Keywords
bone neoplasms/pathology - child - enchondromas - exostoses, multiple hereditary -
osteochondromas
Introduction
Osteochondromas are the most common benign cartilaginous tumor. Osteochondromas are
typically metaphyseal tumors of the long bones (proximal humerus, tibia, and distal
femur). They usually grow as pedunculated or sessile lesions composed of cortical
tissue and with medullary bone tissue covered by a cartilaginous cap.[1]
Enchondromas are the second most common benign cartilaginous tumor after osteochondroma.
They are commonly found within the medullary cavity of the bones of the appendicular
skeleton (more frequent in the hands than in the feet, particularly in the phalanges)
and they are characterized by the formation of mature hyaline cartilage in the medullar
cavity.[2]
Metachondromatosis is a rare autosomal dominant genetic disease with incomplete penetrance
that involves abnormal function of the PTPN11 gene.[1]
Differentiation between chondrogenic tumors is a challenge for orthopedists. We report
the case of a patient with metachondromatosis, a disease that shares attributes with
osteochondromas and enchondromas.
Case Report
A 5-year-old girl was referred to our Pediatric Orthopedics Unit asking for evaluation
of multiple osteochondromas. Physical examination revealed multiple painful tumor
compatible with osteochondromas on radiography. Impairment for proximal interphalangeal
(PIP) and distal interphalangeal (DIP) flexion of the fourth finger of the right hand
was evidenced, which correlated with a middle phalanx osteochondroma. Previous history
of skeletal hereditary diseases could not be confirmed. Surgical excision was performed
without complications.
However, an anatomopathological examination showed multiple osseous and cartilaginous
pieces compatible with the outer cap of a benign enchondroma. Eight months later,
she was also operated for a growing and painful osteochondroma in the third left metacarpal
and in the fourth right metacarpal. Paradoxically, in this case, the anatomopathological
examination showed a 2.3 × 2 cm osseous lesion covered with a pearly-white smooth
cap compatible with benign osteochondroma ([Fig. 1]).
Fig. 1 Images of different histological sections stained with hematoxylin-eosin. A) Sample
of the exostotic lesion constituted by a cartilaginous cap with an osteoid central
trabecular matrix, 2.5X. B) The chondral matrix shows mature characteristics with
endochondral ossification, 4X. C) Transition zone between the peripheral cartilaginous
component and trabecular bone resembling a slightly disorganized growth plate, 4X.
D) Chondrocytes are arranged in isogenic groups, larger in the central portion, without
atypia or atypical mitoses, 10X.
Previous radiographies were examined to find out a reason for this unexpected paradox.
What we found was multiple osteochondroma-like lesions with the atypical characteristic
of guiding its growth toward the neighboring joint (epiphysis) instead of moving away
from it. Furthermore, columnar enchondroma-like lesions were clearly visible in the
right distal radius, in the proximal femoral cervix and in the iliac crests ([Figs. 2] and [3]). The patient reported that some other tumor had disappeared or downsized with time.
This case was debated between a multidisciplinary skeletal dysplasia group. The aforementioned
clinical and radiographic findings reinforced the hypothetical diagnosis of metachondromatosis.
Fig. 2 Anteroposterior view of both hands showing multiple osteochondroma-like lesions with
the atypical characteristic of guiding their growth toward the neighboring joint (epyphisis)
instead of moving away from it.
Fig. 3 Anteroposterior view of the pelvis. In metachondromatosis, enchondromas distribute
mainly around the iliac crest and metaphyseal regions of the long bones.
After 8 years of follow-up, the patient is 13 years old, and new lesions in the right
ankle, the hip, and the middle phalanx or the fourth left finger have grown, while
others have regressed. However, she is asymptomatic, and she leads a normal life.
Discussion
Metachondromatosis combines multiple metaphyseal juxtaepiphyseal exostoses, metaphyseal
enchondromas, periarticular calcifications, and frequent unilateral or bilateral Legg-Calvé-Perthes-like
changes in the femoral head resembling osteonecrosis.[3]
[4]
[5]
Classification: Metachondromatosis is a subtype of enchondromatosis without spinal
affection, autosomal dominant transmission and osteochondroma-like lesions.[6]
Etiology: Metachondromatosis is related with genetic abnormalities. Fisher et al.
found 31 cases published.[1] Mutation of the PTPN11 gene (protein tyrosine phosphatase nonreceptor type 11) and lack of production of
the tyrosine phosphatase SHP2 is related with the pathogenesis of metachondromatosis,
as well as of other developmental diseases (Noonan syndrome, Noonan syndrome with
multiple lentigines) and malignant diseases (juvenile myelomonocytic leukemia).[7] Mutation of the PTPN11 gene is inherited in an autosomal dominant pattern with incomplete penetrance and
parents must be advised of it. Unlike enchondromatosis, EXT-1 and EXT-2 mutation (exostosin
protein) is not observed in metachondromatosis.[1]
[7]
The definitive diagnosis of metachondromatosis requires a combination of clinical,
radiographical, and histopathological findings ([Table 1]).[8]
Table 1
|
Enchondromas
|
Osteochondromas
|
Metacondromatosis
|
|
Frequency
|
10% of benign osseous tumors.[8]
The prevalence of Ollier disease is 1/100,000.[1]
|
20–50% of all benign bone tumors and 10–15% of all bone tumors.[7]
The prevalence of multiple osteochondromas is estimated to be 2/100,000.[1]
|
< 1/1,000,000, < 30 cases described.[2]
|
|
Location
|
Frequently found in the hands more than in the foot and ankle bones, particularly
in the phalanges.[1]
|
Proximal humerus, tibia, and distal femur.[1]
|
Enchondroma-like lesions: Metaphyseal regions of the long bones and iliac crest
Osteochondroma-like lesions are mainly distributed in the hands and feet.[6]
|
|
Genetics
|
Does not follow a clear Mendelian transmission pattern
|
HMO is an autosomal dominant inherited trait.[7]
EXT-1 and EXT-2 mutation (exostosin protein; endoplasmic reticulum transmembrane glycosyltransferase
necessary for the heparan sulfate synthesis and physeal growth)
|
Autosomal dominant PTPN11 gene mutation, lack of tyrosine phosphatase SHP2
|
|
Radiology
|
Formation of hyaline cartilage in the medulla of a bone.[2]
Well-defined, expansile, lytic lesions with varying degrees of stippled or punctate
calcifications in the diaphysis or metaphyseal-diaphyseal regions of the bone.[1]
|
Cartilage pedunculated or sessile lumps outside the metaphyseal region of the long
bones.[2]
|
Epiphyseal-pointing osteochondroma-like lesions combined with calcified enchondroma-like
lesions ([Figs. 1] and [2]). They can spontaneously regress.[3]
|
|
Anatomopathological examination
|
On gross visual inspection, an enchondroma will appear as a bluish, semitranslucent,
hyaline cartilage with a distinctly lobular arrangement. These lobules will vary from
a few millimeters to a few centimeters in diameter.
Cytologically, an enchondroma will appear as small chondrocytes that lie in the lacunar
spaces, with a small, round, regular nucleus, and no significant atypia. No mitoses
will be seen. Occasional binucleate cells will be seen.
Some enchondromas can contain foci of ossification within this cartilage[1]
|
Bony lesion covered with a pearly-white smooth cap
|
42% as osteochondromas, 33% as enchondromas, 17% combined.[1]
|
|
Natural history
|
New lesions do not appear after skeletal maturation
|
New lesions do not appear after skeletal maturation
|
New lesions do not appear after skeletal maturation
|
|
Malignization
|
5% in solitary enchondromas, >20% multiple enchondromatosis.[1]
|
Between 0.4% and 2% in patients with solitary osteochondroma and between 1 and 4%
in patients with HMO.[7]
|
No malignization
|
Clinical findings: The combination of multiple enchondromas and osteochondromas raises
suspicion of metachondromatosis.[3]
[4] Metachondromatosis has characteristically epiphyseal-pointing osteochondroma-like
lesions that can spontaneously regress, in contrast with conventional osteochondromas.[3]
[4]
Radiographical findings: In metachondromatosis, enchondromas distribute mainly around
the iliac crest and the metaphyseal regions of the long bones ([Fig. 3]). In contrast, osteochondroma-like lesions are mainly distributed in the hands and
feet ([Fig. 2]).[6] In our case, we saw that these lesions can distribute in both the axial skeleton
(pelvis, spine, scapula, and hip) and the appendicular skeleton (hands and feet).
The hands were the most frequently affected locations in our case, which is in line
with Fisher et al.[1] Metachondromatosis is not related with shortening and deformity of the long bones,
a common feature of hereditary multiple exostosis.[4] As with osteochondromatosis and enchondromatosis, new lesions do not appear after
skeletal maturation.[1]
Histopathological findings: Histopathological examination reported first multiple
osseous and cartilaginous pieces compatible with the outer cap of a benign enchondroma
and, second, a bony lesion covered with a pearly-white smooth cap compatible with
benign osteochondroma ([Fig. 1]). However, sample size and location might determine a different diagnosis from the
pathologist because they are difficult to differentiate. The histopathological analysis
described by our pathologists is comparable to others that have been published.[1] After a review of the current literature on metachondromatosis, Fisher et al. found
that 12 biopsies were studied; 42% (5/12) of the biopsies were diagnosed as osteochondromas,
33% (4/12) as enchondromas, and 17% (3/12) had multiple biopsies, some diagnosed as
osteochondromas while some as enchondromas, as in our case.[1]
Treatment
Conservative treatment is the treatment of choice, because of the regressive potential
and the near absence of malignization.[2]
[5] Metachondromatosis is an autosomal dominant disorder, so genetic advice must be
given to patients. We recommend periodical monitoring of the lesions.
Surgical treatment is reserved for painful lesions: neurovascular compression (for
example, equinus secondary to nervus fibularis communis compression in the peroneal
head) and avascular necrosis of the femoral head.[1]
[4]
[5]
Differential diagnosis between enchondromas, osteochondromas and metachondromatosis
is vital due to differences in malignization and natural history. When a patient has
multiple enchondromas and osteochondromas with regression of some lesions and osteochondroma-like
lesions with atypical radiographical characteristics pointing toward the epiphysis,
metachondromatosis, a rare disease, must be considered. Risk of malignization is insignificant
and genetic advice must be given due it is an autosomal dominant disease.
