Mixed odontogenic tumors

Upama sishan

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ODONTOGENESIS

CLASSIFICATIONS

IMTRODUCTION and DEFINITIONS

PATHOGENESIS OF MIXED ODONTOGENIC TUMORS

AMLEOBLASTIC FIBROMA

AMELOBLASTIC FIBRO DENTINOMA

AMELOBLASTIC FIBRO ODONTOMA

ODONTOMES

ODONTOAMELOBLASTOMA

Classification of odontogenic tumors

BENIGN• Ameloblastoma• CEOT • Ameloblastic fibroma• AOT• Dentinoma• Ameloblastic fibro-

odontoma

KRAMER & PINDBORG- WHO (1971)

• Odontoameloblastoma• Complex odontoma• Compound odontoma• Odontogenic fibroma• Myxofibroma• Cementoma• Melanotic

neuroectodermal tumor of infancy

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MALIGNANT

Odontogenic carcinoma

a) Malignant ameloblastomab) Primary intra-osseous carcinomac) Other carcinomas arising from odontogenic

epithelium, those arising from cyst

Odontogenic sarcomas

a) Ameloblastic fibrosarcomab) Ameloblastic odontosarcoma

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WHO- 2005• Benign

•I. ) Odontogenic epithelium with mature fibrous stroma without odontogenic mesenchyme Ameloblastoma SOT CEOT AOT KCOT

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•II.) Odontogenic epithelium with odontogenic mesenchyme with/without hard tissue formation

Ameloblastic fibroma Ameloblastic fibro-dentinoma Ameloblastic fibro-odontoma Odontoma Odonto-ameloblastoma Calcifying cystic odontogenic tumor Dentinogenic ghost cell odontogenic tumor

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• III.) Odontogenic mesenchyme with/without odontogenic epithelium Odontogenic fibroma Odontogenic myxoma Cementoblastoma

MALIGNANT Odontogenic carcinoma Malignant ameloblastoma Ameloblastic carcinoma Primary intra osseous carcinoma Clear cell odontogenic carcinoma Ghost cell od. Carcinoma Odontogenic sarcoma Ameloblastic fibrosarcoma Ameloblastic dentinosarcoma Ameloblastic odontosarcoma

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Neville (based on who-2005)

• Ameloblastomao Malignant ameloblastomao Ameloblastic carcinoma Clear Cell Od. Carcinoma AOT CEOT SOT

A) Tumor of odontogenic epithelium

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B) Mixed odontogenic tumor

• Ameloblastic fibroma• Ameloblastic fibro-odontoma• Ameloblastic fibrosarcoma• Adontoameloblastoma

• Compound odontoma• Complex odontoma

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C) Tumor of odontogenic ectomesenchyme

• Odontogenic fibroma

Granular cell odontogenic tumor

Odontogenic myxoma

cementoblastoma

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• Ameloblastic Fibroma ( AF)• Ameloblastic Fibro-odontoma ( AFO)• Ameloblastic Fibro dentinoma ( AFD)• Ameloblastic Fibro Sarcoma• Odonto Ameloblastoma (OA) • Odontoma

Mixed odontogenic tumours

Tumors where both epithelium and connective tissue proliferate.

Epithelial component resembles – Ameloblast like cells

Connective tissue – resembles Dental papilla cells

Ameloblastic Fibroma(1992) (AF) and related lesions (AFD

& AFO) are defined by WHO as “neoplasms composed of

proliferating odontogenic epithelium embedded in a cellular

ectomesenchymal tissue that resembles dental papilla, &

with varying degrees of inductive change and dental hard

tissue formation”

“A group of non-neoplastic malformations containing fully

calcified or mineralized dental tissues” (the odontomas-

WHO).

AFOWHO 1992- "a lesion similar to ameloblastic fibroma, but also showing inductive changes that lead to the formation of dentineand enamel.“

Present authors:A hamartomatous lesion similar to the amelobtastic fibroma and fibrodentinoma, but showing further inductive changes that lead to the formation of enamel matrix in addition to dentin (dentinoid).

Complex odontomaWHO 1992 "a malformation in which all the dental tissues are represented, individual tissues being mainly well formed but occurring in a more or less disorderly pattern."

Present authors: A hamartomatous lesion in which all the dental tissues are represented, individual hard tissues being mainly well developed but occurring in a more or less disorderly pattern.

COMPOUND ODONTOMEBoth WHO & the present authors:

A malformation in which all the dental tissues are represented in a more orderly pattern than in the complex odontoma. so that the lesion consists of many toothlike structures.Most of these structures do not morphologically resemble the teeth of the normal dentition, but in each one enamel, dentin, cementum and pulp are arranged as in the normal tooth.

ODONTOAMELOBLASTOMABoth the 1992 WH0 & the present authors:A very rare neoplasm that includes odontogenic ectomesenchyme, in addition to odontogenic epithelium that resembles an ameloblastoma (SMA) in both structure and behavior. Because of the presence of the odontogenic ectomesenchyme, inductive changes take place leading to the formation of dentin and enamel in parts of the tumor.

Definition used by present authors:

AF comprises two subtypes : Neoplasm

Hamartomatous Lesion.

Two variants – undistinguishable histopathologically

Induction does not takes place neoplastic subtype.

AFD WHO 1992 "a neoplasm similar to ameloblastic fibroma. but also showing inductive changes that lead to formation of dentine."

Present authors:A hamartomatous lesion similar to the ameloblastic fibroma, but also showing inductive changes that lead to formation of dentinoid.

PATHOGENESIS OF MIXED ODONTOGENIC TUMOURS

CONTINUUM CONCEPT- Cahn and Blum(1952) not widely accepted

WHO 1992- a) 22.3 % of cases occuring after the age of 20 are true beningn neoplasm b)AF developing during the period of odontogenesis – Non neoplastic ,hamartomatous lesions.(develop into AFOs and finally into complex odontomes.

HANSEN AND FICARRA- Some AFs may represent the early stage of a developing complex odontoma line (DCO) line.

PHILIPSEN et al (1997) a) Neoplastic line b) Hamartomatous line .

AMELOBLASTIC FIBROMA

AMELOBLASTIC FIBRO-DENTINOMA

AMELOBLASIC FIBRO-ODONTOMA

COMPLEX ODONTOMAS

COMPOUND ODONTOMA

DENTIN FORMATION

ENAMEL FORMATION

SLIGHT SIMILARITY TO TEETH

GOOD RESEMBLANCE

Cahn and Blum proposed the continuum concept an ameloblastic fibroma will, overtime, mature and finally result into the formation of odontoma

Some points contradicting this theory were raised: 

1. Recurrent cases of AF have never shown further steps of differentiation into dental hard tissue forming odontogenic tumor of more advanced histodifferentiation.

2. AFs are known to occur at ages beyond completion of odontogenesis, that is, after the age of 20 years.

AFs occurring after the age of 20 years are true benign neoplasm.

All cases of AF developing during the entire period of odontogenesis represent non neoplastic hamartomatous lesion.

Philipsen et al hypothesis The tumours develop along two separate lines:

(I) the neoplastic line comprising the ameloblastic fibroma (AF) &

the closely related ameloblastic fibrodentinoma (AFD).

(II) The hamartomatous or the developing complex odontoma

(DCO) line

Complex odontoma – terminal stage of the line of hamartomatous

lesions.

COMPOUND ODONTOMA

WHO (1992) –Compound O –Tooth like structures

Complex O –hapazardly arranged soft & hard

odontogenic tissues .

PHILIPSEN & co workers- formation of compound odontomas may be

the result of multiple schizodontia of unknown cause. (locally

hyperactive dental lamina)

Odontoameloblastoma

The pathogenesis of OA is unknown.

1. The mineralized dental tissues are formed as a hamartomatous proliferation in response to inductive stimuli produced by the proliferating epithelium over the mesenchymal tissue. - Thompson et al

2. Another possibility is that both an ameloblastoma & an odontoma develop separately & form a collision tumour.

This last possibility seems unlikely because

Differences between these tumours with respect to age, location & symptomatology.

The microscopic picture of OA shows clearly that the mineralized tissues (odontoma) are intermingled & actively forming within the

ameloblastoma.

(1) AMELOBLASTIC FIBROMA (Soft mixed odontogenic tumor, Soft mixed odontoma, Fibroadamentoblastoma)

• Reported by Kruse in 1891• Later classified as a separate entity by Thoma and

Goldman in 1946.• Rare tumor, only 2.5 – 3% of Odontogenic tumours

Relatively uncommon odontogenic neoplasm characterized by the simultaneous proliferation of both epithelial & mesenchymal tissue without the formation of enamel or dentin.

Thus it is a true mixed Odontogenic tumor.

• M>F ( 1.4 : 1 )

• Age : younger population , 1st 2

decades of life.(14.8 yrs)

Youngest patient reported – 7 week old infant

Common site : mandibular molar region.

• Generally intraosseous

• Rarely in peripheral locations

• Small AF- asymptomatic ,

• Large AF- Pain, tenderness or mild swelling of the

jaw

• Asso with impacted tooth in 72% cases.

• slower clinical growth & does not

tend to infiltrate between trabeculae

of bone.

• Enlarges by gradual expansion so that

the periphery of the lesion often

remains smooth.

MULTILOCULAR / UNILOCULAR RADIOLUCENT DEFECT

RADIOGRAPHIC MARGINS- WELL DEFINED/ CORTICATED

UNERUPTED TOOTH ASSOCIATED WITH 75% OF CASES

Gross appearance

• Cut surface is usually round or oval , well circumscribed & of greyish white color.

• The soft mass appears to be surrounded by thin transparent ,capsule like border.

variants

Granular cell AF

Papilliferous AF

Granular cell AF• Described in 1962 & only 16 cases reported.• Ectomesenchyal component is dominated by

granular cells.• Foci of dystrophic calcifications found among

granular cells• Ultrastructural & IHC studies- granular cells have

strong asso with precursors of langerhan cells.

Papilliferous ameloblastic fibroma

• Rare variant of AF• Marked proliferation of epithelium with

plexiform arrangement & cyst formation

Malignant transformation

• Ameloblastic carcinosarcoma• Ameloblastic fibrosarcoma

D/DRadiological• Odontogenic myxoma• Dentigerous cyst• OKC• Central giant cell granuloma

Histological• Follicular ameloblastoma- microcyst formation

TREATMENT

treatment

• Modified block resection.• Recent reports- risk of recurrence after

conservative therapy• More aggressive surgical excision –

recurrent lesions

2) Ameloblastic fibrodentinoma (AFD)

• Previously known as ‘Dentinoma’ & was 1st described

by Straith in 1963.

• Rare neoplasm composed of odontogenic epi &

immature Connective T & characterrised by formation

of dysplastic dentin.

Dentinoid

- Resembling dentin.

Dysplastic dentin

- Atypical poorly mineralized dentin.

Difficult to identify btwn dysplastic dentin and atypical osteoidBut if an osteoid like tissue develops in direct relationship to odontogenic epithelium, this relationship provides strong presumptive evidence that the material is dysplastic dentin.

Dysplastic enamel- Globules of basophilic mineralized material in contact with

ameloblastic epithelium may represent dysplastic enamel.

Cementoid- Uncalcified cementum matrix

Osteodentin- Rapidly formed teritiary dentin that contains entrapped

odontoblast or fibroblast.

- Lacks tubular dentin structure.

c/f• Age : 1st & 2nd decades (mean – 13.6 yrs)• Gender : M : F = 3:1• Slow growing & Often asymptomatic• May be asso with unerupted teeth.• These tumors behave biologically as do AF or AFO.

R/F :Well delineated RL with varying degrees of RO

Posterior mandible

Pathogenesis • an intermediate stage between AF and AFO in terms

of histologic differentiation (the hamartomatous line described earlier by the present authors).

In the 1992 World Health Organization (WHO) classification it was stated that "until more experience has been gained it may be worthwhile to separately identify the differing patterns or types of ameloblastic fibroma and related lesions, even though some of these may later prove to be nothing more than stages in the evolution of a single type tumour."

histology• WHO definition : A neoplasm similar to AF, but also showing

inductive changes that lead to formation of dentin.H/F: Strands & islands of Od.epi in cell rich ectomesenchyme resembling

DP similar to AF. Dentinoid or osteodentin is deposited often preceded by a zone of

hyalinization. Abortive or poorly mineralized dentin may contain entrapped

odontogenic epithelial and ectomesenchymal cells. Active odontoblasts are rare – so tubular dentin is rare

Malignant transformation Ameloblastic fibrodentinosarcoma

Treatment• Surgical excision• Recurrences not described

Ultrastructure

Authors observed a spectrum of abortive features at

the epithelial mesenchymal interface.

Van wyk et al

Ameloblastic Fibro Odontoma

• WHO definition “A lesion similar to AF but also

showing inductive changes that lead to formation of

dentin & enamel”

• Represent an immature complex odontoma, & therefore

represent a hamartomatous rather than a neoplastic odontogenic

lesion. Because the ameloblastic fibro-odontomam has components of both an odontoma and an ameloblastic fibroma, it will consist of both soft and hard tissues.

C / F : -

Age : 11 yrs, children & young adults (reported by Hooker)

M>F

Site : Post Mandible> maxilla

Asso with impacted tooth.

• asymptomatic painless swelling

• discovered when radiographs are taken to determine the reason

for failure of a tooth to erupt.

R/F• Well circumscribed unilocular, rarely multilocular RL with

calcified material• Calcified material- multiple, small RO or as a solid

conglomerate mass• Some- largely calcified masses with only a narrow rim of

radiolucency at the periphery of the lesion.

PATHOGENESIS

Compared to AF & AFD – inductive changes in the AFO are more

advanced and enamel is present in addition to dentin

H / F : -

• Identical to the AF & has narrow cords & small islands of

odontogenic epi in a loose primitive appearing connective

tissue that resembles the dental papilla.

• The calcifying elements consists of foci of enamel & dentin

matrix in close relationship to the epithelial structures.

• More calcified lesion show mature dental structures in the form

of rudimentary small teeth or conglomerate masses of enamel &

dentin.

D/DRadiological• CEOT• COC• Odontoma• AOT

Histological• Hyperplastic dental follicle- proliferation of odontogenic rests

is seen• Odontoma

Treatment & prognosis

• conservative curettage.

• The tumor is well circumscribed & doesn’t invade the

surrounding bone.

• Prognosis is excellent & recurrence after conservative

removal is unusual.

• Development of ameloblastic fibrosarcoma is exceedingly

rare.

Odontoma • Most common odontogenic tumor

• Considered as a developmental anomaly , represents a hamartoma

rather than a neoplasm.

• Mixed odontogenic tumour - a growth in which both the epithelial

& mesenchymal cells.

• This enamel & dentin are usually laid down in an abnormal pattern

because the organization of the od.cells fails to reach a normal state

of morphodifferentiation.

• The lesion is composed of more than one type of tissue & for this

reason, has been called a composite odontoma.

• Complex form is less common than compound type.

etiology• Trauma • Infection• Hereditary anomalies (Gardner’s syndrome)• Family history• Genetic mutations.

• Anomalous development : Unsuccessful or altered ectomesenchymal interactions. Alterations in mineralization mech.

- multiple colonic polyps, sebaceous cysts and jaw osteomas.

Dental abnormalities are present in around 30% of patients with

Gardner syndrome

• supernumerary teeth,

• compound odontomas

• hypodontia

• abnormal tooth morphology

• impacted or unerupted teeth.

Gardner syndrome

• Macroscopy : large no of tooth like strucuret removed during surgery.

H/F:

Compound odontome:

• multiple structures resembling single rooted teeth in loose fibrous

matrix.

• Mature enamel lost during decalcification. Enamel matrix present.

• Pulp present at coronal and root portion of tooth like structure.

Complex odontome:

• Consist of large mature tubular dentin

• Encloses mature enamel ( removed by decalcificaton)

• So space occupied by smal amt of enamel matrix

• 20% of cases – small island of eosinophilic staining epithelial ghost

cells.

Compound odontomeDenticles seperated by fibrous tissue

Complex odontomeDisorganised but well formed Enamel, dentin, Pulp

Major Characteristics Compound Odontoma Complex Odontoma

Frequency 9% and 37%. 5% and 30%.

AgeThe majority of cases appear before age of 20, childhood/adolescence.

The majority of cases occur beforethe age of 30.peak-2nd decade.

Gender M>F M>F

Sites Ant.Maxilla Post.Mandible .

Clinical presentation Painless, non-aggressive lesion, with a more limited potential growth than complex.odontoma.asso with unerupted tooth.

Painless, slow-growing expanding lesion asso with unerupted permanent tooth.

Radiological features RO mass of multiple, small, calcified structures with an anatomical similarity to normal teeth usually surrounded by a narrow RL zone.

More or less amorphous mass of calcified material with the radiodensity of tooth structure, which bears no anatomical resemblance to tooth,surrounded by a narrow radiolucent rim

Treatment Conservative surgical enucleation

Conservative surgical enucleation.

Compound odontoma – diagnosis and treatment:three case reports Pediatric Dentistry – 23:2, 2001.

Complex odontoma• Radiographically 3 variants : 1st stage : RL due to lack of calcification. Partial calcification seen in intermediate stage Final stage : RO mass surrounded by lucent rim.DD : Focal sclerosing osteitis Osteoma Periapical cemental dysplasia Ossifying fibroma Cementoblastoma

Odontome in Middle ear, Nasopharynx, brain

Intra cranial odontome

Extragnathic odontome

Journal of Cranio-Maxillofacial Surgery (2009)

Craniopharyngioma

Odonto Ameloblastoma

(Ameloblastic Odontoma)

• Extremely rare odontogenic tumor

• Contains an ameloblastomatous component &

odontoma-like elements.

• 22 cases documented

• Earlier confused with AFO – but both have

different clinical behavior.

C / F : -

• Age: more in children

• mandible > maxilla.

• a slowly expanding lesion of the bone, produces considerable

facial asymmetry if left untreated.

• Since it is a central lesion, considerable destruction of bone

occurs. ( a case of peripheral OA reported).

• Mild pain may be a presenting complaint, as well as delayed

eruption of teeth.

R / F : -

• Central destruction of bone with expansion of the cortical

plate is prominent.

• within the lesion proper - numerous small RO masses which

may or may not bear resemblance to teeth.

• Thus the radiological appearance of ameloblastic odontoma is

identical with that of composite odontoma.

h/f

• Proliferating epithelial portion - features of ameloblastoma

most commonly plexiform or follicular pattern,

• The ameloblastic component is intermingled with immature or

more mature dental tissue, similar to compound odontoma or

conglomorate masses of enamel, dentin & cementum as seen

in complex odontoma.

• Some AO may contain ghost cells.

Review of literature of 22 cases of OA showed the histologic criteria

of

Unequivocal ameloblastoma

Mature connective tissue

Fragments of malformed calcified dental structures

Odontoameloblastoma. Alka Dive, Shubhangi Khandekar, Ashish Bodhade, Akshay Dhobley. Year : 2011 | Volume : 15 | Issue : 1 | Page : 60-64

` d/d

1. AFO

2. AFD

3. COC

Treatment & prognosis

• Radical resection – Resection of the jaw, if possible, preserving the inferior

border of the mandible, when this area is uninvolved, will result in a permanent

cure.

• Recurrence associated with continued destruction of tissue is seen after

conservative curettage or enucleation.

CASES OF PIGMENTED MIXED ODONTOGENIC TUMORS REPORTED TILL DATE

1) Ameloblastic fibroma - Edwards and Goubran (1980

2) Odontoma - Gukiran et al

Takeda et al (1989)

Takeda et al ( 1987)

3) AFD - Takeda et al (2000)

4) Odontoameloblastoma - Marin granzio (2004)

Pigmented odontogenic tumors: Adding color to diagnosis? JOMFPYear - 2014 Vol : 18 Issue : 3 Page : 398-402

Ameloblastic fibrosarcoma

It is regarded as the malignant counterpart of the benign AF.

seems to arise de novo, One third of the cases - represents recurrence of AF or AFO 71 cases reported till date

C/F

• M>F• Younger patients- mean age -27.3 years• 80% cases- mandible post region• The tumor is painful,• Grows rapidly & causes destruction of bone with loosening of the teetho Ulceration & bleeding of the overlying mucosa.o Typically, the patients do not develop metastases, they die of a

locally aggressive neoplasm.o regional lymph node involvement or distant metastasis reported

in a few cases

LYTIC DESTRUCTION OF THE POSTERIOR MANDIBLE

Severe bone destruction, with irregular & poorly defined margins.

R/G

H/F

• Epithelial component- does not demonstrate any cytologic atypia

• Mesenchymal portion- highly cellular, shows hyperchromatic &

pleomorphic cells

• Mitosis-prominent

• Few instances-dysplastic dentin or small amounts of enamel may be

formed- ameloblastic dentinosarcomas or ameloblastic fibro-

odontosarcomas

Treatment• Radical surgical excision

1992 WHO classification of odontogenic tumor as "a very rare

neoplasm, similar in pattern to ameloblastic fibrosarcoma, but

in which both the epithelial and the ectomesenchymal

components show cytological features of malignancy.“

• the tumors may arise de novo or from pre-existing lesions

• a fatality rate of more than 50% with high rates of recurrence

and metastasis.

Odontogenic carcinosarcoma

Odontogenic carcinosarcoma of the mandible: a case report and reviewIl-Kyu Kim

Ihc studiesCK 7, 13 14- positive, similar to immunophenotypeof the dental laminaCell proliferation index : (linked to tumor

aggressiveness) Ki67 P53 PCNA Aggressiveness of tumor related to imbalance bet bone

resorption & apposition RANK RANKL OPG

positive (useful markers of malignant transformation of AF to AFS)

POSITIVE in epi & mesenchymal cells of AF

Bcl-2(-)ve = mesenchymal component(+)ve = epithelial component(+)ve in sarcomatous portion in malignant tumor

∴ Bcl-2 exp is imp in AF prog to AFS.

Vimentin Nestin

Amelogenin (+)ve – suggest tumor cells are as undifferentiated as dental lamina cells.

Positive (role in pathogenesis is not clear)

References

• Odontogenic Tumors & Allied Lesions – Peter A. Reichart, Hans P.

Philipsen.

• Shafer’s Text Book of Oral Pathology.

• Neville – Oral & Maxillofacial Pathology

• Oral & Maxillofacial Pathology - Robert E. Marx.

• Luca’s pathology of tumors of oral tissues – 5th edition.

• Pigmented ameloblastic fibro odontoma with melanophages Oral Surgery, Oral Medicine, Oral Pathology Volume 77, Issue 3, March 1994, Pages 271–275

• Hybrid Central Odontogenic Fibroma with Giant Cell Granuloma-like Component: Case Report and Review of LiteratureHead Neck Pathol. Sep 2008; 2(3): 222–226

• Odontogenic myxoma: a clinicopathological study of 33 cases• International Journal of Oral and Maxillofacial Surgery Volume

33, Issue 4, June 2004, Pages 333–337 • S100, alpha-smooth muscle actin and cytokeratin

immunohistochemistry in odontogenic and soft tissue myxomas. J Clin Pathol 1995;48:759-762

• Journal of Cranio-Maxillofacial SurgeryVolume 33, Issue 5, October 2005, Pages 352–355Malignant transformation of ameloblastic fibroma to ameloblastic fibrosarcoma: case report and review of the literature