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

Recommended reading

Qureshi et al  Current Trends in the Management of Adamantinoma of Long Bones  JBJS August 2000: Vol 82 A, No. 8, pg 1122-1131

Jain et al  Adamantinoma: A clinicopathological review and update  Diagnostic Pathology Feb 2008, 3:8