5/21/2015 What we will cover Oral Epithelial Dysplasia, Grading, Management and Significance • Leukoplakia, erythroplakia • Causes of oral epithelial dysplasia • Terminology & grading • Risk of transformation to cancer Richard C. Jordan DDS PhD FRCPath • Treatment Professor of Oral Pathology, Pathology & Radiation Oncology • Verrucous hyperplasia & carcinoma • Proliferative verrucous leukoplakia (PVL) Potentially malignant disorders International Workshop on Oral Potentially Malignant Disorders London, May 2005 Leukoplakia Leukoplakia ‘The term leukoplakia should be used to recognise white plaques of questionable risk having excluded (other) known Erythroplakia diseases or disorders that carry no increased risk for cancer’ 1
5/21/2015 Tobacco smoking Erythroplakia • definite relationship with “a red patch on the oral mucosa which cannot oral cancer be characterised clinically or histologically as • risk is greatest in heavy due to any other condition” users (>20/day) • risk is greater if accompanied by alcohol in ‘ reverse ’ smoking and use • risk may be greater with pipes and cigars 2
5/21/2015 Nicotine stomatitis Epidemiology of leukoplakia ‘Reverse smoking’ Prevalence: • Ranges from 0.9% to 26.9% • Depends on site and size of study Recent systematic review shows worldwide prevalence of: 2.6% Petti (2003). Oral Oncology, 39, 770-780 3
5/21/2015 Leukoplakia - Histology Leukoplakia Homogeneous Up to 80% show no dysplasia flat and plaque-like, uniformly white Non-homogeneous nodular, verruciform, exophytic, speckled Homogeneous Non-homogeneous Leukoplakia Leukoplakia Only about 20% About 50% are are dysplastic dysplastic 4
5/21/2015 Dysplasia grading schemes Dysplasia grading schemes Oral epithelial dysplasia Oral epithelial Squamous intra- Classic larynx Oral epithelial Squamous intra- Classic larynx Hyperplasia Llubljana scheme Llubljana scheme dysplasia epithelial neoplasia scheme dysplasia epithelial neoplasia scheme Hyperplasia N/A Simple hyperplasia Laryngeal keratosis Hyperplasia N/A Simple hyperplasia Laryngeal keratosis Mild Basal/parabasal Basal/parabasal Mild SIN 1 Hyperplasia Mild SIN 1 Hyperplasia hyperplasia hyperplasia Moderate Moderate SIN 2 Moderate SIN 2 Severe Keratosis with Keratosis with Atypical hyperplasia Atypical hyperplasia Severe dysplasia Severe dysplasia SIN 3 SIN 3 Ca-in-situ Ca-in-situ Ca-in-situ Ca-in-situ Ca-in-situ Ca-in-situ Ca-in-situ (Based on Barnes et al, ‘WHO Blue Book’ 2005, Bouquot et al, 2006) (Based on Barnes et al, ‘WHO Blue Book’ 2005, Bouquot et al, 2006) Increasing severity Architectural (Tissue) changes: (Hyperchromatism & crowding) • Loss of polarity • Disordered maturation from basal to squamous cells Includes top-to-bottom change of carcinoma in • Normal situ keratinocytes • Increased cellular density • Basal cell hyperplasia Atypical • Dyskeratosis (premature keratinization and keratinocytes keratin pearls deep in epithelium) Mild Moderate Severe • Bulbous drop shaped rete pegs dysplasia dysplasia dysplasia • Secondary extensions (nodules) on rete tips Progression of dysplasia Barnes L et al: 2005 WHO Classification 5
5/21/2015 Cellular changes Cellular changes: • Abnormal variation in nuclear size and shape (anisonucleosis and pleomorphism) • Abnormal variation in cell size and shape (anisocytosis and pleomorphism) • Increased nuclear/cytoplasmic ratio • Enlarged nuclei and cells • Hyperchromatic nuclei • Increased mitotic figures • Abnormal mitotic figures (abnormal in shape or location) • Increased number and size of nucleoli Pleomorphism of cells and nuclei Barnes L et al: 2005 WHO Classification Courtesy P. Speight U. Sheffield Cellular changes Architectural changes Bulbous rete pegs Hyperchromatism & increased nuclear size and nuc/cyt ratio Loss of basal polarity Basal cell hyperplasia & cell crowding Courtesy P. Speight U. Sheffield Courtesy P. Speight U. Sheffield 6
5/21/2015 Mild epithelial dysplasia Moderate epithelial dysplasia Changes extend in Changes are limited to the middle 1/3 of to the lower 1/3 of the epithelium the epithelium Courtesy P. Speight U. Sheffield Courtesy P. Speight U. Sheffield Severe epithelial dysplasia Carcinoma-in-situ Changes extend Changes extend in through the full to the upper 1/3 of thickness of the the epithelium epithelium Courtesy P. Speight U. Sheffield Courtesy P. Speight U. Sheffield 7
5/21/2015 Doppelgängers Doppelgängers Not so famous pathologist Famous actor Tom Hanks Richard Jordan Doppelgängers Reactive atypia in inflammatory lesions Famous model Fabio His twin with great hair 8
5/21/2015 Reactive epithelial atypia vs epithelial dysplasia Is epithelial dysplasia a useful • Reactive atypia • Epithelial dysplasia marker of potential progression of – Enlarged, vesicular – Basaloid appearing nuclei & prominent oral precursor lesions? – Hyperchromatic nuclei nucleoli – No or minimal – Associated inflammation inflammation, either – Abnormal mitoses at acute or chronic, odd levels – Increase in normal mitotic activity – Degenerate cells What lesions progress to cancer? What becomes of dysplastic lesions? Mild < 5% Malignant 20% Regress 20% Moderate 5% – 15% No change 40% Increase in size 20% Severe 10% - 50% 9
5/21/2015 Grading of oral epithelial dysplasia Epithelial dysplasia is not a good predictor of malignant transformation: Grading is subjective based on a combination of cellular and architectural • Dysplastic lesions: 36% progressed features • Non-dysplastic lesions 16% progressed Grading is regarded as unreliable Lesions without dysplasia may also progress Silverman et al. 1984. Oral leukoplakia and malignant transformation. A follow up study of 257 patients. Cancer; 53: 563-568 Leukoplakia and malignancy Inter-examiner variability in diagnosis Dysplasia % agreement κ s None Mild Moderate Severe 0.51 (0.42 - 0.58) 77 (75 – 85) Brothwell et al, 2003 45 47 Number of lesions 0.35 (0.27 - 0.45) 55 (49 – 69) Karabulut et al, 1995 Number progressed 3 11 0.46 (0.29 - 0.57) 82 (66 – 86) Abbey et al, 1995 6 23 % progressed K values calculated for presence/absence of dysplasia Values show fair to moderate agreement only Schepman KP et al 1998 Malignant transformation of oral leukoplakia: a follow-up study of a hospital-based population of 166 patients with oral leukoplakia from The Netherlands. Oral Oncol ; 34: 270–5. 10
5/21/2015 Binary classification system Low Risk High Risk No dysplasia Moderate Borderline Severe Mild Ca-in-situ Verrucous carcinoma Managing dysplasia • Rare variant of SCC 1-3/million • Remove any residual lesion • Tobacco, not HPV • Don’t chase microscopic margins • Slow growing exophytic verrucous patch • Re-biopsy if lesion changes (they often • Locally destructive, rarely metastasizes recur) • Buccal mucosa>gingiva>tongue>palate>other • Retinoids don’t help • Well differentiated carcinoma; little or no dysplasia • Excision, prognosis excellent 11
5/21/2015 12
5/21/2015 PVL - history • Described by Hansen 1985 in 30 patients • Prior to 1985 “oral florid papillomatosis” • Slowly growing, persistent hyperkeratosis, multifocal • Resistant to treatment • to 2014 – 69 papers on PVL Verrucous hyperplasia Verrucous carcinoma PVL clinical • 80 % women • Mean age 71 years • Gingiva > BM > palate • Starts as a flat white lesion progressing to verruciform lesion • Multifocal 13
5/21/2015 Hyperkeratosis Hyperkeratosis Verruciform Verruciform Papillary SCC Papillary SCC hyperkeratosis hyperkeratosis Verrucous carcinoma Verrucous carcinoma Verrucous hyperplasia Verrucous hyperplasia PVL transform to carcinoma PVL & HPV Author Year # pts Mean age Tobacco % CA % Author Year Method HPV + Palefsky 1995 PCR 8/9 (HPV16: 7/9) Hansen 1985 30 66 62 90 Zakrzewska 1996 10 64 50 90 Gopalakrishnan 1997 PCR 2/10 (HPV16/18) Silverman 1997 54 62 31 85 Fettig 2000 PCR 0/10 Fettig 2000 10 65 38 100 Campisi 2004 PCR 14/58 (24%) Bagan 2003 30 71 23 87 Campisi 2004 58 66 29 - Bagan 2007 PCR 0/10 Gandolfo 2009 47 66 37 - Govea 2010 12 70 25 33 14
5/21/2015 What we will cover Oral Epithelial Dysplasia, Grading, Management and Significance • Leukoplakia, erythroplakia • Causes of oral epithelial dysplasia • Terminology & grading • Risk of transformation to cancer Richard C. Jordan DDS PhD FRCPath • Treatment Professor of Oral Pathology, Pathology & Radiation Oncology • Verrucous hyperplasia & carcinoma • Proliferative verrucous leukoplakia (PVL) Potentially malignant disorders International Workshop on Oral Potentially Malignant Disorders London, May 2005 Leukoplakia Leukoplakia ‘The term leukoplakia should be used to recognise white plaques of questionable risk having excluded (other) known Erythroplakia diseases or disorders that carry no increased risk for cancer’ 1
Recommend
More recommend
