Problem diagnoses. Current issues in Anatomic pathology. Problem Diagnoses in Tumors of the Oral Cavity 5/29/2009
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1 Current issues in Anatomic pathology Problem Diagnoses in Tumors of the Oral Cavity Richard Jordan DDS PhD FRCPath Professor of Oral Pathology & Pathology Director, UCSF Oral Pathology Diagnostic Laboratory University of California San Francisco Problem diagnoses 12 month period: 225 outside consults 70 cases originated by clinician at UCSF 155 cases requesting second opinion 18 cases from academic centers, 137 community hospitals Outside Dx UCSF Dx Outside Dx UCSF Dx Ameloblastic fibroma Desmoplastic fibroma Ameloblastic fibroma Desmoplastic fibroma Chronically inflamed fibrous tissue Chronically inflamed fibrous tissue Angioleiomyomatous neoplasm Low-grade myofibroblastic sarcoma Angioleiomyomatous neoplasm Low-grade myofibroblastic sarcoma BCC - cystic BCC - cystic Benign papillary ductal neoplasm Mucoepidermoid carcinoma, low grade Benign papillary ductal neoplasm Mucoepidermoid carcinoma, low grade Carcinoma in situ Mucin-rich salivary duct carcinoma Carcinoma in situ Mucin-rich salivary duct carcinoma Cementifying fibroma Chronic sclerosing osteitis Cementifying fibroma Chronic sclerosing osteitis Cystic Calcifying Odontogenic Cyst Cystic Calcifying Odontogenic Cyst Glandular odontogenic cyst Dentigerous cyst Glandular odontogenic cyst Dentigerous cyst Necrotic tissue Peripheral T-cell lymphoma Necrotic tissue Peripheral T-cell lymphoma Non-healing ulcer Epithelial dysplasia Non-healing ulcer Epithelial dysplasia Odontogenic Myxoma Dentigerous Cyst Odontogenic Myxoma Dentigerous Cyst Paget's Disease Sclerotic Bone Paget's Disease Sclerotic Bone Pindborg tumor Adenomatoid odontogenic tumor Pindborg tumor Adenomatoid odontogenic tumor Pleomorphic adenoma Mucoepidermoid carcinoma Pleomorphic adenoma Mucoepidermoid carcinoma Schwannoma MPNST Schwannoma MPNST Sialadenoma papilliferum Papillary cystadenocarcinoma Sialadenoma papilliferum Papillary cystadenocarcinoma Subacute inflammation Langerhans cell disease Subacute inflammation Langerhans cell disease 1
2 Outside UCSF Dysplasia/SCC Cyst Combination** 21 0 Odontogenic tumor Mucocutaneous disease BFOL Soft tissue tumor Topics 1. Epithelial dysplasia, grading 2. SCC & HPV 3. Odontogenic cysts & tumors Salivary gland disease/tumor 9 10 Bone 8 10 No diagnosis given 7 0 Lymphoproliferative disorder 2 3 Skin 1 0 **Combination = Dysplasia vs. mucocut = 9; Cyst vs odont tumor = 6; Other = 16 Epithelial Dysplasia 2
3 Idiopathic Leukoplakia Histology Hyperkeratosis 80% Dysplasia 12% In situ carcinoma 3% SCC 5% Leukoplakia Site Dysplastic or SCC (%) FOM 43 Tongue, ventral or lateral 24 Lip, lower 24 Palate 19 Buccal mucosa 17 Max/mand mucosa/sulcus 15 Retromolar area 12 Increasing severity (Hyperchromatism & crowding) Clinical Normal keratinocytes Histologic Molecular Hyperplasia Mild Dysplasia Severe Cancer 9p 3p, 17p 4q, 11q, 13q, 14,q, 17q, 6p, 8p 8q, 13p, 18q Slide from: Lippman NEJM Atypical keratinocytes Mild dysplasia Moderate dysplasia Progression of dysplasia Severe dysplasia 3
4 Microscopic features of dysplasia Normal Mild dysplasia Morphological features Cytological features Drop shaped rete pegs Basal cell hyperplasia Irregular stratification Reduced intercellular adhesion Pleomorphism Altered nuclear cytoplasmic ratios Increased and abnormal mitoses Enlarged nucleoli Moderate dysplasia Severe dysplasia Oral epithelial dysplasia Most oral SCC preceded by dysplasia Most important risk factor for oral cancer Overall risk: 16-32% Overall progression to SCC: Mild: 5% Moderate: 33% Severe: 50% Some sites higher risk: i.e. FOM Single lesion poor prediction Problems in the diagnosis & management of epithelial dysplasia Variations in the natural history Diagnosis and grading is subjective Excision is frequently followed by recurrence UC SF 4
5 Science January 30, 2009 Gillison et al. Human papillomavirus (HPV) and survival of patients with oropharynx cancer. NEJM (submitted) Gillison et al. Human papillomavirus (HPV) and survival of patients with oropharynx cancer. NEJM (submitted) 5
6 HNSCC Oropharyngeal SCC Location Any Oropharynx Tobacco history Yes No Alcohol history Yes No Marijuana association No Yes HPV No HPV 16 Morphology Keratinized Basaloid Odontogenic Cysts & Tumors p16 + No Yes p53 mutations Yes No Pre-existing dysplasia Yes No 5 year survival ~ 30-40% ~70-80% Stage predicts outcome Yes No Odontogenic Cysts & Tumors Epidemiology Jaw cysts common because of abundance of epithelial rests Odontogenic tumors from tooth-forming apparatus Only situation in pathology: primary epithelial tumor within bone Odontogenic cysts and tumors are rare 1-5% of all jaw lesions are odontogenic tumors 0.5/100,000 per year 6
7 Odontogenic cysts Benign Tumors Odontogenic epithelium only: Malignant tumors Odontogenic carcinomas: Developmental Dentigerous cyst Odontogenic keratocyst Gingival cyst of the newborn Gingival cyst of the adult Lateral periodontal cyst Calcifying odontogenic cyst Inflammatory Radicular cyst Residual cyst Squamous odontogenic tumor Calcifying epithelial odontogenic tumor Adenomatoid odontogenic tumor Odontogenic keratocyst Odontogenic epithelium & mesenchyme: Ameloblastic fibroma Odontomas - complex and compound Calcifying odontogenic cyst (and variants) Odontogenic mesenchyme: Malignant ameloblastoma Primary intraosseous squamous cell carcinoma Clear cell odontogenic carcinoma Ghost cell odontogenic carcinoma Odontogenic sarcomas: Ameloblastic fibrosarcoma Odontogenic tumors Odontogenic Fibroma Odontogenic Myxoma Cementoblastoma Frequency of odontogenic tumors Odontogenic Keratocyst Type USA China Nigeria Odontoma 68 * Odontogenic myxoma Adenomatoid odontogenic tumor Ameloblastic fibroma Pindborg tumor * % of total odontogenic tumors From dental lamina Different growth mechanism from other cysts High tendency to recur Posterior mandible, but can occur anywhere in jaws Multiple cysts feature of nevoid basal cell carcinoma (Gorlin) syndrome 7
8 Odontogenic Keratocyst: Diagnosis Thin epithelium 6-10 cell layers Refractile, parakeratotic lining Epithelial budding with daughter cysts Features are lost with inflammation Orthokeratinized odontogenic cyst Less common Not syndrome associated Low recurrence rate Nevoid Basal Cell Carcinoma Syndrome Autosomal dominant High penetrance, variable expressivity Multiple odontogenic keratocysts Multiple basal cell carcinomas Skeletal anomalies (bifid rib, hypertelorism) Intracranial calcification (falx cerebri) Characteristic facies 8
9 : Biologic Subtypes Benign, slow-growing, locally invasive neoplasm 3rd-7th decades, mean ~40 yrs, M=F Asymptomatic or painless swelling 85 % mandible, especially molar-ramus area, 15 % maxilla, mostly posterior regions Solid ameloblastoma (86%) Cystic ameloblastoma (13%) Peripheral ameloblastoma (1%) Malignant ameloblastoma Ameloblastic carcinoma 9
10 Histologic Subtypes/Patterns All subtypes mimic enamel organ Peripheral palisades & budding No hard tissue formation No clinical significance to subtypes Microscopic Desmoplastic follicular, plexiform, granular cell, acanthomatous, basaloid, spindle cell Ameloblasts SR IEE EEE DP Odontoblasts 10
11 Cystic Synonyms: unicystic ameloblastoma, plexiform unicystic ameloblastoma, ameloblastoma Younger patients 90% mandible (posterior regions) Unilocular or multilocular radiolucency Macroscopically resembles cyst Recurrence potential Cystic * Cystic ameloblastoma Multilocularity & cortical perforation >25% Recurrences with curettage >40% (1-9 yrs) * UCSF study of 21 cystic ameloblastomas 11
12 Cystic ameloblastoma 12
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