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Odontogenic Tumors 4/26/20 CONTEMPORARY MANAGEMENT OF ODONTOGENIC TUMORS RUI FERNANDES, DMD, MD,FACS, FRCS(ED) PROFESSOR UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE- JACKSONVILLE 1 2 Benign th 4 Edition Odontogenic 2017 Tumors Malignant 3 4 BENIGN ODONTOGENIC TUMORS BENIGN ODONTOGENIC TUMORS • EPITHELIAL • MESENCHYMAL • AMELOBLASTOMA • ODONTOGENIC MYXOMA • CALCIFYING EPITHELIAL ODONTOGENIC TUMOR • ODONTOGENIC FIBROMA • PINDBORG TUMOR • PERIPHERAL ODONTOGENIC FIBROMA • ADENOMATOID ODONTOGENIC TUMOR • CEMENTOBLASTOMA • SQUAMOUS ODONTOGENIC TUMOR • ODONTOGENIC GHOST CELL TUMOR 5 6 1 4/26/20 BENIGN ODONTOGENIC TUMORS MALIGNANT ODONTOGENIC TUMORS • PRIMARY INTRAOSSEOUS CARCINOMA • MIXED TUMORS • CARCINOMA ARISING IN ODONTOGENIC CYSTS • AMELOBLASTIC FIBROMA / FIBRO-ODONTOMA • AMELOBLASTIC FIBROSARCOMA • ODONTOMA • AMELOBLASTIC SARCOMA • CLEAR CELL ODONTOGENIC CARCINOMA • ODONTOAMELOBLASTOMA • SCLEROSING ODONTOGENIC CARCINOMA New to the Classification • PRIMORDIAL ODONTOGENIC TUMOR New to the Classification • ODONTOGENIC CARCINOSARCOMA 7 8 0.5 Cases per 100,000/year Ameloblastomas 30%-35% Myxoma AOT 3%-4% Each Ameloblastic fibroma CEOT Ghost Cell Tumor 1% Each 9 10 Courtesy of Professor Ademola Olaitan AMELOBLASTOMA • 1% OF ALL CYSTS AND TUMORS • 30%-60% OF ALL ODONTOGENIC TUMORS • 3RD TO 4TH DECADES OF LIFE • NO GENDER PREDILECTION • MANDIBLE 80% • MAXILLA 20% 11 12 2 4/26/20 AMELOBLASTOMA CLASSIFICATION AMELOBLASTOMA HISTOLOGICAL CRITERIA • SOLID OR MULTI-CYSTIC Conventional 2017 • UNICYSTIC 1. PALISADING NUCLEI 2 • PERIPHERAL 2. REVERSE POLARITY 3. VACUOLIZATION OF THE CYTOPLASM 4. HYPERCHROMATISM OF BASAL CELL LAYER 1 3 4 AmeloblAstomA: DelineAtion of eArly histopathologic feAtures of neoplasiA Robert Vickers, Robert Gorlin, CAncer 26:699-710, 1970 13 14 AMELOBLASTOMA CLASSIFICATION OF 3677 CASES AMELOBLASTOMA SLOW GROWTH – RADIOLOGICAL EVIDENCE Unicystic Peripheral 6% 2% Solid 92% ~3 yeArs After enucleAtion of “dentigerous cyst” P.A . Reichart, H.P. Philipsen and S. Sonner Eur J Cancer, Part B, Oral Oncol 31B:86-99, 1995 15 16 AMELOBLASTOMA AGGRESSIVE /DESTRUCTIVE BEHAVIOR 17 18 3 4/26/20 CASE# 1 19 YO WITH AMELOBLASTOMA AMELOBLASTOMA ASPIRATION 19 20 19 YO WITH AMELOBLASTOMA TUMOR RESECTION 21 22 POST-OPERATIVE APPEARANCE CASE #2 • 69 Y.O. MALE REFERRED WITH A BIOPSY PROVEN AMELOBLASTOMA OF THE MANDIBLE • HIS MEDICAL HISTORY AND SURGICAL HISTORY ARE NONE CONTRIBUTORY • OVERALL HEALTHY 23 24 4 4/26/20 Q: How would you maintain the mandibular relationship ? (no VSP) 25 26 27 28 Q: How would you reconstruct this defect? 29 30 5 4/26/20 1 year post surgery, removal of reconstruction plate 31 32 Overall recurrence rates: Facial appearance prior to dentures, vertical collapse consistent 5 year: 9.3% 10 year: 17.6% 15 year: 24.4% with edentulous upper and lower arches Resection Only Independent Prognostic Factor 33 34 AMELOBLASTOMA UNICYSTIC AMELOBLASTOMA AMELOBLASTOMA UNICYSTIC VARIANT First Report • GENERALLY A UNILOCULAR • 20 PATIENTS RADIOLUCENCY ASSOCIATED WITH AN IMPACTED TOOTH THAT IS DIFFICULT TO • PRESENTED WITH UNILOCULAR CYSTIC LESIONS DISTINGUISH FROM A DENTIGEROUS • LESIONS MIMICKED DENTIGEROUS CYSTS CYST. • SIMPLE ENUCLEATION • ROBINSON AND MARTINEZ, 1977 • LESS RECURRENCE I.E. LESS AGGRESSIVE BEHAVIOR ? • ASSOCIATED WITH A LOW RATE OF “RECURRENCE” AFTER ENUCLEATION Robinson L, Martinez MG AND CURETTAGE Unicystic ameloblastomA: a prognostically distinct entity. Cancer. 1977 Nov;40(5):2278-85. • GARDNER AND CORIO, 1984 35 36 6 4/26/20 UNICYSTIC AMELOBLASTOMA Cyst lined by IntrAmurAl nodulAr ameloblastomA ameloblastomA 50 % to 80% associated with an impActed tooth most commonly: mandibulAr 3rd molAr TreAtment: simple (luminAl or intrAluminAl): enucleation murAl or trAnsmurAl: rAdicAl IntrAmurAl infiltrAting IntrAluminAl resection ameloblastomA ameloblastomA Ackermann GL, Altini M, Shear M. The unicystic ameloblastoma: a clinicopathologic study of 57 cases. Journal of Oral Pathology 1988;17:541±546. 37 38 14 Y.O. WITH MANDIBULAR AMELOBLASTOMA 14 Y.O. WITH MANDIBULAR AMELOBLASTOMA 39 40 14 Y. O. WITH MANDIBULAR AMELOBLASTOMA 14 Y.O. WITH MANDIBULAR AMELOBLASTOMA 41 42 7 4/26/20 14 Y.O . WITH MANDIBULAR AMELOBLASTOMA 14 Y.O. WITH MANDIBULAR AMELOBLASTOMA 43 44 14 Y.O. WITH MANDIBULAR AMELOBLASTOMA • U OF MARYLAND’S EXPERIENCE & WORLD LITERATURE • UNDER AGE 20 YEARS • MARYLAND EXPERIENCE 11PTS • 8 PRIMARY, 3 RECURRENT LESIONS • AVERAGE AGE 15.5 Y • 9 OF 11 UNICYSTIC AMELOBLASTOMAS • WESTERN POPULATION 85PTS • AVERAGE AGE 14.3 • UNICYSTIC AMELOBLASTOMAS 76.5% • AFRICAN POPULATION 77PTS • AVERAGE AGE 14.7 • UNICYSTIC AMELOBLASTOMAS 19.5% • RECURRENCES AFTER ENUCLEATION OF UNICYSTIC AMELOBLASTOMAS • FOLLOWED FOR AT LEAST 5 YEARS OR UNTIL RECURRENCES SHOWED A RECURRENCE RATE OF 40% 45 46 STAGED IMMEDIATE IMPLANT PLACEMENT… BRAF and SMO negative 2 years post treatment 47 48 8 4/26/20 49 50 51 52 53 54 9 4/26/20 55 56 CASE #2 CASE # 2 • 39 Y.O. FEMALE NURSE REFERRED WITH A BIOPSY PROVEN AMELOBLASTOMA OF THE MANDIBLE • HIS MEDICAL HISTORY AND SURGICAL HISTORY ARE NONE CONTRIBUTORY • OVERALL HEALTHY • HIGH ESTHETIC DEMAND AND WISHES FOR A RAPID RETURN TO WORK AND DEFINITIVE SURGER 57 58 59 60 10 4/26/20 Q: How would you reconstruct this defect? 61 62 63 64 65 66 11 4/26/20 67 68 CALCIFYING EPITHELIA ODONTOGENIC TUMOR (PINDBORG TUMOR) • ACCOUNTS FOR LESS THAN 1% OF ALL ODONTOGENIC TUMORS • FEWER THAN 200 REPORTED CASES • PATIENTS BETWEEN 30 AND 50 YEARS OLD • 2/3RDS OCCUR IN THE MANDIBLE • PRESENT AS A PAINLESS SLOW GROWING MASS 69 70 CALCIFYING EPITHELIA ODONTOGENIC TUMOR ADENOMATOID ODONTOGENIC TUMOR (A.O.T.) (PINDBORG TUMOR) • UNCOMMON TUMOR • ACCOUNTS FOR 3 TO 7% • DISCRETE ISLANDS OF • YOUNG PATIENTS POLYHEDRAL SHEETS • VERY UNCOMMON IN PTS OLDER • LARGE AREAS OF AMYLOID LIKE THAN 30 Y MATERIAL • ALSO KNOWN AS THE 2/3RDS • CONCENTRIC CALCIFICATIONS TUMOR KNOWN AS LIESENGANG RINGS • 2/3 FEMALES • 2/3 MAXILLA • 2/3 IMPACTED CANINE Treatment: Resection with a 1 cm bony linear margin 71 72 12 4/26/20 A.O.T. HISTOLOGY A.O.T. TREATMENT • WELL DEFINED Due to the thickness of the • THICK CAPSULE capsule, the tumor may be • SPINDLE SHAPED CELLS treated by enucleation and curettage • WHORLED MASSES OF CELLS WITH SCANT FIBROUS STROMA Only one recurrence in the • ROSETTE-LIKE STRUCTURES literature WITH CENTRAL EMPTY SPACES 73 74 A.O.T. CASE EXAMPLE A.O.T. CASE EXAMPLE 75 76 A.O.T. CASE EXAMPLE 77 78 13 4/26/20 MYXOMA MYXOMA HISTOLOGY • UNCOMMON BENIGN NEOPLASM • STELLATE, SPINDLE SHAPED OF THE JAWS CELLS • DEVELOPS FROM • LOOSELY MYXOID STROMA ECTOMESENCHYME • SLOW GROWING WITH POTENTIAL • RESEMBLES STELLATE FOR AGGRESSIVE BEHAVIOR RETICULUM • HIGH RECURRENCE RATE AFTER • FEW COLLAGEN FIBRILS INADEQUATE THERAPY 79 80 MYXOMA RADIOGRAPHIC APPEARANCE 1 MYXOMA TREATMENT • UNILOCULAR OR MULTILOCULAR IN APPEARANCE • MAY DISPLACE OR CAUSE ROOT RESORPTION • TRABECULAE OF RESIDUAL BONE ARRANGED AT RIGHT ANGLES TO ONE ANOTHER “STEPLADDER” Patient with An expAnding mAss on the right mAxillA, diAgnosis: myxomA 81 82 MYXOMA TREATMENT 2 83 84 14 4/26/20 85 86 87 88 89 90 15 4/26/20 91 92 93 94 95 96 16 4/26/20 97 98 99 100 101 102 17 4/26/20 103 104 105 106 26 cases No statistical difference in recurrence between conservative vs radical treatment 107 108 18 4/26/20 Overall recurrence 5/39(13%) X10y Conservative tx 4/22(19%) X11y Resection 1/17(6%) x9y 109 110 AMELOBLASTOMA MALIGNANT AMELOBLASTOMA & AMELOBLASTIC CARCINOMA 111 112 MALIGNANT AMELOBLASTOMA VS. AMELOBLASTIC CARCINOMA WHO Classification 2005 • MALIGNANT (METASTASIZING) AMELOBLASTOMA • IS A NEOPLASM IN WHICH THE FEATURES OF AN AMELOBLASTOMA ARE SHOWN BY THE PRIMARY GROWTH IN THE JAWS AND BY ANY METASTATIC GROWTH. Malignant (Metastasising) Ameloblastoma • AMELOBLASTIC CARCINOMA • IS A NEOPLASM IN WHICH THERE HAS BEEN HISTOLOGICALLY MALIGNANT TRANSFORMATION, WITH OR WITHOUT METASTATIC DEPOSITS. Ameloblastoma Type 1 Primary intraosseous carcinoma, ex odontogenic cyst (Malignant types) Type 2 Primary intraosseous carcinoma, ex ameloblastoma Malignant ameloblastoma Ameloblastic carcinoma arising de novo, ex ameloblastoma, or ex odontogenic cyst Type 3 Primary intraosseous carcinoma arising de novo Non-keratinizing Ameloblastic Carcinoma Keratinizing Slootweg PJ, Muller H: MAlignAnt AmeloblAstomA or AmeloblAstic cArcinomA OrAl Surg 57:168-176; 1984 113 114 19 4/26/20 WHO Classification 2017 AMELOBLASTIC CARCINOMA • 8 CASES Malignant (Metastasising) Metastasizing Ameloblastoma Ameloblastoma • 7 CASES IN THE MANDIBLE, 1 CASE IN THE MAXILLA Benign Category • A DIAGNOSIS OF BENIGN AMELOBLASTOMA WAS MADE FOR ALL CASES BASED ON INCISIONAL BIOPSY Ameloblastoma • ONE CASE HAD CERVICAL METASTASIS AT THE TIME OF INITIAL (Malignant types) PRESENTATION • MOST COMMON PRESENTING SYMPTOMS INCLUDED RAPID GROWTH (6 CASES) AND PAIN (3 CASES) • 3 PATIENTS DEVELOPED RECURRENT DISEASE Ameloblastic Carcinoma Corio RL, GoldblAtt LI, Edwards PA, HartmAn KS. AmeloblAstic cArcinomA: A clinicopAthologic study And assessment of eight cases. Oral Surg Oral Med Oral Pathol. 64:570-6; 1987 115 116 AMELOBLASTIC CARCINOMA 117 118 119 120 20 4/26/20 121 122 123 124 PT WITH METASTATIC DISEASE OR NON-RESECTABLE DX TARGETED SYSTEMIC THERAPY � 125 126 21 4/26/20 MOLECULAR MARKERS IN MELANOMA • BRAF (B-RAF PROTO-ONCOGENE) MUTATIONS V600E • 50 – 70% BRAF • KIT (PROTO-ONCOGENE C-KIT) MUTATIONS • 10 – 15% MUCOSAL (SINONASAL AND CHRONICALLY SUN EXPOSED SKIN) • NRAS (NRAS PROTO-ONCOGENE) MUTATIONS • 15% SKIN WITH CHRONIC AND INTERMITTENT SUN EXPOSURE Sensitivity to agents that inhibit the BRAF or MAPK pathway 127 128 Timeline of treatment options for metastatic
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