Clinicopathologic idiosyncrasies of nasopharyngeal cancer in a moderate-risk Mediterranean region.

Cancer of the nasopharynx displays an unparalleled skewness of its epidemiologic, pathogenic and clinico-prognostic characteristics depending on the geographic location. Between the endemic and sporadic forms, which occur in Southeastern Asia and Northern America, respectively, intermediate incidence is noted around the Mediterranean. This study describes the patterns of the disease affecting the population of Western Greece. The records of 70 patients with nasopharyngeal cancer diagnosed in a single institution between 1994-2014 were retrospectively reviewed. Primary treatment involved irradiation with or without concurrent chemotherapy. Demographic data, patient risk factors, tumour parameters, clinical presentation and treatment outcomes were assessed for potential intercorrelations. Overall (OS) and disease-specific (DSS) 5-year survival rates were determined. Possible predictors of survival were tested on univariate and multivariate analysis. WHO-type 3 histopathology was diagnosed predominantly (74.3%) and associated significantly with nasal symptomatology upon presentation (p = 0.050), metastatic lymphadenopathy (p = 0.028), advanced clinical stage (p = 0.009) and complete response to initial treatment (p = 0.018). Univariate analysis revealed a negative prognostic significance for older age (OS, p = 0.029 DSS, p = 0.041), poor response to treatment (OS & DSS p < 0.001) and cancer recurrence (OS, p = 0.003 DSS, p = 0.001). On multivariate analysis, disease relapse maintained its adverse effect (HR 7.442, 95% CI 2.199-25.187, p = 0.001). In conclusion, among nasopharyngeal carcinomas arising in western Greece, lymphoepitheliomas manifest a distinct clinical behaviour, so that their latest grouping along with WHO-type 2 tumours into the "non-keratinising" category may not apply. Regardless of pathology, cancer recurrence after initial remission is a severe event.

Hyaluronan synthases and hyaluronidases in nasal polyps.

Nasal polyps (NPs) are benign lesions of nasal and paranasal sinuses mucosa affecting 1-4 % of all adults. Nasal polyposis affects the quality of patient's life as it causes nasal obstruction, postnasal drainage, purulent nasal discharge, hyposmia or anosmia, chronic sinusitis, facial pain and snoring. Without treatment, the disease can alter the craniofacial skeleton in cases of extended growth of polyps. The development of NPs is caused by the hyperplasia of nasal or paranasal sinuses mucosa, and edema of extracellular matrix. This is usually the result of high concentration of high molecular mass hyaluronan (HA) which is either overproduced or accumulated from blood supply. The size of HA presents high diversity and, especially in pathologic conditions, chains of low molecular mass can be observed. In NPs, chains of about 200 kDa have been identified and considered to be responsible for the inflammation. The purpose of the present study was the investigation, in NPs and normal nasal mucosa (NM), of the expression of the wild-type and alternatively spliced forms of hyaluronidases, their immunolocalization, and the expression of HA synthases to examine the isoform(s) responsible for the increased amounts of HA in NPs. Hyaluronidases' presence was examined on mRNA (RT-PCR analysis) and protein (immunohistochemistry) levels. Hyaluronan synthases' presence was examined on mRNA levels. Hyaluronidases were localized in the cytoplasm of epithelial and inflammatory cells, as well as in the matrix. On mRNA level, it was found that hyal-1-wt was decreased in NPs compared to NM and hyal-1-v3, -v4 and -v5 were substantially increased. Moreover, HAS2 and HAS3 were the only hyaluronan synthases detected, the expression of which was almost similar in NPs and NM. Overall, the results of the present study support that hyaluronidases are the main enzymes responsible for the decreased size of hyaluronan observed in NPs; thus they behave as inflammatory agents. Therefore, they could be a potential target for the design of a more advanced treatment for nasal polyposis.

Determination of matrix metalloproteinase 9 (MMP-9) protein expression in laryngeal squamous cell carcinomas based on digital image analysis.

PURPOSE: Matrix metalloproteinases (MMPs) is a superfamily of proteins involved in angiogenesis and metastatic tissue invasion in many cancers. Overexpression of MMP- 9 has been detected in significant proportions of laryngeal squamous cell carcinomas (LSCCs), but its prognostic impact remains unclear. In this study we performed a digital image analysis for analyzing MMP-9 protein expression in a series of LSCCs correlating them with clinicopathological factors. METHODS: MMP-9 protein expression level was determined immunohistochemically in 30 tissue sections surgically derived from patients (21 male and 9 female) with LSCC. Using digital image analysis, we measured their corresponding protein expression levels (staining intensity/S.I. range values 0-255). RESULTS: Moderate and high MMP-9 protein expression levels (grouping as 2+/3+ overexpression) were detected in 19/30 (63.3%) cases. Statistical significance was observed correlating stage with SI (p=0.02), whereas a borderline association with differentiation grade of the examined tumors was also registered (p=0.05). Interestingly, high levels of MMP-9 expression were observed in cases that demonstrated a significant level of inflammatory (predominantly lymphocytic) infiltration. CONCLUSION: MMP-9 protein overactivation is a frequent and significant genetic event in LSCC, correlating with its biological behavior (increased TNM stage). MMP-9 seems to mediate an epithelial-stromal intra-reaction correlating also with induction of specific inflammation pathways.

Expression and distribution of aggrecanases in human larynx: ADAMTS-5/aggrecanase-2 is the main aggrecanase in laryngeal carcinoma.

Members of the ADAMTS family of proteases degrade proteoglycans and thereby have the potential to alter tissue architecture and regulate cellular functions. Aggrecanases are the main enzymes responsible for aggrecan degradation, due to their specific cleavage pattern. In this study, the expression status, the macromolecular organization and localization of ADAMTS-1, ADAMTS-4/aggrecanase-1 and ADAMTS-5/aggrecanase-2 in human normal larynx and laryngeal squamous cell carcinoma (LSCC) were investigated. On mRNA level, the results showed that ADAMTS-4 was the highest expressed enzyme in normal larynx, whereas ADAMTS-5 was the main aggrecanase in LSCC presenting a stage-related increase up to stage III (8-fold higher expression compared to normal), and thereafter decreased in stage IV. Accordingly, immunohistochemical analysis showed that ADAMTS-5, but not ADAMTS-4, was highly expressed by carcinoma cells. Sequential extraction revealed an altered distribution and organization of multiple molecular forms (latent, activated and fragmented forms) of the enzymes within the cancerous and their corresponding macroscopically normal laryngeal tissues, compared to the normal ones. Importantly, these analyses indicated that critical macromolecular changes occurred from the earliest LSCC stages not only in malignant parts of the tissue but also in areas that were not in proximity to carcinoma cells and appeared otherwise normal. Overall, the results of the present study show that ADAMTS-5/aggrecanase-2 is the main aggrecanase present in laryngeal carcinoma suggesting a critical role for the enzyme in aggrecan degradation and laryngeal tissue destruction during tumor progression.

Pre-treatment gelatinases' serum levels and post-treatment changes in laryngeal cancer patients.

INTRODUCTION: Laryngeal cancer, especially in the advanced stages, is a highly devastating disease, characterized by increased invasiveness and high rates of metastasis. Gelatinases A and B (MMP-2 and -9 respectively) are of particular interest due to their contribution to various stages of carcinogenesis. There is a growing body of evidence with regard to the prognostic value of certain MMPs and their possible role as tumour markers. AIM: To identify the pattern of alteration of serum gelatinases A and B in patients with laryngeal cancer following treatment, and a possible correlation with various clinicopathological parameters. MATERIALS AND METHODS: Forty nine patients were included in this study. Pre-treatment and post-treatment serum samples were collected and processed by gelatin zymography and western blotting. RESULTS: Only the latent forms of MMP-2 and -9 were identified. Both gelatinases were increased in the serum of laryngeal cancer patients compared to healthy individuals. Patients with supraglottic tumours and active smokers had significantly higher pre-treatment levels of proMMP-2 than patients with glottic tumours (p < 0.05) and ex-smokers (p < 0.05), respectively. Patients with primary disease and patients with lymph node involvement showed lower serum proMMP-9 pre-treatment levels than patients with recurrence (p < 0.05) and patients without neck disease (p < 0.1), respectively. During the follow-up period the proMMP-2 serum levels increased significantly in the first ten to fifteen days after treatment, gradually decreasing over the following months. The proMMP-9 serum levels showed a gradual decrease after treatment, which was statistically significant (p<0.05). CONCLUSIONS: The post-treatment alteration pattern of proMMP-9 serum levels shows a possible role of this molecule as a tumour marker in laryngeal cancer. Further research is necessary to clarify the contribution of both gelatinases to the disease progress and determine their role as prognostic factors and tumour markers.

Factors influencing quality of life after total laryngectomy: a study of 92 patients.

BACKGROUND AND OBJECTIVES: Total laryngectomy is a radical surgery for advanced laryngeal cancer. In the present study we evaluate the influencing factors for long term quality of life of 92 laryngectomees. PATIENTS AND METHODS: 92 patients who underwent laryngectomy for laryngeal cancer in the University Hospital of Patras, Greece were evaluated using a modified version of the EORTC-QOL-C30 questionnaire. The patients were distributed into 6 groups based on time elapsed between surgical treatment and completion of the questionnaire, ranging from 2 years for group 1 to 9-10 years for group 6. RESULTS: The mean value of psychological status (p=0.01), smelling disorders (p=0.032), mood change (p=0.003) were statistically significant in regard to the patient's overall view of their life postsurgically. Coexisting illness (defined as diabetes, hypertension or prostate disease which required medication on daily basis or hospitalization more than two times a year) was also significantly affecting (p=0.021) the patient's oral communication skills. CONCLUSION: Quality of life is affected by functional disabilities and the psychological state of the patients. No statistically significant improvement over time was noted in our series.

Necrotizing fasciitis of the head and neck: report of 5 cases and review of the literature.

BACKGROUND: Necrotizing fasciitis (NF) is a severe, rapidly spreading soft tissue infection of polymicrobial origin. This condition most frequently affects thorax, abdominal wall, extremities, perineum and groin, but according to recent literature the head and neck area is also involved with increasing frequency. PATIENTS AND METHODS: Five cases of head and neck NF were detected among patients who were admitted at the Department of Otorhinolaryngology-Head and Neck Surgery of the University Hospital of Patras, Patras, Greece, over a 5-years period. Various parameters including patients' health status, co-morbidity, etiology, microbiology, affected area, antibiotic therapy, hospital stay, surgical treatment and complications were considered. CONCLUSIONS: The management of NF should comprise of hemodynamic and respiratory evaluation and monitoring, broad-spectrum i.v. antimicrobial therapy, surgical debridement and nutritional support. Close postoperative management of NF patients remains of paramount importance.

Sinonasal sarcoidosis. A case report.

INTRODUCTION: Sarcoidosis is a granulomatous disease of unknown etiology, which in the majority of cases affects the lower respiratory tract. Although neck mass, parotid swelling and facial nerve palsy are considered the primary complaints in cases of head and neck sarcoidosis, sinonasal localization of the disease is also uncommonly reported. CASE: A 46 year old woman presented in our clinic with complaints of nasal congestion over a six month period. The patient reported increasing symptom severity in the last month with occasional purulent discharge. No other symptoms were reported. The patient's medical record was significant only for sarcoidosis localized to the lower respiratory tract. On anterior rhinoscopy, the nasal mucosa presented marked hypertrophy, purplish discoloration and granulomatous appearance of the inferior turbinates on the left side. The diagnosis of sinonasal sarcoidosis was made based on histopathologic examination of biopsy specimens. CONCLUSION: Sinonasal sarcoidosis presents a challenging issue for the clinicial as its mimicking features may be misleading and delay diagnosis. In the present paper we present a case of sinonasal sarcoidosis presenting as chronic rhinosinusitis.

Voice restoration after total laryngectomy using provox 2 (generation II) prosthesis.

BACKGROUND AND OBJECTIVES: Voice restoration after total laryngectomy is of outmost importance for patient and a therapeutic challenge for the surgeon and speech pathologist. Among various rehabilitation methods prosthetic voice yields nowadays the best results. PATIENTS AND METHODS: A total of 12 patients underwent laryngectomy at the Department of Otorhinolaryngology, University Hospital, Patras, Greece, between February 2006 and May 2007. All patients had advanced laryngeal squamous cell carcinoma. Eight patients had primary voice prosthesis inserted and four patients had a tracheo-esophageal puncture (TEP) carried out as a secondary procedure. RESULTS: The majority of the patients (80%) from both the primary insertion or the secondary insertion group, developed good and understood speech using the prosthesis. No significant difference in quality of speech was found between the two subgroups. Four patients required replacement of the prosthesis at intervals of 8 and 10 months after insertion, because of salivary leakage and granulation formation around the fistula, while 3 patients developed a mild mucositis and tracheitis due to postoperative radiotherapy. DISCUSSION: TEP puncture and prosthesis insertion is a relatively simple, safe and effective surgical procedure for voice restoration after laryngectomy. Provox 2 (generation II) voice prosthesis is a new and useful modified device that has overcome the previous prosthesis drawbacks, is well tolerated by the patients and can be easily changed via the front-loading technique.

Cystic thymoma coexisting with vascular dysplasia.

We report the case of a 23-year-old female patient, who was admitted to our hospital because of aggravating pain in the right shoulder, right chest and ear accompanied by cough and dyspnea. Imaging revealed a soft tissue mass in the mediastinum in close relation with an additional large mass extending in the right upper thorax, right axilla and neck. The tissue obtained during surgery showed the former mass to be a cystic thymoma, being in contact with an extensive vascular dysplasia. The characteristic clinical presentation, the contribution of imaging, the results of operation, and the follow-up are rather unique. The review of the literature did not reveal similar cases.

Stage-related decorin and versican expression in human laryngeal cancer.

BACKGROUND: The major proteoglycan of normal human larynx is aggrecan. In laryngeal carcinoma, aggrecan is depleted, with versican and decorin appearing in higher amounts. MATERIALS AND METHODS: Proteoglycans in laryngeal carcinoma samples were characterized immunohistochemically and using Western blotting; their expression was examined by RT-PCR. RESULTS: Aggrecan was totally removed in advanced cancer and its RT-PCR product was not identified. Both versican and decorin were overexpressed in cancer, versican much more than decorin. Decorin expression was higher than that of versican in the normal larynx; therefore, their disproportionate overexpression during cancer resulted in about equimolar expression. Both proteoglycans' expression correlated with their stage-related accumulation within the tissue. CONCLUSION: These data add to our previous findings and support the view that the levels of expression and the extent of accumulation and localization in the tumor stroma of structurally modified versican and decorin could be associated with the degree of aggressiveness of laryngeal carcinoma.

Concurrent tonsillitis and pneumonia due to S. pyogenes.

Tonsillitis is a common disease especially of children and young adults. The diagnosis of tonsillitis generally requires the consideration of Group A beta-hemolytic streptococci infection. Pneumonia is an inflammation of the alveoli and terminal airspaces in response to invasion by an infectious agent that is introduced into the lungs through hematogenous spread or inhalation. We present a case of a concurrent acute tonsillitis and pneumonia due to S. pyogenes. To our knowledge, a similar case has not been previously described in the literature.

Palatine tonsillar metastasis from lung adenocarcinoma.

Tonsillar metastasis from lung cancer is an extremely rare event and is usually related to metastatic spread of the neoplastic disease to other organs with poor prognosis. We present the unusual case of a 71-year-old man who developed a huge metastasis to the left palatine tonsil from a lung adenocarcinoma. The tumor was exophytic with necrotic and hemorrhagic areas, occupying a large portion of the oropharynx and producing airway obstruction, thus necessitating tracheostomy. Radiation therapy was delivered in an attempt to reduce the size of the tumor. Although a mild decrease of the tonsillar mass was noted, the designed therapy had to be discontinued because of a rapid deterioration of the patient's general condition. The patient finally died of disseminated disease. This case highlights the need for a thorough evaluation of a suspicious tonsillar enlargement, as this may be a sign of a primary malignancy elsewhere in the body.

Expression of metalloproteinases and their tissue inhibitors in squamous cell laryngeal carcinoma.

The hallmark of cancer invasion is the degradation of extracellular matrix components. Matrix metalloproteinases are the major enzymes participating in this event and their activity is regulated extracellularly by their presence as proenzymes and the concomitant presence of the specific tissue inhibitors. The present study describes the immunohistochemical localization of gelatinases, matrix metalloproteinase (MMP)-2 and -9 and tissue inhibitor of metalloproteinase (TIMP)-1 and -2 in human laryngeal carcinoma and their expression with respect to tumor classification and compared with the respective healthy subjects. MMP-2 was immunolocalized in the cytoplasm of the epithelial cells and in the loose connective tissue, whereas MMP-9 was also observed in basement membrane and chondrocytes. Both were also found in tumor cells, but staining was decreased with increasing stage of cancer. TIMP-1 was present exclusively in stroma and totally absent from tumor cells and it was overexpressed in normal cells surrounding the tumor. TIMP-2 was identified in the cytoplasm of epithelial cells, in stroma and sometimes in chondrocytes. In addition, it was present in tumor cells of only stage IV samples. The expression level of both gelatinases and TIMPs increased as the stage of cancer increased, suggesting the possible post-transcriptional removal of their mRNA. These observations, performed in a given head and neck site, suggest that the behavior of head and neck tumors seems to depend on the site and additional studies should be performed to obtain a general understanding of the disease and ascertain the role of the constituents examined.

Nasopharyngeal adenoid cystic carcinoma: a rare nasopharyngeal tumor.

Adenoid cystic carcinoma (ACC) is the most common histologic subtype of the salivary gland malignancies, but it is very rare in the nasopharynx with relatively few cases reported in the literature. We report a case of a 57 year-old woman with an ACC in the right Rosenmuller fossa of the nasopharynx, treated with combined radiotherapy and chemotherapy, without any recurrence or intracranial spread detected until the recent follow-up.

Diagnostic and classification value of metalloproteinases in squamous human laryngeal carcinoma.

Metalloproteinases (MMPs) are a class of enzymes largely involved in tumour progression and metastasis. At least twenty different enzymes are recognized that are also present under normal state of tissues. Their activity is regulated by their presence as proenzymes and by the concomitant presence of the respective tissue inhibitors (TIMPs). The present study describes the alterations of MMPs observed in human laryngeal carcinoma with respect to tumour classification and compares their activity in normal and cancerous tissues and biopsy specimens. Samples from five patients who underwent laryngectomy, from five biopsies and three from autopsies were used. The MMPs of normal and malignant human laryngeal cartilage and of biopsy specimens were identified immunochemically and by zymography using gelatin or casein as substrates. Healthy cartilage from autopsies was found to contain almost exclusively MMP-1, proMMP-2 and proMMP-9. Normal parts from laryngectomies contained, in addition, significant amounts of active MMP-2. The respective malignant parts contained both MMP-2 and -9 in increased amounts in their latent and active forms. Similar profile of MMPs was also identified in tissues surrounding affected cartilage. These alterations were found to be in good accordance with tumour stage and were also observed in biopsy samples. Thus, analysis of MMPs in biopsies can be used together with the clinicopathological parameters for the classification or early diagnosis of laryngeal tumours.

Induction of the CBP transcriptional co-activator early during laryngeal carcinogenesis.

PURPOSE: CREB-binding protein (CBP) is a transcriptional "integrator" that is suspected of contributing to tumorigenesis. This is the first systematic morphologic study evaluating CBP expression in a large series of human laryngeal tissues containing normal epithelium, premalignant lesions (hyperplasia and/or dysplasia), and squamous cell carcinoma. METHODS: Immunohistochemical methodology was performed on formalin-fixed paraffin-embedded sections by using a monoclonal anti-CBP antibody. CBP expression was screened and compared in 156 patients with various laryngeal histologic entities. RESULTS: Nuclear expression of CBP was found in 44 out of 91 (48.4%) specimens with normal-appearing epithelium (46.2% weak and only 2.2% moderate positivity), 92 out of 100 (92%) with hyperplastic lesions (56% weak, 36% moderate/strong, and only 8% no positivity), 80 out of 103 (77.7%) with dysplastic lesions (45.6% weak, 32.1% moderate/strong, and 22.3% no positivity), 37 out of 45 (82.2%) with well-differentiated carcinoma (42.2% weak, 40% moderate/strong, and 17.8% no positivity), 31 out of 43 (72.1%) with moderately differentiated carcinoma (32.6% weak, 39.5% moderate/strong, and 27.9% no positivity) and eight out of 12 (66.7%) with poorly differentiated carcinoma (41.7% weak, 25% moderate/strong, and 33.3% no positivity). Statistical analysis and correlation of the intensity of nuclear immunostaining among the various histologic entities revealed statistically significant results. CONCLUSIONS: Overexpression of CBP is detected from the very early stages of laryngeal carcinogenesis, suggesting that CBP may play a role in malignant transformation of precancerous laryngeal lesions. It is possible that overexpression of this protein is a prerequisite for the observed p53 upregulation in premalignant lesions, implying an indirect role of CBP in p53-mediated tumorigenic potential.

S-100 protein-positive dendritic cells and CD34-positive dendritic interstitial cells in palatine tonsils.

Dendritic cells (DCs) are effective antigen-presenting cells and have been shown to mature from precursor CD34-positive stromal cells (dendritic interstitial cells, DICs) or monocytes. To gain insight into the local immune response in human tonsils, we investigated immunohistochemically the presence of DCs and DICs in 17 non-hyperplastic and 13 hyperplastic tonsils. Dense infiltrates of S-100-positive DCs were noted in the majority of hyperplastic tonsils, while there were fewer in non-hyperplastic tonsils. DICs were noted specifically at the periphery in the dense hemi-capsule cap that separates the tonsil from the underlying muscle. In addition, their small number suggests that the accumulation of S-100 dendritic cells in hyperplastic palatine tonsils is achieved through migration from other sites rather than through maturation from precursors locally.

Lateral neck abscess caused by Streptococcus bovis in a patient with undiagnosed colon cancer.

Bacteraemia or endocarditis caused by Streptococcus bovis, a non-enterococcal group D streptococcus, is a very common finding in patients suffering from intestinal tumours or other colon diseases. A case of a patient with a laternal neck abscess caused by S. bovis is reported. During the treatment the patient was found to have colonic malignant lesions. The problems in the appropriate diagnosis and the possible correlation between these two clinical entities are presented and discussed.

Craniofacial osteotomies to facilitate resection of large tumours of the anterior skull base.

Large tumours of the anterior cranial fossa can be a major challenge to the neurosurgeon or the maxillofacial surgeon. However, skull base approaches facilitate their resection. We describe our experience with the extended subfrontal approach in treating tumours of the anterior cranial base. This approach was performed on 29 patients with large tumours of the anterior skull base. The final outcome in all 29 patients was favourable in terms of total resection of the tumour with minimal subsequent neurological deficit. Two patients developed transient oedema of the frontal lobes without persistent neurological sequelae. Another patient developed a postoperative cerebrospinal fluid fistula that was successfully repaired. The patients were followed for a period ranging from 6 to 28 months. There was no recurrence. The operative technique is described. En bloc removal of the roofs of the orbits and part of the anterior cranial fossa permits wide exposure of the lesion with minimal brain retraction. Reconstruction of the anterior cranial base should be meticulous to avoid cerebrospinal fluid leaks and subsequent meningitis. Loss of smell is a sequel to this approach. The possible risks and some important technical details are highlighted.