J. C. Steele

The clinical determinants of malignant transformation in oral epithelial dysplasia

BACKGROUND While the size and clinical appearance are known risk factors for malignant transformation of potentially malignant oral the importance of site, grade of dysplasia and exposure to environmental carcinogens remains controversial. We aim to report the clinical determinants of malignant progression in a series of patients with histopathologically graded oral epithelial dysplasia (OED). METHODS We recruited patients with a histopathological diagnosis of OED to a longitudinal observational study in a tertiary oral dysplasia clinic. Clinical, histopathological and risk factor data were recorded at baseline. One of three clinical endpoints were determined: malignant transformation, progression of dysplasia grade, remission/stable dysplasia grade. RESULTS Ninety-one patients meeting the criteria gave consent for inclusion to the cohort, with outcomes reported after a median follow up of 48 months. An estimated 22% (SE 6%) of patients underwent malignant transformation within 5 years, with significant predictors being: non-smoking status (χ(2)=15.1, p=0.001), site (χ(2)=15.3, p=0.002), non-homogeneous appearance (χ(2)=8.2, p=0.004), size of lesion >200 mm(2) (χ(2)=4.7, p=0.03) and, of borderline significance, high grade (χ(2)=5.8, p=0.06). Gender, age, number of lesions and alcohol history did not predict for malignant transformation. CONCLUSIONS Although a number of these clinical determinants have previously been associated with higher malignant transformation in OED, the high-risk nature of lesions in non-smokers is of particular note and requires a greater emphasis and recognition amongst clinicians dealing with OED. It suggests that those non-smokers with OED, have an inherited or acquired predisposition and should be treated more aggressively; these should form the focus for further investigation.

Outcomes of oral squamous cell carcinoma arising from oral epithelial dysplasia: rationale for monitoring premalignant oral lesions in a multidisciplinary clinic.

Surveillance of oral epithelial dysplasia results in a number of newly diagnosed cases of oral squamous cell carcinoma (SCC). The clinical stage of oral SCC at diagnosis influences the magnitude of treatment required and the prognosis. We aimed to document the stage, treatment, and outcome of oral SCC that arose in patients who were being monitored for oral epithelial dysplasia in a dedicated multidisciplinary clinic. Those with histologically diagnosed lesions were enrolled on an ethically approved protocol and molecular biomarker study. Details of clinical and pathological TNM, operation, radiotherapy, recurrence, second primary tumour, and prognosis, were recorded in patients whose lesions underwent malignant transformation. Of the 91 patients reviewed (median follow-up 48 months, IQR 18-96), 23 (25%) had malignant transformation. All were presented to the multidisciplinary team with stage 1 disease (cT1N0M0). Of these, 21 were initially treated by wide local excision, 2 required resection of tumour and reconstruction, and 2 required adjuvant radiotherapy. At follow-up 3 had local recurrence, one had regional recurrence, one had metachronous lung cancer, and 5 had second primary oral SCC. There were further diagnoses of oral dysplasia in 5 during follow-up, and it is estimated that 76% of patients will have one or other event in 5 years. Disease-specific survival was 100% and overall survival was 96% (22/23). Median follow-up after diagnosis of oral SCC was 24 months (IQR 11-58). Specialist monitoring of oral epithelial dysplasia by a multidisciplinary team allows oral SCC to be detected at an early stage, and enables largely curative treatment with simple and usually minor surgical intervention. The high incidence of second primary oral SCC in high-risk patients with oral epithelial dysplasia further supports intensive targeted surveillance in this group.

Clinically relevant patch test results in patients with burning mouth syndrome.

BackgroundPatients with a sore or burning mouth associated with clinically normal oral mucosa present a difficult diagnostic challenge. ObjectiveThe objective of this study was to assess the value of patch testing in patients with burning mouth syndrome. MethodsWe retrospectively reviewed the results of patch testing to an oral series in patients with burning mouth syndrome seen at Mayo Clinic, Rochester, Minnesota, between January 2000 and April 2006. ResultsOf 195 consecutive patients with a burning or sore mouth, 75 had patch testing to an oral series, and 28 of these patients (37.3%) had allergic patch test reactions. The most common allergens were nickel sulfate hexahydrate 2.5%, balsam of Peru, and gold sodium thiosulfate 0.5%. On follow-up, 15 patients reported improvement, 4 removed or avoided the offending dental metal, and 6 avoided the dietary allergen. Thirteen patients did not improve; 6 avoided identified allergens, but without improvement; 1 removed dental metals without symptom change; and 5 avoided test-positive dietary allergens but without improvement. The remaining 7 nonresponders had nonrelevant patch test results or did not avoid allergens. ConclusionsPatch testing can identify patients who may be allergic to dental metals or dietary additives and who may benefit from removal or avoidance of these.

Pyodermatitis–pyostomatitis vegetans complicated by methicillin-resistant Staphylococcus aureus infection

Pyodermatitis–pyostomatitis vegetans (PPV), a rare disorder of the skin and oral mucosa, is considered a highly specific marker for inflammatory bowel disease, especially ulcerative colitis (UC). Oral lesions (pyostomatitis vegetans) are seen without skin involvement but rarely without gastrointestinal symptoms. Bowel symptoms may be minimal and precede the onset of other lesions by months or years. Dermatologically, PPV is characterized by annular, pustular lesions, which may precede or appear at the same time as the oral lesions. We report a case of PPV and UC in which presentation was confused by acneiform lesions and methicillin‐resistant Staphylococcus aureus colonization. Management was complicated because of the patients job commitments and need to travel, and the involvement of a number of different specialities at different locations.

Oral mucosal hyperpigmentation and horizontal melanonychia caused by imatinib

Imatinib is a protein tyrosine-kinase inhibitor used in the management of chronic myeloid leukaemia (CML) and gastrointestinal stromal tumours. Side-effects reported, albeit rare, include oral lichenoid reactions, hyperpigmentation of the gingivae and palate, hyperpigmentation ⁄ hypopigmentation of skin, hyperpigmentation and dystrophy of the nails, and repigmentation of grey hair. We report a case that, to our knowledge, is the first describing hyperpigmentation of the palatal mucosa together with melanonychia after imatinib treatment. A white man aged 48 years, with a history of CML, was referred by his dentist after a routine dental examination because of an asymptomatic area of palatal discolouration thought to be an ecchymosis. The patient was unaware of the lesion. He had undergone a sibling allograft bonemarrow transplant 9 years previously, and had been taking imatinib (Glivec ; Novartis UK, Frimley, Surrey, UK) 400 mg once daily since then. He had never smoked. On clinical examination, extensive, ill-defined, grey pigmentation was seen on the mucosa of the hard palate, which did not extend to the alveolar processes. The patient also had horizontal melanonychia of the toenails (Fig. 1); the fingernails were spared. On histopathological examination of a palatal punch biopsy, prominent accumulation of pigmented granules were seen within cells of the lamina propria. The granules were positive for Masson–Fontana stain, and did not contain iron demonstrable by the Perls reaction. There was no increase seen in the numbers of melanocytes, and no hyperpigmentation of basal keratinocytes or inflammation (Fig. 2). A diagnosis of pigmentation attributable to imatinib was made. No further action, other than reassurance, was deemed necessary. Our observations indicate that the pigmented cytoplasmic granules are not haemosiderin. Their staining with Masson–Fontana stain indicates argentaffinity. This feature is shared by melanin and lipofuscin, and suggests that the granules are ingested melanosomes or other phagosomes. The cells that contained the granules are probably macrophages. Previous reports of oral lichenoid reactions and repigmentation of grey hair after imatinib treatment, support the view that these granules contain melanin. The intraoral pigmentation could be a sign of a regressed lichenoid reaction, which corresponds with the lack of inflammation, increased melanocyte number and hyperpigmentation of basal keratinocytes seen in our patient. Alternatively, the drug may accumulate within macrophages, where it is processed. This may result in chemical groups similar to those of melanin ⁄ lipofuscin and thus account for the argentaffinity. The limited amount of tissue obtained by the punch biopsy did not allow further histochemical ⁄ immunohistochemical assessment that could potentially resolve the uncertainty concerning the nature of the pigment and its localization. (a)

α‐Lipoic acid treatment of 31 patients with sore, burning mouth

OBJECTIVE To review a series of patients with sore, burning mouth treated with alpha-lipoic acid between 2000 and May 2006 and subjectively evaluate improvement in symptoms. DESIGN Retrospective review of medical records of 195 consecutive patients who sought treatment for sore, burning mouth. Treatment of 47 patients was a prescription/recommendation for alpha-lipoic acid. Of these patients, 35 were available for follow-up. SETTING Tertiary care academic medical center. SUBJECTS Ambulatory patients given prescription /recommendation for alpha-lipoic acid 600 mg per day, in divided doses. MAIN OUTCOME MEASURE Reported improvement in symptoms documented in medical records and at follow-up (visits or telephone interviews). RESULTS Thirty-one of the 35 patients (66% of all 47) actually took alpha-lipoic acid as recommended. No patient reported a complete alleviation of symptoms. Six (19%) of these 31 patients felt mostly better, five (16%) felt somewhat better, and 14 (45%) reported no difference. Two patients (7%) reported a worsening of symptoms and four (13%) did not know whether there had been improvement. CONCLUSION Eleven of 31 patients (35%) reported benefit from taking alpha-lipoic acid. Because we examined only a small number of patients and relied on a subjective outcome assessment, further larger studies using a prospective, randomized, controlled, and double-blind structure are warranted.

World Workshop on Oral Medicine VI: an international validation study of clinical competencies for advanced training in oral medicine.

OBJECTIVE To explore international consensus for the validation of clinical competencies for advanced training in Oral Medicine. STUDY DESIGN An electronic survey of clinical competencies was designed. The survey was sent to and completed by identified international stakeholders during a 10-week period. To be validated, an individual competency had to achieve 90% or greater consensus to keep it in its current format. RESULTS Stakeholders from 31 countries responded. High consensus agreement was achieved with 93 of 101 (92%) competencies exceeding the benchmark for agreement. Only 8 warranted further attention and were reviewed by a focus group. No additional competencies were suggested. CONCLUSION This is the first international validated study of clinical competencies for advanced training in Oral Medicine. These validated clinical competencies could provide a model for countries developing an advanced training curriculum for Oral Medicine and also inform review of existing curricula.

The practical evaluation and management of patients with symptoms of a sore burning mouth

There are many etiologic factors to consider in a patient who presents with symptoms or sensations of a sore burning mouth. These range from local causes within the oral cavity to underlying systemic disease, including psychologic factors. This paper aims to describe the different clinical presentations and to outline a systematic approach to the evaluation and management of such patients. The clinician will be directed to the relevant diagnosis by following the traditional medical model of taking a focused history, performing a thorough clinical examination, considering the potential differential diagnoses, and requesting pertinent and appropriate investigations. The various differential diagnoses and broad treatment options will also be discussed and outlined. This paper will not, however, discuss burning mouth syndrome (oral dysesthesia), which is a diagnosis of exclusion, whereby the oral mucosa is clinically normal and there are no identifiable medical or dental causes to account for the patients symptoms.

Angioedema of the lips and tongue induced by angiotensin-converting enzyme inhibitor. A report of two cases.

The following case reports describe the clinical presentation, diagnosis and management of two patients who attended Liverpool University Dental Hospital with rapidly increasing swelling of the lips and tongue. Both patients were suffering from angioedema and were taking an angiotensin-converting enzyme (ACE) inhibitor (ACEI). A provisional diagnosis of ACEI-induced angioedema was made. An intramuscular injection of chlorpheniramine maleate was given to both patients and they were immediately transferred to the local accident and emergency department. These cases illustrate the potential role of the general dental practitioner in the early recognition and management of this potentially life-threatening condition.

Facial pain: temporomandibular joint disorders

This paper is the first of a series of three looking at the complaint of facial pain. Facial pain may be a presenting complaint of a number of conditions that range from simple dental pathology, to malignancy. Patients with a complaint of facial pain usually present to their GP, however, some will seek advice from their General Dental Practitioner (GDP), as they may suspect a dental cause. In some cases of acute facial pain the cause is readily identifiable and the patient is managed appropriately, either by their GP or GDP. One population-based cross-sectional study undertaken in a North of England GP practice estimated the prevalence of orofacial pain among adult patients (aged 18–65) at 23%. Not only does facial pain have a significant effect on the individual patients quality of life but it also impacts on their family and wider society, because of the economic burden of days taken off work. Facial pain can be difficult to diagnose because of its multifactorial nature. This article outlines the principal causes of facial pain and the clinical assessment of patients presenting with this complaint. The diagnosis and management of temporomandibular joint disorders in primary care is described.