Oncocytic papillary cystadenoma of the larynx: comparative study of ten cases and review of the literature.

OBJECTIVE: Oncocytic papillary cystadenomas (OPCs) of the larynx are rare benign cystic lesions that usually present as supraglottic masses arising from the laryngeal ventricles. OPCs are found in patients older than 60 years, with a female predominance. Symptoms vary from asymptomatic to hoarseness, dyspnea, and dysphagia; often, they mimic a laryngocele. The treatment is surgical. Diagnosis is based on histopathologic examination. MATERIALS AND METHODS: Surgical records for laryngeal masses diagnosed between 2005 and 2020 were searched retrospectively. RESULTS: Ten patients were identified and included in the study. OPCs predominantly occurred in women (9/10), and the mean age at presentation was 73 years. Most patients (8/10) presented with hoarseness and were smokers. OPCs were localized in the ventricle in eight out of ten patients. Surgical treatment was performed in all cases, mostly using transoral endolaryngeal approach (9/10). Histopathologic examination revealed oncocytic cyst or oncocytic papillary cystadenoma (the former term being the older synonym for OPC). CONCLUSION: OPCs present a separate clinicopathologic entity, distinct from other cystic laryngeal lesions. They have a characteristic location, age and sex group, microscopic appearance, and potential for local recurrence.

Microsurgical versus endoscopic surgery for non-functioning pituitary adenomas: a retrospective study.

AIM: To compare microsurgical technique (mTSS) and endoscopic technique (eTSS) in the treatment of non-functioning pituitary adenomas (NFPAs). METHODS: We retrospectively evaluated the charts of 50 patients who underwent either mTSS or eTSS for NFPA in the Department of Neurosurgery, University Hospital Hradec Kralove from 2013 to 2019. We enrolled all patients who were not treated by postoperative adjuvant radiotherapy and who underwent at least two regular postoperative magnetic resonance imaging (MRI) tests. We compared the groups in terms of the extent of resection, surgery duration, blood loss, complication rate, overall clinical effect on the endocrinological and ophthalmological deficit, and postoperative growth pattern of the residual tumor mass. RESULTS: The mTSS group had significantly shorter surgical time (75 min vs 127 min, P<0.001) and lower perioperative blood loss (156 mL vs 256 mL, P=0.027). The groups did not significantly differ in the extent of resection, overall clinical or hormonal effect, and the complication rate. The extent of resection did not correlate with tumor consistency, while the tumor growth rate did not correlate with age or Ki-67 expression. CONCLUSIONS: There was no major difference between the approaches in surgery radicality or safeness. However, eTSS remains the method of choice due to its potentially higher postoperative preservation of hormonal functions.

Medically induced CSF rhinorrhea following treatment of macroprolactinoma: case series and literature review.

PURPOSE: Although several reports have addressed cerebrospinal fluid (CSF) rhinorrhea following dopamine agonist (DA) therapy of macroprolactinomas, further study is warranted for this relatively uncommon entity. Toward this aim, our retrospective series and review of literature further clarifies recommendations in treatment of this rare problem. METHODS: We retrospectively reviewed all macroprolactinoma cases in our hospital for a 15-year period. Our systematic search of PubMed identified original articles and reviews of all macroprolactinoma cases with an associated medication-induced CSF leak. RESULTS: Five patients with drug-induced CSF leak were identified; four of these patients received cabergoline therapy an average of 6 weeks before the onset of rhinorrhea and then underwent surgical repair of the CSF leak. Of 35 published studies included, we identified 60 patients with medication-induced CSF leak. Medical therapy included bromocriptine in 34 patients, cabergoline in 21 patients, and use of both DAs in two patients. Three cases did include complete diagnostic and treatment data. Median time from initiation of the DA treatment to occurrence of rhinorrhea was 6 weeks. For CSF rhinorrhea, 49 patients underwent surgical repair (38 by the transnasal approach) and seven patients were treated nonoperatively. CONCLUSION: Baseline skull base erosion in macroprolactinomas in combination with subsequent tumor shrinkage induced by DA therapy may result in spontaneous CSF rhinorrhea. Therefore, such patients should be advised about and monitored for this potential setback. Once CSF leak is diagnosed, prompt treatment must be carried out to avoid infectious complications. Transnasal surgery appears the most effective therapeutic approach.

Detection of Cervical Lymph Node Micrometastases in Patients with Squamous Cell Carcinoma of the Oral Cavity, Pharynx and Larynx.

BACKGROUND: The goal of this prospective study was to determine the frequency of micrometastases in patients with squamous cell carcinoma (SCC) of the oral cavity, pharynx and larynx in whom elective neck dissection was indicated (cN0). PATIENTS AND METHODS: A total of 12 patients (10 males and 2 females) were enrolled in the study. The age ranged 42-73 years (median 62 years). Elective neck dissection was performed in all patients (8 ipsilateral, 4 bilateral) and a total of 256 lymph nodes were removed and sent for microscopic examination. RESULTS: The presence of tumor cells in cervical lymph nodes was found in 5/12 (42%) patients. Micrometastases of SCC were found in two patients and isolated tumor cells (ITC) in two other patients. In the remaining one patient with oropharyngeal SCC, a micrometastasis of papillary thyroid carcinoma (PTC) was detected. Positive lymph nodes were localized in level II in three patients with SCC of larynx, hypopharynx and tongue base, respectively, in level I in one patient with SCC of oral tongue and in level III in one patient with PTC. CONCLUSION: Our results indicate that SCC of head and neck has a high potential for creating micrometastases which frequency is higher compared to clinically detected macrometastases. Therefore, elective neck dissection or radiotherapy of the neck should be considered in patients with high risk of occult metastases or micrometastases.

Deep neck infections: risk factors for mediastinal extension.

The goal of the study was to find out the risk factors for the development of mediastinitis in patients with deep neck infections (DNI) and describe the differences in symptoms and clinical image between uncomplicated DNI and infections with mediastinal spread. Our study represents the retrospective analysis of 634 patients with DNI. The file was divided into two groups. There were 619 patients (97.6%) in the first group who had an uncomplicated course of DNI without spread of infection into mediastinum (DNI group). The second group included 15 patients (2.4%) with descending mediastinitis as a complication of DNI (mediastinitis group). The most frequent comorbidities were cardiac and pulmonary diseases, which were more frequent in the mediastinitis group comparing to DNI group. Dental origin of the infection was more frequent in DNI group than in the mediastinitis group. On the other hand, tonsillar origin of the infection was more frequent in the mediastinitis group than in DNI group. In both mediastinitis and DNI groups, the typical presenting symptoms were pain, oedema and dysphagia. Furthermore, dysphagia, dyspnoea, dysphonia and restriction of neck movements were more significant in the mediastinitis group than in DNI group. The incidence of airway obstruction, sepsis, pneumonia and death was significantly higher in the mediastinitis group than in DNI group. Due to our results, the predisposing factors for mediastinal extension of DNI are cardiovascular and pulmonary diseases. Mediastinitis is associated with higher morbidity and mortality than DNI. The most common complications are airway obstruction, pneumonia and sepsis.

Tissue contexture determines the pattern and density of tumor-infiltrating immune cells in HPV-associated squamous cell carcinomas of oropharynx and uterine cervix.

The profile of the antitumor immune response is an important factor determining patient clinical outcome. However, the influence of the tissue contexture on the composition of the tumor microenvironments of virally induced tumors is not clearly understood. Therefore, we analyzed the immune landscape of two HPV-associated malignancies: oropharyngeal squamous cell carcinoma (OPSCC) and squamous cell carcinoma of uterine cervix (CESC). We employed multiplex immunohistochemistry and immunofluorescence to evaluate the density and spatial distribution of immune cells in retrospective cohorts of OPSCC and CESC patients. This approach was complemented by transcriptomic analysis of purified primary tumor cells and in silico analysis of publicly available RNA sequencing data. Transcriptomic analysis showed similar immune profiles in OPSCC and CESC samples. Interestingly, immunostaining of OPSCC tissues revealed high densities of immune cells in both tumor stroma and tumor epithelium, whereas CESC samples were mainly characterized by the lack of immune cells in the tumor epithelium. However, in contrast to other immune cell populations, polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) were abundant in both segments of CESC samples and CESC-derived tumor cells expressed markedly higher levels of the PMN-MDSC chemoattractants CXCL1, CXCL5, and CXCL6 than OPSCC tumor cells. Taken together, despite their having the same etiologic agent, the immune infiltration pattern significantly differs between OPSCC and CESC, with a noticeable shift toward prominent MDSC infiltration in the latter. Our data thus present a rationale for a diverse approach to targeted therapy in patients with HPV-associated tumors of different tissue origins.

Oncocytic Schneiderian papilloma of frontal sinus.

Oncocytic Schneiderian papilloma (OSP) is one of the three morphologically distinct tumors that arise from Schneiderian membrane (the others include exophytic papilloma and inverted papilloma). OSP almost always occurs unilaterally in the paranasal sinuses, usually in the maxillary sinus, ethmoid cells or sphenoid sinus. We report a case of a 64-year-old woman with OSP arising from the left frontal sinus. In the report herein, we describe an OSP originating in the region of frontal sinus, which, to the best of our knowledge, represents the first documented example in English literature of OSP developing in this anatomical site.

The Need for Emphasis on Intracranial Hypertension Management in Spontaneous Skull Base Meningoencephaloceles.

OBJECTIVE: To provide an analysis of patients with spontaneous skull base meningoencephaloceles (MECs) to determine whether definitive surgical treatment requires management of elevated intracranial pressure (ICP). METHODS: Data of 10 subjects with spontaneous MECs were collected and retrospectively evaluated. Measurement of ICP, prior interventions, treatment with acetazolamide, and characteristics of long-term elevated ICP, among others, were analyzed. Our own indications for cerebrospinal fluid (CSF) diversion and use of postoperative external lumbar drain were analyzed as well. RESULTS: The sphenoid region was the most common location of MECs. CSF leak was diagnosed in all subjects. The most common graphical signs of elevated ICP were empty sella and arachnoid pits, both of which were present in 90% of cases. Lumbar puncture with opening pressure measurement was performed in 7 patients. Ventriculoperitoneal shunt insertion was indicated in 4 cases before skull base repair and in 2 cases after skull base repair. Two postoperative CSF leaks were managed with external lumbar drain and subsequent shunt installation. CONCLUSIONS: Spontaneous MECs are often associated with CSF leak. ICP assessment should be a standard of care to ensure successful operative repair of MECs. Insertion of a CSF diversion device must be considered where direct or indirect signs of intracranial hypertension are present.

Optical coherence tomography and visual evoked potentials in evaluation of optic chiasm decompression.

Chiasmal compression is a known cause of visual impairment, often leading to surgical decompression of the optic chiasm (OC). A prospective study was held at University Hospital in Hradec Králové to explore sensitivity of optical coherence tomography (OCT) and visual evoked potentials (VEPs) to OC compression and eventual changes after a decompression. 16 patients with OC compression, caused by different sellar pathologies, were included. The main inclusion criterion was the indication for decompressive surgery. Visual acuity (VA), visual field (VF), retinal nerve fibre layer (RNFL) and ganglion cell layer (GCL) thickness, and peak time and amplitude of pattern-reversal (P-VEPs) and motion-onset VEPs (M-VEPs) were measured pre- and postoperatively. The degree of OC compression was determined on preoperative magnetic resonance imaging. For M-VEPs, there was a significant postoperative shortening of the peak time (N160) (p < 0.05). P100 peak time and its amplitude did not change significantly. The M-VEPs N160 amplitude showed a close relationship to the VF improvement. Thinner preoperative RNFL does not present a statistically important limiting factor for better functional outcomes. The morphological status of the sellar region should be taken into consideration when one evaluates the chiasmal syndrome. M-VEPs enable detection of functional changes in the visual pathway better than P-VEPs.

Chronic sclerosing sialadenitis as one of the immunoglobulin G4-related diseases: a clinicopathological study of six cases from Central Europe.

AIMS: Chronic sclerosing sialadenitis (CSS) has been proposed recently to be a member of the group of IgG4-related diseases in Japanese and American series. The aim of our study was to validate these results in a cohort of European patients. METHODS AND RESULTS: Our CSS series included four females and two males, aged 32-76 years, all presenting with unilateral swelling of submandibular gland. Microscopically, all CSS-cases showed similar morphology with preservation of lobular architecture accentuated by cellular fibrous bands, dense lymphoplasmacytic inflammation and varied acinar atrophy. Ductal lymphocytes were detected in three cases. In five cases, the presence of intraductal secretory material accompanied by parenchymal neutrophils was observed. Obliterative phlebitis was seen in three cases. The inflammatory infiltrate was composed of T and B lymphocytes and polyclonal plasma cells. The median number of IgG-positive plasma cells per high-power field (HPF) was 157; median number of IgG4-positive plasma cells per HPF was 133. Median value of the IgG4:IgG ratio was 0.84. CONCLUSIONS: This is the first European series to demonstrate that CSS belongs to the family of IgG4-related disease. Unlike previous studies, in CSS we found rarely described ductal lymphocytes and parenchymal neutrophils. CSS displays consistent morphology with increased numbers of IgG4-positive plasma cells, and should be regarded as a member of the IgG4-related disease group.

MicroRNA Deregulation in Papillary Thyroid Cancer and its Relationship With BRAF V600E Mutation.

BACKGROUND: MicroRNAs (miRNAs) are non-coding regulatory molecules 18-25 nucleotides in length that act as post-transcriptional regulators of gene expression. MiRNAs affect various biological processes including carcinogenesis. Deregulation of miRNAa expression has been described in a variety of tumors including papillary thyroid carcinoma (PTC). The aim of the present study was to investigate the role of selected miRNAs in PTC and find associations between miRNA expression and the BRAF (V600E) mutation. MATERIALS AND METHODS: The study group comprised a total of 62 patients with surgically treated PTC. The control group consisted of 30 patients with nodular goitre that were surgically treated in the same time period. The expression status of miR-146b, miR-181a, miR-187, miR-221 and miR-222 was determined using quantitative real-time PCR. BRAF mutation analysis was performed by PCR with reverse hybridization. RESULTS: MiR-146b, miR-181a, miR-187, miR-221 and miR-222 were up-regulated in PTC compared to normal thyroid gland tissue of the same patient. MiR-146b, miR-187, miR-221 and miR-222 were also up-regulated in PTC compared to nodular goitre. The recurrent tumors were statistically significantly associated with up-regulation of miR-221. The mutation V600E of BRAF gene was significantly associated with up-regulation of miR-146b and with down-regulation of miR-187. CONCLUSION: Over-expression of selected miRNAs in PTC compared to normal thyroid gland tissue and nodular goitre was found. Moreover, miR-221 may serve as a prognostic marker as its over-expression was significantly associated with recurrent tumors.

Tonsillar origin of deep neck infection as a negative prognostic factor for developing complications.

<b>Aim:</b> The aim of this study was to compare the odontogenic and tonsillar origins of deep neck infection (DNI) as a negative prognostic factor for developing complications. </br></br> <b>Methods:</b> This was a retrospective study of 544 patients with tonsillar and odontogenic origins of DNI treated between 2006 and 2015 at 6 ENT Departments and Departments of Oral and Maxillofacial Surgery. Complications from DNI (descending mediastinitis, sepsis, thrombosis of the internal jugular vein, pneumonia, and pleuritis) were evaluated in both groups and compared. Associated comorbidities (cardiovascular involvement, hepatopathy, diabetes mellitus respiratory involvement, gastroduodenal involvement) were reviewed. </br></br> <b>Results:</b> Five hundred and forty-four patients were analyzed; 350/544 males (64.3%) and 19/544 females (35.7%). There were 505/544 cases (92.8%) with an odontogenic origin and 39/544 cases (7.2%) with a tonsillar origin of DNI. Complications occurred more frequently in the group with tonsillar origin of DNI (P < 0.001). There was no difference in diabetes mellitus between the two groups. </br></br> <b>Conclusions:</b> Currently, the tonsillar origin of DNI occurs much less frequently; nevertheless, it carries a much higher risk of developing complications than cases with an odontogenic origin. We recommend that these potentially high-risk patients with a tonsillar origin of deep neck infections should be more closely monitored.

Rhinogenic Orbital Inflammation - What Has Changed over the Past 50 Years?

INTRODUCTION: The purpose of the study was to compare the incidence, diagnostics, and treatment of rhinogenic inflammatory complications over the past 50 years. MATERIAL AND METHODS: Retrospective study of 292 patients of ENT department, University hospital: Group A treated from 1966 to 1995, Group B treated from 1996 to 2015. RESULTS: Preseptal inflammation was the most common type (73% vs. 74%), followed by subperiosteal abscess (21% vs. 20%). Surgery was indicated in 35% vs. 37% of the patients (p = 0.434). The most commonly used surgical approach was the external route (80%) in Group A and endoscopic endonasal surgery (60%) or a combination of endoscopic surgery of the paranasal sinuses and external orbitotomy (30%) in Group B (p < 0.001). The percentage of reoperations was 13% vs. 14%. In cases of revision surgery, the orbit was always treated using the external surgical approach. Complete recovery was achieved in 92% and 98.5% of the patients belonging to Group A and B, respectively (p = 0.622). CONCLUSION: Nowadays, the endoscopic endonasal approach is the most frequently used surgical technique for paranasal sinuses. The technique used to treat the orbital complication itself depends on several factors. Nowadays, the endoscopic approach is preferred. The external approach can be considered in the case of recurrent or persistent abscesses, especially if they are located in the upper or the lateral part of the orbit.

Pretreatment Serum Levels of Soluble Cytokeratin Fragments (Cyfra 21-1, TPS, MonoTotal) in Relation to Clinical and Pathobiological Aspects of Head and Neck Squamous Cell Carcinomas.

BACKGROUND/AIM: The aim of this study was to analyze the pretreatment cytokeratin serum levels in head and neck squamous cell carcinoma (HNSCC) by three assays in relation to selected clinicopathological characteristics in an effort to find diagnostic/prognostic biomarkers for HNSCC and determine the best assay. PATIENTS AND METHODS: In total, 46 patients with HNSCC with different subsite (oropharyngeal-21 cases, hypopharyngeal-4 and laryngeal-21) were included in this prospective study. MonoTotal, Cyfra 21-1, and TPS radioimmunoassay kits were used to analyze cytokeratin fragments serum levels. RESULTS: Statistically significant differences in serum levels of TPS and Cyfra 21-1 were found between low (stage I-II)- and high-stage (stage III-IV) tumors (p=0.0057; p=0.0138 respectively). Cyfra21-1 assay showed significant differences between tumors of different sites with prominent elevation being found in oropharyngeal carcinomas and between patients with p16 positive and p16 negative HNSCC (p=0.0242), being elevated in p16 positive tumors. CONCLUSION: The present study is the first to compare cytokeratin serum levels between various subgroups of HNSCC using three different assays. Cyfra 21-1 seems to be the most useful for clinical practice. The relation between elevated Cyfra 21-1 serum levels and p16 expression requires further investigation.

Tumor-infiltrating B cells affect the progression of oropharyngeal squamous cell carcinoma via cell-to-cell interactions with CD8+ T cells.

BACKGROUND: Standard treatment of oropharyngeal squamous cell carcinoma (OPSCC) is associated with high morbidity, whereas immunotherapeutic approaches using PD-1:PD-L1 checkpoint blockade only show moderate response rates in OPSCC patients. Therefore, a better stratification of patients and the development of novel therapeutic protocols are crucially needed. The importance of tumor-infiltrating B cells (TIL-Bs) in shaping antitumor immunity remains unclear; therefore, we analyzed frequency, phenotype, prognostic value and possible roles of TIL-Bs in OPSCC. METHODS: We utilized transcriptomic analysis of immune response-related genes in 18 OPSCC samples with respect to human papillomavirus (HPV) status. The density and localization of CD20+, CD8+ and DC-LAMP+ cells were subsequently analyzed in 72 tissue sections of primary OPSCC samples in relation to patients' prognosis. The immunohistochemical approach was supplemented by flow cytometry-based analysis of phenotype and functionality of TIL-Bs in freshly resected primary OPSCC tissues. RESULTS: We observed significantly higher expression of B cell-related genes and higher densities of CD20+ B cells in HPV-associated OPSCC samples. Interestingly, CD20+ TIL-Bs and CD8+ T cells formed non-organized aggregates with interacting cells within the tumor tissue. The densities of both intraepithelial CD20+ B cells and B cell/CD8+ T cell interactions showed prognostic significance, which surpassed HPV positivity and CD8+ TIL density in stratification of OPSCC patients. High density of TIL-Bs was associated with an activated B cell phenotype, high CXCL9 production and high levels of tumor-infiltrating CD8+ T cells. Importantly, the abundance of direct B cell/CD8+ T cell interactions positively correlated with the frequency of HPV16-specific CD8+ T cells, whereas the absence of B cells in tumor-derived cell cultures markedly reduced CD8+ T cell survival. CONCLUSIONS: Our results indicate that high abundance of TIL-Bs and high density of direct B cell/CD8+ T cell interactions can predict patients with excellent prognosis, who would benefit from less invasive treatment. We propose that in extensively infiltrated tumors, TIL-Bs might recruit CD8+ T cells via CXCL9 and due to a highly activated phenotype contribute by secondary costimulation to the maintenance of CD8+ T cells in the tumor microenvironment.

High-risk human papillomavirus infection and p16INK4a protein expression in laryngeal lesions.

A total of 88 samples of laryngeal lesions (23 vocal cord nodules (VCNs), 23 papillomas (PAs), 18 dysplasias (DYs), and 24 carcinomas (CAs)) were analyzed for p16INK4a protein (p16) expression by immunohistochemistry and for high-risk human papillomavirus (HR-HPV) infection using chromogene in situ hybridization (CISH) and polymerase chain reaction (PCR). The series comprised 62 males and 26 females, aged 1-87 years (median 55 years). p16 expression was detected in 2 of 23 (9%) VCNs, 18 of 23 (78%) PAs, 9 of 18 (50%) DYs, and 14 of 24 (58%) CAs. Using CISH, HR-HPV DNA was detected in 3 of 23 (13%) VCNs, in 19 of 23 (83%) PAs, in 12 of 18 (67%) DYs, and in 14 of 24 (58%) CAs. HR-HPV DNA was found in six of nine (67%) PAs by PCR. A statistically significant difference in p16 expression and HR-HPV DNA presence detected by CISH was observed between VCNs and PAs (p<0.000001). The sensitivity and specificity of p16 expression for HR-HPV DNA presence detected by CISH was 0.612 and 0.773, respectively. Our study confirms a potential role of HR-HPV infection not only in the pathogenesis of malignant, but also in benign laryngeal lesions.

Unusual manifestation of anaplastic thyroid cancer.

INTRODUCTION: The authors present a rare case of a patient with symptoms consistent with retropharyngeal abscess. The diagnosis of anaplastic thyroid cancer was made after surgery and subsequent histological examination. CASE REPORT: An 80-year-old woman was referred to Dpt. of Otolaryngology, Head and Neck Surgery, Charles University Medicine Faculty, Teaching Hospital in Hradec Králové with odynophagia and pain in the left side of the neck. The patient had pronounced swelling of the left side of her neck. We could also see swelling of the posterior pharyngeal wall, more pronounced on the left side. Inflammation markers were markedly elevated. Administration of antibiotics intravenously (amoxicillin combined with clavulan acid and gentamicin) was started. A computer tomography investigation (CT) was performed and a retropharyngeal abscess was found. The existence of a tumour was considered as well. An acute endoscopic examination and a puncture of the retropharyngeal space at the site of the swelling were performed, but no pus or any other liquid was found. On the sixth day of hospitalization a second CT scan was performed. As the retropharyngeal mass was still present along with continually elevated inflammatory markers, surgical revision of the retropharyngeal space from an external approach was performed. No abscess formation was found. During the surgery, retropharyngeal lymph nodes were removed for histological examination. The histological examination of the lymph nodes identified metastasis of anaplastic thyroid cancer. CONCLUSIONS: The differential diagnosis of diseases affecting deep neck structures can be very difficult. Symptoms of inflammation dominating in the clinical picture do not exclude the possibility of malignancy. The most relevant imaging examination seems to be contrast enhanced computer tomography or magnetic resonance imaging.

Serum Levels of IGF-1 and IGFBP-3 in Relation to Clinical and Pathobiological Aspects of Head and Neck Squamous Cell Carcinomas.

BACKGROUND/AIM: Head and neck squamous cell carcinoma (HNSCC) includes tumors of various anatomical sites sharing multifactorial etiopathogenesis and generally dismal response to conventional treatment. The objective of this study was to determine the clinical significance of serum levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) in HNSCC. PATIENTS AND METHODS: A total of 46 patients, with histologically-confirmed diagnosis of HNSCC (21 oropharyngeal, 21 laryngeal, and 4 hypopharyngeal cancers) were enrolled in this study. IGF-1 and IGFBP-3 serum levels were measured by an immunoradiometric assay using commercial kits. The adjustment of serum levels at 60 years of age was performed. RESULTS: Significant differences were found in IGF-1 serum concentrations between patients with p16 positive and p16 negative HNSCC (p=0.0062), with higher IGF-1 levels in p16 positive tumors, between low-grade and high-grade cancers (p=0.0323) only in larynx, with elevated IGF-1 concentrations associated with high-grade and between recurrent and non-recurrent HNSCC (p=0.0354), with lower IGF-1 levels in recurrent tumors. CONCLUSION: The conflicting results of this study may reflect some abnormality of IGF axis regulation in HNSCC, as well as the influence of other etiological factors (e.g. smoking, HPV infection).

SMARCB1/INI1-deficient sinonasal carcinoma shows methylation of RASSF1 gene: A clinicopathological, immunohistochemical and molecular genetic study of a recently described entity.

The aim of the study was detailed clinicopathological investigation of SMARCB1/INI1-deficient sinonasal carcinomas, including molecular genetic analysis of mutational status and DNA methylation of selected protooncogenes and tumor suppressor genes by means of next generation sequencing (NGS) and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). A total of 4/56 (7%) cases of SMARCB1/INI1-deficient carcinomas were detected among 56 sinonasal carcinomas diagnosed over a 19year period using immunohistochemical screening. The series comprised 3 males and 1 female, aged 27-76 years (median 64 years). All tumors arose in the nasal cavity. Three neoplasms were diagnosed in advanced stage pT4. During the follow-up period (range 14-111 months (median 72 months)), three tumors recurred locally, but none of the patients developed regional or distant metastases. Ultimately, two patients died due to the tumor. Microscopically, all tumors consisted of infiltrating nests of polygonal basaloid cells with a variable component of rhabdoid cells with eosinophilic cytoplasm. Immunohistochemically, there was almost diffuse expression of cytokeratins (CK), p16, p40 and p63 in all cases, while expression of CK5/6, CK7 and vimentin was only focal or absent. The detection of NUT gave negative results. In three cases, the absence of SMARCB1/INI1 expression was due to deletion of SMARCB1/INI1 gene. Methylation of SMARCB1/INI1 gene was not found. One tumor harbored HPV18 E6/E7 mRNA. All 12 genes (BRAF, BRCA1, BRCA2, KIT, EGFR, KRAS, NRAS, PDGFRA, PIK3CA, PTEN, RET, and ROS1) tested for mutations using NGS were wild-type. Regarding DNA methylation, all four SMARCB1/INI1-deficient tumors showed methylation of RASSF1 gene by means of MS-MLPA. There was a statistically significant difference in RASSF1 gene methylation between SMARCB1/INI1-deficient and SMARCB1/INI1-positive tumors (p=0.0095). All other examined genes (ATM, BRCA1, BRCA2, CADM1, CASP8, CD44, CDKN1B, CDKN2A, CDKN2B, CHFR, DAPK1, ESR1, FHIT, GSTP1, HIC1, KLLN, MLH1a, MLH1b, RARB, and VLH) were unmethylated. In summary, we described four cases of SMARCB1/INI1-deficient sinonasal carcinoma with detailed clinicopathological data indicating that these tumors can be regarded as a distinct entity with aggressive behaviour. For the first time, we performed analysis of DNA methylation in SMARCB1/INI1-deficient sinonasal carcinomas, reporting on significantly higher methylation of RASSF1 gene in this neoplasm.

Nasal symptomatology, obstruction, and paranasal sinus opacity in patients with chronic obstructive pulmonary disease.

CONCLUSION: Patients with chronic obstructive pulmonary disease (COPD) more frequently suffer from nasal symptoms as well as upper respiratory tract obstruction compared with the healthy population. OBJECTIVE: The relationship between chronic rhinosinusitis and bronchial asthma has been studied in detail in the past. In recent years, a limited number of authors have also studied involvement of the nose and paranasal sinuses in patients with COPD. METHODS: This was an observational cross-sectional study with subsequent prospective assessment; 42 patients with COPD were included. The control group consisted of 12 healthy subjects. All patients with a history of rhinitis or rhinosinusitis and patients with previous surgery of the nose and sinuses were excluded from the study. Clinical variables evaluated were nasal symptoms (SNAQ-11 questionnaire), nasal endoscopy, nasal patency (active rhinomanometry), and computed tomography of paranasal sinuses. RESULTS: In the COPD group, there was a higher occurrence of nasal symptoms and pathological findings on nasal endoscopy compared with the control group. The overall nasal airflow was higher in the control group (compared with COPD patients) and the overall nasal resistance was higher in the COPD group (compared with controls). Pathological opacity of one or more sinuses was confirmed in 38% of COPD patients.