| Domain | Evidence-based entry | Suggested ontology |
|---|---|---|
| Definition/classification | Adamantinoma of long bone is a rare primary low-grade malignant bone tumor with biphasic epithelial and osteofibrous components, most often arising in the tibial diaphysis. WHO 2020 places it among “other mesenchymal tumours of bone” and recognizes classic adamantinoma, OFD-like adamantinoma, and dedifferentiated adamantinoma. It is distinct from adamantinoma-like Ewing sarcoma, which is a separate EWSR1/FET-ETS–rearranged round-cell sarcoma mimic rather than true adamantinoma. (pqac-00000021, pqac-00000022, pqac-00000016, pqac-00000009) | MONDO: adamantinoma (MONDO_0002422); NCIT: Adamantinoma; MeSH: Adamantinoma; UBERON: tibia, fibula; NCIT/WHO class: other mesenchymal tumours of bone |
| Epidemiology | Reported frequency is ~0.1–0.5% of primary bone tumors. Landmark 85-case series: 70/85 tibial, 11 of those with fibular involvement; age range 3–72 years, average 25.9 years; slight male excess (45 male, 39 female, 1 unknown). Reviews summarize typical presentation at 20–40 years, often 25–35 years. (pqac-00000022, pqac-00000012, pqac-00000016) | NCIT: Rare Neoplasm; HPO onset terms: Adult onset, Adolescent onset |
| Anatomy/localization | Strong predilection for long bones (reported 97%), especially tibia (80–85%), usually anterior cortex/diaphysis; ipsilateral fibular involvement in ~10–15%. Rare sites include femur, ulna, humerus, radius, ribs, spine, and pretibial soft tissue. Lesions are often intracortical but may extend into medulla and soft tissue. (pqac-00000016, pqac-00000017, pqac-00000012, pqac-00000013) | UBERON: tibia, fibula, cortical bone, bone marrow, soft tissue; CL: epithelial cell, fibroblast |
| Phenotype/natural history | Presentation is indolent and nonspecific: pain, swelling, stiffness, deformity/bowing, impaired weight-bearing; pathologic fracture reported up to ~23–25%. Course is slow and progressive, with symptoms sometimes present for years before diagnosis; recurrence/metastasis may appear many years later. (pqac-00000016, pqac-00000022, pqac-00000012, pqac-00000007) | HPO: HP:0012531 Pain; HP:0001382 Joint stiffness; HP:0009826 Limb swelling; HP:0000927 Abnormality of the skeletal system; HP:0002757 Pathological fracture |
| Distinguishing subtypes | Classic adamantinoma: usually >20 years, overt epithelial nests in fibrous stroma, more aggressive malignant behavior. OFD-like adamantinoma: usually younger patients/teens, intracortical lesion with sparse keratin-positive epithelial nests often requiring IHC, better prognosis but long follow-up needed; possible progression to classic tumor reported. Dedifferentiated adamantinoma: classic areas plus high-grade sarcomatous component, more aggressive. Adamantinoma-like Ewing sarcoma differs by molecular fusion status and immunophenotype. (pqac-00000022, pqac-00000023, pqac-00000017, pqac-00000009) | NCIT: Classic Adamantinoma; NCIT: Dedifferentiated Adamantinoma; NCIT/WHO: Osteofibrous dysplasia-like adamantinoma; NCIT: Ewing Sarcoma |
| Molecular findings | Evidence supports epithelial differentiation with cytokeratin expression. Recurrent cytogenetic copy-number abnormalities/gains involving chromosomes 7, 8, 12, 19, and 21 have been reported. Candidate/nonvalidated tumor findings summarized in recent reviews include KMT2D mutation and increased DLK1 expression; these are research-level, not established clinical drivers. Increased epithelial-cell proliferation markers and EGFR expression relative to stromal component have been proposed. No validated germline causal gene, hereditary syndrome, or standard actionable target is established. (pqac-00000022, pqac-00000001, pqac-00000006) | HGNC: KMT2D, DLK1, EGFR, TP53; GO: keratinization/epithelial cell differentiation, cell proliferation; CL: epithelial cell, fibroblast |
| Pathophysiology | Current model is a biphasic neoplasm of epithelial cells embedded in osteofibrous stroma. Reviews propose that the epithelial component is the primary neoplastic population, potentially stimulating stromal proliferation; relation to osteofibrous dysplasia remains debated, with some evidence for a spectrum/continuum in a subset. Mechanistic evidence remains limited and largely histologic/cytogenetic rather than pathway-resolved. (pqac-00000022, pqac-00000018, pqac-00000001) | GO: epithelial cell proliferation, extracellular matrix organization; CL: epithelial cell, fibroblast; UBERON: cortical bone |
| Diagnosis | Diagnosis integrates radiology, biopsy, histology, and IHC. Radiographs typically show multilocular osteolytic lesion with sclerosis and “soap-bubble” appearance; CT defines cortex and pulmonary metastases; MRI is best for intramedullary, cortical, multifocal, and soft-tissue extent. Histology shows epithelial islands/nests/cords in fibrous stroma with tubular, basaloid, squamous, spindle-cell, or OFD-like patterns. Extensive sampling is important, especially for OFD-like lesions. (pqac-00000017, pqac-00000023, pqac-00000006, pqac-00000011, pqac-00000020) | NCIT: Magnetic Resonance Imaging, Computed Tomography, Radiography, Biopsy; HPO: HP:0031837 Osteolytic lesion |
| Diagnostic immunophenotype | Typical tumor epithelial cells are positive for broad cytokeratins, especially CK5/CK14/CK19, and often p63; EMA may be positive in classic lesions but can be variable. IHC is particularly valuable for detecting sparse epithelial nests in OFD-like lesions and excluding mimics. (pqac-00000016, pqac-00000022, pqac-00000006, pqac-00000011) | HGNC/Protein markers: KRT5, KRT14, KRT19, TP63, EPCAM/EMA |
| Differential diagnosis | Key differentials: osteofibrous dysplasia, fibrous dysplasia, Ewing sarcoma/adamantinoma-like Ewing sarcoma, osteosarcoma, metastatic carcinoma, vascular tumors, osteomyelitis. OFD is typically strictly intracortical and benign; adamantinoma-like Ewing sarcoma is separated by fusion testing and a different IHC/genetic profile. (pqac-00000017, pqac-00000019, pqac-00000023, pqac-00000009) | NCIT: Osteofibrous Dysplasia, Fibrous Dysplasia of Bone, Ewing Sarcoma, Osteosarcoma, Carcinoma Metastatic in Bone |
| Prognosis | Landmark series reported local recurrence in 26/85 (31%), lung metastasis in 13/85 (15%), lymph-node metastasis in 6/85 (7%), and disease-specific death in 11 patients. Reviews summarize recurrence ~18–32% and metastasis ~12–30%, often to lung and regional lymph nodes, with very late events possible. Poorer outcomes are associated with male sex, pain, shorter symptom duration, inadequate/intralesional treatment, and lack of squamous differentiation; margin status is a major predictor. (pqac-00000012, pqac-00000015, pqac-00000001, pqac-00000004, pqac-00000007) | NCIT: Local Recurrence, Lung Metastasis, Lymph Node Metastasis, Prognostic Factor |
| Treatment/current practice | Standard treatment is wide en-bloc resection with negative margins, usually with limb-salvage reconstruction when feasible. Amputation is reserved for unresectable recurrence, extensive disease, or reconstructive failure. Chemotherapy and radiotherapy have no established routine benefit in conventional adamantinoma. Reconstruction options reported include allograft, vascularized fibular graft, endoprosthetic approaches, and other limb-salvage methods. (pqac-00000001, pqac-00000007, pqac-00000005, pqac-00000011) | NCIT: Surgical Resection, Limb Salvage Procedure, Bone Grafting, Amputation |
| Follow-up/prevention | No validated primary-prevention strategy, screening program, or hereditary-risk testing framework is established. Because recurrence and metastasis may occur after long latency, prolonged or lifelong imaging surveillance is recommended after definitive surgery. (pqac-00000012, pqac-00000004, pqac-00000005) | NCIT: Surveillance, Follow-Up Care |
| Evidence gaps | No robust evidence for infectious cause, environmental cause, protective factors, gene-environment interaction, validated circulating biomarkers, disease-specific staging system, standard targeted therapy, immunotherapy, liquid biopsy, single-cell or spatial transcriptomics atlas, animal model, or natural nonhuman disease counterpart was established in the retrieved evidence. Clinical-trial search did not identify relevant interventional trials for this disease; false-positive hits referred to ameloblastoma/craniopharyngioma. (pqac-00000000, pqac-00000021, pqac-00000022, pqac-00000023) | Evidence gap annotation; NCIT: Not Available / Unknown |


*Table: This compact table summarizes the most evidence-supported knowledge-base fields for adamantinoma of long bones, emphasizing distinctions among classic, OFD-like, and adamantinoma-like Ewing entities. It is useful for rapid curation because it combines clinical facts, molecular caveats, and suggested ontology mappings in one place.*