ADAMANTINOMA - LOW-GRADE EPITHELIAL BONE MALIGNANCY
Tibial Diaphysis | Biphasic Histology | Soap-Bubble Appearance | Wide Excision
HISTOLOGICAL SUBTYPES
Critical Must-Knows
- Tibial diaphysis is the classic location (85% of cases)
- Biphasic histology - epithelial cells in osteofibrous stroma
- Soap-bubble appearance on X-ray - multilocular lytic lesion
- Wide en bloc excision required - curettage has high recurrence
- Cytokeratin positive - distinguishes from other bone tumours
Examiner's Pearls
- "Anterior tibial cortex involvement is characteristic
- "May arise from or coexist with osteofibrous dysplasia
- "Lymph node and lung metastases occur in 15-30%
- "Late recurrence possible - follow up for decades
Clinical Imaging
Imaging Gallery
Critical Adamantinoma Exam Points
Location is Key
Tibial diaphysis is the hallmark location (85%). The lesion characteristically involves the anterior cortex. If you see a lytic tibial diaphyseal lesion in a young adult, consider adamantinoma in the differential.
Biphasic Histology
The tumour contains epithelial nests within an osteofibrous stroma. Epithelial cells are cytokeratin 14 and 19 positive. This biphasic pattern distinguishes it from pure osteofibrous dysplasia.
Surgical Margins Matter
Wide en bloc resection is mandatory. Curettage or marginal excision leads to unacceptably high local recurrence (up to 90%). Intralesional surgery is the strongest predictor of recurrence and metastasis.
Long-term Follow-up
Recurrence can occur up to 36 years after initial resection. Patients require lifelong surveillance. The 10-year survival is excellent at 92% but late metastases occur.
Quick Decision Guide - Differential of Tibial Lytic Lesions
| Diagnosis | Age | Location | Key Features |
|---|---|---|---|
| Adamantinoma | 20-50 years | Tibial diaphysis (anterior cortex) | Soap-bubble, cytokeratin positive |
| Osteofibrous dysplasia | Under 10 years | Tibial diaphysis (anterior cortex) | Self-limiting, anterior bowing |
| Fibrous dysplasia | Any age | Any bone, often polyostotic | Ground-glass matrix, shepherd's crook |
| Ewing sarcoma | 5-25 years | Diaphysis any bone | Permeative, onion-skin periosteal reaction |
| Osteosarcoma | 10-25 years | Metaphysis long bones | Aggressive, Codman triangle, sunburst |
TIBIA - Key Features of Adamantinoma
Memory Hook:TIBIA helps remember this is the classic tibial tumour with unique biphasic histology
WIDE - Surgical Principles
Memory Hook:WIDE margins are essential - never curettage adamantinoma
SOAP - Imaging Features
Memory Hook:The SOAP-bubble appearance on X-ray is characteristic of adamantinoma
Overview and Epidemiology
Adamantinoma is a rare low-grade malignant bone tumour with distinctive biphasic histology featuring epithelial cells within an osteofibrous stroma. It has a remarkable predilection for the tibial diaphysis and represents less than 0.5% of all primary bone tumours.
Key epidemiological features:
- Incidence: Accounts for less than 1% of primary malignant bone tumours
- Age distribution: Peak between 20-50 years (range 2-86 years)
- Gender: Slight male predominance (5:4 ratio)
- Location: 80-85% occur in the tibial diaphysis
Risk factors:
- No established genetic predisposition identified
- Possible association with osteofibrous dysplasia (OFD)
- History of prior trauma reported in 60% of patients (uncertain significance)
- No association with radiation or chemical exposure
Etymology
The name "adamantinoma" derives from Greek "adamantinos" meaning "very hard", coined by Fischer in 1913. The term was originally used for odontogenic tumours with similar histology. Despite the name suggesting a relationship to dental tumours, skeletal adamantinoma is a distinct entity.
Pathophysiology
Histological Features
Adamantinoma is characterised by its distinctive biphasic histology with epithelial and osteofibrous components that may be intermingled in various proportions.
Epithelial Component:
- Nests, cords, or tubules of epithelial cells
- Positive for cytokeratins 14, 19 (but negative for CK8, CK18)
- Four histological patterns: basaloid, tubular, spindle-cell, squamous
- Peripheral palisading of cells may be seen
Osteofibrous Component:
- Fibrous stroma with woven bone trabeculae
- Similar to osteofibrous dysplasia
- Contains scattered osteoclast-like giant cells
- Positive for vimentin
Relationship to Osteofibrous Dysplasia
A controversial but clinically important relationship exists between adamantinoma and osteofibrous dysplasia (OFD):
| Feature | Osteofibrous Dysplasia | OFD-like Adamantinoma | Classic Adamantinoma |
|---|---|---|---|
| Age | Children (under 10) | Adolescents | Adults (20-50) |
| Epithelial cells | Rare or absent | Scattered, small | Prominent nests |
| Cytokeratin | Negative or focal | Focal positive | Strongly positive |
| Behaviour | Benign, self-limiting | Low malignant potential | Malignant |
| Treatment | Observation (most) | Wide excision | Wide excision |
Proposed pathogenic relationship:
- OFD may represent a precursor lesion in some cases
- OFD-like (differentiated) adamantinoma is an intermediate lesion
- Transformation from OFD to adamantinoma has been documented
- All three may represent a spectrum of the same disease process
Molecular Features
- Chromosomal abnormalities: Extra copies of chromosomes 7, 8, 12, 19, 21
- No specific fusion genes identified (unlike Ewing sarcoma)
- GNAS mutations absent (differentiates from fibrous dysplasia)
- MDM2 amplification absent (differentiates from dedifferentiated liposarcoma)
Classification Systems
Histological Classification
Histological Patterns of Adamantinoma
| Pattern | Features | Frequency | Prognosis |
|---|---|---|---|
| Basaloid | Nests of basaloid cells with peripheral palisading | Common | Standard |
| Tubular | Epithelial cells forming tubular/glandular structures | Common | Standard |
| Spindle-cell | Elongated spindle-shaped epithelial cells | Less common | May be confused with sarcoma |
| Squamous | Squamous differentiation with keratinisation | Less common | May have better prognosis |
| Osteofibrous-like (Differentiated) | Predominantly fibrous with scattered epithelial cells | 10-20% | Better prognosis |
Most tumours show mixed patterns. The osteofibrous-like (differentiated) subtype has a notably better prognosis and occurs in younger patients.
Clinical Assessment
History
Classic Presentation:
- Slowly progressive swelling over the anterior shin
- Dull, aching pain - often present for months to years
- Approximately 30% have symptoms for more than 5 years before diagnosis
- May have history of prior trauma (reported in 60%)
Duration of symptoms is an important prognostic factor - shorter symptom duration (less than 5 years) is associated with higher recurrence risk.
Red Flag Symptoms:
- Rapid increase in swelling
- New or worsening pain
- Constitutional symptoms (weight loss, fever) - rare but concerning
- Pathological fracture (occurs in 16-23% of cases)
Physical Examination
Standard Findings:
- Palpable firm mass over anterior tibial shaft
- Overlying skin may be normal or tense
- Possible anterior tibial bowing
- Tenderness on palpation
- Usually no warmth or erythema (unless fracture)
Examination Sequence:
| Step | Assessment | Findings |
|---|---|---|
| 1 | Inspection | Anterior tibial swelling, possible bowing |
| 2 | Palpation | Firm, fixed mass arising from bone |
| 3 | Range of motion | Usually preserved at knee and ankle |
| 4 | Neurovascular | Usually normal, check dorsalis pedis |
| 5 | Lymph nodes | Palpate popliteal and inguinal nodes |
Differential Diagnosis
Differential Diagnosis of Tibial Lytic Lesions
| Diagnosis | Key Differentiating Features |
|---|---|
| Osteofibrous dysplasia | Age under 10, anterior bowing, self-limiting, cytokeratin negative |
| Fibrous dysplasia | Ground-glass matrix, polyostotic form common, GNAS mutation |
| Ewing sarcoma | Age 5-25, permeative, systemic symptoms, EWSR1 translocation |
| Osteomyelitis | Fever, elevated WCC/CRP, sequestrum on CT |
| Metastatic carcinoma | Known primary, older age, multiple lesions common |
Investigations
Imaging Algorithm
Step 1: Plain Radiographs
- First-line investigation for tibial swelling
- Characteristic "soap-bubble" or multilocular lytic appearance
- Eccentric location in anterior cortex
- Sclerotic margins with cortical expansion
- May show multifocality (skip lesions)
Step 2: CT Scan
- Better cortical definition than X-ray
- Defines extent of bone destruction
- Identifies pathological fracture
- CT chest for pulmonary metastasis staging
Step 3: MRI
- Gold standard for local staging
- Defines intramedullary extent
- Identifies soft tissue extension
- Detects skip lesions (multifocality)
Imaging Characteristics
Imaging Modality Comparison
| Modality | Key Findings | Role |
|---|---|---|
| Plain radiograph | Soap-bubble appearance, eccentric, sclerotic margins | Initial assessment |
| CT scan | Cortical destruction, extent of bone involvement | Surgical planning, staging (chest) |
| MRI | T1 low, T2 high signal, contrast enhancement, skip lesions | Local staging, soft tissue assessment |
| Bone scan | Increased uptake, identifies multifocal disease | Screening for metastases |
| PET-CT | FDG avid, useful for staging and recurrence | Staging, surveillance |
Biopsy
Principles:
- Core needle biopsy preferred (CT or ultrasound-guided)
- Open biopsy if core inconclusive
- Biopsy tract must be excised with definitive resection
- Place biopsy tract in line with planned surgical incision
Biopsy Planning
Always discuss biopsy approach with the operating surgeon before performing. The biopsy tract becomes contaminated and must be excised en bloc with the tumour. Poorly placed biopsies can compromise limb salvage.
Laboratory Studies
- FBC, ESR, CRP - usually normal
- LDH, ALP - usually normal or mildly elevated
- Calcium - rarely hypercalcaemia (paraneoplastic)
- Immunohistochemistry: Cytokeratin 14, 19 positive; CK8, 18 negative
Management
Surgical Principles
Wide En Bloc Resection is the treatment of choice. The goal is complete tumour removal with a cuff of normal tissue.
Margin Types:
| Margin | Description | Local Recurrence |
|---|---|---|
| Intralesional | Through the tumour | Up to 90% |
| Marginal | Through reactive zone | 30-50% |
| Wide | Through normal tissue | Under 10% |
| Radical | Entire compartment | Under 5% |
Never Curettage
Curettage or intralesional excision is contraindicated. This is the strongest predictor of local recurrence and subsequent metastasis. All adamantinomas require wide surgical margins.
Surgical Goals:
- Complete tumour removal with wide margins
- Excision of biopsy tract
- Preservation of limb function when possible
- Durable reconstruction
Limb Salvage Reconstruction Options:
Reconstruction Options After Tibial Resection
| Method | Advantages | Disadvantages |
|---|---|---|
| Intercalary allograft | Anatomical reconstruction, joint preservation | Nonunion, fracture, infection risk |
| Vascularised fibula autograft | Living bone, good incorporation | Donor morbidity, hypertrophy takes time |
| Allograft-prosthesis composite | Immediate stability, joint replacement | Loosening, wear, infection |
| Distraction osteogenesis | Autologous bone, no donor site | Prolonged treatment, pin site issues |
| Endoprosthesis | Immediate function | Loosening, wear, revision |
The choice of reconstruction depends on resection length, patient age, expected activity level, and institutional expertise.
Complications
Tumour-Related Complications
Tumour-Related Complications
| Complication | Incidence | Management |
|---|---|---|
| Pathological fracture | 16-23% | Stabilisation then definitive resection |
| Local recurrence | 10-35% (margin dependent) | Re-resection with wider margins, amputation |
| Pulmonary metastases | 15-30% | Metastasectomy if possible, systemic therapy |
| Lymph node metastases | 5-10% | Lymphadenectomy |
Surgical Complications
| Complication | Incidence | Risk Factors |
|---|---|---|
| Wound infection | 5-15% | Large resection, diabetes |
| Nonunion | 10-30% (allograft) | Long segment, chemotherapy |
| Fracture (allograft) | 15-25% | Stress risers, activity |
| Deep venous thrombosis | 5-10% | Prolonged surgery, immobility |
| Neurovascular injury | Under 5% | Tumour proximity |
Managing Recurrence
Local recurrence is the most significant complication. Assessment includes:
- Imaging: MRI of local site, CT chest, bone scan/PET
- Biopsy: Confirm recurrence histologically
- Surgical planning: Review margins from primary surgery
Treatment Options:
- Wide re-excision if margins achievable
- Amputation if limb salvage not possible
- Palliative care for unresectable/metastatic disease
Recurrence Predicts Metastasis
Local recurrence significantly increases the risk of subsequent metastatic disease. Achieving adequate margins at initial surgery is critical to prevent this cascade of complications.
Postoperative Care
Immediate Postoperative Care
Day 0-3:
- DVT prophylaxis (mechanical and pharmacological)
- Drain management - remove when output under 50ml per 24 hours
- Pain management - PCA then oral analgesia
- Non-weight bearing on affected limb
Week 1-6:
- Wound surveillance - watch for infection
- Protected weight bearing (depends on reconstruction)
- Physiotherapy for ROM and muscle strengthening
- Monitor for DVT/PE
Rehabilitation Protocol
| Phase | Timeframe | Goals |
|---|---|---|
| Phase 1 | Weeks 0-6 | Protected weight bearing, ROM, wound healing |
| Phase 2 | Weeks 6-12 | Progressive weight bearing, strength |
| Phase 3 | Months 3-6 | Full weight bearing, functional activities |
| Phase 4 | After 6 months | Return to recreational activities |
Reconstruction-Specific Considerations:
- Allograft: Non-weight bearing 6-12 weeks until union
- Vascularised fibula: Progressive weight bearing as fibula hypertrophies
- Endoprosthesis: Earlier weight bearing (2-4 weeks)
Return to Activity
- Desk work: 4-6 weeks (depends on pain control)
- Manual work: 3-6 months
- Sports: Generally low-impact activities recommended
- Driving: When off opioids and can weight bear for emergency stop
Allograft Union
Intercalary allograft reconstruction requires careful monitoring for union. Radiographic union at the allograft-host junction may take 12-18 months. Protect the construct during this period.
Outcomes and Prognosis
Survival Outcomes
Overall Survival:
- 5-year survival: 95-98%
- 10-year survival: 87-92%
- Metastatic disease significantly worsens prognosis
Disease-Free Survival:
- Recurrence-free survival at 10 years: approximately 72%
- Late recurrence is a significant concern
Prognostic Factors
Factors Associated with Worse Outcome:
Prognostic Factors
| Factor | Better Prognosis | Worse Prognosis |
|---|---|---|
| Histological subtype | Osteofibrous-like (differentiated) | Classic with high epithelial component |
| Surgical margins | Wide or radical | Intralesional or marginal |
| Symptom duration | Greater than 5 years | Less than 1 year |
| Age | Older (over 20) | Younger (under 20) |
| Pain at presentation | Minimal or absent | Significant pain |
| Squamous differentiation | Present | Absent |
Functional Outcomes
Limb Salvage:
- Achievable in 80-90% of cases at specialised centres
- MSTS functional score typically 70-85% of normal
Quality of Life:
- Generally good with successful limb salvage
- May require walking aids initially
- Long-term surveillance can cause anxiety
Evidence and Guidelines
Surgical Margins and Recurrence
- Intralesional excision associated with 90% local recurrence
- Marginal excision: 30-50% recurrence
- Wide excision: under 10% recurrence
- Local recurrence increases metastasis risk
Long-term Outcomes After Wide Resection
- 10-year survival 87-92%
- Recurrence can occur up to 36 years post-resection
- Pulmonary metastases in 15-30%
- Limb salvage achievable in 80-90%
OFD-Adamantinoma Relationship
- Cytokeratin expression in OFD suggests relationship
- OFD-like adamantinoma represents intermediate lesion
- Possible progression from OFD to adamantinoma
- All may represent disease spectrum
Reconstruction Outcomes
- Allograft nonunion 10-30%
- Allograft fracture 15-25%
- Vascularised fibula may require prolonged protected weight bearing
- Endoprosthesis allows earlier function
Exam Viva Scenarios
Practice these scenarios to excel in your viva examination
Classic Tibial Adamantinoma
"A 28-year-old man presents with a 2-year history of anterior shin swelling. Radiographs show a multilocular lytic lesion in the mid-tibial diaphysis with a soap-bubble appearance and sclerotic margins. There is cortical expansion but no periosteal reaction."
Recurrent Adamantinoma
"A 45-year-old woman had curettage of a tibial lesion 5 years ago at an outside institution. She was told it was 'benign'. She now presents with increasing pain and swelling. MRI shows a large tibial lesion with soft tissue extension. Review of original pathology confirms adamantinoma."
Differential Diagnosis - Child with Tibial Lesion
"A 7-year-old child is referred with anterior tibial bowing and an incidental finding of a lytic lesion in the tibial diaphysis on X-ray. The lesion appears intracortical with slight expansion. The child is asymptomatic."
MCQ Practice Points
Location
Q: What is the most common location for adamantinoma?
A: Tibial diaphysis - 85% of adamantinomas occur in the mid-tibial shaft, characteristically involving the anterior cortex. This location is virtually pathognomonic. Other sites (fibula, humerus, femur) are rare.
Histology
Q: What is the characteristic histological feature of adamantinoma?
A: Biphasic pattern with epithelial nests or cords within an osteofibrous stroma. The epithelial cells are positive for cytokeratins 14 and 19 (but negative for CK8, CK18). This cytokeratin profile distinguishes it from metastatic carcinoma.
Treatment
Q: What is the surgical treatment of choice for adamantinoma?
A: Wide en bloc resection with adequate margins. Curettage is contraindicated and associated with up to 90% local recurrence. Even marginal excision has 30-50% recurrence. The minimum acceptable margin is wide (through normal tissue).
Prognosis
Q: What is the prognosis and metastasis rate for adamantinoma?
A: 10-year survival is approximately 92% with adequate surgical margins. Metastases occur in 15-30% of cases, primarily to lungs and lymph nodes. Late recurrence (up to 36 years post-surgery) mandates lifelong follow-up.
Imaging
Q: What is the characteristic radiographic appearance of adamantinoma?
A: "Soap-bubble" appearance - multilocular lytic lesion with sclerotic margins, eccentric in the anterior tibial cortex. The lesion may show cortical expansion without periosteal reaction. Skip lesions (multifocality) can occur in the same bone.
Australian Context
Epidemiology
Adamantinoma is rare in Australia, consistent with international incidence rates. The rarity of this tumour means that most cases should be managed at specialist sarcoma centres with experience in limb salvage surgery.
Referral Pathways
Suspected bone tumours should be referred to a specialist musculoskeletal oncology unit before biopsy. In Australia, major sarcoma units are located in capital cities with multidisciplinary teams including orthopaedic oncologists, medical oncologists, radiation oncologists, radiologists, and pathologists.
Patients in rural and regional areas may require transfer to metropolitan centres for definitive management. Telemedicine can facilitate initial consultation and follow-up.
Treatment Considerations
Australian practice follows international guidelines with wide surgical resection as the standard of care. Access to reconstruction materials including allografts and custom prostheses is available through major tertiary centres.
Follow-up protocols are similar to international standards with lifelong surveillance recommended. The Australian healthcare system supports long-term follow-up through public and private oncology services.
ADAMANTINOMA
High-Yield Exam Summary
Key Diagnosis
- •Tibial diaphysis location (85%) - anterior cortex
- •Soap-bubble appearance on X-ray
- •Biphasic histology - epithelial + osteofibrous
- •Cytokeratin 14, 19 positive
Treatment Principles
- •Wide en bloc resection mandatory
- •NEVER curettage (90% recurrence)
- •Excise biopsy tract with specimen
- •Reconstruction: allograft, vascularised fibula, prosthesis
Prognosis
- •10-year survival approximately 92%
- •Metastases in 15-30% (lung, lymph nodes)
- •Late recurrence up to 36 years
- •Lifelong follow-up required
Exam Triggers
- •Young adult with tibial diaphyseal lytic lesion
- •Anterior cortex soap-bubble lesion
- •Multilocular lytic with sclerotic margins
- •Positive cytokeratin staining on biopsy
Common Mistakes
- •Performing curettage or marginal excision
- •Not staging with CT chest before surgery
- •Forgetting to excise biopsy tract
- •Stopping follow-up after 5 or 10 years