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Clinicopathological Features,
Diagnosis, and Treatment of
Adamantinoma of the Long Bones
PANAYIOTIS J. PAPAGELOPOULOS, MD, DSC; ANDREAS F. MAVROGENIS, MD; EVANTHIA C. GALANIS, MD;
OLGA D. SAVVIDOU, MD; CARRIE Y. INWARDS; FRANKLIN H. SIM, MD
educational objectives
As a result of reading this article, physicians should be able to:
EPIDEMIOLOGICAL DATA
1. Describe the radiographic characteristics of adamantinoma of the long
bones.
Adamantinoma of the long bones is a
rare tumor that accounts for 0.3%-1% of all
2. List the histological patterns and radiographic characteristics commonly
associated with adamantinoma.
3. Discuss treatment options for adamantinoma of the long bones.
4. Discuss the prognosis of patients with adamantinoma.
A
damantinoma of the long bones
is a low-grade, slow-growing,
primary malignant bone tumor composed of epithelial cells in a
fibrous or osteofibrous stroma.1,2 It has
a wide range of histological patterns.3-18
Despite the considerable range of each
histologic pattern, most current studies
have shown that long bone adamantinoma appears to be of an epithelial nature.
The tibial lesion’s name comes from its
somewhat similar histologic appearance to the more common odontogenic
adamantinoma of the jaw bones.18,19 Despite the histological similarities there is
no proof that these tumors have a similar histiogenetic origin.19
Long bone adamantinomas can be
divided in two main groups with distinct histological and radiographic fea-
MARCH 2007 | Volume 30 • Number 3
tures. The first–classic adamantinoma–is
characterized by an abundance of tumor
cells and a destructive growth pattern.
The second, differentiated adamantinoma, is characterized histologically by
a predominance of an osteofibrous dysplasia-like pattern with a small, inconspicuous component of epithelial tumor
elements.12,18,19 Radiographically, classic
adamantinomas are either intracortical or
associated with complete cortical disruption, intramedullary involvement, and
expansion beyond the periosteum into
adjacent soft tissues, while differentiated
adamantinomas are intracortical and often multicentric lesions.12,19,20
This article discusses the epidemiology, clinicopathological and imaging features, diagnosis, treatment, and prognosis
of adamantinoma of the long bones.
Drs Papagelopoulos and Mavrogenis are from
the First Department of Orthopedic Surgery, Athens University Medical School, Athens, Greece,
Dr Galanis is from the Division of Medical Oncology, Mayo College of Medicine, Rochester,
Minn, Dr Savvidou is from the Department of
Orthopedics, Thriasion General Hospital, Elefsis,
Hellas-Greece, Ms Inwards is from the Division of
Anatomic Pathology, Mayo College of Medicine,
Rochester, Minn, and Dr Sim is from the Department of Orthopedic Surgery, Mayo College of
Medicine, Rochester, Minn.
Drs Papagelopoulos, Mavrogenis, Galanis,
Savvidou, and Sim and Ms Inwards have no industry relationship to declare.
The material presented at or in any Vindico
Medical Education continuing education activity
does not necessarily reflect the views and opinions
of Vindico Medical Education or Orthopedics.
Neither Vindico Medical Education or Orthopedics, nor the faculty endorse or recommend any
techniques, commercial products, or manufacturers. The faculty/authors may discuss the use of
materials and/or products that have not yet been
approved by the US Food and Drug Administration. All readers and continuing education participants should verify all information before treating patients or utilizing any product.
Correspondence should be addressed to:
Panayiotis J. Papagelopoulos, MD, DSc, Athens University Medical School, 4 Christovassili
Street, Neo Psychikon, 15451, Athens, Greece.
211
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2
Figure 2: CT scan of the right leg shows a lytic
expansile lesion within the tibia. There is intramedullary involvement with some calcifications and
thinning of the cortex, particularly posteriorly.
CLINICAL MANIFESTATIONS
1A
1B
Figure 1: AP (A) and lateral (B) plain radiographs
show an expansile mixed lytic and sclerotic lesion of
the mid-portion of the right tibia.
malignant bone tumors.4-9,21 In 1986, Moon
and Mori2 performed a meta-analysis of 200
cases. In 1996, Unni18 reported 36 cases in
an analysis of 5641 primary malignant bone
tumors from a single institution.
The literature suggests a slight male predominance.1,2,4-9,21 Adamantinomas usually
are diagnosed after skeletal maturity. Although 75% of the cases occur between the
second and third decades of life,18 adamantinomas have also been reported in older
patients, as well as in children aged ⬍14
years.18,22,23 Differentiated adamantinomas
tend to occur in younger patients.18,19
More than 90% of adamantinomas appear in the tibia, with fibular involvement
coexisting in 50% of the cases.12,18,19 The
tumor usually is located in the diaphysis
and, less frequently, the tibial metaphysis. Rare cases of adamantinomas of the
olecranon, the ribs, the radius, the spine,
the metatarsus, and the humerus also have
been reported.24-31
212
A history of previous trauma or fracture occurring months or years prior to
the onset of symptoms is reported in approximately 60% of patients. The most
common presentation is of a gradually
evolving mass associated with dull, insidious, aching pain. Bowing deformity
of the tibia and pathologic fractures may
occur. Advanced or recurrent lesions
may be associated with soft-tissue involvement.12,18,21 Severe paraneoplastic,
humorally mediated hypercalcaemia, hypercalcaemic coma, and pancreatitis have
been reported.32-35
tiple lucencies and sclerotic foci characterizes differentiated adamantinoma. These
imaging features may be similar to those
observed in osteofibrous dysplasia.12,18,20
Technetium pyrophosphate bone scan
shows intense increased uptake tracer accumulation, corresponding closely to the
extent of the lesion.18,21,36 In addition,
bone scan may show a coexisting fibular
involvement.
Computed tomography reveals an
osteolytic lesion with expansion and destruction of the cortex (Figure 2), and
probable extension to the surrounding
soft tissues.21,37 Magnetic resonance imaging (MRI) is useful in providing information concerning the intramedullary and
soft-tissue extent of the tumor.9,20,36-38 On
T1-weighted MRI, the lesion has a low
intensity signal, whereas on T2-weighted
MRI the signal is much brighter and does
not diminish with the fat suppression
technique.
Two morphologic patterns
were distinguished in MRI: a
solitary, lobulated focus versus
a pattern of multiple small
modules in one or more foci.
IMAGING FEATURES
Radiographically, adamantinoma usually appears as a mixed lytic and sclerotic
central lesion or multiple, sharply circumscribed lucencies with sclerosis of the
intervening bone (Figure 1). This slowly
growing, expansile tumor eventually
causes endosteal scalloping and thinning,
interruption, or destruction of the cortex
without periosteal reaction. Moderate to
severe anterior bowing deformity is common.19,20 Classical adamantinoma usually
is intracortical with evidence of complete
cortical disruption and intramedullary and
soft-tissue involvement. Involvement of the
anterolateral cortex of the tibia with mul-
In a study of 22 patients, two morphologic patterns were distinguished in
MRI: a solitary, lobulated focus versus a
pattern of multiple small modules in one
or more foci; however, these characteristics were not related to the histologic
subtype.38
HISTOLOGIC FEATURES
Histologically, adamantinoma is composed of epithelial islands in a spindle cell
stroma. The relative amounts of the two
components can vary considerably (Figure
3). Several histologic variants have been
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ADAMANTINOMA OF THE LONG BONES | PAPAGELOPOULOS ET AL
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ARTICLE
3A
3B
Figure 3: Histological appearance of adamantinoma. Low-power view (A) shows islands of epithelial
cells surrounded by fibrous tissue and high-power
view (B) of the cluster of epithelial cells within the
fibrous stroma.
described corresponding to a variety of different epithelial cell patterns that can be
found. Therefore, this range of morphologic
patterns can mimic many primary or metastatic bone lesions.21,39 A number of immunohistochemical and electron microscopic
studies have shown adamantinoma to be of
epithelial derivation.1,9-11,36,40-44 In some tumors the stromal component has a fibrous
dysplsia-like appearance with or without
scattered spicules of woven bone.18,19
DIFFERENTIAL DIAGNOSIS
Because of its rarity and differing histological patterns, adamantinoma histologically may resemble epithelial metastasis,
hemangioendothelioma,
hemangiosarcoma, fibrous and osteofibrous dysplasia,
nonossifying fibromas, and chondromyxoid fibromas.18,19,44-47 Clinical information
such as patient age and history, as well as
the location in the tibial diaphysis, may
aid in diagnosis.
It is important to differentiate adamantinoma from osteofibrous dysplasia.20
MARCH 2007 | Volume 30 • Number 3
Adamantinoma generally is painful, is
observed during adulthood, has different
radiographic features, is progressive during adult age, and may expand into the
soft tissues. However, osteofibrous dysplasia seldom progresses during childhood, and any progression of the lesion
stops after puberty. Exceptional cases
have been reported of adamantinoma that
began during childhood and have radiographic features similar to osteofibrous
dysplasia.45-47
Adamantinoma must be suspected if
a tibial lesion becomes painful or if it
grows after puberty. In such cases, extensive biopsy from the most radiolucent areas is recommended. However, given the
heterogeneity of the histology within different areas of adamantinomas, sampling
errors are possible with limited biopsy
specimens. These errors have led to reclassification of these tumors from osteofibrous dysplasia to adamantinoma after
repeat biopsy with adequate tissue.45-47
TREATMENT AND PROGNOSIS
Owing to the rarity of adamantinomas, data is insufficient concerning the
safest and most effective treatment modality. These tumors are of low-grade
malignancy and highly radioresistant.48,49
Thus surgery is the treatment of choice.
Although limited experience with them
has been reported, chemotherapy and radiation therapy have not been shown to
be effective.8
Operative treatment includes either
surgical resection with wide margins
and reconstruction of the segmental defect,4,5,8,9,12,18,21,50-52 or amputation.1,2,5,9
Limb reconstruction options include the
use of allografts (intercalary, osteoarticular, or morselized), vascularized and nonvascularized fibular autografts, metallic
segmental implants, and distraction osteogenesis.9,21,51,53 Intercalary reconstruction
appears to be the most successful method
(Figure 4). Qureshi et al9 reported a limb
salvage rate of 84%. They used allografts
in 61% of the reconstructions after resec-
4A
4B
Figure 4: AP (A) and lateral (B) plain radiographs
after wide resection of the tumor and reconstruction using a 13 cm intercalary tibial allograft fixed
using a DCP plate and screws and autologous iliac
bone grafting at the host bone allograft junction.
tion of adamantinomas of long bones. The
majority were intercalary reconstructions.
No differences in the efficacy of different
fixation techniques were noted. Complications related to the reconstruction were
unacceptably high (48% of patients), including nonunion (24%) and fracture of the
allograft (23%). Vascularized fibular grafts
have been considered the best type of graft
for large segmental bone defects after bone
tumor resections.54,55
Local recurrence is common in inadequately treated patients.12,21,56,57 Wide
operative margins are associated with a
lower rate of local recurrence than marginal or intralesional margins.8,9,24 However, a 18.6% rate of local recurrence at
213
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ARTICLE
10 years has been reported after widemargin surgical excision of adamantinomas.9 Local recurrences usually occur 5
to 15 years after primary excision of the
tumor. Late local recurrences have been
reported at 24 and 36 years after diagnosis.21,56 No statistically significant difference between local recurrence rate and
tumor stage, duration of symptoms, patient gender and age, type of biopsy, and
type of grafting has been documented.9,12
Wide resection is also indicated for recurrent tumors.56
The near-benign biology and slowgrowing nature of adamantinoma are reflected in the good survival rates even after local recurrences and lung or regional
lymph node metastases.21,39,51 Late metastases may occur in 10%-30% of patients
with adamantinomas, most frequently in
the lungs, the regional lymph nodes, or the
bones.19,21,24,32-35 After wide margin surgical excision of the tumor or amputation,
overall 10-year survival rates vary from
82% to 87%.1,2,8,12
CONCLUSION
Adamantinoma of the long bones is a
rare, primary, low-grade, slow-growing
malignant bone tumor. It is expressed
with a wide range of histological patterns. Histologically, the tumor is composed of an epithelial component surrounded by a fibrous stroma that may or
may not contain spicules of woven bone.
In the majority of cases, adamantinomas
are located in the tibial diaphysis. Limb
salvage with wide surgical resection and
reconstruction or amputation is the most
effective treatment. Local recurrence is
associated with incomplete resection.
Survival rates range from 82% to 87%.
Late metastases, mainly to the lungs,
may occur.
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215
cme
QUIZ
Adamantinoma of the Long Bones
1.
Instructions
A. Adamantinomas of the long bones are rare tumors accounting for 0.3%-1.0% of all malignant bone tumors.
B. Differentiated adamantinomas tend to occur in younger
patients.
C. The tibial diaphysis is the most common location, with
fibular involvement coexisting in 50% of the cases.
D. All of the above.
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216
Which of the following is false regarding imaging of
adamantinomas of the long bones?
A. Classical adamantinomas usually are intracortical, with
evidence of complete cortical destruction and intramedullary
and soft-tissue involvement.
B. A mixed lytic and sclerotic lesion, periosteal reaction, and
the Codman’s triangle usually are observed.
C. Moderate to severe anterior bowing deformity is common.
D. Differentiated adamantinomas usually involve the anterolateral tibial cortex, with imaging features similar to osteofibrous dysplasia.
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Clinical manifestations of adamantinomas of the long
bones at presentation include:
A. A history of trauma or fracture few months or years prior
to the onset of symptoms in approximately 60% of patients.
B. Dull, aching pain associated with a gradually evolving mass.
C. Regional lymph node involvement or distant metastases.
D. A and B.
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6. Send the completed form, with your $15 payment (check or money order
in US dollars drawn on a US bank, or credit card information) to: ORTHOPEDICS
CME Quiz, PO Box 36, Thorofare, NJ 08086, OR take the quiz on-line. Visit www.
ORTHOSuperSite.com for details.
Which of the following is true regarding epidemiology
of adamantinomas of the long bones?
4.
Which of the following is true regarding
histopathology of adamantinomas of the long bones?
A. Adamantinomas show a wide range of morphologic patterns, with a biphasic (epithelial and mesenchymal) origin.
B. In immunohistochemical studies, epithelial cells express
basal cell type cytokeratins, which are probably the malignant
element of the tumor.
C. Mesenchymal component is composed of a loose stroma
of immature spindle cells producing collagen, resembling
osteofibrous dysplasia.
D. All of the above.
5.
Differential diagnosis of adamantinomas of the long
bones includes:
A.
B.
C.
D.
Fibrous and osteofibrous dysplasia.
Haemangioendothelioma and haemangiosarcoma of bones.
Low-grade chondrosarcoma.
A and B.
ORTHOPEDICS | www.ORTHOSuperSite.com
cme
QUIZ
CME Registration Form
Note: $15 payment must accompany this form.
Questions about CME and ORTHOPEDICS?
Call us at 800-257-8290 or write to:
ORTHOPEDICS, PO Box 36, Thorofare, NJ 08086
MARCH 2007
6.
7.
8.
Which of the following is true regarding biopsy of
suspected tibia lesions for adamantinomas of the
long bones?
Adamantinoma of the Long Bones
Black out the correct answers
1.
A
B
C
D
6.
A
B
C
D
2.
A
B
C
D
7.
A
B
C
D
3.
A
B
C
D
8.
A
B
C
D
4.
A
B
C
D
9.
A
B
C
D
5.
A
B
C
D
10.
A
B
C
D
A. Extensive biopsy is recommended from the most radiolucent areas.
B. Sampling errors are rare, even with limited biopsy specimens.
C. The lesion shows histologic homogeneity.
D. B and C.
Number of hours you spent on this activity_____
Current treatment for adamantinomas of the long
bones includes:
Deadline for mailing: For credit to be received, the envelope
must be postmarked no later than March 31, 2008. If paying by credit card, you may
fax your form to (856) 848-6091.
A. Limb salvage and neo-adjuvant chemotherapy.
B. Limb salvage with wide surgical resection and intercalary
reconstruction, or amputation.
C. Limb salvage and adjuvant radiation.
D. Limb salvage, chemotherapy, and radiation.
PLEASE PRINT
After surgical resection of adamantinomas of the
tibial diaphysis, reconstruction of the bone defect can
be achieved by:
Mailing Address
A.
B.
C.
D.
Intercalary allograft.
Vascularized fibular autograft.
Metallic segmental implant.
All of the above.
(reading article and completing quiz)
Date of Birth: (used for tracking credits ONLY)
Last Name
First Name
City
DEGREE
State
Zip Code
Phone Number
Fax Number
Email Address
EVALUATION (must be completed in order for your CME Quiz to be scored)
9.
Which of the following is false regarding local
recurrences of adamantinomas of the long bones?
A. Local recurrences usually occur 5-15 years after the
primary excision of the tumor.
B. Local recurrence depends on the duration of the clinical
symptoms and the stage of the tumor.
C. Very late local recurrences have been reported.
D. Wide resection is also indicated for the recurrent tumors.
10.
Which of the following is false regarding prognosis of
adamantinomas of the long bones?
A. Late metastases may occur in 10%-30% of the patients.
B. Metastases usually are to the lungs, the regional lymph
nodes, or the bones.
C. The overall 10-year survival rates vary from 82%-87%.
D. Poor survival rates are associated with the occurrence of
local recurrences, regional lymph nodes, and lung metastases.
MARCH 2007
1.
The content of the article was accurately described by the learning
objectives.
Yes
a. Describe the radiographic characteristics of adamantinoma of the long
bones.
_____
b. List the histological patterns and radiographic characteristics commonly associated with adamantinoma.
2.
_____
No
_____
_____
c. Discuss treatment options for adamantinoma of the long bones.
_____
_____
d. Discuss the prognosis of patients with adamantinoma.
_____
_____
This activity will influence how I practice orthopedics.
_____
_____
a. If you answered yes, list one new thing you learned as a result
of this activity___________________________________________________________
3.
The quiz questions were at an appropriate level for assessing
my learning.
4.
Please rate the degree to which the content presented in
this activity was free from commercial bias.
No bias
Significant bias
5
4
3
2
1
_____
_____
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Journal: print
CODE: ORTH-0307
MARCH 2007 | Volume 30 • Number 3
217