Objective: To determine the prevalence of a broad spectrum of human papillomavirus (HPV) types in conjunctival papillomas and a possible difference in clinical and histopathological presentation of HPV-positive and HPV-negative papillomas. Methods Formalin-fixed, paraffin-embedded papilloma tissue specimens obtained from 25 patients were analysed using six different PCR-based methods targeting 87 HPV types from four different papillomavirus (PV) genera: alpha-PV, beta-PV, gamma-PV and mi-PV, and in situ hybridisation for HPV-6/HPV-11. Slides were reviewed for pedunculated or sessile growth, the presence of goblet cells, keratinising or non-keratinising epithelium, elastosis, atypia and koilocytes. Results: Alpha-PV types HPV-6 and HPV-11 were detected in 19/25 (76%) conjunctival papilloma tissue specimens, 9 (47%) of which were also HPV-6/HPV-11 positive with in situ hybridisation. Six different beta-PV types - HPV-9, HPV-12, HPV-20, HPV-21, HPV-22, HPV-24 - were additionally detected in four cases, all of which were also HPV-6/HPV-11 positive. No gamma-PVs or mi-PVs were found in any of the tested tissues samples. Extralimbal location (p=0.021), presence of goblet cells (p=0.005), non-keratinising squamous epithelium (p=0.005), and absence of elastosis (p=0.005) were associated with the presence of HPV-6/HPV-11. Conclusions: We demonstrated that certain clinical and histological features are more frequently associated with HPV infection and that HPV genera other than alpha-PV are most probably not significant factors in conjunctival papilloma occurrence.
COBISS.SI-ID: 31957721
A case of combined melanocytic nevus characterized by extensive granular cytoplasmic changes is described. Clinically, the lesion presented as an irregular, slightly asymmetric, and raised pigmented lesion of back with indistinct borders. Microscopically, a congenital pattern of distribution of melanocytes could be recognized growing along follicular and adnexal units. Melanocytes were arranged in sheets of epithelioid cells with abundant granular cytoplasm. A minor component featuring conventional dermal melanocytes was also present. Mitotic figures were not recognized. Immunohistochemistry was positive for Melan A and S100 protein in both conventional melanocytes and granular cells. In addition, the granular cells were also strongly positive for HMB45 and NKI-C3. The proliferative marker Ki67/MIB1 was nonreactive. Ultrastructural examination showed large cells with round to oval nuclei and numerous scattered cytoplasmic granules showing features consistent with lysosomes or autophagosomes. No premelanosomes, glycogen, lipid, or other distinctive organelles could be identified. Clinical follow-up at 2 years was uneventful. This unusual lesion may represent a peculiar dermal melanocytic proliferation in which the abundant granular cytoplasm is most likely due to degeneration of melanosomes induced by autophagocytic activity. The striking cytoplasmic granularity observed in this lesion may lead to confusion with other conditions, thus warranting adding granular cell nevus to the phenotypic spectrum of benign melanocytic proliferations.
COBISS.SI-ID: 32211161
Amyotrophic lateral sclerosis (ALS) is a complex fatal neurodegenerative disease characterized by progressive degeneration and loss of upper motor neurons in the cerebral cortex and lower motor neurons in brainstem and spinal cord. We established the frequencies of mutations in 4 major ALS-associated genes, SOD1, TARDBP, FUS, and C9ORF72 in a representative cohort of 85 Slovenian patients with sporadic form of ALS. Pathogenic massive hexanucleotide repeat expansion mutation in C9ORF72 was detected in 5.9% of patients and was the most common cause of the disease. In the remaining 3 genes, we identified 4 changes in 3 patients, p.Val14Met in SOD1, silent mutation p.Arg522Arg in FUS, and p.Gly93Cys in SOD1 together with a novel synonymous variant c.990A)G (p.Leu330Leu) in TARDBP gene, respectively. This study represents the first genetic screening of major causative genes for ALS in a cohort of sporadic ALS patients from Slovenia and is according to our knowledge the first such study in Slavic population. Overall, we genetically characterized 8.2% sporadic ALS patients.
COBISS.SI-ID: 31780313
It has been shown for hepatitis C virus (HCV) infection that host miRNAs contribute to the replication of the viral RNA genome. However, the clinical impact of these and many other cellular miRNAs on HCV in humans is still largely unclear. We therefore analysed the expression of miR-122, miR-126, miR-181a and miR-136 in HCV-infected patients. The study included liver biopsies of 65 patients infected with HCV of different genotypes (gt 1, gt 1a, gt 1b, gt 3 and gt 4) and nine noninfected individuals. Expression analysis of miRNAs was performed by qPCR, and they were analysed for differences between patient gender and age, genotypes, stage of fibrosis, grade of inflammation, serum level of liver enzymes, serum viral load, the presence of steatosis and mode of transmission. Different target prediction algorithms were used to search for targets of analyzed miRNAs. Statistical analysis revealed significant up-regulation of miR-136 and down-regulation of miR-126 and miR-181a in patients infected with HCV of different genotypes compared with noninfected individuals. The same expression pattern was observed in different stages and grades of liver disease. miR-122 was up-regulated in women relative to men and associated to portal inflammation, miR-122 and miR-126 correlated with serum HCV load and miR-136 and miR-122 correlated with the presence of steatosis. miR-126 and miR-136 were differentially expressed between different modes of HCV transmission. There were approximately 2000 different targets predicted for all four miRNAs and each of the analyzed miRNAs could be involved in more than a 100 different biochemical pathways. miR-122, miR-126, miR-136 and miR-181a have been shown to be involved in HCV infection with different genotypes. Their expression has been associated with the gender, stage and grade of liver disease, mode of transmission, serum HCV load and the presence of steatosis. Numerous target genes and biochemical pathways are predicted for each of the analyzed miRNAs. All these results suggest their role in HCV-infected liver disease.
COBISS.SI-ID: 31500249
Aims: Epithelioid malignant peripheral nerve sheath tumour (E-MPNST) is a distinctive variant of malignant peripheral nerve sheath tumour characterized by the predominance of epithelioid cells, diffuse S100 positivity and infrequent association with neurofibromatosis type 1. The aim of this study was to further delineate clinicopathological features of cutaneous E-MPNST, correlate them with disease outcome and discuss differential diagnosis. Methods and results: We analysed 11 cutaneous E-MPNSTs (six males, five females, median age 49 years, median size 1.6 cm). Tumours showed a predilection for lower extremities (45%) and trunk (45%), followed by upper extremity (9%). Follow-up was available for nine of 11 patients (range 24-100 months, median 52 months). Four patients had an uneventful clinical course (44%), two developed local recurrence(s) (22%) and three died due to disseminated disease (33%). No histological parameters were found to predict local recurrence(s), development of distant metastases or disease outcome, including size, percentage of epithelioid component, number of mitoses per 10 high-power fields, degree of nuclear atypia or site of occurrence (dermis, dermis/subcutis, subcutis) (P ) 0.05). Immunohistochemically, all tumours were diffusely S100-positive, with a subset displaying loss of integrase interactor 1 (INI1) expression (50%). Conclusions: Cutaneous E-MPNST has the potential to pursue an aggressive clinical course, associated with wide dissemination and unfavourable disease outcome.
COBISS.SI-ID: 32195289