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Immune-mediated oral mucosal pathology: a comprehensive review and update for clinicians. Part I

Alrashdan MS, Arzmi MH, Ahmad Kamil WN, Al Kawas S, Leao JC

Ital J Dermatol Venerol, 2023 Oct;158(5):408-418.
PMID: 37916401 DOI: 10.23736/S2784-8671.23.07676-4

The oral mucosa can be involved in a wide variety of mucocutaneous conditions that may present primarily in the mouth or affect other cutaneous or mucosal sites. Many of these conditions are immune mediated and typically present as inflammatory mucosal pathology. Patients experiencing such conditions usually seek medical evaluation and treatment due to the associated pain and discomfort and occasionally taste disturbance or dysphagia and the overall deterioration in the oral health-related quality of life. These conditions share some common features and there could be some overlapping in their clinical presentation, which can lead to delays in diagnosis and proper management of patients. Clinicians dealing with such disorders, including dermatologists, need to be aware of the oral manifestations of mucocutaneous conditions, their clinical features, underlying mechanisms, diagnostic approaches, and treatment options, as well as the recent advances in the research on these conditions. This review provides a comprehensive, evidence-based reference for clinicians, with updated insights into a group of immune mediated conditions known to cause oral mucosal pathology. Part one will cover oral lichen planus, erythema multiforme and systemic lupus erythematosus, while part two will cover pemphigus vulgaris and mucous membrane pemphigoid, recurrent aphthous stomatitis, in addition to the less common disorders linear IgA disease, dermatitis herpetiformis and epidermolysis bullosa.

Matched MeSH terms: Mouth Mucosa/pathology
Calibration improves the agreement in grading oral epithelial dysplasia-Findings from a National Workshop in Malaysia

Kallarakkal TG, Zaini ZM, Ghani WMN, Karen-Ng LP, Siriwardena BSMS, Cheong SC, et al.

J Oral Pathol Med, 2024 Jan;53(1):53-60.
PMID: 38081145 DOI: 10.1111/jop.13501

INTRODUCTION: A major pitfall of many of the established oral epithelial dysplasia (OED) grading criteria is their lack of reproducibility and accuracy to predict malignant transformation. The main objective of this study was to determine whether calibration of practicing oral pathologists on OED grading could improve the reproducibility of the WHO 2017 and the binary OED grading systems.
METHODS: A nationwide online exercise was carried out to determine the influence of calibration on the reproducibility of the WHO 2017 and the binary OED grading systems.
RESULTS: A significant improvement was observed in the inter-observer agreement for the WHO 2017 OED grading system (K 0.196 vs. 0.448; Kw 0.357 vs. 0.562) after the calibration exercise. The significant difference (p = 0.027) in the level of agreement between those with five or more years and less than 5 years of experience was no more observed (p = 0.426) after the calibration exercise. The percent agreement for binary grading was significantly higher (91.8%) for buccal mucosal lesions as compared to lesions on the tongue after the calibration exercise.
CONCLUSION: This study validates the significance of calibration in improving the reproducibility of OED grading. The nationwide exercise resulted in a statistically significant improvement in the inter-observer agreement for the WHO 2017 OED grading system among a large number of oral pathologists. It is highly recommended that similar exercises should be organized periodically by professional bodies responsible for continuing education among oral pathologists to improve the reliability of OED grading for optimal treatment of oral potentially malignant disorders.

Matched MeSH terms: Mouth Mucosa/pathology
Darier disease: a case report

Jalil AA, Zain RB, van der Waal I

Br J Oral Maxillofac Surg, 2005 Aug;43(4):336-8.
PMID: 15993288

The diagnosis of Darier disease of the oral mucosa was made only after biopsying a leukoplakia-like lesion of the palate.

Matched MeSH terms: Mouth Mucosa/pathology
Fulltext Biomechanics of oral mucosa

Chen J, Ahmad R, Li W, Swain M, Li Q

J R Soc Interface, 2015 Aug 06;12(109):20150325.
PMID: 26224566 DOI: 10.1098/rsif.2015.0325

The prevalence of prosthodontic treatment has been well recognized, and the need is continuously increasing with the ageing population. While the oral mucosa plays a critical role in the treatment outcome, the associated biomechanics is not yet fully understood. Using the literature available, this paper provides a critical review on four aspects of mucosal biomechanics, including static, dynamic, volumetric and interactive responses, which are interpreted by its elasticity, viscosity/permeability, apparent Poisson's ratio and friction coefficient, respectively. Both empirical studies and numerical models are analysed and compared to gain anatomical and physiological insights. Furthermore, the clinical applications of such biomechanical knowledge on the mucosa are explored to address some critical concerns, including stimuli for tissue remodelling (interstitial hydrostatic pressure), pressure-pain thresholds, tissue displaceability and residual bone resorption. Through this review, the state of the art in mucosal biomechanics and their clinical implications are discussed for future research interests, including clinical applications, computational modelling, design optimization and prosthetic fabrication.

Matched MeSH terms: Mouth Mucosa/pathology
Oral biopsy turnaround time: 20-year experience of the Department of Oral Pathology, Oral Medicine and Periodontology, Faculty of Dentistry, University of Malaya

Siar CH, Tan BH

J Oral Sci, 2000 Dec;42(4):205-10.
PMID: 11269378

The turnaround time (TAT) for oral biopsies received for histological examination by the Department of Oral Pathology, Oral Medicine and Periodontology, Faculty of Dentistry, University of Malaya, for the years 1978, 1988 and 1998 was evaluated. For the three years studied, TATs for 61, 233 and 463 specimens were retrospectively analysed. Testing intervals, that is, from the dates the surgeons procured the specimens, the laboratories accessioned them and until the pathologists signed off the diagnoses, were used to calculate TAT. The performance level of the respective pathologists, the growth of tissue diagnostic services and the possible variables that influence TAT were also evaluated. As prompt diagnosis means prompt treatment, which in turn has a bearing on prognosis, the TAT pertinent to oral malignant tumors was emphasized. The mean TAT, its mode and median fell significantly in 1998 compared with the previous 2 years; it was lower for soft tissue than for hard tissue specimens, and lower for malignant, than for non-malignant specimens. The progression of tissue diagnostic services is up to a satisfactory level, as 88.89 % of biopsies could render diagnoses within a fair period of time in 1998.

Matched MeSH terms: Mouth Mucosa/pathology
Primary mucocutaneous histoplasmosis

Dutt AK, Garai BK

Med J Malaya, 1970 Mar;24(3):231-3.
PMID: 4246808
Matched MeSH terms: Mouth Mucosa/pathology
Assessment of genotoxic and molecular mechanisms of cancer risk in smoking and smokeless tobacco users

Chandirasekar R, Kumar BL, Sasikala K, Jayakumar R, Suresh K, Venkatesan R, et al.

Mutat Res Genet Toxicol Environ Mutagen, 2014 Jun;767:21-7.
PMID: 24769293 DOI: 10.1016/j.mrgentox.2014.04.007

Inexpensive forms of tobacco are widely used in developing countries such as India. We have evaluated genotoxicity endpoints (chromosome aberrations, micronucleus frequency, comet assay) and polymorphisms of the XRCC1 and p53 genes among smokers and smokeless tobacco (SLT) users in rural Tamilnadu, South India. Cytogenetic, DNA damage and SNP analyses were performed on peripheral blood samples; micronucleus frequency was measured in peripheral blood and buccal mucosa exfoliated cells. Both categories of tobacco users had elevated levels of genotoxic damage. SNP analysis of tobacco users revealed that 17% carry the XRCC1 gln399gln genotype and 19% carry the p53 pro72pro genotype. Both genotypes are associated with increased risk of cancer.

Matched MeSH terms: Mouth Mucosa/pathology
Risk of the contralateral mucosa in patients with oral potentially malignant disorders

Siar CH, Mah MC, Gill PP

Asian Pac J Cancer Prev, 2011;12(3):631-5.
PMID: 21627356

BACKGROUND: It is known that abnormal changes may occur in any part of the oral mucous membrane exposed to a carcinogen. Therefore patients with oral potentially malignant disorders (PMDs) are at risk of developing similar lesions at multiple sites.
OBJECTIVES: To determine the risk of the contralateral mucosa in patients presenting with oral PMDs.
MATERIALS AND METHODS: Sixty individuals with PMDs were selected for this study. These comprised 32 (53.3%) Indians, 23 (38.3%) Chinese, four (6.7%) Malays and one (1.7%) Nepalese. All selected cases had histopathological confirmation of their primary existing lesion as inclusion criteria. Cases that subsequently presented with a lesion in the corresponding anatomical site also underwent scalpel incisional biopsy on this second lesion to verify its diagnosis. The remaining cases that presented with unilateral PMDs at the time of study were subjected to a cytobrush biopsy on the normal looking contralateral mucosa.
RESULTS: A total of 70 primary PMDs were detected in 60 patients. The most common PMD found was oral lichen planus (n=40, 57.1%). Of the 60 patients studied, 28 (46.6%) exhibited bilateral lesions either synchronously (n=21, 35.0%) or metachronously (n=7, 11.6%). The remaining cases that had undergone cytobrush biopsy on the corresponding anatomical site yielded normal cytological results.
CONCLUSIONS: Present findings demonstrated that patients presenting with PMDs in the upper aerodigestive tract are at a greater risk of developing a second lesion most probably in the contralateral anatomical site.

Matched MeSH terms: Mouth Mucosa/pathology*
Fulltext A Consistent Orally-Infected Hamster Model for Enterovirus A71 Encephalomyelitis Demonstrates Squamous Lesions in the Paws, Skin and Oral Cavity Reminiscent of Hand-Foot-and-Mouth Disease

Phyu WK, Ong KC, Wong KT

PLoS One, 2016;11(1):e0147463.
PMID: 26815859 DOI: 10.1371/journal.pone.0147463

Enterovirus A71 (EV-A71) causes self-limiting, hand-foot-and-mouth disease (HFMD) that may rarely be complicated by encephalomyelitis. Person-to-person transmission is usually by fecal-oral or oral-oral routes. To study viral replication sites in the oral cavity and other tissues, and to gain further insights into virus shedding and neuropathogenesis, we developed a consistent, orally-infected, 2-week-old hamster model of HFMD and EV-A71 encephalomyelitis. Tissues from orally-infected, 2-week-old hamsters were studied by light microscopy, immunohistochemistry and in situ hybridization to detect viral antigens and RNA, respectively, and by virus titration. Hamsters developed the disease and died after 4-8 days post infection; LD50 was 25 CCID50. Macroscopic cutaneous lesions around the oral cavity and paws were observed. Squamous epithelium in the lip, oral cavity, paw, skin, and esophagus, showed multiple small inflammatory foci around squamous cells that demonstrated viral antigens/RNA. Neurons (brainstem, spinal cord, sensory ganglia), acinar cells (salivary gland, lacrimal gland), lymphoid cells (lymph node, spleen), and muscle fibres (skeletal, cardiac and smooth muscles), liver and gastric epithelium also showed varying amounts of viral antigens/RNA. Intestinal epithelium, Peyer's patches, thymus, pancreas, lung and kidney were negative. Virus was isolated from oral washes, feces, brain, spinal cord, skeletal muscle, serum, and other tissues. Our animal model should be useful to study squamous epitheliotropism, neuropathogenesis, oral/fecal shedding in EV-A71 infection, person-to-person transmission, and to test anti-viral drugs and vaccines.

Matched MeSH terms: Mouth Mucosa/pathology
Denture hyperplasia and oncocytic metaplasia

Siar CH, Ng KH, Ngui CH

Ann Dent, 1992;51(1):27-8.
PMID: 1632623

A case of denture hyperplasia of the upper labial sulcus with concomitant oncocytic metaplastic changes is described. The patient concerned is an elderly male wearing an ill-fitting upper full denture.

Matched MeSH terms: Mouth Mucosa/pathology*
Intraoral spindle-cell lipoma: report of a case and literature review

Khoo SP, Lian CB

Ann Dent, 1995 Summer;54(1-2):53-5.
PMID: 8572549

Spindle-cell lipoma (SCL) of the oral cavity is very rare. There are only four such reported cases in the literature. A concise literature review of SCL and a case report of a SCL affecting the cheek and lip of a 23-year-old man is presented.

Matched MeSH terms: Mouth Mucosa/pathology
An epidemiological survey of oral mucosal lesions among elderly Malaysians

Taiyeb Ali TB, Razak IA, Raja Latifah RJ, Zain RB

Gerodontology, 1995 Jul;12(1):37-40.
PMID: 8626179

A house to house random survey on elderly subjects was undertaken in the District of Klang in Malaysia. The objective of this study was to investigate the prevalence of oral mucosal lesions (OML) among the elderly in this area. The primary units in the sampling frame were the Enumeration Blocks (EBs) as defined under the population census. All households of the selected EBs were considered as sampling units and members aged 60 and above were considered as respondents. There was a slight preponderance of females, with the Malays comprising the majority of the subjects. Of the 486 respondents, mean aged 69.1 +/- 7.3 yr, 111 had at least one oral mucosal lesion, a prevalence of 22.8%. A total of 145 lesions were detected. The prevalence of OML was highest among Indians and least among the Chinese. The most common finding was tongue lesions, recording a prevalence of 10.7%, followed by oral pigmentation (4.9%) and white lesions (4.3%). Denture related lesions were comparatively low at 2.5%. Two cases of oral cancer if representative would give a relatively high prevalence of 0.4%.

Matched MeSH terms: Mouth Mucosa/pathology*
Prevalence of oral soft tissue lesions in out-patients at two Malaysian and Thai dental schools

Axéll T, Zain RB, Siwamogstham P, Tantiniran D, Thampipit J

Community Dent Oral Epidemiol, 1990 Apr;18(2):95-9.
PMID: 2335069

At the Faculties of Dentistry in Chiang Mai, Thailand (CM), and Kuala Lumpur, Malaysia (KL), 234 and 233 consecutive out-patients of mean ages 33.8 and 31.0 yr, respectively, were examined for the presence of oral mucosal lesions. Tobacco in some form was regularly used by 31.7% and 27.5% of the study populations in CM and KL, respectively. Cigarette smoking was the predominant habit. In CM three persons chewed betel quids and nine smoked banana leaf cigars daily. In addition, there were 24 habitual chewers of tea leaves (miang). In KL six persons chewed betel quids daily. In CM and KL three cases each (1.3%) of tobacco-associated leukoplakias were found. In KL an additional idiopathic leukoplakia was registered. One and three cases of betel related lesions were found in CM and KL, respectively. One case of a squamous cell carcinoma was found in a 45-yr-old Indian woman in KL who had been chewing betel with tobacco daily for many years. High prevalence figures were found for lichen planus, 3.8% in CM and 2.1% in KL, and an extremely high one, 48.3%, in CM for episodes of aphthous ulcers experienced during the last 2 yr. Comparatively low prevalence figures were found for herpes labialis. As could be expected melanin pigmentation was prevalent while only low figures were encountered for denture-related lesions and amalgam tattoos.

Matched MeSH terms: Mouth Mucosa/pathology
The effects of betel-nut chewing on the buccal mucosa: a histological study

Lee KW, Chin CT

Br. J. Cancer, 1970 Sep;24(3):433-41.
PMID: 5475751

Sixty-two "leukoplakias" from the cheeks of betel-nut chewers in West Malaysia were studied histologically. Ten biopsies were from non-tobacco betel-nut chewers. An amorphous von Kossa positive layer was seen on the keratin surface in 42 specimens. Tobacco did not appear essential for its formation, and it appeared to be significantly associated with parakeratosis. Its possible significance as a cuticle-like layer prolonging contact between carcinogens and the mucosa is discussed.Parakeratosis appeared to be the most common form of cornification seen, and the mitotic activity in parakeratinized leukoplakias appeared to be significantly greater than orthokeratinized leukoplakias.Comparison with studies on other population samples using different quids suggested that severe histological changes were more likely to be seen when tobacoo-containing quids were chewed as compared to non-tobacco-containing quids.An attempt to correlate the histological changes seen with the clinical habit in leukoplakias from chewers using tobacco-containing quids suggested that epithelial atrophy appeared to be significantly related to the duration of the habit but not to the "intensity" of the habit.

Matched MeSH terms: Mouth Mucosa/pathology*
Oral fixed drug eruption due to tinidazole

Singh R, Ramachandra SS, Dayakara JK

Cutis, 2016 Dec;98(6):E1-E2.
PMID: 28099544
Matched MeSH terms: Mouth Mucosa/pathology
Fulltext Assessing oral cancer knowledge and awareness among Malaysian dental and medical students

Awan KH, Khang TW, Yee TK, Zain RB

J Cancer Res Ther, 2014 Oct-Dec;10(4):903-7.
PMID: 25579526 DOI: 10.4103/0973-1482.138011

BACKGROUND:
Oral cancer is a foremost health dilemma in several regions of the world. General dental practitioners and general medical practitioners play a major role in recognition of oral mucosal changes that may lead to malignancy. Their knowledge in oral cancer itself and the risk factors associated with the disease need to be sufficient.

OBJECTIVE:
The objective of the present study was to investigate awareness and knowledge of undergraduate dental and medical students in early detection and prevention of oral cancer.

MATERIALS AND METHODS:
Dental and medical students were invited to participate by answering a questionnaire on their habits of the oral mucosa examination and history taking, knowledge on risk factors and changes related with oral cancer, referral of patients as well as their desire to receive further information on oral cancer. Chi-square test was carried out to analyze knowledge and awareness between undergraduate dental and medical students.

RESULTS:
Undergraduate dental students were more likely to examine oral mucosa (96.7%) and advice risk habits to patients (93.9%) compared to medical students (60.6% and 79.8% respectively). Significantly more dental students considered smoking (84.4%), betel quid chewing (76.1%), and alcohol drinking (35%) as risk factors. Clinical changes of oral cancer were better identified by dental students (leukoplakia-52.8%, erythroplakia-45%, and non-healing ulcer-40%) compared to medical students (leukoplakia-12.9%, erythroplakia-4.6%, and non-healing ulcer-10.3%). Both dental and medicals students reported the desire to receive further information in relation to oral cancer.

CONCLUSION:
Dental students have better knowledge and awareness in prevention and early detection of oral cancer compared to medical students.

Matched MeSH terms: Mouth Mucosa/pathology
Fulltext Oral hyperpigmented lesions--a case study

Kwa SK, Gupta ED

Aust Fam Physician, 2013 Jul;42(7):490-1.
PMID: 23826603

An overweight woman, aged 58 years, presented for follow up of hypertension, diabetes and dyslipidaemia. She was noted to have hyperpigmented brown macules on the inner surface of the lower lip and buccal mucosa (Figure 1). She stated that she had first noticed these lesions when aged in her 40s. Her mother died at age 58 years from gastric cancer with extensive metastases, and her brother died at age 45 years from colon cancer with spread to the liver and lungs.

Matched MeSH terms: Mouth Mucosa/pathology*
Prevalence of bilateral 'mirror-image' lesions in patients with oral potentially malignant epithelial lesions

Siar CH, Mah MC, Gill PP

Eur Arch Otorhinolaryngol, 2012 Mar;269(3):999-1004.
PMID: 21789676 DOI: 10.1007/s00405-011-1712-x

Early detection of oral potentially malignant epithelial lesions (PMELs) is aimed at improving survival rates as carcinogenesis is a multistep process and prevention is possible if these lesions are detected at an early and reversible stage of the disease. A prospective clinical study aimed at determining the prevalence of bilateral 'mirror-image' oral PMELs was carried out. Sample consisted of 32 (53.3%) Indians, 23 (38.3%) Chinese, 4 (6.7%) Malays and one (1.7%) Nepalese. All had histopathological confirmation of their primary existing PMEL as inclusion criteria. A total of 70 primary lesions were detected. The most common PMEL found was oral lichen planus. Of these, 28 (46.7%) patients exhibited bilateral 'mirror-image' lesions (n = 42) either synchronously (n = 32/42) or metachronously (n = 10/42). The remaining 32 (53.3%) patients had normal-looking contralateral mucosa. Present findings suggest that patients presenting with oral PMELs are at greater risk of developing a second lesion, most probably in the contralateral 'mirror-image' site.

Matched MeSH terms: Mouth Mucosa/pathology*
Oral mucosal lesions in non oral habit diabetic patients and association of diabetes mellitus with oral precancerous lesions

Saini R, Al-Maweri SA, Saini D, Ismail NM, Ismail AR

Diabetes Res Clin Pract, 2010 Sep;89(3):320-6.
PMID: 20488573 DOI: 10.1016/j.diabres.2010.04.016

AIMS: This study was aimed to determine the prevalence of oral mucosal lesions (OML) in patients with diabetes mellitus (DM) and non-diabetic subjects without any oral habits and to investigate the association of DM with oral precancerous lesions.
METHODS: This cross-sectional study involved 420 diabetic and 420 non-diabetic control subjects without any oral habits. Detailed oral examination was performed based on international criteria.
RESULTS: A significantly greater proportion of subjects with DM (45%) had one or more OML in comparison to non-diabetics (38.3%). Patients with DM showed a significantly greater prevalence of geographic tongue, denture stomatitis and angular cheilitis than non-diabetics (p<0.05). The results also showed an association between occurrence of one or more OML and metabolic control of diabetic patients (p<0.05). For precancerous lesions, lichen planus was found in two diabetic patients while none of controls had any precancerous lesion (p>0.05).
CONCLUSIONS: Prevalence of OML was significantly higher in diabetic patients than non-diabetics and this prevalence was associated with the metabolic control of the patients. However, no association was observed between DM and oral precancerous lesions.

Matched MeSH terms: Mouth Mucosa/pathology*
Cannon's disease: clinical and diagnostic implications: a case report

Ram S, Siar CH

Dent Update, 2004 Nov;31(9):557-9.
PMID: 15612463

Cannon's disease or white sponge naevus is a relatively rare genetically determined skin disorder. It is inherited as an autosomal dominant trait that displays a high degree of penetrance and expressivity. This article describes cases of Cannon's disease in a mother and her son.

Matched MeSH terms: Mouth Mucosa/pathology*

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