edition 2017 - aaomp · 2020-04-26 · 4/26/20 1 contemporary management of odontogenic tumors rui...

4/26/20

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CONTEMPORARY MANAGEMENT OF

ODONTOGENIC TUMORS

RUI FERNANDES, DMD, MD,FACS, FRCS(ED)PROFESSOR

UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE- JACKSONVILLE

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4th Edition 2017

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Benign

Malignant

Odontogenic Tumors

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BENIGN ODONTOGENIC TUMORS

• EPITHELIAL

• AMELOBLASTOMA

• CALCIFYING EPITHELIAL ODONTOGENIC TUMOR• PINDBORG TUMOR

• ADENOMATOID ODONTOGENIC TUMOR

• SQUAMOUS ODONTOGENIC TUMOR

• ODONTOGENIC GHOST CELL TUMOR

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• MESENCHYMAL

• ODONTOGENIC MYXOMA

• ODONTOGENIC FIBROMA

• PERIPHERAL ODONTOGENIC FIBROMA

• CEMENTOBLASTOMA

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• MIXED TUMORS

• AMELOBLASTIC FIBROMA / FIBRO-ODONTOMA

• ODONTOMA

• ODONTOAMELOBLASTOMA

• PRIMORDIAL ODONTOGENIC TUMOR New to the Classification

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MALIGNANT ODONTOGENIC TUMORS

• PRIMARY INTRAOSSEOUS CARCINOMA• CARCINOMA ARISING IN ODONTOGENIC CYSTS

• AMELOBLASTIC FIBROSARCOMA• AMELOBLASTIC SARCOMA

• CLEAR CELL ODONTOGENIC CARCINOMA• SCLEROSING ODONTOGENIC CARCINOMA• ODONTOGENIC CARCINOSARCOMA New to the Classification

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0.5 Cases per 100,000/year

Ameloblastomas 30%-35%

MyxomaAOT 3%-4% EachAmeloblastic fibroma

CEOTGhost Cell Tumor 1% Each

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Courtesy of Professor Ademola Olaitan

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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%

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AMELOBLASTOMA HISTOLOGICAL CRITERIA

1. PALISADING NUCLEI

2. REVERSE POLARITY

3. VACUOLIZATION OF THE CYTOPLASM

4. HYPERCHROMATISM OF BASAL CELL LAYER

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Ameloblastoma: Delineation of early histopathologic features of neoplasiaRobert Vickers, Robert Gorlin, Cancer 26:699-710, 1970

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AMELOBLASTOMA CLASSIFICATION

• SOLID OR MULTI-CYSTIC

• UNICYSTIC

• PERIPHERAL

Conventional 2017

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AMELOBLASTOMA CLASSIFICATION OF 3677 CASES

P.A. Reichart, H.P. Philipsen and S. Sonner Eur J Cancer, Part B, Oral Oncol 31B:86-99, 1995

Solid92%

Peripheral2%

Unicystic6%

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AMELOBLASTOMA SLOW GROWTH – RADIOLOGICAL EVIDENCE

~3 years after enucleation of “dentigerous cyst”

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AMELOBLASTOMA AGGRESSIVE /DESTRUCTIVE BEHAVIOR

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AMELOBLASTOMA ASPIRATION

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CASE# 1 19 YO WITH AMELOBLASTOMA

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19 YO WITH AMELOBLASTOMA TUMOR RESECTION

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POST-OPERATIVE APPEARANCE

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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

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Q: How would you maintain the mandibular relationship ? (no VSP)

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Q: How would you reconstruct this defect?

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1 year post surgery, removal of reconstruction plate

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Facial appearance prior to dentures, vertical collapse consistent with edentulous upper and lower arches

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Overall recurrence rates:5 year: 9.3% 10 year: 17.6% 15 year: 24.4%

Resection Only Independent Prognostic Factor

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AMELOBLASTOMA UNICYSTIC AMELOBLASTOMA

• 20 PATIENTS

• PRESENTED WITH UNILOCULAR CYSTIC LESIONS

• LESIONS MIMICKED DENTIGEROUS CYSTS

• SIMPLE ENUCLEATION

• LESS RECURRENCE I.E. LESS AGGRESSIVE BEHAVIOR ?

Robinson L, Martinez MGUnicystic ameloblastoma: a prognostically distinct entity.Cancer. 1977 Nov;40(5):2278-85.

First Report

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AMELOBLASTOMA UNICYSTIC VARIANT

• GENERALLY A UNILOCULARRADIOLUCENCY ASSOCIATED WITH ANIMPACTED TOOTH THAT IS DIFFICULT TODISTINGUISH FROM A DENTIGEROUSCYST.

• ROBINSON AND MARTINEZ, 1977

• ASSOCIATED WITH A LOW RATE OF“RECURRENCE” AFTER ENUCLEATIONAND CURETTAGE

• GARDNER AND CORIO, 1984

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UNICYSTIC AMELOBLASTOMA

Cyst lined by ameloblastoma

Intramural infiltrating ameloblastoma

Intraluminal ameloblastoma

Intramural nodular ameloblastoma

Ackermann GL, Altini M, Shear M. The unicystic ameloblastoma: a clinicopathologic study of 57 cases. Journal of Oral Pathology 1988;17:541±546.

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50 % to 80% associated with an impacted tooth most commonly: mandibular 3rd molar

Treatment:simple (luminal or intraluminal):

enucleationmural or transmural: radical

resection

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14 Y.O. WITH MANDIBULAR AMELOBLASTOMA

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• 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%

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2 years post treatment

BRAF and SMO negative

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STAGED IMMEDIATE IMPLANT PLACEMENT…

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CASE # 2

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CASE #2

• 39 Y.O. FEMALE NURSE REFERRED WITH A BIOPSY PROVEN AMELOBLASTOMA OF THEMANDIBLE

• 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

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Q: How would you reconstruct this defect?

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CALCIFYING EPITHELIA ODONTOGENIC TUMOR(PINDBORG TUMOR)

• ACCOUNTS FOR LESS THAN 1% OFALL ODONTOGENIC TUMORS

• FEWER THAN 200 REPORTEDCASES

• PATIENTS BETWEEN 30 AND 50 YEARS OLD

• 2/3RDS OCCUR IN THE MANDIBLE

• PRESENT AS A PAINLESS SLOWGROWING MASS

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CALCIFYING EPITHELIA ODONTOGENIC TUMOR(PINDBORG TUMOR)

• DISCRETE ISLANDS OFPOLYHEDRAL SHEETS

• LARGE AREAS OF AMYLOID LIKEMATERIAL

• CONCENTRIC CALCIFICATIONSKNOWN AS LIESENGANG RINGS

Treatment: Resection with a 1 cm bony linear margin

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ADENOMATOID ODONTOGENIC TUMOR (A.O.T.)

• UNCOMMON TUMOR

• ACCOUNTS FOR 3 TO 7%• YOUNG PATIENTS

• VERY UNCOMMON IN PTS OLDERTHAN 30 Y

• ALSO KNOWN AS THE 2/3RDSTUMOR• 2/3 FEMALES

• 2/3 MAXILLA• 2/3 IMPACTED CANINE

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A.O.T. HISTOLOGY

• WELL DEFINED

• THICK CAPSULE

• SPINDLE SHAPED CELLS

• WHORLED MASSES OF CELLSWITH SCANT FIBROUS STROMA

• ROSETTE-LIKE STRUCTURESWITH CENTRAL EMPTY SPACES

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A.O.T. TREATMENT

Due to the thickness of the capsule, the tumor may be treated by enucleation and curettageOnly one recurrence in the literature

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A.O.T. CASE EXAMPLE

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A.O.T. CASE EXAMPLE

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A.O.T. CASE EXAMPLE

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MYXOMA

• UNCOMMON BENIGN NEOPLASMOF THE JAWS

• DEVELOPS FROMECTOMESENCHYME

• SLOW GROWING WITH POTENTIALFOR AGGRESSIVE BEHAVIOR

• HIGH RECURRENCE RATE AFTERINADEQUATE THERAPY

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MYXOMA HISTOLOGY

• STELLATE, SPINDLE SHAPEDCELLS

• LOOSELY MYXOID STROMA

• RESEMBLES STELLATERETICULUM

• FEW COLLAGEN FIBRILS

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MYXOMA RADIOGRAPHIC APPEARANCE

• UNILOCULAR OR MULTILOCULAR IN APPEARANCE

• MAY DISPLACE OR CAUSE ROOT RESORPTION

• TRABECULAE OF RESIDUAL BONE ARRANGED AT RIGHT ANGLES TO ONE ANOTHER“STEPLADDER”

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MYXOMA TREATMENT

Patient with an expanding mass on the right maxilla, diagnosis: myxoma

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MYXOMA TREATMENT

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No statistical difference in recurrence between conservative vs radical treatment

26 cases

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Overall recurrence 5/39(13%) X10y

Conservative tx 4/22(19%) X11yResection 1/17(6%) x9y

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AMELOBLASTOMAMALIGNANT AMELOBLASTOMA

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AMELOBLASTIC CARCINOMA

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MALIGNANT AMELOBLASTOMA VS. AMELOBLASTIC CARCINOMA

• 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.

• AMELOBLASTIC CARCINOMA• IS A NEOPLASM IN WHICH THERE HAS BEEN HISTOLOGICALLY MALIGNANT TRANSFORMATION,

WITH OR WITHOUT METASTATIC DEPOSITS.

Slootweg PJ, Muller H: Malignant ameloblastoma or ameloblastic carcinoma Oral Surg 57:168-176; 1984

Type 1 Primary intraosseous carcinoma, ex odontogenic cyst

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

Keratinizing

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Ameloblastoma(Malignant types)

Malignant (Metastasising)Ameloblastoma

Ameloblastic Carcinoma

WHO Classification

2005

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Ameloblastoma(Malignant types)

Malignant (Metastasising)Ameloblastoma

Ameloblastic Carcinoma

WHO Classification

2017

Metastasizing Ameloblastoma

Benign Category

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• 8 CASES

• 7 CASES IN THE MANDIBLE, 1 CASE IN THE MAXILLA

• A DIAGNOSIS OF BENIGN AMELOBLASTOMA WAS MADE FOR ALL CASESBASED ON INCISIONAL BIOPSY

• ONE CASE HAD CERVICAL METASTASIS AT THE TIME OF INITIALPRESENTATION

• MOST COMMON PRESENTING SYMPTOMS INCLUDED RAPID GROWTH (6 CASES) AND PAIN (3 CASES)

• 3 PATIENTS DEVELOPED RECURRENT DISEASE

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

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TARGETED SYSTEMIC THERAPY

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PT WITH METASTATIC DISEASE OR NON-RESECTABLE DX

🤔

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MOLECULAR MARKERS IN MELANOMA

• BRAF (B-RAF PROTO-ONCOGENE) MUTATIONS

• 50 – 70%

• 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

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BRAFV600E

Sensitivity to agents that inhibit the BRAF or MAPK pathway

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1970Dacarbazine

Timeline of treatment options for metastatic melanoma

1998IL-2

2011IpulimumabVemurafenib

2012Dabrafenib

Dabrafenib:Inhibits BRAFWhen compared to vemurafenib in a phase 3 trialOverall survival favored Dabrafenib

Dabrafenib side effects:Cutaneous side effects

rash, hyperkeratosis, papillomas, plantar-palmar erythrodysaesthesiaCutaneous SCCA 6%

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1970Dacarbazine

Timeline of treatment options for metastatic melanoma

1998IL-2

2011IpulimumabVemurafenib

2012Dabrafenib

2013Trametenib

Trametenib:Orally available small moleculeSelective inhibitor of MEK1 & MEK2Median progression free survival 4-8 monthsOverall survival at 6 months 81%

Tramatenib side effects:Rash common (papulopustular)DiarrhoeaPeripheral edemaDecreased ejection fraction 7%NO SCCA

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BRAF MUTATION IN AMELOBLASTOMA ~60%

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TARGETED THERAPY FOR AMELOBLASTOMA

Case Report:

85 yo male with Mandibular AmeloblastomaRefused SurgeryTested for BRAF mutation: BRAF V600E

Treatment:Dabrafenib 150 mg PO every 12 hours

Side effects: Low energy, plaque like skin lesions (thought to be actinic keratoses) on face, back, and scalp, voice changes

After 73 days opted out of therapyImage: Tumor size unchanged

Later composite resection of tumorPath: 90% response (alteration of ameloblastoma)

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edition 2017 - aaomp · 2020-04-26 · 4/26/20 1 contemporary management of odontogenic tumors rui...

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