oral tumor

PRINCIPLES OF DIAGNOSIS AND MANAGEMENT OF ORAL TUMOURS WITH EMPHASIS ON BENIGN AND MALIGNANT TUMOURS

Introduction to Oral Tumours

  • Odontogenic and non-odontogenic tumors of the jaws are relatively rare and heterogeneously grouped neoplasms.

  • These tumors include benign and malignant neoplasms, hamartomas, and other bone-related lesions.

  • Tumors exhibit significant variability in:

    • Etiology

    • Biological behavior

    • Clinical significance

  • Commonality: All tumors occur in the jaws.

Types of Oral Tumours

Odontogenic Tumors

  • Definition: Derived from tooth-related tissues; typically originate in the maxilla or mandible.

  • Nature: Majority are benign, locally aggressive, rarely metastasize.

  • Examples: Includes lesions such as dermoid cysts and teratomas.

Non-Odontogenic Tumors

  • Develop from epithelial and/or mesenchymal tissues in various body sites, often originating in non-tooth-bearing facial bones.

  • Clinical Significance: Ranges from requiring only observation/local excision to necessitating multimodal therapy for malignant variants.

Tumor Classification

  • Tumors or neoplasms represent new growths of abnormal tissue.

  • Classification: Based on behavior and structure into benign and malignant.

    • Majority of lesions in human jaws are benign.

  • Benign Tumours:

    • Grow slowly, encapsulated, expand by pushing adjacent structures, may be locally invasive.

  • Malignant Tumours:

    • Rapidly infiltrate surrounding tissues, may metastasize via lymphatic or hematogenous spread, life-threatening.

Classification of Jaw Tumors

Odontogenic Tumors

  • General Info:

    • Account for <2–3% of all oral and maxillofacial specimens sent for oral pathology diagnosis.

    • Estimated incidence in the whole body is 0.002–0.003%.

  • Odontogenesis Process: Involves the enamel organ, dental follicle, and dental papilla.

    • Enamel organ: Epithelial structure from oral ectoderm.

    • Dental follicle & papilla: Derived from neural crest cells (ectomesenchymal in nature).

  • Classification: Based on tissue type:

    • Odontogenic Epithelium:

    • Ameloblastoma

    • Calcifying Epithelial Odontogenic Tumor (CEOT, Pindborg Tumor)

    • Keratocystic Odontogenic Tumor

    • Adenomatoid Odontogenic Tumor (AOT)

    • Clear Cell Odontogenic Tumor

    • Squamous Odontogenic Tumor

    • Odontogenic Ectomesenchyme (Mixed):

    • Ameloblastic Fibroma

    • Ameloblastic Fibrodentinoma (Dentinoma)

    • Odontoameloblastoma

    • Ameloblastic Fibro-Odontoma

    • Calcifying Cystic Odontogenic Tumor

    • Dentinogenic Ghost Cell Tumor

    • Complex Odontome

    • Compound Odontome

    • Odontogenic Mesenchyme:

    • Odontogenic Fibroma

    • Odontogenic Myxoma (or Fibromyxoma)

    • Benign Cementoblastoma

Non-Odontogenic Tumors

  • Examples include:

    • Central Fibroma

    • Ossifying Fibroma

    • Osteoma

    • Osteoid Osteoma

    • Benign Osteoblastoma

    • Chondroma

    • Giant Cell Granuloma

    • Central Haemangioma

    • Neuroma

    • Neurofibroma

  • Fibro-osseous lesions include:

    • Fibrous Dysplasia of Bone

    • Cherubism (inherited fibro-osseous bone disease)

    • Ossifying (Cementifying) Fibroma

    • Central Giant Cell Granuloma

Malignant Neoplasms

A). Types of Malignant Odontogenic Tumours

  • Malignant Ameloblastoma

  • Ameloblastic Fibrosarcoma

  • Ameloblastic Odontosarcoma

  • Primary Intraosseous Carcinoma

  • Clear Cell Odontogenic Carcinoma

  • Metastasizing (Malignant) Ameloblastoma:

    • Primary type

    • Secondary type (dedifferentiated)

    • Intraosseous

    • Peripheral

  • Primary Intraosseous Squamous Cell Carcinoma:

    • Solid type

    • Derived from Keratocystic Odontogenic Tumor

    • Derived from Odontogenic Cysts

  • Ghost Cell Odontogenic Carcinoma

  • Odontogenic Sarcomas

  • Ameloblastic Fibrodentino- and Fibro-Odontosarcoma

B). Fibro-Osseous Lesions

  • Fibrosarcoma

  • Osteogenic Sarcoma

  • Chondrosarcoma

  • Ewing's Sarcoma

C). Additional Malignant Tumors

  • Neurofibrosarcoma

  • Others: Secondaries from distant metastasis (e.g., prostate, lungs, thyroid, kidneys).

Molecular Biology of Tumors

  • Genetic and molecular changes promote tumor development through complex processes.

  • Oncogenes: Normal cellular genes contributing to neoplastic transformation via:

    • Gene amplification

    • Translocation

    • Mutation

  • Functions of oncogenes:

    • Growth factors (e.g., PDGF, FGF)

    • Growth factor receptors (e.g., EGFR, HER-2, Ret)

    • Nonreceptor tyrosine kinases (e.g., Src, Abl)

    • Serine/threonine kinases (e.g., Mos)

    • Signal transducers (e.g., Ras)

    • Transcription factors (e.g., Myc, Fos)

  • Ameloblastomas:

    • EGFR positive

    • Products encoded by Ras genes (p21Ras) show preferential expression in odontogenic epithelium of ameloblastomas, ameloblastic fibromas, and odontogenic myxomas.

    • C-Myc oncoprotein: expressed in neoplastic cells adjacent to the basement membrane of ameloblastomas.

  • Tumor-Suppressor Genes:

    • Regulate cell growth; inactivation through mutation/loss of heterozygosity can lead to tumor development.

    • Notable genes include:

    • p53 (most studied)

    • Retinoblastoma (RB), Adenomatous Polyposis Coli (APC), ST-1, Patched (PTC)

  • p53 mutations: Infrequent in benign ameloblastomas but detected in malignant variants.

  • Hypermethylation of p16: May influence malignant transformation of ameloblastoma.

  • Ki-67, p53, p63: High levels are noted in Keratocystic Odontogenic Tumors (KOTs), favoring tumorigenesis.

Clinical Features of Ameloblastoma

  • Four recognized variants of ameloblastomas include:

    1. Solid/Multicystic Ameloblastoma

    2. Extraosseous/Peripheral Ameloblastoma

    3. Desmoplastic Ameloblastoma

    4. Unicystic Ameloblastoma

  • Demographics:

    • Variable clinical features and biologic behavior contribute to treatment consensus difficulties.

  • The WHO 2017 classification includes:

    • Conventional Ameloblastoma

    • Unicystic Ameloblastoma

    • Extraosseous/Peripheral Ameloblastoma

    • Metastasizing (Malignant) Ameloblastoma

  • In 2022, the WHO included Adenoid Ameloblastoma in the classification, featuring ameloblastoma-like constituents and varied histological patterns.

Risk Factors for Ameloblastoma

  • Factors contributing to the genesis of ameloblastoma:

    • Chronic inflammation

    • Chemical exposure

    • HPV infections

    • Nutritional deficiencies

    • Poor oral hygiene

    • Genetic polymorphisms

Symptoms of Ameloblastoma

  • Asymptomatic initially, may present with:

    • Intraoral and/or extraoral jaw swelling

    • Disturbances in dental occlusion

    • Incidental findings on radiographs

  • Symptoms may develop over time:

    • Slow-growing, painless, hard, non-tender, ovoid swelling, often large in size.

    • Associated complaints: mobile teeth, halitosis, ill-fitting dentures, malocclusion, ulcerations, nasal obstruction.

  • Size of lesions may range from 1-16 cm, with lesions in the maxilla often extending to other structures (e.g., maxillary sinus, nasal cavity).

  • Diagnosis is typically made between 20 to 40 years of age, equally affecting both sexes yet more prevalent in the mandible.

Classification of Ameloblastoma

  • Central/Intra-osseous

  • Peripheral/Extra-osseous: Present in gingiva and mucosa of alveolar process.

  • If untreated, late-stage spread may occur, with factors contributing to spread including

    1. Duration

    2. Extensive local spread

    3. Multiple surgeries/radiotherapy

    4. Proximity to anatomical passages

  • Malignant Transformation: Can occur in about 2-4% of cases, primarily metastasizing to the lungs and other organs.

Specific Odontogenic Tumors

  • Adenomatoid Odontogenic Tumor:

    • Comprises 3-7% of odontogenic tumors; occurs mainly in patients aged 10-20 years.

    • Painless swelling, often associated with an impacted canine.

  • Odontomes:

    • Considered a hamartomatous malformation; composite lesions containing multiple tissue types.

    • Most common in the 1st and 2nd decades of life across both jaws.

  • Odontogenic Myxoma:

    • Benign, slowly growing infiltrative tumor, primarily found in tooth-bearing areas.

    • Typically unilateral, can cross the midline, and presents with facial asymmetry.

    • Affects females more than males, with a higher occurrence in children.

Principles of Management

Patient History

  • Duration:

    • Prolonged duration may indicate congenital causes.

    • Long duration without pain suggests benign growth; rapid growth indicates potential malignancy.

  • Mode of Onset and Progress:

    • Prior trauma or radiation exposure may be significant in lesions like fibrous dysplasia or osteogenic sarcoma.

    • Spontaneous swelling may indicate malignancy.

  • Changes:

    • Ulceration, fluctuation, or softening that has developed recently could signify secondary infection.

    • Symptoms such as pain, abnormal sensations, or functional impairments should be documented.

  • Recurrence History:

    • Any previous surgical interventions?

  • Habits and Lifestyle Factors:

    • Smoking, alcohol, and other habits may contribute to lesion development.

Palpation Findings

  • Consistency of the Lesion:

    • Variations in texture (e.g., soft, hard, bony, cystic) will guide management.

  • Fixity:

    • Evaluating fixity to adjacent skin/mucosa/structure is vital.

  • Examination of Regional Lymph Nodes:

    • Vital in assessing malignancy.

  • 5S Evaluation:

    • Site, shape, surface, size, surrounding structures should be documented.

Imaging Techniques

  • Imaging options include plain radiographs, CT scans (including 3-D reconstructions), MRI, and angiographic studies for vascular tumors.

  • Bone Scans/Scintigraphy: Recommended in cases of malignancy to assess for distant metastases.

  • Confirmatory Diagnosis:

    • Histopathological examination is crucial.

    • Biopsy types:

    • Aspiration biopsy (for fluid-containing lesions)

    • Incisional or excisional biopsy

    • Exfoliative cytology should be avoided due to a risk of false negatives.

    • Intra-operative frozen section study may assist in determining the extent of surgery.

Treatment Approaches

  • Surgical Options:

    • Complete excision of the lesion is paramount, aiming for restoration of function and form.

    • Types of Surgical Procedures:

    • Enucleation

    • Curettage

    • Marginal and En Bloc Resection, Resection with Continuity Defect, Disarticulation.

  • Indications for Surgical Methods:

  • Enucleation is indicated for tumors with distinct separation from surrounding tissues (e.g., odontoma, ameloblastic fibroma).

  • Marginal resection is necessary for incompletely encapsulated tumors.

  • Multi-modality Approach for Malignancies:

    • Incorporating surgery, chemotherapy, and radiotherapy as necessary.

  • Postoperative Management:

    • Monitoring vital signs, maintaining fluid and electrolyte balance, and administering prophylactic antibiotics.

  • Long-Term Follow-Up:

    • Essential to monitor for recurrence and manage complications.

Complications Post-Surgery
Early Complications

  • Swelling

  • Facial asymmetry

  • Numbness of oral tissues

  • Bleeding (primary, reactionary, or secondary)

  • Airway obstruction

  • Asphyxia

Late Complications

  • Recurrence of growth

  • Hypertrophied scars or keloids

  • Impaired oral functions (e.g., speech, mastication).

Oral Cancer

Overview

  • Majority (over 90%) of malignant oral neoplasms are squamous cell carcinomas, with adenocarcinomas and other malignancies representing the remainder.

  • Incidence Statistics:

    • Approximately 300,000 new cases globally each year, mostly in developing countries.

    • Dismal 5-year survival rates of 20-50% for patients presenting with advanced disease.

    • Annual deaths: 145,000 worldwide; incidence increases with age (98% of cases occur in individuals over 40).

Risk Factors and Etiology

  • Higher incidence in males than females, with a 3:2 ratio.

  • Alcohol: Acts as an irritant and solvent, enhancing mucosal penetration by carcinogens.

  • Tobacco & Alcohol Synergism: Combined usage increases oral carcinoma risk significantly.

  • Infection: HPV and syphilis linked to oral cancer.

  • Poor Oral Hygiene: Associated with chronic trauma leading to disrupted cellular growth control.

  • Sunlight Exposure: UV radiation risk factors contribute mainly to lip cancers, particularly in outdoor workers.

  • Genetic Disorders: Rare conditions may increase risk.

Clinical Features of Oral Cancer

  • Early Signs:

    • White/red patches or shallow ulcers that are typically painless.

    • Non-healing ulcers, exophytic growths, or submucosal presentations developing over weeks/months.

  • Advanced Symptoms:

    • Swelling, pain, fixation to surrounding structures, nerve palsies, and loosening of teeth.

  • Local Effects: Can interfere with nutrition, leading to malnutrition and impaired healing.

Investigations

  • Biopsy: Incisional or excisional to evaluate differentiation and spread.

  • Imaging Techniques:

    • Choice guided by clinical findings; includes CT and MRI for soft tissue assessment.

  • Staging: TNM classification used for assessment.

Treatment Strategies

  • General Treatment Options:

    • Surgery, radiotherapy, chemotherapy, with a focus on curative or palliative care.

    • Treatment and survival linked closely to tumor size and nature.

  • Multidisciplinary Approach:

    • Involvement of various specialists (surgeons, oncologists, pathologists, etc.) is crucial for optimal patient care.

  • Rehabilitative Treatment: Implemented a minimum of one year post-surgery, addressing functional and aesthetic needs.

  • Factors Affecting Survival: These may include delayed treatment, advanced age, male gender, poor overall health, tumor size, location, differentiation, and lymph node involvement.

Specific Variants of Oral Cancer

  • Verrucous Carcinoma:

    • Low-grade neoplasm common in elderly males; presents as a well-circumscribed white, warty mass.

    • Differential diagnosis includes papilloma; often associated with habits such as snuff-dipping.