The application of the anterior cervical flap in major head and neck surgery.

We present a case of a 79-year-old male patient, who was diagnosed with a primary squamous cell carcinoma of the left parotid region that was fungating through the skin and infiltrating the sternocleidomastoid muscle. Clinically and radiologically, the patient was staged as T3 N2b M0. He underwent a near-total parotidectomy with facial nerve preservation in conjunction with a modified radical neck dissection and wide excision of the involved skin to remove all the disease in a monobloc fashion. A regional cutaneous flap, the anterior cervical flap was used for reconstruction of a large surgical defect.

Synchronous Bilateral Laryngeal Oncocytic Papillary Cystadenoma: An Uncommon Occurrence.

Oncocytic papillary cystadenoma is a rare, benign tumor highly uncommon in the larynx. Although controversy exists regarding its true nature it is considered a phenomenon of metaplasia. We present the case of a 57-year-old patient with synchronous, bilateral oncocytic papillary cystadenoma of the ventricles and we discuss the current literature.

Genetic Variation in the Vascular Endothelial Growth Factor (VEGFA) Gene at rs13207351 Is Associated with Overall Survival of Patients with Head and Neck Cancer.

Head and neck cancer (HNC) is a significantly heterogeneous disease and includes malignancies arising from different anatomical sites, such as nasopharyngeal cancer (NPC) and laryngeal cancer (LC). In the current study, polymorphisms located in angiogenesis- and apoptosis-related genes (VEGFA, FAS, EDNRA and NBS1) were evaluated regarding their clinical significance in HNC patients. In total, 333 HNC patients were enrolled in this study and 34 variants located on the aforementioned genes were genotyped via Sanger sequencing. LC patients, homozygous A for VEGFA rs13207351, had shorter overall survival (OS) as opposed to homozygous G (Hazard ratio (HR) = 2.06, Wald's p = 0.017) upon adjustment for age, disease stage, and surgery. Following the dominant model, LC patients carrying the A allele had a marginally significantly higher risk for death (HR = 1.72, p = 0.059). NPC patients heterozygous (CT) for FAS rs2234768 had a marginal but significantly higher risk of death compared to those with homozygosity for the T allele (HR = 2.22, p = 0.056). In conclusion, rs13207351 (VEGFA) and rs2234768 (FAS) polymorphisms seem to have prognostic significance in HNC, with VEGFA rs13207351 showing the most promise in this subgroup of LC patients.

Extramedullary plasmacytoma of temporal bone: report of 2 cases and review of literature.

OBJECTIVE: The aim of the study was to report 2 cases of extramedullary plasmacytoma (EP) with localization to middle ear that were diagnosed and managed in our department. METHODS: The first patient was a 60-year-old man with progressive hearing loss, tinnitus, recurrent episodes of otalgia, and otorrhea in his right ear during the last 2 years. The second patient was a 66-year-old man who presented with aural fullness in his right ear and a mild pain in the region of right mastoid. Mild hearing loss and episodes of dizziness with sensation of falling for about 6 months were reported in the clinical history. CONCLUSIONS: The prognosis of EP is considered favorable in regard to the solitary bone plasmacytoma and multiple myeloma (MM). The differential diagnosis of EPs from other plasma cell dyscrasias and especially from MM is considered essential. It is a radiosensitive tumor and, especially for EPs of temporal bone, the combined treatment of surgery resection and postoperative radiation seems to provide the best local control and the lower risk of occurrence. The therapeutic strategy includes a close follow-up of the patients because of the risk of occurrence and/or dissemination into MM. The 10-year survival rate reaches 70% with the appropriate therapy.

Protein and mRNA expression of notch pathway components in operable tumors of patients with laryngeal cancer.

BACKGROUND: There exist substantial evidence that laryngeal cancer represents a unique entity among squamous head and neck carcinomas. MATERIALS AND METHODS: Tumors from 289 patients with squamous cell laryngeal cancer were assessed for protein (immunohistochemistry) and mRNA (qRT-PCR) expression of Notch pathway components (Notch1 to 4 receptors and Jagged1 ligand) on tissue microarrays. RESULTS: In univariate analysis, enhanced nuclear Jagged1 expression conferred a longer disease-free survival (DFS) (p=0.013) and overall survival (OS) (p=0.004), in contrast to the unfavorable prognostic value of Notch3 for both DFS (p=0.009) and OS (p=0.024). In multivariate analysis, overexpression of either Notch or cytoplasmic Jagged1 conferred an unfavorable effect on DFS (Hazard Ratio=1.88, 95% Confidence Interval=1.03-3.43, p=0.04). CONCLUSION: Our study indicates a consistent unfavorable effect of Notch3 and cytoplasmic Jagged1 protein expression, a favorable impact of nuclear Jagged 1 localization, and a differential prognostic value of Notch2 expression according to the presence of cytoplasmic Jagged 1.

Prognostic significance of the Wnt pathway in squamous cell laryngeal cancer.

OBJECTIVES: We sought to determine the prognostic significance of the Wnt signaling pathway in operable squamous cell carcinoma of the larynx. MATERIALS AND METHODS: In an annotated cohort of 289 operable laryngeal cancers we evaluated the prognostic impact of E-cadherin, P-cadherin and ß-catenin protein expression with immunohistochemistry, as well as the mRNA expression of 7 key effectors of the Wnt pathway including secreted frizzled-related protein 4 (SFRP4), SNAI2 (SLUG) and WNT5A with qPCR (relative quantification [RQ]). RESULTS: Using median immunoreactive scores as a pre-defined cut-off, patients whose tumors overexpressed both cytoplasmic E-cadherin and ß-catenin experienced longer median OS as compared to those whose tumors overexpressed ß-catenin only (median OS 124 vs. 72 months, p=0.0301) and patients whose tumors overexpressed both cytoplasmic and membranous E-cadherin experienced longer DFS as compared to those whose tumors overexpressed cytoplasmic E-cadherin only (median 118 vs. 91 months, p=0.0106). Upon hierarchical clustering of SFRP4, SNAI2 and WNT5A RQ values, profiles including co-expression of all 3 genes but also profiles with under-expression of SNAI2 and WNT5A were associated with worse outcome as compared to profiles not related to the Wnt pathway. In multivariate analysis, clustering was an independent predictor for DFS (p=0.0221) and OS (p=0.0077). CONCLUSION: We identified gene expression profiles and IHC patterns associated with aberrant Wnt signaling conferring aggressive clinical behavior in operable squamous cell carcinoma of the larynx. Prospective validation of these results will determine whether targeting the Wnt pathway merits investigation in this disease.

Hybrid carcinoma of the larynx: a case report (adenoid cystic and adenocarcinoma) and review of the literature.

Introduction. The nonsquamous carcinomas of the larynx are considered rare with the majority of malignant tumors in this area, reaching the rate of 95%, to be squamous cell neoplasms. Case Report. The case refers to a 53-year-old man that presented with symptomatology of motor nerve disease. During the evaluation of the neurologic disease, a subglottic mass of the larynx was revealed accidentally in the imaging examination. Under general anesthesia, we performed direct laryngoscopy and biopsy of the mass. The histopathologic examination revealed a hybrid carcinoma coexistence of two different carcinomas, an adenoid cystic carcinoma and an adenocarcinoma, not otherwise specified with poor differentiation. Regarding the therapeutic plan, the mass was considered inoperable due to its expansion to trachea and the patient received radiotherapy. Conclusions. Both the adenocarcinoma and adenoid cystic carcinoma are extremely rare types of malignant tumors in the larynx. The special interest of the present case is the coexistence of these two rare tumors in the same region of the larynx, being a hybrid tumor of the salivary glands in the larynx, which is the second reported case, based on our systematic literature review.

Insulin-like growth factor 1 receptor (IGF1R) expression and survival in operable squamous-cell laryngeal cancer.

INTRODUCTION: Prognosis of patients with operable laryngeal cancer is highly variable and therefore potent prognostic biomarkers are warranted. The insulin-like growth factor receptor (IGFR) signaling pathway plays a critical role in laryngeal carcinogenesis and progression. PATIENTS AND METHODS: We identified all patients with localized TNM stage I-III laryngeal cancer managed with potentially curative surgery between 1985 and 2008. Immunohistochemical (IHC) expression of IGF1R-alpha, IGF1R-beta and IGF2R was evaluated using the immunoreactive score (IRS) and mRNA levels of important effectors of the IGFR pathway were assessed, including IGF1R, IGF-binding protein 3 (IGFBP3), suppressor of cytokine signaling 2 (SOCS2) and members of the MAP-kinase (MAP2K1, MAPK9) and phosphatidyl-inositol-3 kinase (PIK3CA, PIK3R1) families. Cox-regression models were applied to assess the predictive value of biomarkers on disease-free survival (DFS) and overall survival (OS). RESULTS: Among 289 eligible patients, 95.2% were current or ex smokers, 75.4% were alcohol abusers, 15.6% had node-positive disease and 32.2% had received post-operative irradiation. After a median follow-up of 74.5 months, median DFS was 94.5 months and median OS was 106.3 months. Using the median IRS as the pre-defined cut-off, patients whose tumors had increased IGF1R-alpha cytoplasm or membrane expression experienced marginally shorter DFS and significantly shorter OS compared to those whose tumors had low IGF1R-alpha expression (91.1 vs 106.2 months, p = 0.0538 and 100.3 vs 118.6 months, p = 0.0157, respectively). Increased mRNA levels of MAPK9 were associated with prolonged DFS (p = 0.0655) and OS (p = 0.0344). In multivariate analysis, IGF1R-alpha overexpression was associated with a 46.6% increase in the probability for relapse (p = 0.0374). Independent predictors for poor OS included node-positive disease (HR = 2.569, p<0.0001), subglottic/transglottic localization (HR = 1.756, p = 0.0438) and IGF1R-alpha protein overexpression (HR = 1.475, p = 0.0504). CONCLUSION: IGF1R-alpha protein overexpression may serve as an independent predictor of relapse and survival in operable laryngeal cancer. Prospective evaluation of the IGF1R-alpha prognostic utility is warranted.

Identification and validation of a multigene predictor of recurrence in primary laryngeal cancer.

PURPOSE: Local recurrence is the major manifestation of treatment failure in patients with operable laryngeal carcinoma. Established clinicopathological factors cannot sufficiently predict patients that are likely to recur after treatment. Additional tools are therefore required to accurately identify patients at high risk for recurrence. This study attempts to identify and independently validate gene expression models, prognostic of disease-free survival (DFS) in operable laryngeal cancer. MATERIALS AND METHODS: Using Affymetrix U133A Genechips, we profiled fresh-frozen tumor tissues from 66 patients with laryngeal cancer treated locally with surgery. We applied Cox regression proportional hazards modeling to identify multigene predictors of recurrence. Gene models were then validated in two independent cohorts of 54 and 187 patients (fresh-frozen and formalin-fixed tissue validation sets, respectively). RESULTS: We focused on genes univariately associated with DFS (p<0.01) in the training set. Among several models comprising different numbers of genes, a 30-probe set model demonstrated optimal performance in both the training (log-rank, p<0.001) and 1(st) validation (p=0.010) sets. Specifically, in the 1(st) validation set, median DFS as predicted by the 30-probe set model, was 34 and 80 months for high- and low-risk patients, respectively. Hazard ratio (HR) for recurrence in the high-risk group was 3.87 (95% CI 1.28-11.73, Wald's p=0.017). Testing the expression of selected genes from the above model in the 2(nd) validation set, with qPCR, revealed significant associations of single markers, such as ACE2, FLOT1 and PRKD1, with patient DFS. High PRKD1 remained an unfavorable prognostic marker upon multivariate analysis (HR=2.00, 95% CI 1.28-3.14, p=0.002) along with positive nodal status. CONCLUSIONS: We have established and validated gene models that can successfully stratify patients with laryngeal cancer, based on their risk for recurrence. It seems worthy to prospectively validate PRKD1 expression as a laryngeal cancer prognostic marker, for routine clinical applications.

Primary pleomorphic adenoma of the external ear canal. Report of a case and literature review.

INTRODUCTION: Primary neoplasms of the external ear canal are rare, and 5% of these tumors are of glandular origin. Ceruminal glands are modified sweat glands of the skin of the external auditory meatus that may give rise to (a) benign tumors such as ceruminous adenoma, pleomorphic adenoma, and syringocystadenoma papilliferum, and (b) malignant tumors such as ceruminous adenocarcinoma, adenoid cystic carcinoma, and mucoepidermoid carcinoma. An alternative theory holds that pleomorphic adenomas may well arise from ectopic salivary tissue present in the external ear canal. These tumors are very rare and usually have a benign course. In this report, we describe an unusual case of pleomorphic adenoma of the external auditory canal associated with chronic infection of the middle ear. CASE REPORT: A 60-year-old woman presented with exacerbation of left otalgia over a 6-month period. She had been affected with chronic otitis media and aural polyps for the last 13 years, for which she had received medical treatment only. A canal-filling aural polyp was noted on clinical examination. Subsequent biopsy and histologic examination revealed pleomorphic adenoma of the external ear canal, possibly with malignant elements. Magnetic resonance imaging showed no intracranial extension or any association with the adjacent parotid gland. The patient underwent modified radical mastoidectomy and complete resection of the tumor and the entire skin of the external auditory canal. Final histology and immunohistochemistry confirmed the absence of malignancy, and no recurrence has been reported 1 year postoperatively. CONCLUSIONS: Pleomorphic adenoma is an extremely rare tumor arising from the ceruminal glands of the external ear canal. Nonspecific presentation and difficult histologic diagnosis characterize this benign neoplasm. Wide local excision is the mainstay of treatment.