Oncology: Study of tumors

Tumor means swelling

Today the word “tumor” is applied to only neoplastic masses

Neoplasia – Definition

Literally means “new growth”

Willis Definition: An abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissues and persists in the same excessive manner after the cessation of the stimuli.

Neoplasia is an abnormality of

1. Cellular Differentiation

2. Maturation

3. Control of growth

Fundamental to the origin of all neoplasms is loss of responsiveness to normal growth controls.

Neoplastic cells are said to transformed, i.e. they continue to replicate oblivious to the regulatory influences that control normal cell growth and division

Neoplastic cells behave as parasites and compete with normal cells and tissues for their metabolic needs.

Neoplastic cells enjoy certain degree of autonomy and they steadily increase in size regardless of their local environment and the nutritional status of the host

Tumors

• Non odontogenic

• Odontogenic

Non odontogenic

• Benign• Malignant• Hamartoma• Choristoma

• Epithelial• Fibrous Connective tissue• Adipose• Cartilage• Bone• Vascular• Neural• Muscle• Lymphoid• Neural crest cell – melanoma• Teratoma• Giant cell lesions• Myeloma• Salivary gland tumors

Hamartomas and Choristomas:

1. These are tumor-like growths that are thought to be developmental anomalies.

2. They are not true neoplasms, i.e. they do not show continuous growth

Hamartoma: These tumor-like lesions are composed of tissues that are normally present with in an organ in which the tumor arises e.g.. Odontoma comprises of tooth material and tooth forming tissues.

Choristoma: These are tumor like lesions that contains tissues that are not normally present in its site of origin e.g.. Tooth in the ovary or disorderly mass of smooth muscle and pancreatic acini in the stomach wall.

Classification of Odontogenic Tumors: WHO – Krammer et al

Benign Tumors1. Odontogenic epithelium with mature, fibrous stroma without odontogenic

ectomesenchyme \

Ameloblastoma, solid/multicystic type

Ameloblastoma, extraosseous/peripheral type

Ameloblastoma, desmoplastic type

Ameloblastoma, unicystic type

Squamous odontogenic tumour

Calcifying epithelial odontogenic tumour

Adenomatoid odontogenic tumour

Keratocystic odontogenic tumour

2. Odontogenic epithelium with odontogenic ectomesenchyme, with or without hard tissue formation Ameloblastic fibroma Ameloblastic fibrodentinoma Ameloblastic fibro-odontoma Odontoma Odontoma, complex type Odontoma, compound type Odontoameloblastoma Calcifying cystic odontogenic tumour

Dentinogenic ghost cell tumour

3. Mesenchyme and/or odontogenic ectomesenchyme with or without odontogenic epithelium Odontogenic fibroma Odontogenic myxoma/myxofibroma Cementoblastoma

Classification of Odontogenic Tumors: WHO 2005– Philipsen and Reichart - IARC

Malignant Tumors

1. Odontogenic Carcinomas: -Malignant Ameloblastoma- Primary Intraosseus Carcinoma- Malignant variants of other odontogenic epithelial tumors- Malignant changes in odontogenic cysts

2. Odontogenic Sarcomas :- Ameloblastic fibrosarcoma (Ameloblastic sarcoma)- Ameloblastic fibrodentinsarcoma and ameloblastic fibro-odontosarcoma- Odontogenic carcinosarcoma

Ameloblastoma : Definition

A true neoplasm of enamel organ type tissue which does not undergo differentiation to the point of enamel formation.

Robinson defines it as : Tumor that is “usually unicentric, non-functional, intermittent in growth, anatomically benign, and clinically persistent

The first time………

Malassez first called it Admantinoma in 1885 but was replaced by amelobalstoma as it did not produce any hard tissue

Term Ameloblastoma first applied to this tumor was suggested by Churchill in 1934

An unconfirmed first report by Guzack in 1826

The first neoplasm reported by Broca in 1868

First thorough description by Falkson in 1879

Frequency:

Second most common odontogenic neoplasm; only outnumbered by Odontoma

Excluding odontoma, the incidence of amelobalsotma is at least equal to the incidence of all other odontogenic neoplasms combined

Its incidence combined with its clinical behavior makes ameloblastoma the most significant odontogenic neoplasm of concern to oral and maxillofacial surgeons

Pathogenesis: Ameloblastoma is of varied origin and stimulus initiating it is unknown. Possible sources:

1. Cell rests of the enamel organ, either remnants of the dental lamina or remnants of Hertwig’s sheath namely Rests of Malassez

2. Epithelium of odontogenic cysts particularly dentigerous cyst and odontomas

3. Disturbances in the developing enamel organ

4. Basal cells of the surface of the jaws

5. Heterotrophic epithelium in other parts of the body, especially pituitary gland

6. Presently it is thought that it is likely the result of alterations or mutations in the genetic material of cells that embryologically preprogrammed for tooth development. Environmental factors and individual patient variables (eg. General health status, nutritional status) also likely to have a modulating role- demonstrated by higher incidence in industrialized nations – 10 to 15 %

At present, it is known that the potential sources to developan odontogenic tumor are varied, and these include:1. The pre-functional dental lamina (odontogenic epitheliumwith ability to produce a tooth), which is moreabundant for obvious reasons distally to the lower thirdmolars.2. The post functional dental lamina, a concept that coversthose epithelial remnants such as Serre´s epithelial rests,located within the fibrous gingival tissue; the epithelialcell rests of Malassez in the periodontal ligament and thereduced enamel organ epithelium, which covers the enamelsurface until tooth eruption.3. The basal cell layer of the gingival epithelium, whichoriginally gave rise to the dental lamina.4. The dental papilla, origin of the dental pulp, which hasthe potential to be induced to produce odontoblasts andsynthesize dentin and/or dentinoid material.5. The dental follicle.6. The periodontal ligament, which has the potential toinduce the production of fibrous and cemento-osseousmineralized material.

Ameloblastoma types:

1. Intraosseous

A. Admantinoma of long bones

B. Ameloblastoma of Jaws – two main histologic types

I-The conventional solid/multicystic

a. Follicular:

acanthomatous,

granular cell,

desmoplastic,

basal cell

b. Plexiform

II- Unicystic

2. Extraosseous: Soft tissue

Another interesting classification:

1.Ameloblastoma in situ a)Mural Ameloblastoma: Limited within the lining, curable by enucleation

b) Intraluminal Ameloblastoma: Arising from the epi lining – proliferating into the lumen, cyst enucleation

II. Microinvasive Ameloblastoma

a) Intramural Microinvasive Ameloblastoma: Arising from the Epi lining and proliferating into the connective tissue layer of the cyst wall. More aggressive pathology and requires resection approaches for cure

b) Transmural Microinvasive Ameloblastoma: Arising from the Epi lining and proliferating through the complete thickness of the connective tissue layer of the cyst wall. More aggressive and invasive pathology and requires resection approaches for cure

III. Invasive Ameloblastoma

a)Invasive Ameloblastoma arising from the lining of a cyst: Arising from the Epi lining and proliferating through the complete thickness of the connective tissue layer of the cyst wall and into the adjacent bone. More aggressive and invasive pathology and requires resection approaches for cure

b) Invasive Ameloblastoma : A solid or multicystic Ameloblastoma unassociated with a cyst. More aggressive and invasive pathology and requires resection approaches for cure

Clinical features:

AGE: Lesion of Adults, 4 –5th decades of life. Age range is broad , extending from childhood to adulthood (mean age, approx 40 years).

GENDER: There appears to be no gender predilection.

Race: No racial predilection, though some studies indicate a higher frequency in blacks

Site: Mandibular molar-ramus area is the most favored site. In maxilla, it is usually molar and anterior area

Clinical features: contd.

Lesions are usually asymptomatic and are discovered either during routine radiographic examination or because of asymptomatic jaw expansion. Occasionally, tooth movement or malocclusion may be the initial presenting sign.

Radiography: Ameloblastomas are osteolytic, typically found in the tooth bearing areas of the jaws. The most typical radiographic presentation is that of a multilocular radiolucent lesion. The lesion is often described as having a “SOAP BUBBLE APPEARANCE” when the radiolucent loculations are large and “HONEY COMBED” when the loculations are small. Buccal and lingual cortical expansions are frequently present. Resorption of roots of teeth adjacent to the tumor is common. Solid ameloblastomas may appear unilocular and these usually have irregular scalloping. These features are not diagnostic of ameloblastomas as other lesions may show similar picture. Desmoplastic ameloblastomas appear differently as they are seen in anterior mandible and shows mixed radiolucent radiopaque like fibro osseous lesions due to osseus metaplasia within dense fibrous septa, the tumor does not produce mineralized prodcut.

Pathogenetic mechanism: Mechanisms by which ameloblastomas gain growth and invasion advantage include overexpression of antiapoptotic proteins (Bcl-2, Bcl-xL) and inerface proteins (FGF, MMPs). Ameloblastomas have a low proliferation rate as shown by staining for cell-cycle related protein, Ki-67.

AMELOBLASTOMA: BIOLOGIC SUBTYPES:

Solid ameloblastoma

Cystic ameloblastoma

Peripheral ameloblastoma

Malignant ameloblastoma

Ameloblastic carcinoma

Cystic Ameloblastoma: formerly called unicystic ameloblastoma

Change in name as these lesions are often multilocular,

Considered a separate entity based on clinical, radiographic, and pathologic features and its response to treatment.

10 to 15 % of all intra osseous ameloblastomas.

Whether it arises de novo or arises from cyst epithelium cannot be obtained, but noth processes may be possible

Usually asymptomatic, large lesions may cause painless swellings

Site: 90% in mandible, posterior region

Cortical perforation in 25% of the cases

Recurrence: as high as 40% as treated by curettage as late as 9 yrs post op

Age: Seen in younger age groups-mean age –23yrs, 35 yrs. Second decade of life

Radiographically: may appears as a circumscribed radiolucency that surrounds the crown of an unerupted mandibular third molar and clinically resembling a dentigerous cyst and diagnosis of ameloblastoma is only made by microscopic study of specimen

Histopathologic features: Three variants:

1. Luminal unicystic ameloblastoma: confined to luminal surface of the cyst. The lesion consists of fibrous cyst wall with a lining that consists of totally or partially of ameloblastic epithelium. The epithelium demonstrates a basal layer of columnar to cuboidal cells with hyperchromatic nuclei that shows reverse polarity and basilar cytoplasmic vacuolization. The overlying epithelial cells are loosely cohesive and resemble stellate reticulum and is not related to inflammatory edema

2. Intraluminal unicystic ameloblastoma: one or more nodules of ameloblastoma project from cystic lining into the lumen of the cyst. Nodule may be small or large to fill the lumen. Sometimes nodule demonstrates edematous, plexiform pattern and hence called plexiform unicystic ameloblastoma. Intraluminal cellular proliferation does not always meet the strict histopathologic criteria for amelobalstoma and may be secondary to inflammationthat nearly always accompanies this pattern.

3. Mural unicystic ameloblastoma: Here the fibrous wall of the cyst is infiltrated by typical follicular or plexiform ameloblastoma. The extent and depth of ameloblastic infiltration may vary considerably. Multiple sections through many levels of specimen are necessary to rule out the possibility of mural invasion of tumors.

Malignant Ameloblastoma and Ameloblastic carcinoma:

Rarely exhibits frank malignant behavior, less than 1 %

Malignant Ameloblastoma includes lesions where the primary and secondary metastatic tumor shows histopathologic features of ameloblastoma. Metastases from ameloblastoma are most often found in the lungs. These are sometimes are regarded as aspiration or implant metastases. However, the peripheral location of some of these suggest that they must have occurred through blood or lymphatic routes rather than aspiration. Cervical nodes are the second most common site for metastasis of an ameloblastoma. Spread to vertebrae, other bones, and viscera has been confirmed. Prognosis is poor

Ameloblastic carcinoma includes ameloblastoma that has cytologic features of malignancy in the primary tumor, in a recurrence or in any metastatic deposit. These include an increased nuclear to cytoplasmic ratio, nuclear hyperchromatism and the presence of mitoses. Necroses in tumor islands and dystrophic calcification may also be present These lesions may follow a markedly aggressive local course, but metastases do not necessarily occur.

PERIPHERAL AMELOBLASTOMA:

Uncommon, only 1% of al ameloblastomas

Arises from the rests of dental lamina beneath the oral mucosa or from the basal epithelial cells of the surface epithelium

Histopathologically same features as the intraosseus form of the tumor.

Clinically: Painless, non-ulcerated sessile or pedunculated gingival or alveolar mucosal lesion. Usually misdiagnosed as pyogenic granuloma or Fibroma as features are non specific

Lesions are less than 1.5 cm, average age abt 52 yrs.

Site: Posterior gingival/alveolar mucosa , mandible greater than maxilla

Peripheral Ameloblastoma: Histologic features

Islands of ameloblastic epithelium that occupy the lamina propria underneath the surface epithelium. The proliferating epithelium may show any of the features of the intraosseus ameloblastoma namely the follicular and Plexiform

Connection the basal cell layer of the surface eptiehlium is seen in 50% of the lesions, whether represent origin of tumor or merging has not been ascertained.

Basal cell carcinomas of the oral mucosa but may represent peripheral ameloblastoma.

May be even confused with peripheral odontogenic fibroma, differentiated by the presence of dentin or cementum like material in the tumor.