Bone & joints
Other tumors
Adamantinoma
Resident / Fellow Advisory Board: Erna Forgó, M.D.
Editorial Board Member: Jose G. Mantilla, M.D.
Last author update: 19 April 2021
Last staff update: 4 March 2022
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PubMed Search: Adamantinoma [title] bone osteofibrous dysplasia-like
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Etiology | Clinical features | Diagnosis | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Positive stains | Negative stains | Electron microscopy description | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Alexiev BA, Laskin WB. Adamantinoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/boneadamantinoma.html. Accessed November 27th, 2024.
Definition / general
- Rare malignant primary bone tumor of uncertain histogenesis characterized by epithelial structures embedded in a mesenchymal (osteofibrous dysplasia-like) stroma
Essential features
- Primary biphasic fibro-osseous tumor of bone
- Almost exclusively involves the tibia or fibula
- 3 clinicopathologic variants:
- Osteofibrous dysplasia (OFD)-like (differentiated) adamantinoma: inconspicuous clusters of epithelial cells embedded in fibro-osseous stroma
- Classic adamantinoma: obvious epithelial elements embedded in fibro-osseous stroma
- Dedifferentiated adamantinoma: loss of epithelial differentiation, sarcomatoid change
Terminology
- Not recommended: well differentiated adamantinoma
ICD coding
- ICD-O:
- ICD-11:
- 2B5J & XH1SV4 - malignant miscellaneous tumors of bone or articular cartilage of other or unspecified sites and ameloblastoma, NOS
Epidemiology
- Rare tumor that accounts for less than 1% of all primary bone tumors (Acta Orthop Traumatol Turc 2019;53:189)
- Wide age range: 4 - 75 (median age: 30.8 years) (J Oncol 2020;2020:2809647)
- M:F = 5:4 (Diagn Pathol 2008;3:8)
Sites
- In 85 - 90% of cases, the tumor is localized to median third of the diaphysis of the tibia (Pathol Oncol Res 2009;15:209)
- Has been reported in the ulna, femur, humerus, radius, ribs, tarsal and metatarsal bones, as well as extraskeletal pretibial soft tissue (J Surg Oncol 2020;122:273, Clin Orthop Relat Res 2003:256, Skeletal Radiol 1992;21:205, J Med Case Rep 2016;10:185)
- Synchronous involvement of tibia and fibula is reported in 10% of cases (Skeletal Radiol 2003;32:245, Cancer 1989;64:730)
- Multifocal involvement of the tibia is frequently present
Etiology
- Previous studies provide strong arguments that the epithelial component of adamantinoma directly derives from the mesenchymal tissue and gradually increases in amount (Am J Surg Pathol 2003;27:1530, J Pathol 1998;184:24, Cancer Genet Cytogenet 1997;97:5)
- Progression to an aggressive subtype may be associated with epithelial to mesenchymal transition (sarcomatoid dedifferentiation), in which the epithelial immunophenotype is conserved (Am J Surg Pathol 2003;27:1530)
- Osteofibrous dysplasia may be a precursor of adamantinoma (Diagn Pathol 2008;3:8, Pathol Oncol Res 2009;15:209, Clin Orthop Relat Res 1994:234)
Clinical features
- Initial symptoms are often indolent and nonspecific and depend on location and extent of the disease (Diagn Pathol 2008;3:8)
- Onset is insidious and its course shows a slow, progressive character (Diagn Pathol 2008;3:8)
Diagnosis
- Despite advances in imaging techniques, the definitive diagnosis is mainly established by histopathological examination (StatPearls: Adamantinoma [Accessed 18 January 2021])
- Open biopsy is better to obtain additional samples
- Any difficult or nondiagnostic biopsies of solitary bone lesions should be referred to subspecialty expert for a second opinion
Radiology description
- Single or multiple variably sized lytic lesions with sclerotic borders (soap bubble appearance) involving the diaphyseal and less commonly, the metaphyseal cortex; multifocality within the bone and invasion of the medullary cavity or extraosseous soft tissue invasion may occur (best visualized with MRI) (J Surg Oncol 2020;122:273, Pediatr Radiol 2006;36:1068)
- Computed tomography of the primary site elucidates the cortical involvement and is important for detection of metastases (J Surg Oncol 2020;122:273)
- Osteofibrous dysplasia-like adamantinoma is strictly intracortical (like osteofibrous dysplasia)
Radiology images
Contributed by Borislav A. Alexiev, M.D.
Tibia lesion, radiography
Tibia lesion, MRI
Prognostic factors
- Classic variant pursues an indolent but unpredictable course (Mod Pathol 2019;32:231)
- High rate of recurrence with incomplete excision and recurrent potential correlates with a high epithelial to stroma ratio
- Excellent prognosis with complete radical excision
- Osteofibrous dysplasia-like adamantinoma has a better outcome than classic adamantinoma (J Orthop Surg Res 2020;15:268)
- Dedifferentiated adamantinoma has an aggressive clinical course (Am J Surg Pathol 2003;27:1530, Am J Surg Pathol 2010;34:1388)
Case reports
- 17 year old girl with a 14 year history of a slowly enlarging left tibial mass (Pediatr Dev Pathol 2003;6:173)
- 30 year old woman with lytic lesion involving the right mandible (Int J Oral Maxillofac Surg 2020;S0901)
- 34 year old woman with cutaneous metastasis from an adamantinoma of right tibia (Cutis 2019;104:E15)
- 38 year old woman with a bone tumor at the distal end of the fibula (Rare Tumors 2017;9:6823)
- 48 year old woman with tumor in the entire right tibia (Case Rep Orthop 2018;2018:3656913)
Treatment
- Typically, adamantinomas are treated surgically with wide local resection; intralesional or marginal excision carries an increased risk of local recurrence (J Surg Oncol 2020;122:273)
- Long term follow up is necessary due to the possibility of late complications
Gross description
- Most often the tumor is yellow-gray or grayish white and fleshy or firm in consistency (Diagn Pathol 2008;3:8)
- Occasionally, tumors show macroscopic cysts containing a straw colored or blood-like fluid on gross examination (Cancer 1974;34:1796)
Gross images
Contributed by Mark R. Wick, M.D.
Tibial lesion
Microscopic (histologic) description
- Biphasic tumor characterized by epithelial and osteofibrous components that may be intermingled with each other in various proportions and differentiating patterns (Diagn Pathol 2008;3:8, J Bone Joint Surg Am 1994;76:1482, J Surg Oncol 2020;122:273)
- Fibrous component may be loose myxoid, hyalinized or sclerotic (Cancer 1989;64:730)
- Mitotic figures are usually infrequent, most reporting 0 - 2 mitoses per 10 high power fields (Cancer 1989;64:730, J Bone Joint Surg Am 1994;76:1482)
- Morphologic variants:
- Classic adamantinoma
- Prominent epithelial component composed of mildly atypical epithelial cells within an osteofibrous dysplasia-like stroma forming conspicuous solid basaloid nests with peripheral palisading or less often, tubular structures, keratinized squamous nests or spindled cell bundles (Am J Surg Pathol 2013;37:710)
- Osteofibrous dysplasia-like adamantinoma
- Characterized by small scattered epithelial clusters highlighted with keratin immunostaining within a prominent osteofibrous dysplasia-like stroma (Head Neck Pathol 2015;9:32)
- Dedifferentiated adamantinoma
- Exhibits sarcomatoid features including mitotically active, highly pleomorphic cells and oftentimes, osteoid and chondroid deposition or clear cell change
- Keratin immunostaining may be negative in sarcomatous areas (Am J Surg Pathol 2013;37:710)
- Classic adamantinoma
Microscopic (histologic) images
Contributed by Borislav A. Alexiev, M.D. and William B. Laskin, M.D.
Fibro-osseous lesion
Trabecular growth pattern
Anastomosing trabeculae of epithelial cells
Epithelial cells
Classic adamantinoma
Osteofibrous dysplasia-like adamantinoma
CK AE1 / AE3 expression
CK19 expression
Cytology description
- Biphasic admixture of epithelioid cells and cells with prominent spindling seen singly and in fragments (Diagn Cytopathol 2010;38:198)
- Epithelioid cells with indistinct cytoplasm, bland round to oval nuclei with finely dispersed chromatic, occasional micronucleoli and well formed nuclear grooves (Diagn Cytopathol 1994;10:347)
- Other population has more elongated nuclei, ample clear cytoplasm and spindled appearance (Diagn Cytopathol 2010;38:198)
Positive stains
- Keratin AE1 / AE3, basal epithelial cell keratins (CK5, CK14 and CK19) (Diagn Pathol 2008;3:8, Pathol Int 2000;50:801)
- Vimentin (Pathol Int 2000;50:801)
- EMA (Virchows Arch 2011;459:41)
- p63 (Virchows Arch 2011;459:109)
- Podoplanin (D2-40) (Virchows Arch 2011;459:41)
Negative stains
Electron microscopy description
- Epithelioid tumor cells possess epithelial ultrastructural features including tonofilaments, hemidesmosomes and desmosomes (Clin Orthop Relat Res 1984:299)
Molecular / cytogenetics description
- KMT2D (MLL2) is recurrently mutated in adamantinomas (Am J Surg Pathol 2019;43:965)
- EPHB4-MARCH10 somatic gene fusion in an adamantinoma, described in a single case (Am J Surg Pathol 2019;43:965)
- Elevated expression of DLK1 gene in adamantinomas, serving as a potential molecular biomarker (Am J Surg Pathol 2019;43:965)
- Recurrent pattern of numerical abnormalities featuring extra copies of chromosomes 7, 8, 12, 19 and 21 has been detected in osteofibrous dysplasia, osteofibrous dysplasia-like and classic adamantinoma, supporting a common histogenesis for all 3 lesions and a tendency for stepwise neoplastic progression (Am J Surg Pathol 2008;32:363, Radiographics 2008;28:1215, J Mol Diagn 2001;3:16)
Sample pathology report
- Left tibia, bone biopsy:
- Adamantinoma, classic variant (see comment)
- Comment: MRI demonstrates a T1 isointense, T2 hyperintense, mildly enhancing lobulated lesion in the left distal tibia, not significantly different in appearance or number from the prior exam. The neoplasm is composed of basaloid cells with eosinophilic cytoplasm arranged in cords and nests. Nuclei are monomorphic, ovoid or round, with minimal atypia. Interspersed between the cells there is abundant fibrous stroma. No mitotic figures are identified (0 mitoses/10 high power fields). The tumor cells are positive for keratin AE1 / AE3 and p63 and negative for CD99, CAM5.2 and ERG. The findings support the above diagnosis. Adamantinomas are considered malignant neoplasms that frequently recur locally and can rarely metastasize.
Differential diagnosis
- Osteofibrous dysplasia:
- Clusters of epithelial cells (keratin positive), as seen in osteofibrous dysplasia-like adamantinoma, are not present (Clin Orthop Relat Res 1992:235, Skeletal Radiol 1992;21:493)
- Metastatic carcinoma:
- Unusual below knee and oftentimes diffuse
- Older patients
- More malignant cytology with vascular invasion
- No osteofibrous dysplasia-like stroma
- Adamantinoma-like Ewing sarcoma:
- Ewing sarcomas may exhibit overt epithelial differentiation in the form of diffuse cytokeratin and p63 expression, resembling adamantinoma of long bone (Am J Surg Pathol 2015;39:1267, Pathol Res Pract 2017;213:422)
- NKX2.2, CD99 and FLI1 expression (Mod Pathol 2016;29:370)
- Specific chromosomal rearrangements, the most common fusions are between the EWSR1 gene on chromosome 22 and the ETS family of transcription factors
- Rarely, FUS (on chromosome 16) substitutes for EWSR1 (J Mol Diagn 2011;13:313)
Additional references
Board review style question #1
The most common gene mutated in adamantinomas is
- KMT2D (MLL2)
- FUS
- SS18
- ZNF444
- FOS
Board review style answer #1
Board review style question #2
A 40 year old man presents with a left tibia mass. Radiography demonstrates a radiolucent lesion in mid / distal shaft with 2 satellite lesions proximally. Hematoxylin eosin stains show a nested and trabecular growth of basaloid and spindle cells with uniform, round to ovoid nuclei and eosinophilic or pale cytoplasm in fibrous background. Occasional mitotic figures are identified (1 mitosis/10 high power fields). Immunohistochemical stains for keratin AE1 / AE3, CK19 and vimentin are positive in tumor cells, while all of the following are negative: CAM5.2, MDM2, CD34, ERG, NKX2.2 and CD99.
Which of the following is most likely the correct diagnosis?
Which of the following is most likely the correct diagnosis?
- Ewing sarcoma
- Low grade central osteosarcoma
- Metastatic carcinoma
- Pseudomyogenic hemangioendothelioma
- Adamantinoma
Board review style answer #2
