Adamantinoma

Tumor biology and incidence

Primary low-grade, locally aggressive, malignant bone tumor of unknown histogenetic origin
- Current opinion suggests may be epithelial in origin
Slow-growing tumors with limited propensity for metastasis and local recurrence; usually amenable to curative resection
May arise from osteofibrous dysplasia
Very rare neoplasm; estimated 0.1-0.5% of all primary bone tumors
- First reported example attributed to Maier in 1900; Fischer in 1913 named lesion "primary adamantinoma of the tibia" due to its resemblance of mandibular amelobastoma
Location is predominantly in the tibial diaphysis, but can occur in the fibula and other long tubular bones

Age

Most commonly occurs in the second to fifth decades
Median patient age 25-35 years; range, 2 to 86 years
Rarely occurs in children

Gender

M:F = 1:1

Presentation

Initial symptoms often indolent and nonspecific; depend on location and extent of disease
Insidious onset, slow progressive character; patients often tolerate symptoms for many years before seeking medical attention
Lesion may be discovered incidentally on radiographs after patient experiences trauma to involved extremity
May present with complaints of dull ache or nonspecific bone pain present for months to years

Physical findings

Pretibial soft tissue swelling with or without pain
Possibly bowing deformity of tibia due to involvement of anterior tibial surface
Pathological fracture may be present in nearly to one quarter of patients
Spinal lesions may be manifested by neurologic symptoms in addition to pain

Plain films

Site

Classic location in the tibial diaphysis (90% of cases)
- Appears as a central or eccentric, multilocular, slightly expansile, sharp or poorly delineated osteolytic lesion
- Metaphyseal extension or isolated involvement may occur
Other sites of involvement (in order of decreasing frequency): humerus, ulna, femur, fibula, innominate bones, ribs, spine, small bones of hand/foot.

Size

Varying sizes; typical range, 3-15 cm

Tumor effect on bone

Multiple osteolytic defects of varying sizes
Bony expansion common
Lesions typically geographic and well defined
- More aggressive lesions may have moth-eaten borders

Bone response to tumor

Eccentric lucencies with surrounding reactive bony sclerosis
Cortex may be eroded; well organized periosteal expansion

Matrix

Osteolytic; variable regions of mixed ground glass density

Cortex

Anterior cortically based lesion in tibia

Soft tissue mass

May be present

Bone scan and chest CT

Necessary for systemic staging
Bone scan Will likely show increased blood flow in the region of the tumor, increased blood pooling, and increased accumulation of technetium-99m methylene diphosphate
- May also show coexisting fibular involvement

CT scan

Not specific in the differentiation of adamantinoma from other conditions
Shows cortical involvement and soft tissue extension when it exists

MRI

Best for local staging of intra- and extra-osseous tumor extent
Not specific in the differentiation of adamantinoma from other conditions
Depicts distant cortical foci, soft tissue, and intramedullary extension; therefore, useful for determination of tumor-free margins and preoperative planning for reconstructive surgery

Differential diagnosis

Osteofibrous dysplasia
Fibrous dysplasia
Aneurysmal bone cyst
Unicameral bone cyst
Chondromyxoid fibroma
Giant cell tumor
Eosinophilic granuloma
Nonossifying fibroma
Hemangioendothelioma of bone
- Will also present with multiple separate regions of bone involvement
Osteomyelitis
Chondrosarcoma
Metastases

Pathology

Gross: Varies, but most often tumor is yellow-gray or gray-white and fleshy or firm in consistency
- Epithelial and osteofibrous components; intermingled in various proportions and differentiating patterns
Microscopic: Neoplastic cells ranging from small to large in size, with finely dispersed chromatin and overall bland appearance; mitotic figures usually infrequent
- Several patterns of growth: tubular, basaloid (classic), squamous, spindle-cell, osteofibrous dysplasia-like variant
Classified into 2 distinct types: classic and differentiated (osteofibrous dysplasia-like)
- Regardless of histologic subtypes, all adamantinomas uniformly stain positive for keratins 14 and 19
IHC: Epithelial cells show coexpression of keratin and vimentin
Cytogenetic analysis has revealed extra copies of chromosomes 7, 8, 12, 19, and/or 21 in classic and differentiated adamantinomas

Natural history

Locally aggressive but extremely slow growing
Have the potential to metastasize (lung, lymph nodes, bone, abdominal viscera)
- Metastases occur in about 15-30% of cases, by both hematogenous and lymphatic routes
Recurrence frequent after inadequate treatment (ie, marginal resection)
- Recurrent neoplasm behaves more like a sarcoma
- Local recurrence rates vary from 18-32%
No correlation between tumor histology and clinical course
- Unfavorable clinical outcomes associated with other factors, such as intralesional treatment, male gender, pain at presentation, short duration of symptoms, young age (<20 years), and lack of squamous differentiation of the tumor
Determining mortality statistics difficult due to rarity of adamantinomas; however, mortality rates of 13-18% have been reported

Diagnosis and treatment

Biopsy, in consultation with a musculoskeletal oncologist
Adamantinoma highly radioresistant, and chemotherapy has not been shown to be effective
Surgery is current standard of care: amputation or en bloc resection with wide margins and limb salvage
- Wide margins associated with a significantly lower risk of local recurrence
- En bloc resection with wide margins and limb salvage has 10-year survival rate of 82% (Qureshi et al)
- Amputation not shown to improve survival when compared with limb-preserving surgery
Limb reconstruction can be performed with distraction osteogenesis, allografts, vascularized fibular autografts, nonvascularized autografts, and metallic segmental replacement
- Intercalary reconstruction appears to be most successful method; no consensus in literature, however, regarding which is superior form of fixation

Complications

Reconstruction-related complications: nonunion, fracture, infection