Suspicious Oral Lesions Research Articles

Abstract B56: Autofluorescence visualization to screen for premalignant and malignant lesions of oral cavity and oropharynx

Abstract B56 Objective To determine if the addition of autofluorescence (AF) visualization to conventional white light exam (WL) improves the efficiency in detecting pre-malignant and malignant lesions in the oral cavity of high risk patients, compared to WL exam alone. Methods A total of 47 patients underwent the screening procedure at the department of Dentistry and Head and Neck Surgery at Roswell Park Cancer Institute, between October 2006 and June 2007, either to investigate suspicious oral lesions or to identify any co-existing lesions in patients with a recently diagnosed untreated oral pre-malignant lesions or cancer of oral cavity. Four patients had a second exam at least 6 months after the initial visit, making up a total of 51 screening visits. The patients underwent a comprehensive oral exam with an autofluorescence device which was equipped with WL source, an AF source (blue excitation light at 405 nm and imaging at 530-550 & 630-650 nm) and a video camera. Any area that looked fluorescent green was classified as normal and any area that showed loss of fluorescence (grey or black) was considered to be suspicious on AF. All oral exams were performed by one dentist and the biopsies were reviewed by the same pathologist. A total of 170 lesions were identified on either WL or AF and biopsied, and 1 contra-lateral control biopsy from a normal looking area was taken per visit. For convenience of analysis, the pathologic diagnoses were grouped into four categories: (1) ‘benign lesions’(BL) - normal/ unremarkable samples with benign conditions and parakeratosis without atypia (2) ‘low grade lesions’(LGL) - parakeratosis with atypia and mild dysplasia (3) ‘high grade lesions’(HGL) - moderate dysplasia (MD), severe dysplasia (SD) and CIS (4) ‘Carcinoma’(CA). These groups contributed 48, 129, 26 and 15 biopsies respectively. Results On lesion-by-lesion basis, while WL exam did not identify 8 HGLs (4 MD and 4 CIS), AF missed only one HGL (1 MD). Similarly, WL exam did not identify 4 CAs, whereas AF exam missed only 1 cancerous lesion. On combined sequential screening by WL followed by AF (WL+AF), none of the HGLs or CAs was missed. For the LGLs, the sensitivity improved from 44% with WL to 63% with AF and 76% with WL+AF exam. Similarly, sensitivity for detecting HGLs increased from 69% with WL to 96 and 100% with AF and WL+AF, respectively. For CAs, the sensitivity improved from 73% to 93 and 100% with AF and WL+AF respectively. The negative predictive value of WL for HGLs and CAs was 96 and 97% respectively, which increased to 100% with AF alone. The specificity for HGLs and CAs was superior with WL at 75% compared to 52% with AF alone. The addition of AF to WL increased the relative sensitivity by 83%, 47% and 45% in identifying LGLs, HGLs and CAs respectively. One per-person basis, we examined the efficiency of AF in identifying the highest grade lesion in a person. While, WL missed the highest grade lesions in 2 patients with MD, 2 with CIS and 4 with CAs; AF did not miss the worst lesion in any patient with a HGL or CA. The efficacy of AF in identifying the highest grade lesion in each individual was 100%. Conclusion Our results demonstrate that sequential exam by AFL visualization following a WL exam is very efficient in identifying pre-malignant and malignant oral lesions not detected with WL alone. This technique has the potential as a non-invasive and effective tool for oral cancer screening. Citation Information: Cancer Prev Res 2008;1(7 Suppl):B56.

Oral cancer awareness for the general practitioner: new approaches to patient care

In Australia, oral cancer accounts for approximately 2-3 per cent of all cancers, and approximately 1 per cent of deaths from cancer. The incidence of intra-oral cancer is gradually increasing. It is now well established that early detection of potentially malignant disease can improve the clinical outcome for patients, and as such it is the responsibility of dentists to identify such lesions early. To facilitate early detection of suspicious oral lesions several clinical methods of detection can be used. In addition to conventional visual screening of oral tissues with the naked eye under projected incandescent or halogen illumination, there are many clinical diagnostic aids that can be undertaken to help detect oral cancer. In this article we explore clinically available modalities that may be used by the general dental practitioner, and highlight their inherent strengths and weaknesses.

Delays in Referral of Oral Cancer Patients, A10 yr Retrospective Study at Base Hospital, Yaba, Lagos, Nigeria

The study attempts to find out who delays in the management of oral cancer patients viz: the General Medical Practitioner (GMP), the Consultants or on the other hand, the patients. All oral cancer patients referred to our Hospital between 1987 and 1996 were reviewed. The most important findings are that 68 patients were referred with suspicious oral lesions, out of 54 (79.4%) had histologically confirmed oral Cancer. The delay in referral patterns by both GMP and GDP are similar since most of their patients were not referred until 6 months after initial examination. Only 16% and 21% of their patients respectively, were referred within the first month. In contrast to this trend, the consultants referred 45.4% of their patients within the first month. Thus the GMP and GDP are more culpable than consultants in the delay of patients' referral. The patient's delay in seeking medical treatment after noticing symptoms of their oral cancer was the most significant factor as only 6.1% consulted doctor within one month, while 62.3% failed to consult until over one year. In conclusion, a public enlightenment programme to increase awareness of oral cancer is stressed. In addition, a 3 monthly review of suspicious lesions such as oral leukoplakia, candidiasis, erythroplakia by practitioners is suggested. A yearly oral screen for the over 40's with papaconilau 2- stage staining procedure is recommended. NQJHM Vol. 14 (1) 2004: pp. 81-83

Wertigkeit der konventionellen oralen Bürstenbiopsie

This study evaluated the performance of oral brush biopsies using standard morphological analysis and haematoxylin and eosin (HE) staining for detecting oral squamous cell carcinomas and their respective precursor lesions Brush biopsies were obtained in 169 consecutive patients who underwent routine biopsies and histological examination for clinically suspicious oral lesions. Air-dried smears were processed by acetone fixation and HE staining. Cytological assessment used well-established criteria of atypia to classify the specimen as either "tumor negative" (no signs of atypia, no malignant cells) or "tumor positive" (malignant cells, any sign of atypia or doubtful cells). Despite a sufficient number of cells, a definite cytological diagnosis could not be established in six cases. According to the criteria specified above, these specimens were classified as "tumor positive." The cytological analysis identified 49 out of 62 oral malignancies (sensitivity 79%). Seven out of 107 benign lesions were classified as false positive (specificity 93%). The positive and negative predictive values were each 88%. Oral brush biopsies will identify only about 80% of oral malignancies when the smears are processed by routine HE stains and are analysed via standard morphological criteria. Thus, this technique should not be used for diagnostic proof or to exclude malignant cells in a lesion suspicious for cancer. However, oral brush biopsy provides a versatile back-up strategy to uncover the true nature of the disease if a lesion is clinically considered benign by mistake.

Detection of Oral Pathologies Using Optical Coherence Tomography

Optical biopsy techniques can provide immediate in vivo diagnosis of suspicious oral lesions. Other advantages include their non-invasive nature and reducing patient stress and anxiety while waiting for the diagnosis. Some of these techniques have already been incorporated into clinical practice and have become indispensable tools in oral dysplasia clinics (e.g. fluorescence spectroscopy); others continue to be applied in clinical research studies and results show great promise for their use in clinical practice in the near future (e.g. elastic scattering spectroscopy, microendoscopy and optical coherence tomography).

Oral cancer screening

Oral and oro‐pharyngeal cancer is a global health problem, with over 500 000 new cases diagnosed per annum worldwide. The geographical incidence varies and in parts of in the Indian subcontinent oral cancer constitutes up to 40% of all cancers. Early detection is an essential part of reducing mortality and morbidity.Our Cochrane systematic review (Kujan et al, Cochrane Database Systematic Review. 2006, 3: CD004150) demonstrated that there is insufficient evidence to include or exclude population screening for oral cancer into healthcare systems. Only one large scale cluster randomized controlled trial has been reported. However the final round of the study showed that is some benefit in visual screening if the high risk group (alcohol, tobacco and paan users) is targeted.Improved detection of pre‐cancerous oral lesions and clinically inconspicuous cancers can be achieved by improving clinicians’ awareness of suspicious oral lesions and by encouraging a systematic approach to oral examination. Fluorescent instruments (Velscope) and tolonium chloride rinsing can also aid early detection of suspicious oral lesions. At present, all patients with suspicious oral lesions detected by opportunistic dental screening are referred for scalpel biopsy. Non‐attendance following referral for biopsy is a major problem reported in many oral cancer screening studies. Cytology may go some way to solve this problem.Oral exfoliative cytology using a spatula was widely used in the 1970s but fell out of favour because of the reported high false negative rates. It is likely that false negative results were due to inadequate sampling of keratinizing lesions. Several recent studies have reported that cytobrush collection is superior to spatula use as a sampling method in the oral cavity. High rates of sensitivity and specificity are reported for detection of oral dysplastic cells, enabling patients for whom biopsy is mandatory, to be selected and properly counselled.A novel cytobrush utilizing ‘thin hair technology’, the Rovers Orcellex® brush, has been devised specifically for oral use and we have evaluated it in 50 normal volunteers using liquid based cytology. Adequate samples can be obtained by rotating the brush ten times against the oral mucosa. Cells from all epithelial layers are obtained. No participants reported experiencing pain and only a few experienced discomfort during sample collection. We found that samples were sufficient for effective immunostaining for p16 and FHIT, as well as high risk HPV detection by PCR. Excellent results were obtained with both SurePath® and ThinPrep® liquid based cytology systems. We are currently building up our experience of the cytological features of oral and oro‐pharyngeal cancers, pre‐cancerous lesions and benign disorders.A body of evidence is accumulating that suggests that high risk HPV positive head and neck cancers have a greater radiosensitivity and better clinical outcome than their non‐HPV counterparts. Brush collection of fresh cells combined with real time PCR may offer an excellent way to detect integrated HPV in these tumours.Whilst biopsy will remain as the gold standard for diagnosis, it is likely that brush cytology will be increasingly used for screening, surveillance and for the detection of biomarkers of response and prognosis in established head and neck cancers.

Detection of non-diploid cells in premalignant and malignant oral lesions using combined morphological and FISH analysis – a new method for early detection of suspicious oral lesions

Alteration in DNA content is an early event in oral carcinogenesis. We have examined oral brush samples to detect non-diploid cells (NDC) using simultaneous morphological and cytogenetic analysis. The study included 8 oral squamous cell carcinomas (OSCC), 22 premalignant lesions (OPLs), and 25 control individuals. Slides stained with Giemsa followed by FISH using chromosome 2 centromeric DNA probe, were scanned and fluorescent signals were simultaneously analyzed in parallel with the morphology. The proportion of NDC increased with the severity of the diagnosis. In two control subjects, 1–1.5% of the examined cells were NDC. Over 2% NDC were present in all OSCC cases and in 11 of the OPLs, of which, in 8 the histologic diagnosis was either epithelial hyperplasia or mild dysplasia. A significant number of NDC had normal morphology when cytomorphology and FISH were compared. Two patients with OPLs developed OSCC these patients had a significant proportion of NDC. We suggest that the combined morphological and cytogenetic analysis of cells collected by a non-invasive brush sampling can enhance early detection of potentially malignant cells.

Clinical and pathological analysis of oral manifestations of 40 patients with secondary syphilis

To analyze the clinical and pathological features of 40 patients with secondary syphilis. A total of 40 cases of secondary syphilis confirmed by serology were collected during 1994-2004 and were first diagnosed on presentation with oral lesions. The white patch in oral mucosa was found in 32 cases with painless or slight pain in most cases. The most common site of the lesion was the tongue. The histological examination on eight cases was initially misdiagnosed as oral candidosis or lichen planus, but confirmed as syphilis after serology revealed nonspecific inflammation with intraepithelial microabscess and dense perivascular infiltration of lymphocytes and plasma cells in connective tissue. The symptoms showed dramatic improvement in 16 cases after benzathine penicillin treatment. The oral manifestations of syphilis have specific clinical and pathological feature and attention should be paid to the suspicious oral lesions when patients are first presented in a dental office.

Knowledge of Oral Cancer and Screening Practices of Primary Care Providers at Federally Qualified Health Centers

Primary care providers (PCPs) who worked in Federally-Qualified Health Centers (FQHC) in Michigan were surveyed to assess their knowledge level and practices related to screening and preventing oral cancer. A questionnaire was developed with the assistance of dental and medical experts, and revised through focus groups. The questionnaire included one case scenario describing a suspicious oral lesion in a 55-year old female patient, followed by questions assessing PCPs' knowledge level, attitude, opinion, and screening practices for oral cancer. This mail survey was conducted in 2003. Survey response rate was 56.4%. Over 70% of the respondents reported that they screen patients for oral cancer during a routine physical examination. Forty-four percent of PCPs had high knowledge level, based on the scenario questions. Those who had high knowledge level were more likely to be physicians, males, and more likely to perform screening for oral cancer than those with low knowledge level. There was no difference in age and race/ethnicity between high and low knowledge groups. Perceived barriers included (1) lack of education; (2) lack of specialists to refer patients; and (3) lack of reimbursement. The majority of PCPs in this survey had positive attitudes about performing screening for oral cancer. To involve PCPs in screening for oral cancer, oral health programs should focus on providing up-to-date education, setting up a referral system, and providing proper reimbursement.

Interobserver reliability in the histopathologic diagnosis of oral pre-malignant and malignant lesions.

The histologic classification of pre-cancerous and cancerous oral lesions has generally shown poor agreement between pathologists, but lesion and patient characteristics that may affect diagnostic reliability have not been explored. Eighty-seven clinically suspicious oral lesions biopsied from 81 patients with previous upper aerodigestive tract cancer were independently classified by their local pathologist and a central pathology committee. Interobserver reliability between the local pathologist and the central pathology committee was measured with weighted kappa (kappa w) statistics and corresponding 95% confidence intervals (CI). The kappa w for pathologic diagnosis was 0.59 (95% CI: 0.45, 0.72), and was higher for lesions without inflammation (0.67 (95% CI: 0.53, 0.80) than inflamed lesions (-0.10 (95% CI: -0.27, 0.07)). Greatest agreement was seen for lesions located in the buccal mucosa/vestibule (kappa w = 0.68 (95% CI: 0.46, 0.91)) and tongue (kappa w = 0.62 (95% CI: 0.40, 0.84)). Least agreement was found for lip/labial mucosa lesions (kappa w = -0.04 (95% CI: -0.34, 0.27)). Punch biopsies (kappa w = 0.67 (95% CI: 0.54, 0.80)) had greater interobserver reliability than wedge biopsies (kappa w = 0.38 (95% CI: 0.12, 0.64)). These data suggest that the presence of inflammation, lesion site, and biopsy technique modifies the reliability of oral lesion histologic diagnoses.

Discussion

Five-year survival rates for early (T1, T2) squamous cell carcinoma (SCC) of the oral cavity are greater than 85%. Local and/or regional recurrence of SCC occurs in greater than 20% of cases, with significant functional and cosmetic consequences. Although early biopsy of suspicious oral cavity lesions is encouraged, excisional biopsy can make definitive therapy more difficult. This article reports a comprehensive review of 26 cases of SCC presenting with inadequate excisional biopsy and presents a rational approach to subsequent management.

Cytologic and DNA-cytometric early diagnosis of oral cancer.

Objective. The aim of this prospective study was to report on the diagnostic accuracy of conventional oral exfoliative cytology taken from white‐spotted, ulcerated or other suspicious oral lesions in our clinic. In addition we checked DNA‐image cytometry as an adjuvant diagnostic tool. Our hypothesis is that DNA‐aneuploidy is a sensitive and specific marker for the early identification of tumor cells in oral brushings. Study design. 251 cytological diagnoses obtained from exfoliative smears of 181 patients from macroscopically suspicious lesions of the oral mucosa and from clinically seemingly benign oral lesions which were exisiced for establishing histological diagnoses were compared with histological and/or clinical follow‐ups of the respective patients. Additionally nuclear DNA‐contents were measured after Feulgen restaining using a TV image analysis system. Results. Sensitivity of our cytological diagnosis on oral smears for the detection of cancer cells was 94.6%, specificity 99.5%, positive predictive value 98.1% and negative predictive value 98.5%. DNA‐aneuploidy was assumed if abnormal DNA‐stemlines or cells with DNA‐content greater 9c were observed. On this basis the prevalence of DNA‐aneuploidy in smears of oral squamous cell carcinomas in situ or invasive carcinomas was 96.4%. Sensitivity of DNA‐aneuploidy in oral smears for the detection of cancer cells was 96.4%, specificity 100%, positive predictive value 100% and negative 99.0%. The combination of both techniques increased the sensivity to 98.2%, specificity to 100%, positive predictive value to 100% and negative to 99.5%. Conclusions. Brush cytology of all visible oral lesions, if they are clinically considered as suspicious for cancer, are an easily practicable, cheap, non‐invasive, painless, safe and accurate screening method for detection of oral precancerous lesions, carcinoma in situ or invasive squamous cell carcinoma in all stages. We conclude that DNA‐image cytometry is a very sensitive, highly specific and objective adjuvant tool for the early identification of neoplastic epithelial cells in oral smears.

Management of tongue cancer in the patient who is systemically immunosuppressed: a preliminary report.

Renal transplantation is being improved, and life expectancy for patients with transplanted kidneys is being prolonged, but the incidence of malignant tumors in other body organs or tissues is increasing progressively. We investigated effective clinical plans for treating lingual cancer in persons who are long-term renal transplant recipients. The group included 3 cases of lingual cancer after renal transplantation. All were men. The mean age was 47.5 years (range, 40 to 55). The lingual cancer occurred a mean of 9 years after renal transplantation. The lesions of two patients were in the left lingual margins; the other patient had multiple bilateral lesions. All diagnoses were confirmed microscopically to be squamous cell carcinomas stage I to II. The doses of immunosuppressive agents were decreased, and two patients accepted surgery, chemotherapy, and radiotherapy. The third patient died 1 year after the cancer was diagnosed because of metastases. The other 2 patients had regular follow-up for 2 to 3 years and did not have either local recurrence or metastasis. Patients who have lingual cancer develop after renal transplantation have received long-term immunosuppressive therapy. We suggest the following clinical protocol: (1) Besides regular evaluation after renal transplantation, physical examination and biopsy of suspicious oral lesions are necessary because of the possibility of postrenal malignancy. (2) Surgery, along with chemotherapy and radiotherapy, is the main treatment of lingual cancer after renal transplantation. (3) The lingual tumor should be comprehensively treated despite the poor immune state of the body, or tumor recurrence can accelerate and metastases can occur. (4) Treating cancer thoroughly and maintaining the function of the transplanted kidney can decrease the patient's immune status. We should continue to observe and to report the patients' protocol, even if the patients' clinical follow-up periods are limited.

IMPROVING DETECTION OF PRECANCEROUS AND CANCEROUS ORAL LESIONS: Computer-Assisted Analysis of the Oral Brush Biopsy

A study group composed of researchers from across the United States undertook a study to evaluate the sensitivity and specificity of OralCDx (OralScan Laboratories Inc.), a computer-assisted method of analysis of the oral brush biopsy, in the detection of precancerous and cancerous lesions of the oral mucosa. The study group conducted a multicenter double-blind study comparing results of OralCDx analysis with those of scalpel biopsy of suspicious oral lesions, as well as using OralCDx on oral lesions that appeared benign clinically. In 945 patients, OralCDx independently detected every case of histologically confirmed oral dysplasia and carcinoma (sensitivity = 100 percent, false-negative rate = 0 percent). Every OralCDx "positive" result was subsequently confirmed by histology as dysplasia or carcinoma. The specificity for the OralCDx "positive" result was 100 percent, while the specificity for the OralCDx "atypical" results was 92.9 percent. In 4.5 percent of clinically benign-appearing lesions that would not have received additional testing or attention other than clinical follow-up, OralCDx uncovered dysplasia or carcinoma (statistical sensitivity > 96 percent, P < .05, n = 131; statistical specificity for the OralCDx "positive" result > 97 percent and for the "atypical" result > 90 percent, P < .05, n = 196). The authors propose that this multicenter trial demonstrates that OralCDx is a highly accurate method of detecting oral precancerous and cancerous lesions. OralCDx can aid in confirming the nature of apparently benign oral lesions and, more significantly, revealing those that are precancerous and cancerous when they are not clinically suspected of being so. All OralCDx "atypical" and "positive" results should be referred for scalpel biopsy and histology to completely characterize the lesion. Given the difficulty in clinically differentiating premalignant and malignant lesions from benign lesions with a similar appearance, OralCDx appears to determine the significance of an oral lesion definitively and detect innocuous-appearing oral cancers at early, curable stages.

The Role of the Dentist in Diagnosing Infection in the AIDS Patient

A case report of an AIDS patient afflicted with disseminated histoplasmosis is presented. Characteristic granulomatous-appearing lesions on the tongue were observed during the patient's initial workup, but the patient became unavailable for a scheduled biopsy. Consequently, the diagnosis of a histoplasmosis infection was established only after the performance of several time-consuming, stressful, and, at times, invasive diagnostic procedures. It is proposed that early histologic evaluation of the suspicious oral lesions would have resulted in the diagnosis, thus making more extensive diagnostic testing unnecessary. This case illustrates the need for the dentist to pursue an aggressive approach in evaluating oral lesions in the AIDS patient.

Atrophic luetic glossitis: Report of a case

This case report of luetic glossitis should alert us to several important points which must be recognized by the dentist and the physician alike. Even though tertiary syphilis occurs with less frequency now than in previous years, luetic glossitis still warrants consideration in the differential diagnosis of suspicious oral lesions. A thorough examination of the patient's past medical history may uncover evidence of previous exposure to syphilis. The latent potential of this disease is one reason we should not exclude it or its manifestations from our differential diagnosis. We would also like to emphasize the importance of adequate treatment for any patient with a positive serologic test reaction and clinical evidence of syphilis.

Examination of suspicious oral lesions and cancer detection

Examination of suspicious oral lesions and cancer detection