Adamantinoma

Adamantinoma is a rare, low-grade malignancy of bone with mesenchymal and epithelioid features. Adamantinoma almost always occurs in the diaphysis of the tibia (more than 90% of cases) initially involving the anterior cortex. Adamantinoma is slow-growing and is characterized clinically by the gradual development of pain and swelling at the tumor site, most commonly in young adults. Radiographically, adamantinoma resembles osteofibrous dysplasia (also known as cortical fibrous dysplasia), a benign bone lesion of the tibia seen in pediatric patients.

Epidemiology

Adamantinoma is an extremely rare bone tumor, accounting for 0.1-0.5% of all malignant bone tumors. Adamantinoma tends to develop in patients 20-40 years old.

Clinical Features

Adamantinoma most commonly develops in the anterior cortex of the tibial diaphysis, leading to swelling and deformity of the tibial crest with progressive pain. Adamantinoma occasionally presents with a pathological fracture. This tumor can be confused with cortical fibrous dysplasia of the tibia and must be distinguished by a high index of clinical suspicion and appropriate biopsy.

Radiological Features

On radiographs, adamantinoma displays a classic multi-cystic, “soap-bubbly” appearance along the anterior tibial cortex (Figure 1). The lesion is characterized by mixed lytic and sclerotic regions. Over time, the tumor can progress through the width of the tibia to eventually involve the entire cross section of the bone. The average length of the lesion is approximately 10 cm. Radiographs may reveal bowing of the tibia due to chronic bone remodeling and an extraosseous soft-tissue mass.

Figure 1: Anteroposterior and lateral plain radiographs of the right lower limb showed a well-defined, expansile lytic-sclerotic lesion (red arrow). (Image courtesy of Adamantinoma: An Uncommon Cause of Bone Pain in a Young Adolescent Male. Cureus 15(12): e50214. doi:10.7759/cureus.50214)

On computed tomography (CT) scans, adamantinomas are characterized by cortical thinning and reactive sclerosis. There may be frank cortical disruption, soft-tissue extension, and involvement of the medullary canal and posterior cortex.

Magnetic resonance imaging (MRI) will demonstrate cortical thinning, expansion, and marrow replacement on T1 sequences. Fluid-sensitive sequences will demonstrate areas of cyst formation, which can be blood-filled and demonstrate fluid-fluid levels. There may also be perilesional or intralesional edema (Figure 2). Adamantinomas enhance with contrast.

Figure 2: Coronal PD-SPAIR, coronal T2WI, coronal T1WI, and coronal post-contrast images (left to right) showing altered signal intensity lesion appearing hyperintense on PD-SPAIR (red arrow), showing intermediate signal on T2WI (blue arrow), appearing hypointense on T1WI (yellow arrow), and showing intense post-contrast enhancement (orange arrow). (PD-SPAIR: proton density-spectral adiabatic inversion recovery, T2WI: T2-weighted imaging, T1WI: T1-weighted imaging) (Image courtesy of Adamantinoma: An Uncommon Cause of Bone Pain in a Young Adolescent Male. Cureus 15(12): e50214. doi:10.7759/cureus.50214)

Pathology

Grossly, adamantinoma is a rubbery, well-defined tumor that may contain areas of cyst formation and hemorrhage. The tumor is predominantly intracortical, although expansion both out of the bone and into the intramedullary space are common.

Microscopically, the defining feature of adamantinoma is a biphasic pattern of bland spindle cells and epithelioid cells. The spindle cells are found in a fibrous stroma that stains positively for vimentin; the epithelioid cells are found in nests which stain positively for cytokeratin. The epithelial component is thought to represent the primary neoplastic cell population, which in turn stimulates reactive fibrous growth and cortical thinning (Figure 3).

Figure 3: H&E stain of adamantinoma, demonstrating bland spindle cell stroma surrounding nests of epithelioid cells.

The three musculoskeletal malignancies that stain positively for mesenchymal (Vimentin) and epithelial (Cytokeratin) tissue include Adamantinoma, Synovial Sarcoma and Epithelioid Sarcoma.

In studies of adamantinoma pulmonary metastasis, only the cytokeratin-positive, epithelial-cell population was present in the nodules.

Differential Diagnosis

The radiographic appearance of adamantinoma of the tibia can be confused with that of osteofibrous dysplasia, fibrous dysplasia, osteomyelitis, an intracortical abscess, or osteosarcoma. Histologically, the epithelial cells of adamantinoma can be misdiagnosed as metastatic carcinoma, although the finding that the epithelial cells are uniformly positive for keratin 14 and keratin 19 can assist in the correct diagnosis. The spindle cells of adamantinoma can be misdiagnosed as primary bone sarcoma especially if epithelial cells are not seen.

Disease Course: Treatment and Prognosis

Adamantinoma is typically treated with surgery. Wide en bloc resection of the lesion is necessary to achieve durable local control. Reconstruction is based on the size and location of the lesion and may involve an endoprosthesis, bulk allograft, autograft, alloprosthetic composite, or distraction osteosynthesis (Figure 4).

Figure 4: AP X-ray demonstrating internal fixation and placement of free vascularized fibula graft after wide excision of an adamantinoma.

Chemotherapy is not indicated due to the low-grade nature of this tumor and radiation has not proven useful for treating either primary or recurrent disease.

Local recurrence after wide excision occurs in up to 15% of cases and is thought to be due to satellite lesions that exist beyond the primary tumor mass. Metastasis occurs in 15 to 25% of cases, often many years after a margin-negative excision. The mortality rate associated with adamantinoma is approximately 10% overall.

Long-term surveillance is necessary for both local and distant recurrences. Local recurrence has been reported 5 to 15 years after treatment, and distant recurrences have been reported even 20 years after initial resection. Local recurrences are treated surgically, with overall limb salvage rates of approximately 70%.

Key Test Topics

Classic appearance and location on X-ray
Biphasic histological characteristics with cytokeratin-positive epithelial cell nests and vimentin-positive spindle cells
Surgical treatment with wide excision, no chemotherapy or radiation