Lymphoepithelial Subtype of Oral Squamous Cell Carcinoma: Report of an EBV-Negative Case and Literature Review.

Lymphoepithelial carcinoma (LEC) of the oral mucosa is a rare histopathologic subtype of squamous cell carcinoma (SCC), which shares morphologic similarities with nasopharyngeal carcinoma (NPC), non-keratinizing undifferentiated subtype. The admixture of neoplastic epithelial tumor cells and a dense lymphoplasmacytic infiltrate makes microscopic diagnosis challenging. LEC etiopathogenesis has been variably associated with Epstein-Barr virus (EBV) infection, depending on the specific anatomic location and racial predilection, with a higher incidence in endemic populations. Although described in several subsites of the head and neck region, including the major salivary glands, the oral mucosa is considered an infrequent location for LEC development, deriving either from minor salivary glands (MSGs) or the surface epithelium. Herein, we report a rare case of an EBV-negative LEC arising from the oral surface epithelium, presenting as gingival swelling, and review the pertinent English-language literature, which revealed only 26 previously reported oral LECs. Our case is only the fourth oral LEC originating from the surface epithelium and the first one to affect the gingiva.

Effects of sociodemographic, treatment variables, and medical characteristics on quality of life of patients with maxillectomy restored with obturator prostheses.

STATEMENT OF PROBLEM: Restoration of maxillary defects resulting from tumor ablative surgery presents a difficult challenge, with both functional and esthetic issues. Whether rehabilitation with an obturator prosthesis could significantly contribute to improved quality of life in patients with maxillary resection has been scarcely studied, with relatively small study samples. PURPOSE: The purpose of this survey study was to assess the overall functioning of the obturator prosthesis and the effect of specific sociodemographic, medical, and treatment variables on obturator functioning and quality of life in patients with maxillectomy. MATERIAL AND METHODS: Global quality of life (QOL) and satisfaction with the obturator prosthesis of 57 patients who underwent maxillectomy and prosthetic rehabilitation at the National and Kapodistrian University of Athens were assessed using 3 questionnaires: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30), the EORTC QLQ-HN35, and the obturator functioning scale. The data were analyzed using the Kruskal-Wallis 1-way ANOVA on ranks, hierarchical multiple regression analysis, and the Spearman rank order correlation (α=.05). RESULTS: Satisfactory functioning of the obturator prosthesis was the most significant predictor of improved QOL (P<.05). QOL was significantly related to additional treatments (P<.05), the size of the primary tumor (P<.05), and the size of the maxillectomy defect (P<.05). The most significant predictors of good obturator functioning were additional treatments (P<.01), age at the time of surgery (P<.05), presence of mandibular teeth (P<.05), and previous maxillary removable prosthetic experience (P<.05). Obturator functioning scale appearance and insertion subscales (r=0.47, P<.01), followed by speech (r=0.42, P<.01), were significantly related to better QOL. CONCLUSIONS: A well-functioning obturator prosthesis was the most significant determinant for improved QOL in patients with maxillary resection. Age at the time of surgery, adjuvant treatments, presence of mandibular teeth, and previous maxillary removable prosthetic experience were the most significant predictors for better obturator functioning, whereas the size of the maxillectomy defect had a significant effect on QOL but did not influence the functional outcome.

Phosphorylated signal transducer and activator of transcription-1 immunohistochemical expression is associated with improved survival in patients with oral squamous cell carcinoma.

PURPOSE: To estimate whether the immunohistochemical (IHC) expression patterns of the tumor suppressor gene signal transducer and activator of transcription-1 (STAT1) and its active phosphorylated form (PSTAT1) serve as potential prognostic and predictive markers in patients with oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: STAT1 and PSTAT1 protein expressions were examined immunohistochemically in OSCC tumor tissues and adjacent normal mucosa from 49 patients who underwent primary surgery. The IHC scores were correlated with all available clinicopathologic parameters that were obtained from a maximum of 7 years of follow-up, including survival and response to adjuvant therapy treatment. RESULTS: There was a shift toward lower percentages of cells with STAT1 (P < .014) and PSTAT1 (P < .001) detected in OSCC tumors compared with adjacent normal tissue sites. No association with patients' clinicopathologic characteristics was shown. However, for the group of patients who received adjuvant chemotherapy, increased PSTAT1 intensity of staining in OSCC tumors was strongly associated with better overall survival (P = .008). CONCLUSIONS: This is the first study to concurrently evaluate STAT1 and PSTAT1 IHC expression patterns and their prognostic significance in patients with OSCC, highlighting the potential role of PSTAT1 as a biomarker in therapeutic decision making. Large prospective studies are needed to verify these findings.

Feasibility of Induction Docetaxel, Cisplatin, 5-Fluorouracil, Cetuximab (TPF-C) Followed by Concurrent Cetuximab Radiotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma.

PURPOSE: To report our experience with a sequential regimen of induction TPF-C followed by radioimmunotherapy with cetuximab in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: Toxicity and outcome was retrospectively analyzed in 22 patients receiving sequential therapy with induction TPF-C followed by radioimmunotherapy between October 2008 and December 2011. Outcome was estimated using Kaplan-Meier analyses. In addition, we performed mutation analysis for PIK3CA genes and high risk HPV DNA detection using PCR. RESULTS: Mean time of follow-up was 16 months. Six patients were TNM Stage III, 15 patients IV (IVA or IVB), and one patient Stage II with bulky disease. During TPF-C, Grade 3 and 4 toxicities occurred in eight patients, dose modifications in seven, delays in one, and unplanned admissions in five. Clinical tumor response was documented in 18 of the 21 patients who completed at least three cycles of TPF-C with three patients developing complete response and 15 partial responses. Grade 3/4 mucositis was observed in six patients. At a median follow-up of 19 months, 13 patients were alive and nine had died including seven patients as a result of disease persistence or recurrence and two as a result of unrelated causes. PIK3CA mutations were not identified and our two oropharynx cases were HPV negative. CONCLUSION: The combination of induction TPF-C with concurrent cetuximab radioimmunotherapy in patients with locally advanced HNSCC is tolerable, with encouraging efficacy.

Novel mutations of the HRAS gene and absence of hotspot mutations of the BRAF genes in oral squamous cell carcinoma in a Greek population.

Oral squamous cell carcinoma (OSCC) is the sixth most common cancer in the world. The phosphatidylinositol 3 kinase (PI3K) signalling pathway has been reported to play an important role in OSCC. Since we have previously detected absence of hotspot PIK3CA gene mutations in the Greek population, we hypothesized that BRAF or HRAS may be activated as upstream effectors of the pathway. Furthermore, the status of the HRAS and BRAF mutations in OSCC has never been assessed before in the Greek population. Eighty-six primary paraffin-embedded tumors were screened for BRAF and HRAS hotspot mutations. In HRAS, two hotspot mutations in codon 12 (2.3%) and eight new genetic alterations were detected (8.6% overall). One new missense mutation, Alanine53Valine (Ala53Val), one silent mutation, two mutations in the 5'UTR region and four mutations in intron 1 were detected. No hotspot mutations in Braf were found. A new silent mutation/polymorphism T1803C was detected at a percentage of 30%. This study is the first to report HRAS mutations in the Greek population. The results suggest that RAS is an important member of the PI3K signalling pathway and may play a role in the tumorigenesis of OSCC.

Transfusion of allogenic leukocyte-depleted packed red blood cells is associated with postoperative morbidity in patients undergoing oral and oropharyngeal cancer surgery.

Evidence indicates that allogenic packed red blood cell transfusion results in the host's immunomodulation, and is associated with adverse clinical outcomes after surgery. The aim of this study was to test whether allogenic leukocyte-depleted blood transfusion represents a significant risk factor for postoperative morbidity after oral and oropharyngeal cancer surgery. A total of 142 patients, diagnosed for the first time with oral and oropharyngeal squamous cell carcinoma, and receiving neoadjuvant chemoradiotherapy followed by surgery between 2000 and 2008 were retrospectively included in this study. Univariate and multivariate logistic regression models were calculated to identify predictors of postoperative complications. We found a significantly higher complication rate in the group of transfused patients compared to patients not exposed to transfusion (complication rate of 84% and 39%, respectively, p<0.001). On multivariate analysis, the amount of packed red blood cells transfused (for 1-4 units transfused: adjusted OR, 2.59; 95% CI, 1.24-5.39; p=0.011; for more than >4 units transfused: adjusted OR, 5.29; 95% CI, 2.01-13.88; p=0.001) and Charlson's comorbidity score ≥1 (adjusted OR, 2.81; 95% CI, 1.38-5.70; p<0.004) were independently associated with the development of postoperative complications. Allogenic leukocyte-depleted blood transfusion is independently associated with increased postoperative complications in patients undergoing surgery for oral and oropharyngeal cancer. This association follows a dose-response relationship, as patients who received larger amounts of packed red blood cells showed a significant trend toward higher postoperative morbidity.

Evaluation of immunohistochemical expression of p53, p21, p27, cyclin D1, and Ki67 in oral and oropharyngeal squamous cell carcinoma.

BACKGROUND: The purpose of this study was to evaluate whether the immunohistochemical expression of p53, p21, p27, cyclin D1, and Ki67 can predict therapy response and survival in patients with oral and oropharyngeal squamous cell carcinoma treated with preoperative chemoradiation. METHODS: Biomarker expression was evaluated by immunohistochemistry in formalin-fixed, paraffin-embedded pretreatment biopsies of 111 homogenously treated patients. We assessed the association between clinicopathological variables including response to neoadjuvant chemoradiotherapy as well as the survival of the patients and the expression of the biomarkers as both dichotomized (positive vs. negative) and continuous variables. RESULTS: Biomarker overexpression on the basis of pre-selected cutoff points was seen in 66 of 111 (59%) cases for p53, in 77 (69%) for p21, in 48 (43%) for p27, in 81 (73%) for cyclin D1, and in 54 (49%) cases for Ki67, respectively. None of the examined biomarkers was able to predict response to neoadjuvant chemoradiotherapy or was associated with survival outcome. Post-treatment pathologic TNM stage (P < 0.001), pathologic response (P < 0.001), and perineural invasion (P < 0.001) were the only factors having a significant effect on recurrence-free survival. Post-treatment pathologic N stage (P = 0.005), post-treatment pathologic TNM stage (P < 0.001), pathologic response (P < 0.001), and perineural invasion (P = 0.001) had a significant impact on overall survival. CONCLUSIONS: Our results suggest that the biomarkers p53, p21, p27, cyclin D1, and Ki67 have no impact on treatment response and survival in patients with oral and oropharyngeal cancer treated with preoperative chemoradiation.

Management of malignant parotid tumors.

INTRODUCTION: The aims of this study were to review our experience in the treatment of malignant parotid tumors in material from one center over a 12-year period and to assess treatment outcome and particularly survival. MATERIALS AND METHODS: Thirty-one patients treated primarily by surgery were included in the study. Complete data regarding the demographic details of the patients, tumor stage, presence of regional/distant metastases, treatment, tumor histology, grade, and follow up were compiled. With reference to the extent of tissue removed, partial superficial parotidectomy was performed in 11 patients, superficial parotidectomy, in 14 patients, and total radical parotidectomy, in six patients. RESULTS: The median time of follow-up was 64 months, ranging from 8 to 144 months. Eight patients developed recurrences. Six patients died within the follow-up time. The overall survival rates at 5 and 10 years were 82.2% and 76.7%, respectively. The 5- and 10-year disease-free survival rates were 74.8% and 69.8%, respectively. DISCUSSION: For patients with malignant parotid tumors, the treatment should be individualized according to the findings of each specific case, and regarding surgery, particular care and attention should be paid to maintaining all or part of the facial nerve whenever possible.

Complications after free flap surgery: do we need a standardized classification of surgical complications?

Our main objective was to apply a standard classification to surgical complications after free flap surgery for reconstructions of the head and neck. We used the modified Clavien-Dindo classification in a cohort of 79 patients who were having reconstructions with jejunal free flaps simultaneously with resections of oral and oropharyngeal cancer. The most common minor complication was the need for a blood transfusion, and the most common major complication of a respiratory nature. The medical complications, and those at the recipient site and the donor site were 53/79 (67%), 44/79 (56%), and 9/79 (11%), respectively. The Clavien-Dindo classification is suitable and can easily be used to evaluate postoperative complications after free tissue transfer.

Partial superficial parotidectomy as the method of choice for treating pleomorphic adenomas of the parotid gland.

We present our experience of 156 patients with parotid pleomorphic adenomas who were treated from 1995 to 2009 by partial superficial parotidectomy. In each case the main trunk of the facial nerve was identified and dissected. Only the division of the nerve adjacent to the tumour was dissected, and only the parotid tissue surrounding the tumour was excised. The results were satisfactory, as no patient developed permanent partial or total facial nerve paralysis, and transient paresis was noticed in only 23 patients (15%). Only one tumour recurred, and Frey syndrome developed in only 6 patients (4%). Enucleation was required in 55 patients (35%) because the tumour was so close to the branches of the facial nerve. Partial superficial parotidectomy is a safe treatment for parotid pleomorphic adenomas with relatively few postoperative complications. When it is done by experienced surgeons no permanent deficits are likely, it has low rates of recurrence, and gives excellent aesthetic results.

Histopathologic study of the carotid sheath in patients with oral squamous cell carcinoma.

PURPOSE: The carotid sheath has not been adequately assessed in the literature as a potential site of neck recurrence. The purpose of this prospective study was to investigate the histopathologic characteristics of the carotid sheath in patients with oral cancer, in an effort to clarify whether it is essential or redundant to include the carotid sheath in the neck dissection specimen. PATIENTS AND METHODS: A total of 29 patients underwent 32 selective neck dissections in the Department of Oral and Maxillofacial Surgery at "Evangelismos" General Hospital of Athens, Greece. Twenty-six unilateral and 3 bilateral neck dissections were performed. The carotid sheath specimens were examined to identify possible traces of metastatic disease. The existence of lymphatic vessels and the possible presence of cancer cells within their lumen was also investigated. RESULTS: Light microscopy of the 32 carotid sheath specimens showed that there was no evidence of tumor invasion. Immunohistochemical evaluation showed an abundance of lymphatic vessels in the carotid sheath with no evidence of microscopic intraluminal metastatic emboli. CONCLUSIONS: There was no evidence of carotid sheath invasion or presence of intraluminal lymphatic tumor emboli. Evidence of extracapsular spread warrants carotid sheath excision. Our findings suggest that if no extracapsular spread is present, there is no need to perform a tedious dissection of the carotid sheath. Preserving the carotid sheath adds protection to the neurovascular bundle, cuts operating time, and avoids possible injury to the major vessels and vagus nerve, as well as stimulation of the carotid body.

Acantholytic squamous cell carcinoma of the gingiva: report of a case and review of the literature.

Adenoid squamous cell carcinoma differs from common squamous cell carcinoma in histologic features and its aggressive nature. Microscopically, the tumor shows cystic degeneration of the neoplastic epithelium, producing a prominent alveolar pattern and pseudoglandular structures with acantholytic cells. It occurs most commonly on the lips, rarely intraorally, and it is associated with a poor prognosis. This case concerns a 72-year-old woman who presented with the chief complaint of burning tongue and soreness of the lips. Clinical examination revealed an ulcerated and elevated mass on the edentulous left maxillary ridge, beneath the base of a partial denture. An incisional biopsy rendered the diagnosis of adenoid squamous cell carcinoma. The patient was referred to a specialized maxillofacial surgery center for diagnostic work-up and treatment. She underwent partial maxillectomy and radiotherapy, and 17 months after treatment, she died of uncontrollable recurrence.

A case of successfully treated rhinocerebral mucormycosis: dental implications.

This paper presents a case of rhinocerebral mucormycosis in a 22-year-old female patient with type I diabetes mellitus, who was successfully treated with surgery and long-term antifungal medication. The patient had initially been submitted to extraction of an upper third molar by a general dental practitioner but was referred to our department three days postoperatively because of double vision. Immediately following histopathological confirmation of the infection, the patient was administered Amphotericin B and Posaconazole intravenously. Surgical excision of the affected site was relatively conservative. The patient was free of the disease 15 months after initial admission to the hospital and has recently returned for reconstruction. The aim of this paper is to increase the awareness of general dental practitioners regarding uncommon serious conditions in diabetic patients, which may be confused with periodontal or dental diseases.

Large olfactory neuroblastoma (esthesioneuroblastoma) surgically treated with an Altemir technique modification: a case report.

INTRODUCTION: Olfactory neuroblastomas are rare malignant tumors that usually occur in the upper nasal cavity. The purpose of this paper is to present a case of a large olfactory neuroblastoma filling the entire nasal cavity, treated with an Altemir technique modification. METHODS: A 39-year-old woman presented with a large tumor of the nasal cavity. After the laboratory examinations, the tumor was classified as a Kadish stage A olfactory neuroblastoma. The selected treatment was the surgical excision after an Altemir technique modification combined with midfacial degloving and additional radiotherapy. RESULTS: Histopathology revealed a Hyams grade III olfactory neuroblastoma completely removed. Although the patient refused the additional radiotherapy, 18 months postoperatively, there were no signs of recurrence, and the patient shows big improvement on her sense of smell. CONCLUSIONS: Large olfactory neuroblastomas filling the entire nasal cavity extending back to the postnasal space can be completely removed using a transfacial approach as the Altemir technique modification is.

Metastases to supramandibular facial lymph nodes in patients with squamous cell carcinoma of the oral cavity.

PURPOSE: This study evaluated the frequency of metastases to supramandibular facial lymph nodes (SFLNs) in patients with squamous cell carcinoma (SCC) of the oral cavity. PATIENTS AND METHODS: SFLNs were identified and removed during neck dissection from 43 patients with oral SCC. All of them were histopathologically and immunohistochemically examined, to detect possible metastases and micrometastases. RESULTS: Metastases to SFLNs were present in 6 patients (13.95%). Metastases were much more common among patients with palpable neck nodes, larger size of the primary site, advanced TNM stage, and greater age and those in whom the primary site was located in the mucosa of the alveolar ridge of the mandible. CONCLUSIONS: Surgical procedures in the region of the SFLNs must be performed very carefully, because of their close relation with the marginal mandibular nerve. In patients with oral SCC and palpable neck nodes, those with advanced disease, and those in whom the primary site is located in the mucosa of the alveolar ridge of the mandible, removal of SFLNs must be considered.

Branchial cleft cysts in adults. Diagnostic procedures and treatment in a series of 18 cases.

PURPOSE: Branchial cleft anomalies may be presented as branchial cysts, fistulas, or sinuses. Purpose of this paper is to present the diagnostic procedures and the treatment in a series of branchial cleft cysts. METHODS: Eighteen patients with branchial cleft cysts were surgically treated. All of them were subjected in laboratory examinations with ultrasonography, CT or/and MRI, and fine needle aspiration cytology (FNAC). Complete excision was the treatment in all cases. RESULTS: Eight patients had Type I, seven Type II, two Type III, and one a Type IV cyst. In all cases the surgical removal was successful and after 1 to 7 years post-surgical follow-up, no recurrences have been developed. CONCLUSIONS: Branchial cleft cyst diagnostic procedure must be the same as for other neck swellings. FNAC is very useful for the diagnosis and the surgical approach must ensure safe and complete cyst removal in order to avoid intraoperative complications and recurrences.

Intramuscular myxoma of the masseter muscle. A case report.

PURPOSE: Myxomas are benign, locally infiltrative, connective tissue tumors that rarely occur in the head and neck region. The purpose of this paper is to describe a very rare case of an intramuscular myxoma of the masseter muscle. METHODS: A 74-year-old man presented with a 2-year history of a painless swelling over his left preauricular region. Computed tomography scan showed an intramasseter well-defined soft tissue mass. After a preauricular approach, a circumscribed solid gelatinous tumor was excised with thin margins including adjacent muscle tissue. RESULTS: Histopathology revealed an intramuscular myxoma, completely resected. The patient made an uneventful recovery, and there were no signs of recurrence 26 months after surgery. CONCLUSIONS: Intramuscular myxoma of the masseter is an extremely rare entity, but it must be considered in the differential diagnosis of the swellings of the preauricular region.

Use of a porcine dermal collagen graft (Permacol) in parotid surgery.

Our aim was to present the results of the use of porcine dermal collagen graft (Permacol) in the prevention of Frey's syndrome and face-contouring aesthetic deformities after operations on the parotid. We treated 19 patients with parotid tumours. After resection, a Permacol sheet was applied to the perimeter of the tissue deficit so that it was fully covered, and was sutured firmly. This technique produced satisfactory aesthetic results with good facial contouring in all patients. It also protected the exposed parotid nerve plexus, and none of the patients developed Frey's syndrome. Permacol produced good results in both postoperative facial contouring and prevention of Frey's syndrome.

Hypoglossal nerve palsy caused by a large vagal paraganglioma: case report.

We present a vagal paraganglioma in a 74-year-old woman, who presented with dysphagia, dysarthria and hoarseness.

Vascular fractal dimension and total vascular area in the study of oral cancer.

BACKGROUND: Microvessel quantification has been studied extensively as a factor reflecting angiogenesis in various malignant tumors. The aim of our study was to evaluate the vascular fractal dimension and the immunohistochemically positive total vascular area in oral cavity carcinomas in order to assess their potential value as factors reflecting angiogenesis. METHODS: Histologic sections from 48 carcinomas and 17 nonmalignant mucosa specimens were evaluated by image analysis using fractal analysis software. Total vascular area was also quantified. RESULTS: Carcinomas presented higher mean values of vascular fractal dimension and total vascular area compared to normal mucosa. The difference for the vascular fractal dimension was statistically significant. CONCLUSIONS: This study provides evidence that vascular fractal dimension could be used as a reliable factor reflecting angiogenesis in oral squamous cell carcinoma and that there are several statistically significant correlations among total vascular area, vascular fractal dimension, nuclear size, and clinicopathologic factors.