Analysis of DNA methylation and microRNA expression in NUT (nuclear protein in testis) midline carcinoma of the sinonasal tract: a clinicopathological, immunohistochemical and molecular genetic study.

The aim of this study was a detailed clinicopathological investigation of sinonasal NUT midline carcinoma (NMC), including analysis of DNA methylation and microRNA (miRNA) expression. Three (5%) cases of NMC were detected among 56 sinonasal carcinomas using immunohistochemical screening and confirmed by fluorescence in situ hybridization. The series comprised 2 males and 1 female, aged 46, 60, and 65 years. Two tumors arose in the nasal cavity and one in the maxillary sinus. The neoplasms were staged pT1, pT3, and pT4a (all cN0M0). All patients were treated by radical resection with adjuvant radiotherapy. Two patients died 3 and 8 months after operation, but one patient (pT1 stage; R0 resection) experienced no evidence of disease at 108 months. Microscopically, all tumors consisted of infiltrating nests of polygonal cells with vesicular nuclei, prominent nucleoli and basophilic cytoplasm. Abrupt keratinization was present in only one case. Immunohistochemically, there was a diffuse expression of cytokeratin (CK) cocktail, CK7, p40, p63, and SMARCB1/INI1. All NMCs tested negative for EBV and HPV infection. Two NMCs showed methylation of RASSF1 gene. All other genes (APC, ATM, BRCA1, BRCA2, CADM1, CASP8, CD44, CDH13, CDKN1B, CDKN2A, CDKN2B, CHFR, DAPK1, ESR1, FHIT, GSTP1, HIC1, KLLN, MLH1a, MLH1b, RARB, TIMP3, and VHL) were unmethylated. All NMCs showed upregulation of miR-9 and downregulation of miR-99a and miR-145 and two cases featured also upregulation of miR-21, miR-143, and miR-484. In summary, we described three cases of sinonasal NMCs with novel findings on DNA methylation and miRNA expression, which might be important for new therapeutic strategies in the future.

Discordance between clinical and pathological TNM classification: influence on results of treatment and prognosis in patients with laryngeal cancer.

The goals of this retrospective cohort study were to compare the results of clinical and pathological TNM staging in patients with laryngeal squamous cell carcinoma and to determine the impact of the discordance on prognosis and treatment results. A total of 124 patients with laryngeal cancer, primarily indicated for surgical treatment, were enrolled. The concordance or discordance between the clinical and pathological staging was compared with the frequency of cancer relapse and disease-specific survival. Other potential prognostic factors, like age, the stage and location of the primary tumor, the status of neck lymph nodes, histological margins, and an indication for postoperative radiotherapy, were also evaluated. A disparity in at least one component of TNM staging was found in 40 patients (32%). The discordance had significant negative influence on both disease-free survival (DSF) and disease-specific survival (DSS). Other significant negative prognostic factors were the stage of the primary tumor, nodal status and postoperative radiotherapy. Our results indicate that the discordance between clinical and pathological staging affects the results of cancer treatment significantly. Some improvement can be probably achieved with higher preoperative diagnostic method accuracy.

[Discordance between Clinical and Pathological TNM Classifications in Patients with Oropharyngeal Cancer - Influence on Treatment and Prognosis]. / Shoda a neshoda klinické a patologické TNM klasifikace u karcinomu orofaryngu - vliv na prognózu a výsledky lécby.

BACKGROUND: The aim of this study was to determine the percentage of discordance between clinical (c) and pathological (p) TNM classifications in cases of oropharyngeal carcinoma and whether it influences recurrence rate and prognosis of primary disease. MATERIALS AND METHODS: Fifty-one patients with oropharyngeal carcinoma who underwent primary surgical treatment were included in this retrospective study. Clinical TNM was determined on the basis of clinical examinations and imaging (US, CT, or MRI), and pathological TNM was determined by a histopathologist (analysis of the primary tumor and neck lymph nodes). Concordance and discordance were statistically evaluated. As potential prognostic factors, we statistically analyzed tumor recurrence, specific and nonspecific patient survival, patient age, extent of primary tumor, lymph node positivity, number of removed lymph nodes, and positive tumor margins. RESULTS: Discordance in the TNM classification was found in 27 cases. Disease-free survival was shorter in patients with discordance in T, and this was statistically significant (p = 0.034). Six patients died due to primary disease (11.8%). Disease-specific survival was at the limit of statistical significance (p = 0.069). CONCLUSIONS: Discordance between clinical and pathological TNM classifications was 52.9% patients with oropharyngeal carcinoma. Discordance in T is a potential prognostic factor. Improvement in cancer treatment to some extent relies on preoperative staging and should influence the decision about whether or not to administer adjuvant oncological treatment.

Biologic importance and prognostic significance of selected clinicopathological parameters in patients with oral and oropharyngeal squamous cell carcinoma, with emphasis on smoking, protein p16(INK4a) expression, and HPV status.

The aim of this study is to evaluate the biologic importance and prognostic significance of selected clinicopathological parameters in patients with oral (OSCC) and oropharyngeal (OPSCC) squamous cell carcinoma, with emphasis on smoking, protein p16(INK4a) (p16) expression, and human papillomavirus (HPV) status.The study sample consisted of 48 patients with OSCC and 44 patients with OPSCC. Half of the patients were nonsmokers and the other half were gender-, age- and tumor localization-matched smokers. p16 expression was detected in 17/48 (35 %) OSCCs and in 36/44 (82 %) OPSCCs and HPV DNA was present in 7/48 (15 %) OSCCs and in 35/44 (80 %) OPSCCs. The sensitivity and specificity of p16 expression for HPV DNA presence were 0.74 and 0.88, respectively. The OPSCCs were more frequently basaloid (p < 0.001) while the OSCCs were more frequently conventional (p < 0.000001). The OSCCs were more likely to recur locally and to be the cause of death (p = 0.009 in both parameters).The HPV-positive tumors were more frequently localized in oropharynx, were basaloid SCCs and were p16- and HPV-positive (p < 0.000001 in all 4 parameters). The HPV-negative tumors were more frequently localized in oral cavity (p < 0.000001), more frequently asociated with local, regional and locoregional recurence (p = 0.011, p = 0.019 and p = 0.030, respectively) and with tumor-related death (p = 0.003). There was no significant difference with regard to smoking history (p > 0.05). The survival of patients with HPV-positive tumors was significantly longer (median 112 months; 95% CI 54 - 112 months) than that of patients with HPV-negative tumors (median 17 months; 95% CI 12 - 39 months) (p < 0.001). The HPV status of OSCC/OPSCC is an important biological and prognostic parameter and should be examined in all cases, using PCR or immunohistochemical detection of surrogate marker p16. Smoking itself does not seem to be an important prognostic factor.

Expression of galectin-3, cytokeratin 19, neural cell adhesion molecule and E-cadhedrin in certain variants of papillary thyroid carcinoma.

The immunohistochemical expression of galectin-3 (Gal3), cytokeratin 19 (CK19), neural cell adhesion molecule (NCAM), and E-cadherin (Ecad) was evaluated to assess their use in diagnostics of papillary thyroid carcinoma (PTC). A total of 84 PTCs - 36 classical variants (cPTCs), 26 follicular variants (fPTCs), and 22 papillary microcarcinomas (mPTCs) were studied. Expression of Gal3 was found in 36/36 (100%) cPTCs, 24/26 (92%) fPTCs, and 19/22 (86%) mPTCs. CK19 expression was detected in 34/36 (94%) cPTCs, 17/26 (65%) fPTCs, and 13/22 (59%) mPTCs. Expression of NCAM was seen in 5/36 (14%) cPTCs, 7/26 (27%) fPTCs, and 9/22 (41%) mPTCs. Ecad expression was found in 23/36 (64%) cPTCs, 17/26 (65%) fPTCs, and 18/22 (82%) mPTCs. A significant difference in CK19 expression was observed between cPTC and both fPTC and mPTC (p < 0.001). Furthermore, extrathyroid tumor spread significantly correlated with both level of CK19 expression and loss of Ecad expression (p = 0.001, p = 0.04). Our findings suggest that Gal3 and CK19 are useful markers for PTC, although decreased CK19 expression in mPTC and fPTC must be considered. Furthermore, CK19 and Ecad may play a role in extrathyroid tumor spread.

Intraoperative Thermography of the Electrical Stimulation Mapping: A Safety Control Study.

A standard procedure for continuous intraoperative monitoring of the integrity of the corticospinal tracts by eliciting muscle responses is the electric stimulation mapping (ESM). However, standard ESM protocols are ineffective in 20% of young children. We have developed a novel, highly efficient paradigm consisting of short-time burst (30 ms) of high frequency (500 Hz) and high peak current (≤100 mA), which may cause local tissue overheating. The presented safety control study was therefore designed. The infrared thermography camera captured to-be-resected cortex of 13 patients in vivo during ESM. Thermograms were image processed to reveal discrete ESM thermal effect of currents from 10 to 100 mA. Peak 100 mA currents induced a maximal increase in temperature of 3.1 °C, 1.23±0.72 °C in average. The warming correlated with stimulating electrode resistance ( ). The measurement uncertainty was estimated ± 1.01 ºC for the most skeptical conditions. The histopathological evaluation of stimulated tissue (performed in all cases) did not show any destructive changes. Our study demonstrates the ability of the thermographic camera to measure the discrete thermal effect of the ESM. The results provide evidence for the safety of the proposed protocol for full range currents with minimal risk of brain tissue damage.

Univariate and multivariate models for the prediction of life-threatening complications in 586 cases of deep neck space infections: retrospective multi-institutional study.

OBJECTIVE: To identify deep neck infection factors related to life-threatening complications. METHODS: This retrospective multi-institutional study comprised 586 patients treated for deep neck infections between 2002 and 2012. The statistical significance of variables associated with life-threatening complications of deep neck infections was assessed. RESULTS: During treatment, life-threatening complications occurred in 60 out of 586 cases. On univariate analysis, life-threatening complications were linked to: dyspnoea, neck movement disturbance and dysphonia (all p < 0.001); and parapharyngeal, anterior visceral or pretracheal deep neck involvement (all p < 0.002). Aetiology was significantly linked to tonsils (p < 0.001). Regarding infection type, fasciitis was a significant factor (p < 0.001). Candida albicans was a significant bacterial culture (p < 0.001). A multivariate step-wise model disclosed fewer significant variables: retropharyngeal space (p = 0.005) and major blood vessels area (p = 0.006) involvement, and bacterial culture C albicans (p < 0.001). CONCLUSION: It can be predicted that patients with deep neck infections, with neck movement disturbances, dysphonia, dyspnoea and swelling of the external neck, accompanied by severe pain, and inflammatory changes in the retropharyngeal space and large vessel areas, with culture-confirmed infection of C albicans, are likely to develop life-threatening complications.

[Anaplastic carcinoma of the thyroid gland with chondrosarcomatous component]. / Anaplastický karcinom stítné zlázy s chondrosarkomatózní komponentou.

The case of an 83-year-old female with a history of a two months enlarging goiter is presented. Clinically, a firm goiter with fixation to surrounding soft tissues was found. Fine needle aspiration cytology was performed with the conclusion of a sarcomatoid variant of anaplastic carcinoma of the thyroid gland; biopsy was recommended. The patient was operated on and died six months after operation with metastatic dissemination in lymphatic nodes and lungs. Histologically, an invasive high-grade tumor composed of irregular, sometimes bizarre spindled or polygonal cells intermingled with foci of chondroid tissue was seen. The cartilage comprised lobularly arranged chondrocytes with irregular nuclei; bi- or multinucleated chondrocytes were present as well. The diagnosis of thyroid anaplastic carcinoma with chondrosarcomatous component was established. Differential diagnostics of this tumour is discussed.

Bacteriology of deep neck infections: analysis of 634 patients.

BACKGROUND: The aim of this study was to review the bacteriology of deep neck infections (DNI) and identify the factors that influence the incidence of causative bacteria. METHODS: A retrospective analysis of 634 patients with DNI was performed. Statistical analysis was used to compare the incidence of common pathogens in various conditions such as age of the patients, aetiology and associated diabetes mellitus. RESULTS: Bacteria were isolated in 514 cultures (81%). Aerobic bacteria were isolated from 246 cultures (39%) and anaerobic bacteria from 61 cultures (10%). Both aerobic and anaerobic bacteria were isolated from 207 cultures (32%). The most common aerobic bacteria were Streptococcus pyogenes (41%) and Staphylococcus aureus (32%). The most common anaerobic bacteria were Peptostreptococcus species (28%), followed by Prevotela species (8%) and Proprionibacterium species (7%). The incidence of anaerobic bacteria was higher in adults, in patients with infections of dental origin and in non-diabetic patients. CONCLUSIONS: The bacteriology of DNI is polymicrobial, including both aerobic and anaerobic bacteria. The incidence of anaerobic bacteria is higher in adults, in patients with infections of dental origin and in non-diabetic patients.

Acute purulent thyroiditis with retropharyngeal and retrotracheal abscesses.

An unusual case of acute purulent thyroiditis in a 45-year-old man forming a large abscess in the left lobe of the thyroid gland is described. It perforated the capsule at the posterior wall of the thyroid, causing extensive retropharyngeal and retrotracheal abscesses. The patient was treated with broad-spectrum antibiotics and surgical excision of the infected tissues. He has remained well one year after the operation.