Combination of Cytopathology and DNA Ploidy Increases the Performance of Oral Epithelial Dysplasia Prediction in Oral Potentially Malignant Disorders

Background: Grading of oral epithelial dysplasia (OED) by a pathologist is currently the key guide used for treatment planning of oral potentially malignant disorders (OPMDs). Conventional oral examination (COE) clinically detects OPMDs but may not predict their risk status to transform to cancer. Therefore, there is a need for a reliable test to predict OED in OPMDs. Aim: This study was conducted to evaluate COE, liquid based cytology (Cytopath) and DNA image cytometry (Ploidy) in predicting OED in OPMDs. Methods: A total of 179 patients from Malaysia, India and Indonesia underwent COE followed by brush biopsies and scalpel biopsies. Brush-biopsy samples were analyzed for cytopathology and DNA ploidy at Dental Faculty, University of Malaya. Histopathological findings of presence/absence of OED were used as the reference standard. Calculations for sensitivity (Sn), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) and accuracy (A) were done for individual tools and in combinations. The Youden index (Sn+Sp-1) was used as a measure of overall performance. The relevant medical ethics committees of the different research locations approved the study. Results: For COE, the sensitivity (Sn) was high (100%) and the specificity (Sp) was low (5.9%), while both Cytopath and Ploidy showed a low sensitivity (Sn) (28.6% and 22.2%) and high specificity (Sp) (94.3% and 82.3%). All 3 tools individually have high negative predictive value (NPV) for predicting presence of OED (COE-100%, Cytopath-66.7%, Ploidy-78.5%). When combining outcomes from all 3 tools, the best performance indicated by Youden index (42.1) is which defines a positive case when both COE and Cytopath show abnormal. In general, using results from at least 2 tools had better Youden indices than using these tools individually. Conclusion: COE as a screening tool by virtue of its high Sn would be a suitable first level diagnostic test, while the Cytopath and the Ploidy individually with high Sp may be used as a second level test to predict presence of OED. Combining the COE with cytopathology would be the best combination for a high performance of the tools. Cytopathology (when performed by a trained cytologist) would allow for most of the false positives from the first level test to be correctly identified as true negative at the second level. Longitudinal data are needed to assess which of these may correctly identify the malignant potential of OPMDs. Acknowledgment: Grant: High Impact Research - Ministry of Higher Education (HIR-MOHE UM000025/C3)

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Oral epithelial dysplasia, atypical verrucous lesions and oral potentially malignant disorders: focus on histopathology

Oral Surgery Oral Medicine Oral Pathology and Oral Radiology ◽

10.1016/j.oooo.2018.02.012 ◽

2018 ◽

Vol 125 (6) ◽

pp. 591-602 ◽

Cited By ~ 36

Author(s):

Susan Müller

Keyword(s):

Epithelial Dysplasia ◽

Oral Potentially Malignant Disorders ◽

Oral Epithelial Dysplasia ◽

Potentially Malignant Disorders ◽

Potentially Malignant ◽

Oral Epithelial

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APPLICABILITY OF ORAL EPITHELIAL DYSPLASIA GRADING IN POTENTIALLY MALIGNANT DISORDERS OF ORAL CAVITY-AN INSTITUTIONAL REVIEW

Oral Surgery Oral Medicine Oral Pathology and Oral Radiology ◽

10.1016/j.oooo.2019.02.077 ◽

2019 ◽

Vol 128 (1) ◽

pp. e40

Author(s):

Dr. Karpagaselvi Sanjai ◽

Dr. Lalita Jayaram Thambiah

Keyword(s):

Oral Cavity ◽

Epithelial Dysplasia ◽

Oral Epithelial Dysplasia ◽

Institutional Review ◽

Potentially Malignant Disorders ◽

Potentially Malignant ◽

Oral Epithelial

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A retrospective analysis of clinical features of oral malignant and potentially malignant disorders with and without oral epithelial dysplasia

Oral Surgery Oral Medicine Oral Pathology and Oral Radiology ◽

10.1016/j.oooo.2013.08.005 ◽

2013 ◽

Vol 116 (6) ◽

pp. 725-733 ◽

Cited By ~ 40

Author(s):

Fatima Dost ◽

Kim-Anh Lê Cao ◽

Pauline J. Ford ◽

Camile S. Farah

Keyword(s):

Retrospective Analysis ◽

Clinical Features ◽

Epithelial Dysplasia ◽

Oral Epithelial Dysplasia ◽

Potentially Malignant Disorders ◽

Potentially Malignant ◽

Oral Epithelial

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Clinical Review and Management of Oral Potentially Malignant Disorders with Epithelial Dysplasia

10.31219/osf.io/cgfmd ◽

2021 ◽

Author(s):

Mustafa Mohammed Abdulhussain ◽

Ali Sami Muhsin

Keyword(s):

Oral Mucosa ◽

Precancerous Lesion ◽

Oral Lesion ◽

Epithelial Dysplasia ◽

Premalignant Lesions ◽

Oral Potentially Malignant Disorders ◽

Oral Epithelial Dysplasia ◽

Normal Oral Mucosa ◽

Potentially Malignant Disorders ◽

Potentially Malignant

Background: Oral potentially malignant disorders (OPMDs) comprise any disorders, tumors, in addition to any microscopic alterations that have a risk of malignant development of cancers of the mouth. When epithelial dysplasia is detected in an oral lesion, it is termed as a precancerous lesion. Finding: Several changes in the color or thickness of normal oral mucosa might be detected during the clinical diagnosis of the oral lesions. Leukoplakia of the oral cavity is a clinical name for one of the most predominant OPMDs of the oral mucosa. When comparing oral examination with naked eyes to planning to apply staining with special stain or using an image of optical fluorescence, the incidence of patients with oral epithelial dysplasia may rise, as well as the clearing of the lesion boundary. Increased size of more than 2cm2, the presence of colored regions with a red hue, the presence of lichenoid process characteristics, and severe epithelial dysplasia are all considered risk factors. One-third of premalignant lesions may progress to cancer, whereas the other two-thirds may stay stable or regress without progressing to malignancy. Conclusion: It is critical to research the patients' unique characteristics, which include psychological, genetic, dietary, and dental problems. When epithelial dysplasia is present in an oral lesion, it is termed a precancerous lesion. Oral potential malignant diseases with epithelial dysplasia may or may not develop into carcinoma and may or may not be recurrent.

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Clinical Review and Management of Oral Potentially Malignant Disorders with Epithelial Dysplasia

Journal of Health and Medical Sciences ◽

10.31014/aior.1994.04.04.186 ◽

2021 ◽

Vol 4 (4) ◽

Author(s):

Mustafa Mohammed Abdulhussain ◽

◽

Ali Sami Muhsin

Keyword(s):

Oral Mucosa ◽

Precancerous Lesion ◽

Oral Lesion ◽

Epithelial Dysplasia ◽

Premalignant Lesions ◽

Oral Potentially Malignant Disorders ◽

Oral Epithelial Dysplasia ◽

Normal Oral Mucosa ◽

Potentially Malignant Disorders ◽

Potentially Malignant

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Sistemas de gradação histológica em queilites actínicas: revisão de literatura

ARCHIVES OF HEALTH INVESTIGATION ◽

10.21270/archi.v9i6.4898 ◽

2020 ◽

Vol 9 (6) ◽

pp. 582-586

Author(s):

Elton Fernandes Barros ◽

Livian Isabel de Medeiros Carvalho ◽

Itainar Henriques Carvalho ◽

Amanda Pereira Ferraz ◽

Hellen Bandeira de Pontes Santos

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Epithelial Dysplasia ◽

Actinic Cheilitis ◽

Oral Epithelial Dysplasia ◽

Potentially Malignant Disorders ◽

Potentially Malignant ◽

Oral Epithelial

Introdução: A queilite actínica (QA) é uma desordem potencialmente maligna associada à exposição crônica à luz solar como principal fator etiológico. A QA tem como principal sítio de acometimento o vermelhão do lábio inferior, apresentando características clínicas marcantes. Porém, a análise histopatológica desta lesão merece um enfoque especial pelas características bastante expressivas para o potencial de malignidade. Assim, para essa análise, são elencados dois sistemas principais: o sistema da Organização Mundial da Saúde (OMS), e o binário. Objetivo: Realizar uma revisão da literatura para demonstrar os pontos avaliados e o valor preditivo dos sistemas de gradação histológica em QA. Metodologia: Trata-se de um estudo de revisão bibliográfica, utilizando artigos da base de dados da SCIELO e PUBMED, encontrados com o uso dos descritores: “actinic cheilitis”, “WHO system”, “binary system”, “oral potentially malignant disorders”, “histological features in actinic cheilitis”, fazendo uso do operador booleano “AND”. Conclusão: Diante da revisão realizada, percebeu-se a importância da adoção dos sistemas de gradação histológica da OMS, e o binário para uma análise minuciosa de lesões de QA, que apresentam potencial de malignidade. Ademais, constatou-se o favorecimento do sistema binário na redução da subjetividade entre os patologistas quanto à gradação das avaliações histopatológicas. Descritores: Queilite; Patologia Bucal; Neoplasias Labiais; Classificação; Diagnóstico. Referências Lopes MLDS, Silva Junior FLS, Lima KC, Oliveira PT, Silveira EJD. Clinicopathological proﬁle and management of 161 cases of actinic cheilitis. An Bras Dermatol. 2015;90(4):347-50. Arnaud RR, Soares MSM, Paiva MAF, Figueiredo CRLV, Santos MGC, Lira CC. Queilite actínica: avaliação histopatológica de 44 casos. Rev Odontol UNESP. 2014;43(6):384-89. Pilati S, Bianco BC, Vieira D, Modolo F. Histopathologic features in actinic cheilitis by the comparison of grading dysplasia systems. Oral Dis. 2017 Mar;23(2):219-224. Pilati S, Bianco BC, Vieira D, Modolo F. Histopathologic features in actinic cheilitis by the comparison of grading dysplasia systems. Oral Dis. 2017;23(2):219-24. Maia HCM, Pinto ANS, Pereira JS, Medeiros AMC, Silveira EJD, Miguel MCC. Lesões orais potencialmente malignas: correlações clínico-patológicas. Einstein. 2016;14(1): 35-40. Savage NW, McKay C, Faulkner C. Actinic cheilitis in dental practice. Aust Dent J. 2010; 55(Suppl 1):78-84. Vieira RA, Minicucci EM, Marques ME, Marques SA. Actinic cheilitis and squamous cell carcinoma of the lip: clinical, histopathological and immunogenetic aspects. An Bras Dermatol. 2012; 87(1):105-14. Dancyger A, Heard V, Huang B, Suley C, Tang D, Ariyawardana A. Malignant transformation of actinic cheilitis: A systematic review of observational studies. J Investig Clin Dent. 2018; 9(4):e12343. de Santana Sarmento DJ, da Costa Miguel MC, Queiroz LM, Godoy GP, da Silveira EJ. Actinic cheilitis: clinicopathologic profile and association with degree of dysplasia. Int J Dermatol. 2014; 53(4):466-72. Wood NH, Khammissa R, Meyerov R, Lemmer J, Feller L. Actinic cheilitis: a case report and a review of the literature. Eur J Dent. 2011; 5(1):101-6. Mello FW, Melo G, Modolo F, Rivero ER. Actinic cheilitis and lip squamous cell carcinoma: Literature review and new data from Brazil. J Clin Exp Dent. 2019;11(1):e62-9. Warnakulasuriya S, Johnson NW, van der Waal I. Nomenclature and classification of potentially malignant disorders of the oral mucosa. J Oral Pathol Med. 2007;36(10):575-80. Paiva MAF, Soares MSM, Figueiredo CRLV, Luna AH, Oliveira VEN, Brasil Júnior O. Associação entre displasia e inflamação em queilite actínica. J Bras Patol Med Lab. 2012; 48(6):455-58. Warnakulasuriya S, Reibel J, Bouquot J, Dabelsteen E. Oral epithelial dysplasia classification systems: predictive value, utility, weaknesses and scope for improvement. J Oral Pathol Med. 2008;37(3):127-33. Câmara PR, Dutra SN, Takahama Júnior A, Fontes K, Azevedo RS. A comparative study using WHO and binary oral epithelial dysplasia grading systems in actinic cheilitis. Oral Dis. 2016; 22(6):523-9. Kujan O, Oliver RJ, Khattab A, Roberts SA, Thakker N, Sloan P. Evaluation of a new binary system of grading oral epithelial dysplasia for prediction of malignant transformation. Oral Oncol. 2006;42(10):987-93. Nagata G, Santana T, Queiroz A, Caramez RH, Trierveiler M. Evaluation of epithelial dysplasia adjacent to lip squamous cell carcinoma indicates that the degree of dysplasia is not associated with the occurrence of invasive carcinoma in this site. J Cutan Pathol. 2018. doi: 10.1111/cup.13270. Mello FW, Miguel AFP, Dutra KL, Porporatti AL, Warnakulasuriya S, Guerra ENS, Rivero ERC. Prevalence of oral potentially malignant disorders: A systematic review and meta-analysis. J Oral Pathol Med. 2018;47(7):633-40. Izumo T. Oral premalignant lesions: from the pathological viewpoint. Int J Clin Oncol. 2011;16(1):15-26. Kujan O, Khattab A, Oliver RJ, Roberts SA, Thakker N, Sloan P. Why oral histopathology suffers inter-observer variability on grading oral epithelial dysplasia: an attempt to understand the sources of variation. Oral Oncol. 2007; 43(3):224-31. El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ. World Health Organization Classification of Head and Neck Tumours. WHO/IARC Classification of Tumours 2017; 4th ed. Lyon, France: IARC Press. R SA, B N P, Hegde U, K U, G S, G K, Sil S. Inter- and Intra-Observer Variability in Diagnosis of Oral Dysplasia. Asian Pac J Cancer Prev. 2017;18(12):3251-54. Olinici D, Cotrutz CE, Mihali CV, Grecu VB, Botez EA, Stoica L, Onofrei P, Condurache O, Dimitriu DC. The ultrastructural features of the premalignant oral lesions. Rom J Morphol Embryol. 2018;59(1):243-48.

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Evaluation of Diagnostic Value of Sediment Cytology in Oral Malignant and Oral Potentially Malignant Disorders

JOURNAL FOR CLINICAL AND DIAGNOSTIC RESEARCH ◽

10.7860/jcdr/2021/48017.14538 ◽

2021 ◽

Author(s):

Shreyas N Shah ◽

Falguni H Patel ◽

Niraj Patil ◽

Uday Patel

Keyword(s):

Indian Subcontinent ◽

Diagnostic Value ◽

Histopathological Study ◽

Oral Potentially Malignant Disorders ◽

Oral Epithelial Dysplasia ◽

Study Results ◽

Potentially Malignant Disorders ◽

Potentially Malignant ◽

Malignant Lesions ◽

Oral Epithelial

Introduction: Globally, highest prevalence of oral cancer has been observed in Indian subcontinent due to exposure to carcinogens such as betel nut extracts, smoking and chewing form of tobacco. Usually, cancer develops through rising grades of oral epithelial dysplasia which can arise from Oral Potentially Malignant Disorders (OPMD) and lead to fatal invasive malignancy. Being rapid, simple, cheaper and easy, sediment cytology may provide early diagnostic value in such cases. Aim: To estimate the role of sediment cytology from biopsy specimen fixatives in early diagnosis of OPMDs and oral malignant lesions. Materials and Methods: Cytological smears from total 30 cases, 15 subjects had Oral Potentially Malignant Disorders and 15 subjects each of Oral Potentially Malignant Disorders and Oral Malignant lesions were prepared by centrifuging fixatives of the biopsy specimens from February 2015 to January 2016. Analyses of prepared cytological smears were done and obtained results were compared with histological diagnosis. Results: The study results revealed that, out of 15 oral malignant lesions, 12 lesions were properly diagnosed with one inconclusive result and only three out of 15 OPMDs were properly diagnosed, where as three cases were inconclusive. Thus, in case of sediment cytology, the overall diagnostic accuracy was 50% and specifically 80% in case of oral malignant lesions. Conclusion: The Biopsy sediment cytology procedure is rapid, simple and inexpensive and can be applied with possible benefit in any laboratory for preliminary diagnosis. Thus, it is a good compliment for histopathological study of oral biopsies.

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Nuclear F-actin Cytology in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma

Journal of Dental Research ◽

10.1177/0022034520973162 ◽

2020 ◽

pp. 002203452097316

Author(s):

M.P. McRae ◽

A.R. Kerr ◽

M.N. Janal ◽

M.H. Thornhill ◽

S.W. Redding ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Oral Potentially Malignant Disorders ◽

Oral Epithelial Dysplasia ◽

Diagnostic Models ◽

Potentially Malignant Disorders ◽

Potentially Malignant ◽

Cytological Features ◽

Oral Epithelial

Oral cavity cancer has a low 5-y survival rate, but outcomes improve when the disease is detected early. Cytology is a less invasive method to assess oral potentially malignant disorders relative to the gold-standard scalpel biopsy and histopathology. In this report, we aimed to determine the utility of cytological signatures, including nuclear F-actin cell phenotypes, for classifying the entire spectrum of oral epithelial dysplasia and oral squamous cell carcinoma. We enrolled subjects with oral potentially malignant disorders, subjects with previously diagnosed malignant lesions, and healthy volunteers without lesions and obtained brush cytology specimens and matched scalpel biopsies from 486 subjects. Histopathological assessment of the scalpel biopsy specimens classified lesions into 6 categories. Brush cytology specimens were analyzed by machine learning classifiers trained to identify relevant cytological features. Multimodal diagnostic models were developed using cytology results, lesion characteristics, and risk factors. Squamous cells with nuclear F-actin staining were associated with early disease (i.e., lower proportions in benign lesions than in more severe lesions), whereas small round parabasal-like cells and leukocytes were associated with late disease (i.e., higher proportions in severe dysplasia and carcinoma than in less severe lesions). Lesions with the impression of oral lichen planus were unlikely to be either dysplastic or malignant. Cytological features substantially improved upon lesion appearance and risk factors in predicting squamous cell carcinoma. Diagnostic models accurately discriminated early and late disease with AUCs (95% CI) of 0.82 (0.77 to 0.87) and 0.93 (0.88 to 0.97), respectively. The cytological features identified here have the potential to improve screening and surveillance of the entire spectrum of oral potentially malignant disorders in multiple care settings.

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Visual Analytics: A Method to Explore Natural Histories of Oral Epithelial Dysplasia

Frontiers in Oral Health ◽

10.3389/froh.2021.703874 ◽

2021 ◽

Vol 2 ◽

Author(s):

Stan Nowak ◽

Miriam Rosin ◽

Wolfgang Stuerzlinger ◽

Lyn Bartram

Keyword(s):

Visual Analytics ◽

Clinical Presentation ◽

Epithelial Dysplasia ◽

Biological Processes ◽

Oral Potentially Malignant Disorders ◽

Oral Epithelial Dysplasia ◽

Potentially Malignant ◽

Oral Epithelial ◽

Natural Histories

Risk assessment and follow-up of oral potentially malignant disorders in patients with mild or moderate oral epithelial dysplasia is an ongoing challenge for improved oral cancer prevention. Part of the challenge is a lack of understanding of how observable features of such dysplasia, gathered as data by clinicians during follow-up, relate to underlying biological processes driving progression. Current research is at an exploratory phase where the precise questions to ask are not known. While traditional statistical and the newer machine learning and artificial intelligence methods are effective in well-defined problem spaces with large datasets, these are not the circumstances we face currently. We argue that the field is in need of exploratory methods that can better integrate clinical and scientific knowledge into analysis to iteratively generate viable hypotheses. In this perspective, we propose that visual analytics presents a set of methods well-suited to these needs. We illustrate how visual analytics excels at generating viable research hypotheses by describing our experiences using visual analytics to explore temporal shifts in the clinical presentation of epithelial dysplasia. Visual analytics complements existing methods and fulfills a critical and at-present neglected need in the formative stages of inquiry we are facing.

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