Heat shock proteins HSP90, HSP70 and GRP78 expression in medullary thyroid carcinoma.

BACKGROUND: Medullary thyroid carcinoma management consists mainly of surgical resection and is largely chemoresistant. There is ongoing effort to discover novel therapies for medullary thyroid carcinoma. Increased levels of heat shock proteins have been associated with multiple cancers and are being studied as potential therapeutic targets. The purpose of this study was to determine the expression levels of heat shock proteins 90 and 70 and of glucose related protein 78 in medullary thyroid carcinoma tissues compared with normal thyroid tissues. METHODS: 20 tissue specimens of medullary thyroid carcinoma and 10 specimens of thyroids without malignancy were analyzed by immunohistochemistry. RESULTS: Medullary thyroid carcinoma specimens showed 27% higher expression level of heat shock protein 90 immunostaining, and a 43% higher expression level of heat shock protein 70 immunostaining versus normal controls. These differences, however, were not statistically significant. A significantly higher expression level was noted for glucose related protein 78 in the medullary thyroid carcinoma specimens than in the controls. CONCLUSION: This study indicates increased expression levels of heat shock proteins 90 and 70 and glucose related protein 78 levels in medullary thyroid carcinoma. These findings, though preliminary imply that these proteins may have a role in medullary thyroid carcinoma's tumor biology and may have and future therapeutic options. Larger cohorts are needed to corroborate these results.

Bacteriology of the Middle Meatus in Chronic Rhinosinusitis with and without Polyposis.

There are only limited data in the literature, and none specifically from the Middle East, on the pathogenic bacteria in chronic rhinosinusitis (CRS) as opposed to healthy nasal cavities and their association with disease severity. The present study was conducted in the department of head and neck surgery of a tertiary medical center. Middle meatal swabs were taken preoperatively from patients with CRS with nasal polyposis (CRSwNP) (n = 60), CRS without nasal polyposis (CRSsNP) (n = 50), and control patients with septal deviation (n = 26) or no nasal abnormalities (n = 27). Culture findings were compared among the groups and correlated with CRS severity. Positive pathogenic culture rates were 78% in the CRSwNP group and 64% in the CRSsNP group. Twenty pathogenic bacterial species were identified; the most common was Staphylococcus aureus (27%). The most common Gram-negative isolate was Citrobacter spp. (17%). Gram-negative species were significantly more prevalent in the CRSwNP group than the others. Mean Lund-Mackay scores were 12.8 in the CRSwNP group and 6.9 in the CRSsNP group, and were unrelated to the culture findings. Positive culture rates were significantly higher in the septal deviation (54%) than the nasal healthy group (26%), although both values were significantly lower than in the CRS groups. In conclusion, patients with CRS have higher rates of bacterial isolates than patients without CRS. CRSwNP is associated with more Gram-negative bacteria than CRSsNP, regardless of disease severity. The relatively high positive culture rate in patients with septal deviation merits investigation.

Prognostic significance of nodal ratio in cutaneous squamous cell carcinoma of the head and neck.

The TNM classification is not specific for head and neck skin cancer and makes no allowance for disease extent. Studies have shown that the relative number of metastatic-to-examined lymph nodes, termed the Nodal ratio, is a reliable independent prognosticator in several types of cancer. The study was designed as a retrospective analysis in a university affiliated tertiary care center setting. The files of all patients (n = 71) with cutaneous head and neck squamous cell carcinoma and regional lymph node metastasis who attended a tertiary medical center between 1990 and 2008 were reviewed for clinical variables and outcome, and Nodal ratio was calculated. Data were analyzed for impact on survival. On multivariate analysis Nodal ratio and age were found to be significant predictors of overall survival. The N-ratio was the only significant predictor of disease-specific survival. Age, type of treatment (selective/modified neck dissection), pathologic N stage, and radiotherapy had no effect. The Nodal ratio is a potentially valuable prognostic index in cutaneous squamous cell carcinoma. The minimal number of nodes that need to be excised has to be determined.

Post-laryngectomy voice rehabilitation: comparison of primary and secondary tracheoesophageal puncture.

BACKGROUND: Voice restoration following total laryngectomy is an important part of patients' rehabilitation and long-term quality of life. OBJECTIVES: To evaluate the long-term outcome of indwelling voice prostheses inserted during (primary procedure) or after (secondary procedure) total laryngectomy. METHODS: The study group included 90 patients who underwent total laryngectomy and tracheoesophageal puncture (TEP) with placement of voice prosthesis at a tertiary medical center during the period 1990-2008. Background, clinical and outcome data were collected by medical file review. Findings were compared between patients in whom TEP was performed as a primary or a secondary procedure. RESULTS: TEP was performed as a primary procedure in 64 patients and a secondary procedure in 26. Corresponding rates of satisfactory voice rehabilitation were 84.4% and 88.5% respectively. There was no association of voice quality with either receipt of adjuvant radiation/chemoradiation or patient age. The average lifetime of the voice prosthesis was 4.2 months for primary TEP and 9.06 months for secondary TEP (P= 0.025). CONCLUSIONS: Primary TEP provides almost immediate and satisfactory voice rehabilitation. However, it is associated with a significantly shorter average prosthesis lifetime than secondary TEP. Chemoradiotherapy and patient age do not affect voice quality with either procedure.

Novel grading system for quantifying upper-airway obstruction on sleep endoscopy.

BACKGROUND: The aim of this study was to present a novel anatomically comprehensive and clinically applicable system for the quantification of sleep endoscopy findings in patients with obstructive sleep apnea/hypopnea syndrome (OSAHS). METHODS: Fifty-five adult patients with a polysomnographic diagnosis of OSAHS were referred for midazolam-induced sleep endoscopy following failure of continuous positive airway pressure. Five anatomical sites of possible obstruction along the upper airway were documented: nose/nasopharynx (N), uvulopalatine plane (P), tongue base (T), larynx (L), and hypopharynx (H). Each involved site was assigned a severity grade of 1 (partial obstruction) or 2 (complete obstruction). The digits representing the obstruction pattern at each level were then added to yield a severity index (SI). The SI for each patient was determined by two independent observers. Findings were correlated with the respiratory disturbance index (RDI) and body mass index (BMI). RESULTS: The SI was significantly correlated with the RDI (R=0.746, Pearson; P<0.0001) and predicted disease severity with 65% accuracy. There was no association with BMI. By site, the tongue base and hypopharynx were significantly correlated with obstruction severity; obstruction in the tongue base predicted disease severity with a sensitivity of 68.8 and sensitivity of 81.1. CONCLUSION: Our easy-to-use endoscopic grading system provides physicians with an accurate picture of the pattern of the upper-airway system obstruction in patients with obstructive sleep apnea/hypopnea syndrome. It is a promising tool for estimating the location and severity of upper airway disease and may have implications for treatment planning.

Early death from papillary thyroid carcinoma.

PURPOSE: The natural history of papillary thyroid carcinoma (PTC) is characterized by a slow growth rate and an excellent prognosis at 20 and 30 years. However, there is a small subset of patients with poorer outcome. METHODS: Twenty patients who died of PTC within 10 years of diagnosis were studied to identify prognostic indicators and biological markers of early death. Findings were statistically compared with a previous review of all patients with PTC treated in the same institute and studies in the literature. RESULTS: The study group included 6 men and 14 women with a mean age of 65 years at diagnosis. Average tumor size was 3.6 cm; 16 patients had extracapsular extension. All tumor samples studied histologically stained poorly for p53, Ki67, and CD34. Regional metastases were present in half the patients, and distal metastases in all. All patients had an advanced disease stage (Tumor, Node, Metastases classification), and only 4 had a low score on the Metastases, Age, Completeness of resection, local Invasion, tumor Size risk stratification. Analysis of the findings against data in the literature for the whole population of patients with PTC, who had a considerably better survival (<8% mortality within 8-15 years vs 100% within 10 years in our sample), yielded significant differences for rates of extrathyroidal extension (P = .0001), regional metastases (P = .016), and distant metastases (P = .0001). CONCLUSION: Extrathyroid extension, late regional metastases, and distant metastases may be risk factors for early death from PTC.

Expression of MMP-1 in invasive well-differentiated thyroid carcinoma.

The objective of this study is to examine the expression of matrix metalloproteinase 1 (MMP-1) in invasive well-differentiated thyroid carcinoma (WDTC) and its relation to clinicopathological features. This retrospective case study group included 26 patients with invasive WDTC who were treated at our center between January 1985 and May 2007. Clinical data were collected from the medical files. MMP-1 expression was tested in samples from paraffin-embedded tumor by immunohistochemical staining. MMP-1 expression correlated with laryngotracheal invasion (p = 0.032), multifocality of the tumor (p = 0.044), and presence of regional (p = 0.034) and distant metastases (p = 0.048). In conclusion, the expression of MMP-1 in invasive WDTC is consistent with tumor aggressiveness, manifested by laryngotracheal invasion, multifocality, and regional and distant metastases. MMP-1 expression may serve as a prognostic marker and an indicator for the need for more aggressive surgical treatment.

Histopathological changes of the nasal mucosa induced by smoking.

Changes in the histopathology of the respiratory epithelium in response to cigarette smoking have been studied in depth in the lungs, but data on the nasal lining are lacking. The aim of the present retrospective study was to investigate the histological changes that occur in the nasal mucosa of smokers compared with non-smokers. The study group included 47 patients who underwent partial resection of the inferior turbinates. Archival nasal tissue samples were collected and examined by light microscopy: the number of goblet cells was counted, and the degree of inflammation, congestion, and edema was graded as mild, moderate, or severe. Epithelial thickness was measured as well. Findings were compared between smokers (n = 21) and non-smokers (n = 26). On statistical analysis, significant differences were found between the smokers and non-smokers in mean number of goblet cells in the nasal epithelium, 43.43 +/- 16.80 vs. 16.23 +/- 5.65 respectively (p < 0.0001), mean edema grade, 2.43 +/- 0.75 vs. 1.12 +/- 0.33 respectively (p < 0.0001), and mean epithelial thickness, 111.9 +/- 25.8 microm vs. 60.4 +/- 18.4 microm respectively (p < 0.0001). The corresponding mean values of congestion were 2 +/- 0.71 and 1.27 +/- 0.67 (p < 0.001), and of inflammation, 1.81 +/- 0.60 and 1.81 +/- 0.85 (NS). In conclusion, the histopathological findings in the nasal mucosa of smokers resemble reported findings in the bronchial respiratory epithelium. The main differences from non-smokers are greater goblet cell hyperplasia and thicker epithelium.

Cholesterol granuloma in thyroglossal cysts: a clinicopathological study.

Thyroglossal duct cyst (TDC) is a congenital anomaly caused by retention of epithelial remnants from the descent of the thyroid gland during embryological development. Cholesterol granuloma represents a granulomatous reaction to precipitates of cholesterol crystals in tissue, usually related to middle-ear disease. The association of TDC with cholesterol granuloma has hardly been reported. This study describes five patients with TDC and cholesterol granuloma over a 16-year-period. The treatment consisted of excision of the TDC and the mid-portion of the hyoid bone and excision of a core of tissue between the hyoid bone and the foramen cecum (Sistrunk procedure). We speculate that the pathogenesis of cholesterol granuloma in TDC resembles that in the paranasal sinuses, as both sites provide a closed, poorly ventilated hollow structure with slow drainage. Our five patients accounted for 13% of all patients with TDC treated in our center during the same period, indicating that cholesterol granuloma in TDC may not be as rare as previously thought.

Laryngeal carcinoma in nonsmoking patients.

OBJECTIVES: Smoking is a known risk factor for laryngeal carcinoma. We sought to describe the clinicopathologic characteristics and outcomes of nonsmoking patients with laryngeal carcinoma. METHODS: Of 1,443 patients treated for laryngeal carcinoma between 1960 and 2006, 55 (3.8%) were nonsmokers: 40 (73%) had never smoked and 15 (27%) had stopped smoking 12 years or more before diagnosis. Patient characteristics and outcomes were reviewed. RESULTS: The study group consisted of 87% men; the mean age at diagnosis was 67 years. All lesions but one were located in the glottis. The 5-year survival rate for the whole group was 85%. Most tumors were detected early. Of 38 patients (69%) with stage T1 disease, there was no significant difference in prognostic features between those who had never smoked and those who had smoked in the past. CONCLUSIONS: Fewer than 5% of patients with laryngeal carcinoma were nonsmokers. Like smokers, this subgroup was characterized by a male predominance and an approximate age at diagnosis in the seventh decade. Unlike smokers, nonsmokers show a greater predilection for glottic rather than supraglottic disease. There was no difference in prognosis between smokers and nonsmokers, regardless of whether they had smoked in the past.

Endoscopic transnasal repair of choanal atresia.

OBJECTIVES: To present our experience with a new endoscopic technique for transnasal repair of choanal atresia. METHODS: Seventeen patients aged 2 months to 13 years with choanal atresia, bilateral in 6 and unilateral in 11, underwent endoscopic repair using a mucoperichondrial flap developed from the nasal septum. The bony stenosis was opened with a surgical curette or drill, and the raw surface was covered by the flap. All patients in these case series with bilateral atresia had been treated with dilatation at birth and had restenosis. RESULTS: A total of 23 choanae were operated. Follow-up ranged from 10 to 60 months. There was one case of complete restenosis and one of partial restenosis, for a success rate of 91%. CONCLUSIONS: Endoscopic repair of choanal atresia is a safe and rapid procedure even in very young children, with no complications and a high rate of success.

Repair of caudal septal deviation: the fishing line technique.

BACKGROUND: Repair of caudal septal deviation using currently described methods is challenging technically. The aim of this work is to describe a novel and simple technique for the treatment of caudal septal deviations that protects the nasal tip, by fixating of cartilage to the columella. METHODS: All patients with caudal septal deviation operated on between June 2008 to November 2013 in 2 major medical centers were operated using the "fishing line technique." Patient satisfaction was recorded by a standard questionnaire (16-item Sino-Nasal Outcome Test [SNOT-16]), before and after surgery. The fishing line technique was performed in 63 patients with a severe caudal septal deviation of which 14 also had rhinoplasty. A mucoperichondrial flap was elevated on either side of the damaged septal cartilage. The cartilage was excised and remodeled into a straight sheet, and then repositioned between the mucoperichondrial flaps, and fixed to the septal columella. RESULTS: Mean age of the study group was 36 years. Follow-up ranged from 24 to 70 months. At the last follow-up, the septum was straight in all cases, with no deviation from the nostrils to the choana. Good airway was found in 53 patients. Eight patients had partial turbinate hypertrophy with an impaired airway, and 2 had severe turbinate hypertrophy. SNOT-16 mean score improved from 27 to 10 (p < 0.001). All patients were satisfied with the aesthetic outcome. CONCLUSION: The fishing-line technique for severe caudal septum deviations is easy to perform and yields satisfactory anatomic and aesthetic results.

Acute Rhinosinusitis in Immunosuppressed Children: Diagnostic and Therapeutic Management.

BACKGROUND: Immunosuppressive therapy places pediatric patients at risk of developing life-threatening sinonasal infections. Diagnosis and treatment are challenging owing to nonspecific signs and symptoms. The aim of this study was to present our department's experience with the surgical management of acute rhinosinusitis in immunosuppressed children. METHODS: The records of all children with a hematologic or oncologic disease who underwent endoscopic sinus surgery (ESS) for acute rhinosinusitis from January 2005 to May 2014 were reviewed. Data were retrospectively collected on demographics, clinical and imaging characteristics, microbiology, pathology, treatment and outcome. RESULTS: Thirty-four-immunosuppressed children underwent ESS for acute rhinosinusitis. Most patients had a fungal infection. Nineteen patients died at the end of follow-up; 10 deaths were infection-related. Facial swelling was the only symptom that correlated with death of infection. Relapse of the underlying disease, bone marrow transplantation, and long duration of neutropenia correlated with infection-related mortality. Fungal infection, and specifically Aspergillus, correlated with death from infection. CONCLUSIONS: ESS is a safe and efficient procedure for diagnosing and treating immunosuppressed pediatric patients with acute rhinosinusitis. Early detection and aggressive medical and surgical treatment, with control of underlying risk factors, are crucial to improve outcome.

Can molecular profiling enhance radiotherapy? Impact of personalized targeted gold nanoparticles on radiosensitivity and imaging of adenoid cystic carcinoma.

Personalized molecular profiling has an established role in selection of treatment for metastatic disease; however, its role in improving radiosensitivity and functional imaging has not been evaluated. In the current study, we examined molecular profiling as a tool for designing personalized targeted gold nanoparticles (GNP) to serve as dual-modal tumor radiosensitizers and functional imaging enhancers. To this end, molecular profiling of a patient's salivary gland adenoid cystic carcinoma (ACC) was performed, and anaplastic lymphoma kinase (ALK) mutation was detected. The extracted tumor was subcutaneously injected into mice, which were then treated either with radiation, the specific ALK inhibitor crizotinib, or a combination of therapies. One of these combinations, namely, ALK-targeted GNP (via crizotinib coating), was found to enhance radiation treatment, as demonstrated by a significant decrease in tumor volume over 24 days. In parallel, ALK-targeted GNP substantially augmented tumor visualization via computed tomography. The mechanism of radiosensitivity enhancement was mostly related to a diminished cell repair mechanism in tumors, as demonstrated by proliferating cell nuclear antigen staining. These findings indicate that personalized molecular profiling is an effective technique for enhancing cancer theranostics.

Prognostic factors in metastatic cutaneous squamous cell carcinoma of the head and neck.

Metastatic cutaneous squamous cell carcinoma (SCC) of the head and neck poses a significant therapeutic challenge due to its aggressive biologic behavior. We conducted a retrospective study of 71 patients-58 men and 13 women, aged 28 to 88 years (mean: 71)-who had been treated at our university-affiliated tertiary care medical center for metastatic cutaneous SCC over a 15-year period. In addition to demographic data, we compiled and analyzed information on tumor characteristics, the site and extent of metastasis, treatment, follow-up, and outcome. Among the tumor factors, poorly differentiated carcinoma was an independent predictor of poorer disease-free survival, and older age was found to be an independent predictor of poorer overall survival. We found no significant difference in disease-free or disease-specific survival among patients with parotid involvement, neck involvement, or both. In our series, the site of nodal involvement appeared to have no prognostic significance in patients with metastatic cutaneous SCC of the head and neck.

Brachytherapy for radiotherapy-resistant head and neck cancer: A review of a single center experience.

OBJECTIVES/HYPOTHESIS: Despite advances in radiotherapy and chemotherapy treatments for head and neck cancers, the local failure rate is high. In most radiotherapy-resistant cases, surgery is performed; however, some cases are considered unresectable. No standard treatment for these situations has been established. In this study, we review our experience with brachytherapy (BT), which has a different biological mechanism than standard radiotherapy. METHODS: All patients received prior radiation to the recurrence area. Median high-dose radiation BT dose was 50 Gy, administered in 5 to 10 Gy fractions twice daily for 5 days. High-dose radiation was given via four to 10 catheters inserted under local anesthesia (3 patients) or general anesthesia with preventive tracheostomy (10 patients). RESULTS: Thirteen patients received BT from 2010 to 2014. Male:female ratio was 1.6:1, and median age was 66 years (range 23-89). Of those 13 patients, 10 patients were diagnosed with squamous cell carcinoma (SCC) of the oral cavity, two patients with SCC of the nasal mucosa, and one patient with eccrine duct carcinoma. Prior radiation dose ranged from 60 to 70 Gy. Local control was achieved in 11 of 13 patients; only 15.3% (2 of 13) had in-field recurrence. Five patients developed local out-of-field recurrence, and two developed distant metastases. Five patients are alive with no evidence of disease. No major toxicities were encountered. Two patients had severe mucositis and recovered within several weeks. CONCLUSION: Brachytherapy for radiotherapy-resistant head and neck cancers is feasible with minor adverse events, which enables good local control. However, many advanced head and neck cancers develop regional or distant metastases; therefore, additional treatment should be suggested. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:2246-2251, 2016.

Expression of p53, Ki-67 and Bcl-2 in parathyroid adenoma and residual normal tissue.

The aim of this study was to investigate the expression of Ki-67, bcl-2 and p53 in parathyroid adenomas and their residual rim of normal parathyroid tissue. Specimens from 26 parathyroid adenomas were studied by immunohistochemical analysis for Ki-67, bcl-2 and p53 expression. Positive findings were noted for p53 in 4 (15%) adenomas and none of the residual rims of normal parathyroid tissue (p = 0.055); for Ki-67 in 15 (56%) adenomas and none of the residual rims of normal parathyroid tissue (p = 0.00002); and for bcl-2 in 19 (73%) adenomas and 8 (31%) residual rims of normal parathyroid tissue (p < 0.01). The high rate of Ki-67 expression may indicate susceptibility of parathyroid adenomas to clonal proliferation. The weak immunoreactive expression of p53, combined with a relatively strong expression of bcl-2, may contribute to the characteristic slow progression of these tumors.

Comparative efficacy of two anti-bacterial/anti-inflammatory formulations (Auricularum otic powder and Dex-Otic drops) in the medical treatment of otitis externa.

BACKGROUND: Otitis externa (OE) is a common disorder which can cause severe pain and discomfort with discharge and hearing loss. The majority of topical preparations for OE treatment contain a combination of steroids and antibiotics and are administered as ear drops. Otic powder preparations are less common. We found no studies which compared the efficacy of the two dosage forms. OBJECTIVE: The purpose of the study was to compare the healing process of the external ear canal when treated locally either with otic powder (Auricularum), a preparation containing antibiotic, steroidal and antimycotic components, or with otic drops (Dex-Otic), a commercial ear drop preparation containing antibiotic and steroidal components. METHODS: The study was designed as an open, randomised, comparative clinical trial. Ambulatory patients suffering from OE were examined by an ear specialist and randomly divided into an otic powder (Auricularum) treatment group and an ear drop (Dex-Otic) treatment group. Each treatment group was treated in accordance with the daily doses recommended by the manufacturers. Patients were treated for a period of 14 days and examined on days 0, 3, 7, 10 and 14. Clinical signs and symptoms recorded were pain, erythema, swelling and discharge. RESULTS: A total of 67 patients entered the study. The probability of healing within 7 days was 74% in the otic powder group as opposed to 40% in the ear drops group (log rank test, p = 0.0013). The probability of total pain relief after 3 days of treatment was 60% in the otic powder group compared to 53% in the ear drops group (log rank test, p = 0.0001). CONCLUSION: We conclude that treatment with an otic powder (Auricularum) may promote earlier healing and pain relief than does treatment with otic drops (Dex-Otic).

[CO2 laser surgery for the treatment of vocal cord carcinomas in early stages (T1 T2)].

BACKGROUND: The standard treatment for patients with early vocal cord carcinoma has been radiotherapy. In recent years, encouraging results with CO2 laser surgery has changed our treatment strategy in selective cases. During the past four years at the Rabin Medical Center we have treated patients with carcinoma of the vocal cord using CO2 laser surgery. PURPOSE: We conducted a retrospective study to investigate the results of the Head and Neck Surgery department with CO2 laser treatment for squamous cell carcinoma of the vocal cord during early stages (T1, T2) without radiotherapy. MATERIALS AND METHODS: Twenty one patients with carcinoma of the vocal cords in early stages were treated with CO2 laser. Nineteen patients suffered from stage T1 carcinoma located in one vocal cord, three of these patients suffered from involvement of the anterior commissure and one patient also had involvement with the anterior part of the second vocal cord. Two patients with carcinoma in stage T2, one with involvement of the ventricular band and one with limited movement of the vocal cord. The follow-up period for the patients ranged from one month to four years. RESULTS: Only one patient in stage T1 developed local recurrence after half a year, no patients died during the follow-up. CONCLUSION: Careful patient selection with endoscopic staging also during the biopsy, removal of the carcinoma in free border, strict follow-up and stroboscopic examination are essential to secure good results in the treatment of CO2 laser for early stages of vocal cord carcinoma.

Cancer of the head and neck region in solid organ transplant recipients.

BACKGROUND: Solid organ recipients are at an increased risk of developing various malignancies. We investigated the incidence, clinical features, and outcome of patients diagnosed with head and neck cancer after organ transplantation. METHODS: A retrospective analysis was undertaken of patients who underwent solid organ transplantation (kidney, liver, lung, heart) treated at our institution from 1992 to 2010. RESULTS: Of 2817 organ recipients, 175 patients (6.1%) developed 391 head and neck malignancies. Cutaneous malignancies were the most common (93%): squamous cell carcinoma (SCC; 51%) and basal cell carcinoma (BCC; 42%). The average interval from transplantation to diagnosis of head and neck malignancy was 7.3 years, with liver recipients diagnosed earlier. Eighteen percent of patients presented with an aggressive pattern of head and neck cancer, including 24% of patients with cutaneous SCC. CONCLUSION: Organ transplantation recipients are at a higher risk to develop head and neck cancer with an aggressive behavior characterized by multiple recurrences and decreased survival.