Bilateral Otic Manifestation of Pseudogout: A Unique Case Report of Conductive Hearing Loss.

Pseudogout is characterized by the deposition of calcium pyrophosphate dihydrate crystals (CPPD), primarily affecting large joints. Extra-articular manifestations, particularly in the head and neck region, are exceedingly rare. We report a unique case of bilateral isolated pseudogout of the middle ear manifesting with progressive conductive hearing loss as the first and only symptom of pseudogout. Otoscopy and CT scan often yield a differential diagnosis that includes tumors or cholesteatoma, necessitating surgery with histopathological examination. The definitive diagnosis is confirmed upon identification of calcium pyrophosphate dihydrate crystals. In most cases, removal of the crystals results in resolution of conductive hearing loss. Laryngoscope, 2024.

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.

An Effect of Cyclosporin A in a Treatment of Temporal Bone Defect Using hBM-MSCs.

Background. The treatment of middle ear cholesteatoma requires surgical treatment and the reconstruction of the temporal bone, which represents an ongoing problem. Otologists have focused on the research of materials allowing an airy middle ear and the preservation of hearing function to reconstruct the temporal bone. Methods. This study evaluated the effect of cyclosporin A (CsA) and a combined biomaterial in the healing process of postoperative temporal bone defects in an animal model. Cultured human Bone Marrow Mesenchymal Stromal Cells (hBM-MSCs) were mixed with hydroxyapatite (Cem-Ostetic®), and subsequently applied as a bone substitute after middle ear surgery, showing that the therapeutic potential of hBM-MSCs associated with bone regeneration and replacement is directly influenced by CsA, confirming that it promotes the survival of MSCs in vivo. Results. The therapeutic efficacy of the combination of MSCs with CsA is greater than the sole application of MSCs in a hydroxyapatite carrier. Conclusion. The reconstruction of a temporal bone defect using hBM-MSCs requires an immunosuppressant to improve the results of treatment.

The Relationship between Bone Conduction Hearing Threshold Shifts after Surgery for Chronic Otitis Media with Cholesteatoma According to STAM, EAONO/JOS, and SAMEO-ATO Classifications.

Background: This study focuses on the hearing threshold for bone conduction (BC) after middle-ear surgery. Methods: A total of 92 patients (120 ears) were treated for newly diagnosed chronic otitis media with cholesteatoma (2013−2018). BC was examined at frequencies of 0.5, 1, 2, and 4 kHz prior to and 1 year after surgery. STAM classification for cholesteatoma location, EAONO/JOS for stage, and surgery according to SAMEO-ATO classification were applied. The bone conduction threshold was compared for individual frequencies in patients with occurrence/absence of cholesteatoma in different locations. Results: For the occurrence of cholesteatoma in the attic (A), a statistically significant difference was found at 4 kHz (p < 0.001), in the supratubal recess (S1) at 4 kHz (p = 0.003), and for the mastoid (M) at 0.5 kHz (p = 0.024), at 1 kHz (p = 0.032), and at 2 kHz (p = 0.039). Conclusions: Cholesteatoma location can influence the post-operative hearing threshold for bone conduction.

Invasive Aspergillus infection of middle ear in a patient treated with secukinumab, methotrexate, and corticosteroids for psoriasis and psoriatic arthritis.

Mucocutaneous mycotic infections are common complications in patients on IL-17 inhibitor therapy. We report a case of a 33-year-old male with severe psoriasis and psoriatic arthritis on secukinumab combined with methotrexate and prednisone with swelling, otorrhea, and pain of the right ear and external auditory canal. Due to progressive hypacusis, a surgical solution was chosen. Tissue samples taken during surgery revealed the presence of Aspergillus fumigatus. Aspergillosis should be suspected in prolonged otorrhea, especially in immunocompromised patients. Without intervention, the disease could be fatal.

Changes of taste perception after stapes surgery: a prospective cohort study.

PURPOSE: Taste perception is often affected after stapes surgery despite effort to preserve chorda tympani nerve. The aim was to examine changes of particular taste qualities and their recovery after operation of otosclerosis. MATERIALS AND METHODS: Taste function was prospectively investigated with a questionnaire and a taste strip test (TST) preoperatively, 3-5 days and 1 year after stapes surgery with the preservation of CTN. RESULTS: In the early postoperative examination, 34/42 patients had a lower TST score, 7/42 decrease of taste in the questionnaire. One year after surgery, 11/42 patients had a lower TST score, 1/42 patients decrease of taste in the questionnaire. The most pronounced decrease in the TST score was in sweet (- 1.76 points, p < 0.001), followed by bitter (- 1.71 points, p < 0.001), salty (- 1.64 points, p < 0.001) and sour taste (- 1.33 points, p < 0.001). The sour taste had a significant lower alteration compared to others. Men had significantly pronounced alteration in salty taste compared to women. The complete recovery was proved in bitter taste. Better recovery in bitter taste was observed in patients younger than 45 years of age. CONCLUSIONS: Gustatory changes after stapes surgery are mostly transient with different impairment and recovery rate for particular taste qualities. A sour taste seems to be relatively resistant to damage. The best recovery rate is in a bitter taste, especially in younger patients.

Diagnostic Value of Narrow Band Imaging in Visualization of Pathological Lesions in Larynx and Hypopharynx.

INTRODUCTION: Narrow Band Imaging (NBI) is an endoscopic optical imaging enhancement technology that improves the contrast of mucosal surface texture and enhances visualization of mucosal and submucosal vasculature. Due to its properties, it can visualize suspected malignant or precancerous lesions earlier than conventional white light endoscopy. The aim of this study was to analyze the benefit of NBI in visualization of precancerous and malignant lesions in preoperative and intraoperative diagnostics and correlation with histopathologic results. METHODS: A total of 589 patients with suspicious laryngeal or hypopharyngeal lesion were investigated using conventional white light endoscopy (WLE) and NBI endoscopy with high-definition TV (HDTV NBI) from 10/2013 to 12/2019. Patients were divided into two groups based on pre-operative NBI examination (group A, 345 patients) and intraoperative NBI examination (group B, 244 patients). All suspicious lesions were graded to 5 types of Ni classification and correlated with histopathologic results. The SPSS version 8.0.4 statistical software package was used for statistical analysis. In diagnosing premalignant and malignant lesions sensitivity, specificity, positive predictive value, and negative predictive value were calculated. RESULTS: The agreement between NBI endoscopy and histopathological analysis in group A was statistically significant (Қ = 0.76, p < 0.001), with a sensitivity of 86.2% (95% IS: 65.4-95.2) and specificity of 90.9% (95% IS: 70.6-94.1). Moreover, in group B was proven almost perfect agreement between NBI and histopathological analysis (Қ = 0.8461, p < 0.001), with a sensitivity of 84.0% (95% IS: 60.2-92.4) and specificity of 96.0% (95% IS: 87.0-99.2). CONCLUSIONS: Based on our results, NBI using the Ni classification has great potential in improving diagnosis of precancerous and malignant lesions and correlates strongly with histopathologic results. It serves as a useful adjunct to white light endoscopy in the diagnosis of laryngeal and hypopharyngeal lesions, especially using HDTV NBI.

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.

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.

Novel variants in EDNRB gene in Waardenburg syndrome type II and SOX10 gene in PCWH syndrome.

Waardenburg syndrome (WS) is a clinically and genetically heterogeneous group of inherited disorders manifesting with sensorineural hearing loss and pigmentary anomalies. Here we present two Caucasian families with novel variants in EDNRB and SOX10 representing both sides of phenotype spectrum in WS. The c.521G>A variant in EDNRB identified in Family 1 leads to disruption of the cysteine disulfide bridge between extracellular segments of endothelin receptor type B and causes relatively mild phenotype of WS type II with low penetrance. The novel nonsense variant c.900C>A in SOX10 detected in Family 2 leads to PCWH syndrome and was found to be lethal.

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.

Effect of Balloon Eustachian Tuboplasty in Adults That Only Have Symptoms of Chronic Eustachian Tube Dysfunction, With a 1-Year Follow-Up: Prospective Clinical Trial.

OBJECTIVES: Balloon eustachian tuboplasty (BET) is a promising therapeutic option for eustachian tube (ET) dysfunction. However, data are lacking on the effect of BET in adults with symptoms of chronic ET dysfunction but without a contributing pathology. This study investigated the effect of BET in adult patients with only symptoms of chronic ET dysfunction. METHODS: This prospective clinical trial included adult patients with aerated physiological middle ears and symptoms of ET dysfunction for more than 6 months. Compliance with follow-up was 93.3%. We evaluated the effects of BET with tympanometry, assessment of the Valsalva or Toynbee maneuver with tympanometry verification, a Eustachian Tube Dysfunction Questionnaire (ETDQ-7), and pure-tone audiometry. Data were recorded 1 day before surgery and 2, 6, and 12 months after BET. Therapy was considered successful when the patient exhibited a newly acquired ability to perform the Valsalva or Toynbee maneuver or when the ETDQ-7 score improved by 20% or more. RESULTS: We included 14 ears in the analysis. After 2, 6, and 12 months, therapy was successful, according to the ETDQ-7, in 11/14 (78.6%; 95% CI: 48.8-94.3), 13/14 (92.9%; 95% CI: 64.2-99.6), and 12/14 (85.7%; 95% CI: 56.2-97.5) ears, respectively. These results were statistically significant. The ETDQ-7 scores also significantly decreased at 2, 6, and 12 months after the BET, when any change was observed. All patients experienced improvement. Only 1 patient reported temporary deterioration after 2 months. Treatment was more frequently successful in patients without nasal polyps or pollinosis. CONCLUSIONS: Adults with only symptoms of chronic ET dysfunction benefitted more and had longer lasting results from BET, compared to patients with pathologies caused by ET dysfunction. Balloon eustachian tuboplasty could be recommended for these patients.

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.

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.

The Transplantation of hBM-MSCs Increases Bone Neo-Formation and Preserves Hearing Function in the Treatment of Temporal Bone Defects - on the Experience of Two Month Follow Up.

Temporal bone reconstruction is a persisting problem following middle ear cholesteatoma surgery. Seeking to advance the clinical transfer of stem cell therapy we attempted the reconstruction of temporal bone using a composite bioartificial graft based on a hydroxyapatite bone scaffold combined with human bone marrow-derived mesenchymal stromal cells (hBM-MSCs). The aim of this study was to evaluate the effect of the combined biomaterial on the healing of postoperative temporal bone defects and the preservation of physiological hearing functions in a guinea pig model. The treatment's effect could be observed at 1 and 2 months after implantation of the biomaterial, as opposed to the control group. The clinical evaluation of our results included animal survival, clinical signs of an inflammatory response, and exploration of the tympanic bulla. Osteogenesis, angiogenesis, and inflammation were evaluated by histopathological analyses, whereas hBM-MSCs survival was evaluated by immunofluorescence assays. Hearing capacity was evaluated by objective audiometric methods, i.e. auditory brainstem responses and otoacoustic emission. Our study shows that hBM-MSCs, in combination with hydroxyapatite scaffolds, improves the repair of bone defects providing a safe and effective alternative in their treatment following middle ear surgery due to cholesteatoma.

Two Different Causes of Paediatric Hypercalcaemia.

Paediatric hypercalcaemia is a rare condition which can be easily overlooked or misdiagnosed. We report two paediatric patients who presented to the Department of Paediatrics, Pardubice Hospital, Pardubice, Czech Republic, in 2009 and 2010, respectively. Each patient was diagnosed with hypercalcaemia due to a different cause. The first case involved a seven-month-old infant who presented with failure to thrive, vomiting and psychomotor retardation. Fluorescent in situ hybridisation revealed Williams-Beuren syndrome. The second patient was a 16-year-old girl with abdominal pain and renal colic due to hypercalcaemia-induced urolithiasis. High parathyroid hormone serum levels suggested primary hyperparathyroidism. An adenoma of the left upper parathyroid gland was diagnosed via technetium-99m-labelled methoxyisobutyl isonitrile single photon emission computed tomography and removed surgically. Hypercalcaemia should be considered in the differential diagnosis of various disease states, particularly among infants who fail to thrive or children with abdominal pain.

Rheopheresis in treatment of idiopathic sensorineural sudden hearing loss.

BACKROUND: Only few therapeutic options exist for patients with refractory sudden idiopathic sensorineural hearing loss (SISHL). Little is known about the efficacy of second-line therapies. Rheopheresis seems to be an effective therapeutic possibility. METHODS: Between 2012 and 2015, 106 patients with SISHL were enrolled in the study, of whom 52 were refractory to initial treatment. As salvage therapy, these patients were offered either 3 sessions of rheopheresis (33 pts) or intratympanic steroid treatment through MicroWick application (19 pts). Pure tone audiometry was performed at diagnosis, at the 1st month and the 1st year during the follow-up. RESULTS: Patients in the rheopheretic arm had higher hearing loss than in the MicroWick arm (81% vs. 52%, p = 0.04). In spite of this, there was a significant improvement for patients in the rheopheretic arm (27% of hearing loss reduction, p < 0.001) after the 1st month and this remained unchanged during the 1st year, while no improvement was seen in the MicroWick arm (0% of hearing loss reduction, p = 0.424). We found no predictive factor for steroid-failure in first-line therapy. Older age (p = 0.003), presence of vertigo (p = 0.006) and more profound initial hearing loss (p < 0.001) were identified as negative prognostic markers. CONCLUSION: Rheopheresis can be used as a potentially effective and safe salvage therapy for patients with cortico-refractory SISHL.

Human Multipotent Mesenchymal Stromal Cells in the Treatment of Postoperative Temporal Bone Defect: An Animal Model.

Canal wall down mastoidectomy is one of the most effective treatments for cholesteatoma. However, it results in anatomical changes in the external and middle ear with a negative impact on the patient's quality of life. To provide complete closure of the mastoid cavity and normalize the anatomy of the middle and external ear, we used human multipotent mesenchymal stromal cells (hMSCs), GMP grade, in a guinea pig model. A method for preparing a biomaterial composed of hMSCs, hydroxyapatite, and tissue glue was developed. Animals from the treated group were implanted with biomaterial composed of hydroxyapatite and hMSCs, while animals in the control group received hydroxyapatite alone. When compared to controls, the group implanted with hMSCs showed a significantly higher ratio of new bone formation (p = 0.00174), as well as a significantly higher volume percentage of new immature bone (p = 0.00166). Our results proved a beneficial effect of hMSCs on temporal bone formation and provided a promising tool to improve the quality of life of patients after canal wall down mastoidectomy by hMSC implantation.

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.

The presence of high-risk human papillomavirus (HPV) E6/E7 mRNA transcripts in a subset of sinonasal carcinomas is evidence of involvement of HPV in its etiopathogenesis.

The aim of the study was to investigate prevalence of high-risk human papillomavirus (HR-HPV) infection in sinonasal carcinomas by immunohistochemistry, in situ hybridization, and polymerase chain reaction, detecting p16(INK4a) protein (p16) expression and presence of both HPV DNA and HPV E6/E7 messenger RNA (mRNA). The study comprised 47 males and 26 females, aged 23-83 years (median 62 years), mostly (67 %) with a squamous cell carcinoma (SCC). Of the tumors, 53 % arose in the nasal cavity, 42 % in the maxillary sinus, and 5 % in the ethmoid complex. The follow-up period ranged 1-241 months (median 19 months). HPV16, HPV18, or HPV35 were detected in 18/73 (25 %) tumors, 17 SCCs, and 1 small cell neuroendocrine carcinoma. There was a strong correlation between results of HPV detection methods and p16 expression (p < 0.005). HPV-positive SCCs occurred more frequently in smokers (p = 0.04) and were more frequently p16-positive (p < 0.0001) and nonkeratinizing (p = 0.02), the latter occurring more commonly in nasal cavity (p = 0.025). Median survival for HPV-positive SCC patients was 30 months, while for HPV-negative SCC patients was 14 months (p = 0.23). In summary, we confirm that HR-HPV is actively involved in the etiopathogenesis of a significant subset of sinonasal SCCs. p16 may be used as a reliable surrogate marker for determination of HPV status also in sinonasal SCCs. Although we observed a trend toward better overall survival in HPV-positive SCCs, the prognostic impact of HPV status in sinonasal carcinomas needs to be elucidated by further studies.