Nada Tomanovic

Parapharyngeal space tumors: 61 case reviews.

Parapharyngeal tumors account for 0.5% of head and neck tumors. They are difficult to diagnose because they have few symptoms and are surgically inaccessible. This retrospective study included 61 patients with parapharyngeal space tumors, treated in the last 20 years. The data, obtained from the medical records, included symptoms and clinical signs, diagnostic procedures, surgical approach, postoperative complications and histopathological findings. The most common symptoms were dysphagia, foreign body sensation, pain, and symptom-free patients. For precise tumor localization and its relation to adjacent structures, computerized tomography, magnetic resonance imaging and contrast angiography were used. All the patients were treated surgically. The commonest surgical approach was transcervical, followed by transoral and combined transcervical-transoral. Histopathological examination verified that the origin of these tumors was most frequently salivary or neurogenic.

Cyclin A and β-catenin expression in actinic keratosis, Bowen's disease and invasive squamous cell carcinoma of the skin

Background  Actinic keratosis (AK) has been defined as a precancerous lesion or an early phase in the evolution of squamous cell carcinoma (SCC) and histological changes seen in the individual cells of an AK are indistinguishable from those seen in SCC, which invade the dermis. Cyclin A is an increasingly utilized proliferation marker that has functions in both S phase (DNA replication) and initiation of mitosis, whereas alterations of β‐catenin, the molecule involved in cell–cell adhesion and in signalling transduction, could promote invasive and proliferative capacities of malignant tumours.

Chronic administration of fluoxetine or clozapine induces oxidative stress in rat liver: a histopathological study.

Chronic exposure to stress contributes to the etiology of mood disorders, and the liver as a target organ of antidepressant and antipsychotic drug metabolism is vulnerable to drug-induced toxicity. We investigated the effects of chronic administration of fluoxetine (15mg/kg/day) or clozapine (20mg/kg/day) on liver injury via the measurement of liver enzymes, oxidative stress and histopathology in rats exposed to chronic social isolation (21days), an animal model of depression, and controls. The activity of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the liver content of carbonyl groups, malonyldialdehyde (MDA), reduced glutathione (GSH), cytosolic glutathione S-transferase (GST) and nitric oxide (NO) metabolites were determined. We also characterized nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2) and CuZn-superoxide dismutase (CuZnSOD) protein expression as well as histopathological changes. Increased serum ALT activity in chronically-isolated and control animals treated with both drugs was found while increased AST activity was observed only in fluoxetine-treated rats (chronically-isolated and controls). Increased carbonyl content, MDA, GST activity and decreased GSH levels in drug-treated controls/chronically-isolated animals suggest a link between drugs and hepatic oxidative stress. Increased NO levels associated with NF-κB activation and the concomitant increased COX-2 expression together with compromised CuZnSOD expression in clozapine-treated chronically-isolated rats likely reinforce oxidative stress, observed by increased lipid peroxidation and GSH depletion. In contrast, fluoxetine reduced NO levels in chronically-isolated rats. Isolation induced oxidative stress but histological changes were similar to those observed in vehicle-treated controls. Chronic administration of fluoxetine in both chronically-isolated and control animals resulted in more or less normal hepatic architecture, while clozapine in both groups resulted in liver injury. These data suggest that clozapine appears to have a higher potential to induce liver toxicity than fluoxetine.

Primary cutaneous carcinosarcoma: case report with expanded immunohistochemical analysis

An 83‐year‐old woman presented with a nodular, eroded tumor on the skin between the nose and the upper lip of 18 months’ duration. There were no palpable lymph nodes and no infiltrates on chest radiography. Complete surgical excision showed a tumor measuring 65 × 40 × 30 mm. On histopathologic examination, it was composed of typical basal cell carcinoma (BCC) nodules and large sheets of oval or short spindle cells ( Fig. 1a ), with vesicular nuclei, distinct nucleoli, moderate pleomorphism, and pronounced mitotic activity (more than 40 mitoses/10 high‐power fields). In parts abutting the upper lip, BCC nodules were found in the muscle layer, but the small salivary glands were uninvolved ( Fig. 1b ). Immunohistochemical analysis ( Table 1 ) revealed a cytokeratin (CK)‐positive, Ber‐EP4‐positive, and vimentin‐negative BCC component ( Fig. 2a ), and a vimentin‐positive, CK‐negative sarcomatous component ( Fig. 2b ). In addition, mesenchymal tumor components were focally positive for smooth muscle actin (SMA). The BCC component showed irregular reaction with CK7, which stained some lobules and parts of individual nests ( Fig. 2c ). The final diagnosis was primary cutaneous carcinosarcoma. At the last visit, 3 months after operation, no signs of recurrence or metastatic spread were observed. Additional immunohistochemical analyses showed preserved membranous β‐catenin staining in the BCC component, without nuclear reaction in the mesenchymal component. The labeling index (LI) is expressed as the percentage of positive cells, and is calculated from the number of positive tumor cells divided by the total number of tumor cells counted (minimum 300 cells) in the areas with most pronounced immunopositivity. Counting was performed on images taken from microscopic high‐power fields with an Olympus DP70 digital camera (Olympus Corporation, Tokyo, Japan). The program analySYS (Soft Imaging System, Munster, Germany) was used, with the screen grid and the manual touch‐count method. The LI values of Ki‐67 and telomerase reverse transcriptase (hTERT) were higher in the sarcomatous component. hTERT displayed enhanced nucleolar localization and diffuse staining of mitotic cells. Histone deacetylase 1 (HDAC1) was expressed in a smaller percentage of cells than HDAC2, with a higher LI in the sarcomatous component. HDAC2 was the only marker analyzed that stained more cells in the BCC component ( Fig. 2d ).

Olanzapine modulation of hepatic oxidative stress and inflammation in socially isolated rats

Olanzapine, an atypical antipsychotic, is efficient in stress associated psychiatric diseases, but its effect on the liver, a primary organ for drug activation and detoxification, still remains unclear. The effect of olanzapine administration (7.5mg/kg/day), on rat hepatic glutathione (GSH)-dependent defense and proinflammatory cytokines following 6weeks of chronic social isolation (CSIS), which causes depressive- and anxiety-like behavior in adult male Wistar rats, was investigated. The subcellular distribution of nuclear factor-κB (NF-κB), cytosolic inducible nitric oxide synthase (iNOS) protein levels and hepatic histological alterations were also determined. Decreased GSH content and glutathione reductase activity associated with increased catalase and glutathione S-transferase activity following CSIS indicated hepatic oxidative stress. Moreover, CSIS caused NF-κB nuclear translocation and the concomitant increase in iNOS together with increase in interleukin-1beta and tumor necrosis factor alpha protein levels, but no effect on interleukin-6. Olanzapine treatment suppressed NF-κB activation and iNOS expression and caused modulation of GSH-dependent defense systems but failed to reverse CSIS-induced increase in hepatic proinflammatory cytokines. Portal inflammation, focal hepatocyte necrosis and an increased number of Kupffer cells in CSIS rats (vehicle- or olanzapine-treated) were found. Olanzapine-treated socially reared rats showed portal inflammation and focal hepatocyte necrosis. Data suggest that CSIS compromised GSH-dependent defense, triggered a proinflammatory response and histological alterations in rat liver. Olanzapine treatment partially reversed the alterations in hepatic GSH-dependent defense, but showed no anti-inflammatory effect suggesting that it may provide protective effect against hepatic CSIS-induced oxidative stress, but not against inflammation.

Expression of toll-like receptors 2, 4 and nuclear factor kappa B in mucosal lesions of human otitis: pattern and relationship in a clinical immunohistochemical study.

Objectives: The objectives were to detect and compare the expression of toll-like receptors (TLRs) 2, 4 and nuclear factor kappa B in mucosal lesions of chronic otitis. Methods: Fifty-five tissue samples obtained from children and adults operated on for otitis were investigated by semiquantitative immunohistochemical methods using polyclonal antibodies for TLR 2, 4 and NFkB. Kruskal–Wallis, Mann–Whitney, and Kendall’s tau rank correlation tests were used. Results: Stronger expression of TLR2, 4 was found in inflamed mucosa than in the control for children and adults (TLR2: H = 23.86, P < .001; TLR4: H = 22.80, P < .001) (TLR2: H = 17.53, P < .001; TLR4: H = 11.99, P < .001); in cholesteatoma perimatrix compared to tubotympanic lesions in children (TLR2: H = 11.06, P = .004; TLR4: H = 10.61, P = .005) and adults (TLR2: H = 10.73, P = .013; TLR4: H = 9.65, P = .021). No differences were found in NFkB expression (H = 0.042, P = .99). Significant correlations were found for all pairs of molecules in cholesteatoma and tubotympanic mucosa of adults (TLR2, 4: P = .002, P < .001; TLR2-NfkB: P = .032, P = .021; TLR4-NFkB: P = .035, P = .0013), only TLR4-NFkB in tubotympanic otitis of children (P = .026). Conclusions: Toll-like receptors 2, 4 and NFkB mediate inflammation in cholesteatoma and mucosal lesions of tubotympanic otitis in children and adults. Significant correlations between all pairs of molecules in all samples were detected in adults, but only TLR4-NFkB in children.

Polymorphisms in Toll-like receptors 2 and 4 genes and their expression in chronic suppurative otitis media

OBJECTIVE Toll-like receptors (TLRs) have a prominent role in inducing innate immune response. It has been suggested that regulation of TLRs is involved in the pathogenesis of chronic otitis media. TLR 2 and TLR 4 polymorphisms were connected with susceptibility to acute otitis and chronic otitis with effusion. The objective of this study was to establish expression of TLR 2 and 4 on middle ear mucosa in different types of chronic suppurative otitis media (CSOM), and the influence of gene polymorphisms TLR 2 Arg753Gln and TLR 4 Thr399Ile and Asp299Gly to susceptibility to CSOM. MATERIAL AND METHODS Middle ear mucosa and full blood samples were obtained from 85 patients with chronic suppurative otitis media with and without cholesteatoma. Control group for mucosal TLR expression consisted of 71 samples of middle ear mucosa taken from patients with otosclerosis, and control group for DNA polymorphism consisted of 100 full blood samples in healthy subjects. DNA polymorphism detection was done with restriction fragment length polymorphism in RT PCR. Expression of TLR 2 and 4 was determined with immunohistochemical staining. RESULTS TLR 2 and TLR 4 expression on the middle ear mucosa was not influenced by age of the patients with chronic otitis media. Incidence of TLR 2 Arg753Gln polymorphism was significantly higher in patients with chronic otitis media, compared to control group. Significant association between TLR 2 Arg753Gln polymorphism and different types of mucosal changes in patients with chronic otitis media was established. TLR 2 and 4 expression on experimental group mucosa was significantly different compared to control group, where there was no expression (p=0.000). Strong dependence of TLR 2 and TLR 4 expression on middle ear mucosa with different mucosal changes and immunohistochemical activity after staining was detected. CONCLUSION Certain polymorphisms in TLR genes could be indicative for susceptibility to chronic otitis media. Expression of TLR 2 and 4 on middle ear mucosa was more dependable on different types of mucosal changes and type of CSOM than on bacteria found in the specimens. This can indicate that the type of mucosal changes are closely correlated with TLRs activity in middle ear.

Intramuscular hemangioma of the retropharyngeal space.

BACKGROUND Intramuscular hemangioma (IMH) is a distinctive type of hemangioma occurring within skeletal muscle. Most IMH are located in the lower extremity, particularly in the muscles of the thigh. When present in the head and neck region, the masseter and trapezius muscle are the most frequently involved sites. CASE REPORT We reported a case of unusual localization of the head and neck IMH occurring within the retropharyngeal space (RPS). To our knowledge, this is the second such case reported in the English literature. The tumor presented as a left-sided neck mass with bulging of the posterior and left lateral oropharyngeal wall on indirect laryngoscopy. Computed tomography (CT) scan revealed an ill-defined mass in the RPS at the oropharyngeal level. The lesion was excised via a transoral approach and microscopically diagnosed as IMH, the complex malformation subtype. Although surgical margins were positive, no recurrence of the tumor was noted in the 17-month follow-up. CONCLUSION Intramuscular hemangioma should be considered in the differential diagnosis of deep head and neck masses. The knowledge of the infiltrative nature and recurrence rate of an IMH is useful for appropriate managment.

Expression of G1/S‐cyclins and cyclin‐dependent kinase inhibitors in actinic keratosis and squamous cell carcinoma

Actinic keratosis (AK) and Bowens disease (squamous cell carcinoma in situ, SCCIS) are pre‐invasive stages in the development of squamous cell carcinoma (SCC).

Histopathology of chronic hepatitis C in relation to virus genotype

BACKGROUND/AIM The natural history of hepatitis C virus (HCV) infection is variable and the factors determining the course of the illness are unclear. There are geographical variations in the distribution of different HCV genotypes, and some of them are related to the specific infection routes. Regarding our country, the dominant genotype is genotype 1b. It is unclear and still remains a question whether the distinct histopathological manifestations are related to the particular genotypes of HCV. Thus, the aim of this study was to determine whether the distinct histopathological manifestations of HCV infection might be in relation to the individual virus genotype. METHODS In this study we examined 126 patients with chronic HCV infection regarding the histopathological features, demographic data, and virus genotype. The observed groups of patients were predominantly infected with HCV genotypes 1b and 3a. RESULTS In this study we found that the patients infected with HCV genotype 1b had more frequently moderate or severe necroinflammatory activity of the disease, significantly higher grading score as compared with other genotypes (p < 0.0001). A higher degree of fibrosis was, also, more common in the patients infected with genotype 1b of HCV as compared with other genotypes (p < 0.05). There were no significant correlations between the necroinflammatory activity of the disease and the stage of fibrosis in 1b, 4 and mixed genotypes. CONCLUSION The present data support the hypothesis that distinct genotypes of HCV are associated with the particular histopathological manifestation of the disease.