Optical coherence tomography in the assessment of suspicious oral lesions: an immediate ex vivo study.

BACKGROUND: Optical coherence tomography (OCT) is an evolving optical technology that is capable of delivering real-time, high-resolution signatures of tissue. OBJECTIVES: The purpose of this immediate ex vivo prospective clinical study was: (1) to assess the sensitivity and specificity of OCT on biopsy material in identifying potentially malignant and malignant oral lesions, (2) to determine the inter-observer agreement in the analysis of specific image parameters, and (3) to find out the oral epithelial thickness for different pathology groups. MATERIALS AND METHODS: This prospective study involved 125 suspicious oral lesions from 125 patients. The lesions were surgically biopsied and subjected to OCT in the immediate ex vivo phase. Two independent readers (surgeon and pathologist) examined the OCT images and assessed several cellular features including keratin layer, epithelial layer, basement membrane and lamina propria, and recorded their findings using special OCT reading score. The sensitivity, specificity and accuracy of OCT to predict "the future need for surgical biopsy in case of any similar lesion" were calculated. The epithelial thickness was also measured. The degree of agreement between the two readers was recorded. RESULTS: The pathological diagnosis revealed that the majority of lesions demonstrated microinvasive carcinomas (n=43). Forty-one had different degree of dysplasia. Benign oral lesions were less common and included 22 keratosis, 11 non-specific lesions, 6 mucocels and 2 papillomas. Optical coherence tomography achieved a sensitivity of 85% and a specificity of 78% in the assessment of oral potentially malignant and malignant disorders. The positive and negative predictive values were 86.5% and 77.5%, respectively. The accuracy was 82% and the kappa coefficient of inter-observer agreement was 0.72 on "the need for biopsy". OCT imaging of oral lesions provided valuable information on the oral epithelial thickness. CONCLUSION: This study proposes that OCT can accurately identify wide spectrum of oral tissue pathologies. Further studies can assess the role of OCT in evaluating and guiding surgical biopsies and monitoring disease.

Oral sex, cancer and death: sexually transmitted cancers.

We briefly highlight the growing body of recent evidence linking unprotected oral sex with the development of some types of head and neck cancer in younger patients. These tumours appear to be increasing in incidence although the development of more sensitive methods of HPV detection may be a confounding factor.

A patient with primary Burkitt's lymphoma of the postnasal space: case report.

INTRODUCTION: Burkitt's lymphoma is a highly aggressive lymphoma. The endemic form is present with Epstein - Barr virus. The most common sites are the mandible, facial bones, kidneys, gastrointestinal tract, ovaries, breast and extra-nodal sites. We present the first reported case of a primary Burkitt's lymphoma of the postnasal space occurring in an elderly Caucasian male. CASE PRESENTATION: A 72-year-old Caucasian male farmer presented with a 6-week history of a productive cough and a painless left sided cervical swelling. Examination of the neck revealed a 5 cm by 5 cm hard mass in the left anterior triangle. A CT scan of the head and neck showed a soft tissue swelling in the postnasal space. Histology of the postnasal space mass showed squamous mucosa infiltrated by a high grade lymphoma. Immunohistochemical staining and in situ hybridisation confirmed the tumour to be Epstein - Barr virus Ribonucleic acid negative suggesting this was a rare sporadic form of the tumour presenting in a location that is atypical for the clinical subtype and age of the patient. CONCLUSION: This is the first reported case of sporadic Burkitt's lymphoma of the postnasal space of an elderly Caucasian male in the absence of Epstein - Barr virus or human immunodeficiency virus infection and further serves to illustrate the diversity of histological subtypes of malignancies that may develop at this concealed site.

Elastic scattering spectroscopy in assessing skin lesions: an "in vivo" study.

INTRODUCTION: Elastic scattering spectroscopy (ESS) has been shown to be accurate in the identification of abnormalities of soft tissue. These include ischemia and inflammation, pre-cancer and cancer. The aim of this study was to compare findings of ESS with gold standard histopathology in patients with various skin lesions. MATERIALS AND METHODS: Seventy-three patients with clinically suspicious facial skin lesions were included. Those lesions with the surrounding innocuous skin were interrogated by ESS, biopsies were taken and examined histopathologically; the results were then compared. RESULTS: The preliminary analysis showed obvious spectral differences between normal and pathological skin. Spectral differences were identified when comparing benign skin conditions to malignant ones. Spectral differences were identified between basal cell carcinomas and other skin lesions. CONCLUSIONS: This preliminary study shows that ESS can distinguish between normal, benign and malignant skin conditions.

The palliative role of PDT in recurrent advanced nasopharyngeal carcinoma: case series.

We report on the application of photodynamic therapy in the management of recurrent advanced carcinoma of the nasopharynx. A selected cohort of 7 patients, only suitable for palliative therapy, was offered this modality to assess the palliative role of PDT. All 7 patients had at least 2 previous recurrences, which were managed with surgery and chemoradiotherapy but ultimately failed to respond. PDT was offered after careful discussion at a multidiscipline meeting. The photosensitiser "mTHPC" was introduced intravenously 96 h prior to delivering the light with nasoendoscopic guidance. Six patients' symptoms were reduced markedly post photodynamic therapy. Five patients have to had another round of treatment which was found to be as effective as the first round in terms of controlling disease progression as well as symptoms. Magnetic resonance images showed variable reduction of tumour volume with the majority of the patients having moderate to significant response. Photodynamic therapy was very successful palliative therapy for this small group of recurrent advanced nasopharyngeal cancer patients.

The use of specific anti-growth factor antibodies to abrogate the oncological consequences of transfusion in head & neck squamous cell carcinoma: an in vitro study.

INTRODUCTION: Perioperative blood transfusion is associated with reduced prognosis in a number of solid malignancies. We investigate its role in a head & neck squamous cell cancer (HNSCC) cell lines. Growth of these cell lines was analogous to endothelial growth. Direct exposure to transfusion products exaggerated this effect. It was logical therefore to assess the effects of anti-endothelial antibodies on this interaction. MATERIALS AND METHODS: Control (HUVEC) and tumour cell lines were exposed to transfusion products. The pre-incubation of the transfusion product with anti-endothelial growth factors was assessed by a growth assay. Where appropriate cells were pre-incubated for 1 hour with 10 µl of a mixture of 100 µl of each and anti-ligand antibodies, the corresponding blood product supplement was incubated with 10 µl of a mixture of 100 µl each of anti-ligand antibodies 1 hour before supplementation to the appropriate cell line. All results are representative of at least two independent experiments carried out in triplicate. RESULTS: The antibody did not directly reduce growth in the tumour cell line, however there was a significant reduction (p<0.001) in tumour cell line vascular mimicry caused by transfusion products pre-incubation with anti-endothelial growth factor antibody. This was found in several other tumours. CONCLUSION: Perioperative blood transfusion is associated with reduced prognosis in a number of solid malignancies including HNSCC. However this phenomenon is abrogated by the use of anti-endothelial growth factor antibodies. This suggests that the original effect was mediated by the endothelial growth factor family.

Branchial cysts within the parotid salivary gland.

Cystic lesions within the parotid gland are uncommon and clinically they are frequently misdiagnosed as tumours. Many theories have been proposed as to their embryological origin. A 20-year retrospective review was undertaken of all pathological codes (SNOMED) of all of patients presenting with any parotid lesions requiring surgery. After analysis seven subjects were found to have histopathologically proven parotid branchial cysts in the absence of HIV infection and those patients are the aim of this review. Four of the most common embryological theories are also discussed with regard to these cases, as are their management.

A patient with ulcerated calcifying epithelioma of Malherbe in the pinna: case report.

INTRODUCTION: Although pilomatrixomas are frequently encountered by dermatologists and pathologists in the differential diagnosis of head and neck lesions, this is not usually the case among head and neck surgeons. A pilomatrixoma (calcifying epithelioma of Malherbe) is a benign tumour of the hair matrix cells. Histologically it is characterised by the presence of ghost cells, basophilic cells and foreign body cells. It may sometimes be difficult to histologically distinguish it from its malignant counterpart, the pilomatrix carcinoma. We report an interesting case of an ulcerated pilomatrixoma of the pinna in a middle-aged Caucasian female. CASE PRESENTATION: A 46-year-old Caucasian female presented with a one-month history of tender brownish lump on the pinna. Initially it was thought to represent a pyogenic granuloma. The lesion was treated by wide circular excision. Histopathological evaluation reported a benign calcifying epithelioma of Malherbe. CONCLUSION: A search of the world's literature has led us to believe that this is a rare case of a calcifying epithelioma of Malherbe of the pinna. The rapid growth and ulcerative nature of this tumour makes this case even more unique.

Delay in pathological tissue processing time vs. mortality in oral cancer: short communication.

Several factors have been identified to affect morbidity and mortality in oral cancer patients. The time taken to process a resected cancer specimen in a patient presenting with primary or recurrent disease can be of interest as delay can affect earlier interventions post-surgery. We looked at this variable in a group of 168 consecutive oral cancer patients and assessed its relationship to mortality from the disease at 3 and 5 years. It is expected that delay in pathological processing time of surgical specimens acquired from patients with recurrent disease may increase or contribute to the increased rate of mortality. Further high evidence-based studies are required to confirm this.

The effect of tobacco and alcohol and their reduction/cessation on mortality in oral cancer patients: short communication.

BACKGROUND: The use of tobacco is known to increase the incidence of developing oral cancer by 6 times, while the additive effect of drinking alcohol further increases the risk leading to higher rate of morbidity and mortality. In this short communication, we prospectively assessed the effect of tobacco smoking and alcohol drinking in oral cancer patients on the overall mortality from the disease, as well as the effect of smoking and drinking reduction/cessation at time of diagnosis on mortality in the same group. MATERIALS AND METHODS: A cohort, involved 67 male patients who were diagnosed with oral squamous cell carcinoma, was included in this study. The smoking and drinking habits of this group were recorded, in addition to reduction/cessation after diagnosis with the disease. Comparisons were made to disease mortality at 3 and 5 years. RESULTS: Follow-up resulted in a 3-year survival of 46.8% and a 5-year survival of 40.4%. Reduction of tobacco smoking and smoking cessation led to a significant reduction in mortality at 3 (P < 0.001) and 5 (P < 0.001) years. Reduction in drinking alcohol and drinking cessation led to a significant reduction in mortality at 3 (P < 0.001) and 5 (P < 0.001) years. CONCLUSION: Chronic smoking and drinking does have an adverse effect on patients with oral cancer leading to increased mortality from cancer-related causes. Reduction/cessation of these habits tends to significantly reduce mortality in this group of patients. Smoking and drinking cessation counseling should be provided to all newly diagnosed oral cancer patients.

cTNM vs. pTNM: the effect of not applying ultrasonography in the identification of cervical nodal disease.

Accurate clinical staging of oral squamous cell cancer can be quite difficult to achieve especially if nodal involvement is identified. Radiologically-assisted clinical staging is more accurate and informs the clinician of loco-regional and distant metastasis.In this study, we compared clinical TNM (cTNM) staging (not including ultrasonography) to pathological TNM (pTNM) staging in 245 patients presenting with carcinoma of the oral cavity and the oro-pharyngeal region. Tumour size differences and nodal involvement were highlighted. US reports of the neck were then added to the clinical staging and results compared.Tumour size was clinically underestimated in 4 T1, 2 T2 and 2 T3 oral diseases. Also 20 patients that were reported as nodal disease free had histological proven N1 or N2 nodal involvement; while 3 patients with cTNM showing N1 disease had histologically proven N2 disease.Overall the agreement between the 2 systems per 1 site was 86.6% (Kappa agreement = 0.80), per 2 sites 90.0% (Kappa agreement = 0.68) and per 3 sites 90.5% (Kappa agreement 0.62).An accurate clinical staging is of an utmost importance. It is the corner stone in which the surgical team build the surgical treatment plan and decide whether an adjuvant therapy is required to deal with any possible problem that might arise. The failure to achieve an accurate staging may lead to incomplete surgical planning and hence unforeseen problems that may adversely affect the patient's survival.

Treatment of Kimura disease with photodynamic therapy: a case study.

We report on the application of photodynamic therapy (PDT) in the management of Kimura disease. A 58-year-old Asian male was offered this modality to assess the possibility to control disease progression. The patient was managed with surgery and the disease recurred and caused facial disfigurement. PDT was offered after careful discussion at UCLH multidiscipline meeting. The photosensitiser "mTHPC" was introduced intravenously 96h prior to delivering the light under ultrasound guidance. Magnetic resonance images showed moderate-significant reduction of the disease volume. Fourteen months post-PDT, the disease started re-growing and the patient subsequently underwent one further round of PDT which was as successful as the first round in reducing the facial disfigurement. Photodynamic therapy was very effective in controlling disease progression in this patient who suffers from Kimura disease.

CO2 laser of oral dysplasia: clinicopathological features of recurrence and malignant transformation.

The use of the CO(2) laser in the management of oral dysplastic lesions has become a more common practice. Very few studies have evaluated recurrence, residual disease malignant transformation, and overall outcome in patients undergoing such a procedure. In this prospective study, a total of 123 oral dysplastic lesions from 77 consecutive patients were treated with the CO(2) laser (resection and/or ablation). The average age was 58 ± 4.8 years. The patients' recovery was uneventful and no complications were reported. Comparisons with the clinical and histopathological features and rate of recurrence as well as malignant transformation were made. The patients were followed-up for a mean of 6.4 years, and biopsies taken in case of changes suggestive of malignant development. Homogenous leukoplakias were identified in 31 patients, non-homogenous leukoplakias in 34 patients, whereas 12 patients had erythroplakias. Ex- and life-long smokers formed 88.3% of the recruited patients. While people who currently smoke and drink formed 55.8% of the cohort. Erythroplakias were solely identified in heavy life-long smokers. The most common identified primary anatomical locations were the lateral border of tongue, floor of mouth, and buccal mucosa. Moderate dysplasia was identified in 42 patients while 18 patients had severe dysplasia. Laser resection margins in selected cases (68 patients) were clear in 53 and showed mild-moderate dysplasia in the involved margins. The rate of recurrence had no significant association with the location but the severity of epithelial dysplasia. The rate of first recurrence after laser surgery was approximately 19.5%. Malignant transformation was observed in eight patients (10.4%), in the tongue and the floor of mouth. Recurrence and malignant transformation was mainly identified in erythroplakias and non-homogenous leukoplakias. Laser resection/ablation is recommended for oral dysplasia to prevent not only recurrence and malignant transformation but also postoperative oral dysfunction encountered by other conventional modalities.

Identification of novel cholesteatoma-related gene expression signatures using full-genome microarrays.

BACKGROUND: Cholesteatoma is a gradually expanding destructive epithelial lesion within the middle ear. It can cause extensive local tissue destruction in the temporal bone and can initially lead to the development of conductive hearing loss via ossicular erosion. As the disease progresses, sensorineural hearing loss, vertigo or facial palsy may occur. Cholesteatoma may promote the spread of infection through the tegmen of the middle ear and cause meningitis or intracranial infections with abscess formation. It must, therefore, be considered as a potentially life-threatening middle ear disease. METHODS AND FINDINGS: In this study, we investigated differentially expressed genes in human cholesteatomas in comparison to regular auditory canal skin using Whole Human Genome Microarrays containing 19,596 human genes. In addition to already described up-regulated mRNAs in cholesteatoma, such as MMP9, DEFB2 and KRT19, we identified 3558 new cholesteatoma-related transcripts. 811 genes appear to be significantly differentially up-regulated in cholesteatoma. 334 genes were down-regulated more than 2-fold. Significantly regulated genes with protein metabolism activity include matrix metalloproteinases as well as PI3, SERPINB3 and SERPINB4. Genes like SPP1, KRT6B, PRPH, SPRR1B and LAMC2 are known as genes with cell growth and/or maintenance activity. Transport activity genes and signal transduction genes are LCN2, GJB2 and CEACAM6. Three cell communication genes were identified; one CDH19 and two from the S100 family. CONCLUSIONS: This study demonstrates that the expression profile of cholesteatoma is similar to a metastatic tumour and chronically inflamed tissue. Based on the investigated profiles we present novel protein-protein interaction and signal transduction networks, which include cholesteatoma-regulated transcripts and may be of great value for drug targeting and therapy development.

Photodynamic therapy and end-stage tongue base cancer: short communication.

We previously reported on the outcome of 21 patients with stage IV advanced and/or recurrent tongue base carcinoma subjected to mTHPC-PDT. We continue to develop on the previous work by treating more patients with this unforgiving disease. PDT has shown to be a very successful minimally-invasive surgical tool in managing this pathology. Tumour-associated symptoms were reduced significantly. The overall morbidity and mortality following PDT, in this group of patients, were far less when compared with other conventional modalities.

How to do it: the difficult thyroid.

There is a paucity of publications detailing how to deal with the difficult thyroid cancer. When compared to other cancers, it is relatively rare with several histopathological subtypes which run differing clinical courses and respond to different therapies. It is a condition predominately treated by specifically trained General and now ENT surgeons who already have a thorough knowledge of vocal fold assessment and rehabilitation as well as emergency airways management both to avoid and treat common complications should they occur.Good surgery involves a team effort to produce good results consistently. All members of the team are essential to quality service delivery. Communication with the team and the patient is paramount. We describe our approach to the difficult thyroid.

Vascular mimicry in cultured head and neck tumour cell lines.

INTRODUCTION: Vascuologenesis is the de novo establishment of blood vessels and vascular networks from mesoderm-derived endothelial cell precursors (angioblasts). Recently a novel mechanism, by which some genetically deregulated and aggressive tumour cells generate "micro-vascular" channels without the participation of endothelial cells and independent of angiogenesis, has been proposed. This has been termed "vasculogenic mimicry" and has implications beyond angiogenesis and adds another layer of complexity to the current concept for the generation of tumour micro-circulation. We suggest this is common phenomenon in head and neck squamous cell carcinoma (HNSCC) cell lines and other aggressive tumour cell lines. We present experimental evidence of vasculogenic mimicry in HNSCC cell lines and compare them with other tumours and a positive control vascular cell line. MATERIALS AND METHODS: The cell lines used were HUVEC, HN 2a, 2b (primary and metastatic tongue base squamous carcinoma cell line), HCT116 (colonic carcinoma cell line) and DU145 (prostate carcinoma cell line).Pilot experiments were undertaken to assess growth of a bank of tumour cell lines on (growth factor reduced) matrigel (Sigma) with standard media (DMEM with 10% Fetal Calf Serum).A functional growth assay was performed by preparing the appropriate cell suspension in serum free medium plated onto either bare plastic or a well pre-coated with growth factor reduced type 4 collagen analogues.Phase contrast photomicrographs were taken at 4 hours and 24 hours. Image analysis was performed; particular features of interest were two dimensional area (surrogate of growth and migration), branch points and end point measurements (surrogate of intercellular complexity). RESULTS: There were observable differences in growth of the cells on laboratory plastic and collagen matrix. Tumour cells formed capillary like networks similar to HUVEC cells. Metastatic HNSCC cells lines were found to have vasculogenic properties similar to HUVEC cell lines when compared to cell lines from their corresponding primary tumour. The endothelial growth factor antibodies used did not inhibit or stimulate cell growth when compared to control but did discourage vascular mimicry. Other tumour cell lines also displayed this property. DISCUSSION: Tumour "vasculogenic mimicry" must still be regarded as a controversial issue whose existence is not proven. The clinical importance of this phenomenon however, is that it does explain the lack of complete efficacy of current anti-angiogenic treatments due to the added layer of complexity. It provides a feasible mechanism of early tumour vascular supply which can co-exist and incorporate with later angiogenic mechanisms. We suggest that "vasculogenic mimicry" maybe a common neoplastic phenomena which appears to also be dictated by the cells micro-environment. Its existence also suggests a further process that of the development of tumour mosaic vessels as the neo-vasculature integrates with the existing endothelial lined systems.

Photodynamic therapy vs. photochemical internalization: the surgical margin.

Controlling tumour margins in head and neck surgery is of the utmost importance in preventing loco-regional spread and distant metastasis, which will ultimately lead to a significant reduction in morbidity and mortality. We comment on the surgical margins in photodynamic therapy and photochemical internalization.