Dermatofibrosarcoma protuberans with fibrosarcomatous transformation of the head and neck

Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous neoplasm associated with a high cure rate. We present a case of aggressive DFSP with fibrosarcomatous areas in the head and neck. A 28-year-old Mediterranean female presented with a 45-day history of rapidly growing cutaneous lesion of the face. Surgical biopsy confirmed the diagnosis of DFSP. Subsequently, the patient underwent wide local surgical resection, followed by reconstruction. Histopathology report revealed fibrosarcomatous transformation and the patient underwent adjuvant radiotherapy. The patient continues to be disease free at the 35-month follow-up

Screening for EGFR Mutations in Patients with Head and Neck Cancer Treated with Gefitinib on a Compassionate-Use Program: A Hellenic Cooperative Oncology Group Study

Background and Aim. EGFR is commonly expressed in cancers of the head and neck (H and N), and anti-EGFR agents have demonstrated improvements in outcomes (TTP and OS). The aim of this study was to determine EGFR gene status in H and N cancer patients treated with gefitinib and to correlate mutational status with clinico-pathological data and response. Patients and Methods. Patients with histologically confirmed H and N cancer having failed prior treatment for advanced disease entered this compassionate-use-program. Nineteen patients received gefitinib. EGFR expression was assessed by IHC, gene copy number by FISH, and mutation analysis was conducted for EGFR (18-21), KRAS, BRAF (V600E), and HER-2 exon 20. An additional TKI naive cohort of 73 patients was also screened. Results. Mutations were detected in 6/19 patients (3× EGFR, 1× KRAS, and 2× HER2-exon 20). There were no significant differences in TTP or OS for patients with somatic EGFR mutations. No BRAF mutations were detected. Conclusions. The incidence of EGFR mutations in H and N cancer in this study was 5.3%. No statistically relevant correlations between mutation or gene gain and response or survival were observed. Due to the limited number of patients and low incidence of genetic aberrations in the genes analyzed, additional studies are warranted

Muscle disorders and dentition-related aspects in temporomandibular disorders: controversies in the most commonly used treatment modalities

This review explores the aetiology of temporomandibular disorders and discusses the controversies in variable treatment modalities

Dysaesthesia in the mental nerve distribution triggered by a foreign body: a case report

INTRODUCTION: Foreign bodies' entrapments in the mandibular and submandibular regions are quite common. CASE PRESENTATION: We report an unusual case of foreign body (amalgam filling) entrapment over the mental foramen causing dysaesthesia in the distribution of the mental nerve. An interesting sign was blue discoloration of the overlaying oral mucosa which was interpreted as amalgam tattooing. CONCLUSION: Surgical removal of the foreign object eliminated the reported symptoms

Vascular endothelial growth factor in patients with advanced head and neck cancer

Background: The main prognostic variables of head and neck squamous cell carcinoma (HNSCC) are the location and size of the tumor and the presence of cervical lymph node metastasis. Differential gene expression of members of the VEGF family is a common feature in HNSCC. To elucidate the prognostic value and the interrelation of these factors we performed a detailed gene expression analysis within HNSCC tissue samples. Methods: We analyzed fresh frozen tissue from 41 recurrent HNSCC tumors stored at -80°C. RNA was isolated with the RNeasy kit (Qiagen, Inc.), followed by real time TaqMan PCR for the expression of the VEGF family genes (VEGF-A total, VEGF-A₁₂₁ VEGF-A₁₆₅, VEGF-A₁₈₉, VEGF-B, VEGF-C and VEGF-D) and their receptors VEGF-R1(Flt1), VEGF-R2(KDR/Flk1) and VEGF-R3(Flt4). Raw data (Ct values) were normalized to GAPDH expression (housekeeper gene) and candidate gene expression between patient groups with differential clinical outcomes was analyzed by using the SPSS 11.0.1 software package. Median patient follow-up from initial diagnosis of the relapse was 28 months. Results: Overexpression of VEGF-A total, VEGF-A₁₆₅ and VEGF-A₁₈₉ was prominent in most tumors, but did not appear to have any prognostic value. Both VEGF-A total and VEGF-A₁₆₅ significantly correlated with smoking abuse (number of cigarettes). However, VEGF-C expression was significantly higher in the tumors of patients with poor overall survival (<24 months). Median survival of patients with tumor VEGFC expression was calculated to be 42 months (Kaplan-Meier Survival Analysis), compared to 182 months in the rest of the patients. Conclusions: We have found that elevated VEGFC expression correlates with poor outcome in recurrent HNSCC patients. VEGFC preferably binds to the VEGFR3, which is predominantly expressed on lymphatic vessels. Overexpression of VEGFC may therefore result in the establishment of intratumoral lymphatic vessels, which have been shown to facilitate and enhance the dissemination of tumor cells into lymph nodes and the formation of distant metastases. We conclude that the determination of VEGFC expression may be of high prognostic value in HNSCC patients and that it may serve in the early identification of aggressive HNSCC subtypes.Εισαγωγή: οι κυριότεροι προγνωστικοί παράγοντες, σχετικά με την εξέλιξη του καρκινώματος της κεφαλής και του τραχήλου από πλακώδες επιθήλιο(ΚΚΤΠΕ), είναι η εντόπιση, το μέγεθος και η ύπαρξη μεταστατικών τραχηλικών λεμφαδένων. Η έκφραση των παραγόντων της οικογένειας VEGF, που σχετίζονται με την αγγειογένεση, η προγνωστική τους αξία στο προχωρημένο ΚΚΤΠΕ και η συσχέτιση με τα χαρακτηριστικά της νόσου, αποτέλεσαν το αντικείμενο της μελέτης μας. Μέθοδος: διατηρήσαμε νεοπλασματικό ιστό 41 ασθενών με υποτροπή ΚΚΤΠΕ στους -80°C, από το οποίο απομονώσαμε το RNA (RNeasy kit, Qiagen, Inc.) και με τη μέθοδο TaqMan PCR ανιχνεύσαμε την έκφραση των παραγόντων της οικογένειας VEGF(VEGF-A total, A₁₂₁, A₁₆₅, A₁₈₉, B,C,D) και των υποδοχέων τους VEGF-R1(Flt1), VEGF-R2(KDR/Flk1) και VEGF-R3(Flt4). Ο μέσος χρόνος του επανελέγχου, από τη διάγνωση της υποτροπής ήταν 28 μήνες. Αποτελέσματα: η έκφραση των παραγόντων VEGF-A ολικό και VEGF-A₁₆₅ συσχετίστηκε με τον αριθμό των τσιγάρων, ενώ η έκφραση του παράγοντα VEGF-C βρέθηκε σημαντικά υψηλότερη στους όγκους ασθενών με φτωχή ολική επιβίωση. Συμπεράσματα: διαπιστώσαμε ότι η αυξημένη έκφραση του VEGF-C σε ασθενείς με υποτροπή του ΚΚΤΠΕ, σχετίζεται με φτωχή πρόγνωση. Συμπεραίνουμε ότι το γονίδιο αυτό θα μπορούσε να αξιοποιηθεί ως προγνωστικός δείκτης στους ασθενείς με ΚΚΤΠΕ

Transcriptional Activity of Human Epidermal Growth Factor Receptor Family and Angiogenesis Effectors in Locoregionally Recurrent Head and Neck Squamous Cell Carcinoma and Correlation with Patient Outcome

Locoregional recurrence is the most common failure pattern in patients with head and neck squamous cell carcinoma (HNSCC). We retrospectively identified 41 HNSCC patients with locoregional relapse and used kinetic reverse transcription-polymerase chain reaction (kRT-PCR) in order to study fresh-frozen tumour messenger RNA (mRNA) levels of the Human Epidermal growth factor family members HER1-4, the Vascular Endothelial Growth Factors (VEGFs) A, B, C, D, and their receptors VEGFR1, 2, 3. High VEGF-C and VEGFR3 tumour mRNA expression correlated with relapse beyond the primary locus (neck nodes or soft tissues, P < .05). Tumours with regional nodal involvement at diagnosis more often exhibited high transcriptional activity of VEGFR1 and VEGFR3 at the time of relapse (P < .05). At a median follow-up of 52 months from the time of locoregional recurrence, patients with high VEGF-C tumours at relapse had significantly poorer postrelapse progression-free survival (R-PFS, 5 versus 47 months, log-rank P = .052) and a trend for inferior postrelapse overall survival (R-OS, 22 versus 44 months, log-rank P = .076) in comparison to low VEGF-C tumours. Similar association with dismal outcome was seen for its receptor, VEGFR3 tumoural mRNA levels (log-rank P = .060). In contrast, suppressed tumour transcription of VEGF-D was associated with poorer post-relapse survival, though statistical significance was not reached. Active transcription of the VEGF-C/VEGFR3 axis in recurrent HNSCC is associated with failure at neck soft tissues/lymph nodes and inferior survival post-relapse

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&lt;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&lt;0.001) and 1st validation (p = 0.010) sets. Specifically, in the 1st 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 2nd 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