavity, epipharinx and left sphenoid sinus. The prognosis for this group of tumour is good and patient didn't receive any kind of therapy except surgical treatment. To our knowledge, this is a rare report in the world literature of polypoid angiomiofibroblastoma tumour of nasal cavity. This case indicates that angiomiofibroblastoma tumour of nasal cavity and paranasal sinuses is a rare disease including its localisation which otolaryngologists should be aware of and one which should be included in the differential diagnosis of tumours involving sinonasal tract.

Direct molecular detection of Mycobacterium tuberculosis suspected to be the specific infection in a case of recurrent tonsillitis.

We report a case of a 21-year-old man with recurrent tonsillitis caused by Mycobacterium tuberculosis. For a period of 5 months, the patient had tonsillitis seven times and was treated with several oral or parenteral antibiotics. On one of these occasions, tonsillitis was complicated with a peritonsillar abscess that was treated by incision. According to relevant bibliographic data, this is the first case of Mycobacterium tuberculosis confirmed by direct molecular microbiology methods from the tonsillar tissue of a young immunocompetent male reported in Europe. In a case of recurrent tonsillitis, Mycobacterium tuberculosis infection should be considered as a possible cause.

Endobronchial ALK+ anaplastic large-cell lymphoma resembling asthma in a 13-year-old girl.

Anaplastic large-cell lymphoma is a rare disease in children, and endobronchial localization is extremely rare in any age group. We report the case of a 13-year-old girl with endobronchial anaplastic lymphoma kinase-positive anaplastic large-cell lymphoma presenting as asthma, and discuss the diagnostic, therapeutic, and clinical implications.

Her-2/neu assessment for gastric carcinoma: validation of scoring system.

BACKGROUND/AIMS: Gastric cancer is the second leading cause of cancer mortality in the world. Amplification of HER-2/neu oncogene has become an important biomarker for identifying patients who respond to HER-2 targeting therapy. A number of studies have analyzed HER-2/neu overexpression in gastric carcinoma, and the rate of HER2 positivity is variable, ranging from 6% to 35%. METHODOLOGY: In our study HER-2/neu expression was assessed on 73 samples of primary gastric cancer, using immunohistochemistry. For 19 patients preoperative biopsy samples and resected specimens were available. Additionally, internal ring study was performed to estimate intraobserver variability of IHC scoring among pathologists at our department. RESULTS: HER-2/neu overexpression was found in 10 (13.6%) of the tested samples, and it was more common in intestinal (22.5%) than the diffuse type (3.7%). Not one of the 6 analyzed mixed type tumors showed HER-2/neu expression. For the paired samples (preoperative biopsy samples and resected specimens) the concordance rate for HER-2/neu expression was 94.7%. CONCLUSIONS: According to high concordance rate in paired samples we consider it appropriate to evaluate HER2 expression on biopsy specimens, especially in unresectable cases, and to re-evaluate it on resected specimens if available, due to high heterogeneity of a gastric cancer.

Expression of nestin, mesothelin and epithelial membrane antigen (EMA) in developing and adult human meninges and meningiomas.

The spatial and temporal pattern of appearance of nestin, epithelial membrane antigen (EMA) and mesothelin proteins was immunohistochemically determined in the cells of normal developing and adult human meninges and meningiomas. Human meninges developed as two mesenchymal condensations in the head region. The simple squamous epithelium on the surface of leptomeninges developed during mesenchymal to epithelial transformation. Nestin appeared for the first time in week 7, EMA in week 8, while mesothelin appeared in week 22 of development. In the late fetal period and after birth, nestin expression decreased, whereas expression of EMA and mesothelin increased. EMA appeared in all surface epithelial cells and nodules, while mesothelin was found only in some of them. In adult meninges, all three proteins were predominantly localized in the surface epithelium and meningeal nodules. In meningothelial meningiomas (WHO grade I), EMA was detected in all tumor cells except in the endothelial cells, mesothelin characterized nests of tumor cells, while nestin was found predominantly in the walls of blood vessels. The distribution pattern of those proteins in normal meningeal and tumor cells indicates that nestin might characterize immature cells, while EMA and mesothelin appeared in maturing epithelial cells. Neoplastic transformation of these specific cell lineages contributes to the cell population in meningiomas.

Atypical non-small cell lung cancer presentation: inguinal lymph node metastases as the first sign of disease relapse.

A case is presented of a 67-year-old male patient with atypical non-small cell lung cancer, where inguinal lymph node metastases were the first sign of disease relapse. The patient had a long-term smoking history of 30 cigarettes per day, with no other important personal or family medical history data. Because of prolonged cough, the patient underwent diagnostic procedure, which revealed squamous cell carcinoma of the lung (stage IIIB, T3N2M0). Concomitant radiochemotherapy and consolidation chemotherapy according to PE protocol was administered. Multislice computed tomography performed upon chemotherapy completion showed almost complete tumor regression and withdrawal of mediastinal lymph node enlargement, and the patient felt well. However, in the next few months, enlarged lymph nodes appeared in both inguinal regions. Histopathologic analysis revealed metastatic lung cancer. Four months after the presentation of enlarged inguinal lymph nodes, lung cancer metastases were also diagnosed in the liver and lumbosacral spine. Despite additional treatments, the patient died four months later. Although it is well known that inguinal lymph nodes can harbor lung cancer metastases, in our patient inguinal lymph node metastases were the first sign of lung cancer relapse.

Apocrine adenoma of the breast coexistent with invasive carcinoma.

We describe a case of apocrine adenoma with simultaneous occurrence of invasive ductal carcinoma in the breast of a 53-year-old woman. Apocrine adenoma affecting the breast is very rare. The lesion is composed of back-to-back ducts and papillary fronds covered with apocrine cells, and it is sharply demarcated from the surrounding breast tissue. The patient presented with a palpable nodule with skin retraction in her right breast, where ultrasound examination identified a 5-mm hypoechogenic nodule. The ultrasound also revealed in the surrounding breast parenchyma an additional abnormal finding suggestive of carcinoma. Histologic examination of the excised specimen showed that the hypoechogenic nodule represented an apocrine adenoma in proximity to the invasive ductal breast carcinoma. This is the first report that describes the simultaneous occurrence of these two lesions in the same breast.