What are the epidemiology, typical presentation, diagnostic work‑up, treatment options, and prognosis of adamantinoma in adolescents and young adults?

Adamantinoma: Clinical Overview

Epidemiology

Adamantinoma is an exceedingly rare, low-grade malignant bone tumor accounting for only 0.3% to 1% of all primary malignant bone tumors, occurring predominantly in young to middle-aged adults between 20 and 40 years of age. 1

• The male-to-female ratio is approximately 1.3:1 1
• Mean age at presentation is approximately 30 years (range 4-80 years), with a median age of 22 years in surgical series 2, 3, 4
• Five-year survival rates are 98.8% and ten-year survival rates are 91.5%, reflecting the low-grade nature of this malignancy 3

Typical Presentation

The tibial shaft (medial or distal diaphysis) is affected in the overwhelming majority of cases, with the anterior cortex being the characteristic location. 1

• Pain is the cardinal presenting symptom, often accompanied by localized swelling 1
• The tumor produces lytic and sometimes destructive areas which can lead to pathological fracture 1
• Median tumor size at presentation is 5.7 cm (range 0.5-15.5 cm) 4
• The fibula or both tibia and fibula may be involved, though involvement of other bones is extremely rare 1

Diagnostic Pitfalls

Adamantinoma is frequently misdiagnosed initially, with common misdiagnoses including fibrous dysplasia, osteofibrous dysplasia, bone cyst, non-ossifying fibroma, and even carcinoma metastasis. 2

Diagnostic Work-Up

All patients with suspected adamantinoma must be referred to a specialized bone sarcoma center before any biopsy is performed, as inappropriate diagnostic procedures can compromise treatment outcomes. 1, 5

Imaging Algorithm

• Conventional radiographs in two orthogonal planes are mandatory as the first investigation 1, 5
• CT should be performed to visualize calcification, periosteal bone formation, cortical destruction, and soft tissue involvement 1, 5
• MRI of the entire bone with adjacent joints is essential for local staging and must be completed before biopsy 1, 5
• Chest CT is required to evaluate for pulmonary metastases 1

Histopathology

• Basaloid pattern on a background of fibrotic stroma is the most common histologic appearance, though spindle cell and squamous features may be present 2
• All adamantinomas are positive for cytokeratins, often in coexpression with vimentin 2
• The osteofibrous dysplasia-like subtype is low-grade but will recur if incompletely resected 1
• No correlation exists between histologic pattern and clinical outcome, making prognosis difficult to predict based on histology alone 2

Treatment Options

Wide surgical resection with adequate margins is the definitive treatment of choice and significantly reduces recurrence rates compared to intralesional curettage. 1, 2

Surgical Management

• Intralesional curettage is inadequate and invariably leads to local recurrence 2
• Wide resection should be performed in all cases, with reconstruction using intercalary fibula autografts or other techniques 2
• Reconstruction-related complications occur in approximately two-thirds of cases but can be managed with repeat surgery 2
• Complete excision is the treatment of choice, as chemotherapy and radiotherapy have no established role in the management of adamantinoma 1

Role of Systemic Therapy

• Higher-grade areas within the primary tumor may warrant consideration of systemic therapy, though this is not standard practice 1
• There is no evidence supporting routine use of chemotherapy or radiotherapy for typical adamantinoma 1

Prognosis and Long-Term Outcomes

Despite being classified as low-grade malignant, adamantinoma has significant potential for both late local recurrence (approximately 30% of cases) and distant metastases (10-20% of cases, usually to the lungs). 1

Recurrence Patterns

• Local recurrence is frequent (about 30%) after incomplete excision and can occur extraordinarily late—more than 20 years after initial surgery 1, 2, 6
• Median time to local recurrence is 11.4 years (range 6 months to 19 years) 4
• Six recurrences occurred in four patients in one series, with two recurrences appearing 20 and 16 years after initial surgery 2

Metastatic Disease

• The metastatic rate is 10% to 20%, with the lungs being the most common site 1
• Lymph node metastases can occur but are less common 7, 4
• Median time to distant metastasis is 15.8 years (range 4 months to 23 years) 4
• Local and distant recurrence can occur more than 20 years after initial diagnosis 4

Survival Outcomes

• Mean survival duration is 287.8 months (approximately 24 years) 3
• Survival time is independent of gender, age groups, race, marital status, tumor location, and year of diagnosis 3
• In long-term follow-up series, approximately 70% of patients have no evidence of disease, 10% are alive with disease, and 20% die from disease 4

Critical Management Principles

Life-long follow-up with clinical examination and imaging is absolutely required due to the potential for recurrence and metastases decades after initial treatment. 2, 4

• Follow-up should include physical examination of the tumor site and chest imaging at regular intervals 1
• Recurrences have been documented as late as 24 years after diagnosis, mandating surveillance that extends throughout the patient's lifetime 6
• Wide surgical margins at initial resection are the single most important factor in reducing recurrence risk 2