ENCHONDROMATOSIS-OLLIER DISEASE-CASE REPORT

ENCHONDROMATOSIS-OLLIER DISEASE-CASE REPORT

O Adam¹,ES Boia², Ramona Mandrusca³

Childrens Hospital Louis Turcanu-Department of Pediatric Surgery, Timisoara

2University of Medicine and Pharmacy Victor BabesTimisoara

ABSTRACT

Enchondromas are common intraosseous, usually benign cartilaginous tumors, that develop in close proximity to growth plate cartilage. When multiple enchondromas are present, the condition is called enchondromatosis also known as Ollier disease. Clinical manifestation often appear in the first decade of life. Ollier disease is characterized by an asymmetric distribution of cartilage lesions and these can be extremely variable.Clinical problems caused by enchondromas include skeletal deformities, limb-length discrepancy and the potential risk for malignant change to chondrosarcoma. The condition in which multiple enchondromatosis is associated with soft tissue hemangiomas is known as Maffucci syndrome.The diagnosis is based on clinical and conventional radiological evaluations.Histological analysis has a limited role and is mainly used if malignancy is suspected.

Key words:Ollier disease, enchondromatosis, multiple enchondromatosis, dyscondroplasia

Definition

Enchondromas are common benign, usually asymptomatic cartilage tomors, which develop in the metaphyses and may become incorporated into the diaphyses of long tubular bones, in close proximity to growth plate cartilage.

Enchondromatosis or Ollier disease is defined by the presence of multiple enchondromas and characterized by an asymmetric distribution of cartilage lesions that can be extremely variable in terms of size, number, location, evolution of enchondromas, age of onset and of diagnosis, requirment for surgery.

The condition in which multiple enchondromatosis is associated with soft tissue hemangiomas  

known as Maffucci syndrome.

Epidemiology

The estimated prevalence of Ollier disease is 1/100.000.Maffucci disease is even rare.

Solitary endochondromas are most commonly

discovered between 20 and 40 years of age but

Ollier disease tends to present before 10 years old.

Boys are affected twice as often as girls.

Etiology and pathogenesis

Endochondral bone ossification is a highly regulated process, which requires the progression of

Undifferentiated mesenchymal cells into hypertophic chondrocytes and the subsequent replacement of a cartilaginous matrix by mineralized bone.Enchondromas develop n the methaphysis of long tubular bones in close proximity to the growth plate.Consequently, it was

proposed that they result from abnormalities in   signaling pathways controlling the proliferation and

differentiation of chondrocytes, leading to the development of intraosseous cartilaginous foci.

Genetics

Ollier disease and Maffucci syndrome are usually non-familial disorders and both disorders thus appear to occur spontaneously and are not inherited.The irregular distribution of the lesions

in Ollier disease strongly suggest that it is a disor-

der of endochondral bone formation that occurs due

to a post-zygotic somatic mutation that result in mo

saism

Although an identical heterozygous mutation in the PTHR1 gene has been identified other mutations in this gene were identified in additional patients with this disorder.These studies suggest that the cause of

Ollier disease is heterogenous and raise the possibi-

lity that two or more genetic mutations are required to develop the disease.

Additional mutational events may underly progression from enchondromas to tumors.

Histopathology

Macroscopic examination of enchondromas usually

shows multiple oval-shaped or round cartilaginous nodules in osseous portions of bone.The individual

nodules are limited at their periphery by woven or

lamellar bone and are separated from each other by

intertrabecular marrow spaces.

The cartilaginous tumor matrix is usually solid,with

myxoid changes, which manifest as frayings of the matrix.Enchondromas are characterized by the pre-

sence of a striking heterogeneity and diversity in the degree of cellularity and chondrocyte phenoty-

pe.This heterogeneity depends to some extent on factors such as localization and the patients age.

In part, due to this important cellular heterogeneity

the distinction between benign enchondromas and

malignant chondrosarcomas by histochemical cri-

teria is difficult.The histological criteria for malignancy that are used for conventional chondro-

sarcoma can not be used in Ollier disease because of the increased cellularity and therefore the distinction between enchondroma and grade I

chondrosarcoma in the context of enchondroma-

tosis is extremely difficult or even impossible.

Classification

There are six types of enchondromatosis but three are more common:

-In Ollier disease there are multiple enchondromas that are mostly unilateral or une-

venly distributed throughout the metaphases of the long bones , sparing the cranium and spine.

-In Maffucci syndrome the enchondromas occur with multiple cutaneous hemangiomas that

appear as soft tissue calcifications or phleboliths on

x-ray.

-If there is symmetrical involvement through-

out the body including the cranium, hands and feet

it is known as generalised enchondromatosis.

Clinical description

Clinical manifestations in Ollier disease often appear in the first decade of life and usually start

with the appearance of palpable bony masses on a finger or a toe, an asymetric shortening of an extremity with limping,osseous deformities asso-

ciated or not with pathologic fractures.Upon physical examination, enchondromas present

on the extremities are usually visible as masses

embedded within phalanges, metacarpal and me-

tatarsal bones.The masses increase in size as the

child grows along with asymmetrical shortening of a limb and either genu varus or genu valgus deformities. Varus deformity is very common.

Enchondromas frequently affect the long tubular

bones, particularly the tibia, the femur and/or the

fibula;flat bones, especially the pelvis, can also be

affected.The lesions are usually asymetrically dis-

tributed exclusively or predominantly affecting one

side of the body.

Affected bones are often shortened and deformed.

Bone shortening may be the only clinical sign of the disease and these bone shortenings are often associated with bone bending and curving and may lead to limitation in articular movement.

Forearm deformities are frequently encountered and

these are similar to those observed in hereditary multiple exostosis(HME).Ulnar shortening is usually more relevant than shortening of the radius.

The trunc is usually not affected except for rib en-

chondromas and scoliosis resulting from pelvis imbalance.

In childhood, the lesions are subjected to pathologic fractures.

Diagnostic methods

The diagnosis of Ollier disease is based on clinical and conventional radiological evaluations.

Histological analysis has a limited role and is mainly used if malignancy is supected.

Additional investigations such as scintigraphy,

Ultrasound, magnetic resonance imaging(MRI)

are not useful for establishing the diagnosis and they are indicated for the evaluation and survei-

llance of lesions that become symptomatic(pain,

increase in size).

Biopsy of suspicious lesions may be required.

Radiography

Enchondromas are rarely observed at birh,although

The lesions are most likely already present.X-ray

Show multiple, radiolucent, homogenous lesions who run parallel with long bone axis. The lesions usually calcify with time and become diffusely punctated or stippled, a light trabeculation may be

visible.Enchondromas are frequently assembled as

clusters, thus resulting in the metaphyseal wide-

ning.When localized at the bone border, the enchondromas produce a typical notch-like image.

The lesions are almost exclusively localized in the metaphysis of long bones and in the small bones of

the hands and feet. They are initially localized close to growth plate cartilage and then migrate progressively towards the diaphysis.The epiphyseal region next to an affected metaphysis may show irregularities.In the hands, the lesions almost never affect all metacarpal bones and phalanges.

Signs of malignant transformation should be looked for, as it is a major complication of enchondromato-

sis.These signs includes cortical erosion, extension of the tumor into soft tissues and irregularity or indistinctness of the surface of the tumor.

Enchondromas tend to be well circumscribed and to show a uniform pattern of mineralization, whereas chondrosarcomas show poor demarcation and the presence of unmineralized parts.

Differential diagnosis

The differential diagnosis may include:

-Hereditary multiple endochondromatosis-HME

Is an autosomal dominant disorder characterized by multiple bone tumors capped by cartilage, that occur mostly in the metaphyses of long bones.

-Other rare forms of chondromatosis which

include metachondromatosis,spondyloenchondro-

sia and genochondromatosis type I and II

-Polyostotic fibrous dysplasia

-Diaphyseal aclasis

-Kaposi sarcoma

-Klippel-Trenaunay-Weber syndrome

Treatment

There is no medical treatment for Ollier disease.

Surgery is indicated in case of complications-patho-

logical fractures, growth defect, malignant transfor-

mation.

Complications

As well as the problem of asymmetrical growth there can be pathological fracture and malignant change as chondrosarcoma and osteosarcoma.

In Ollier disease about 25% of patients will have had malignant change by the age of 40.

Prognosis

The prognosis for Ollier disease is difficult to assess.As in generally the case, forms with an early

onset appear more severe.Research has shown that patient with numerous lesions may have a better

prognosis than patients with localized cartilaginous changes, which may induce major shortening of a

lower extremity and thus limb asymmetry.

After puberty, the enchondromas typically stabilize as cartilage is replaced by bone.

The reported incidence of malignant trandformation is variable and estimated to occur in 5-50%.

Case report

We present a case of a six year old boy that was admitted in our department four years ago for pain and limping in the right lower extremity.

After an x-ray examination, the diagnosis of bone cyst of the proximal right femur was established.

A biopsy of suspicious lesions was performed and

the histopathological diagnosis was mistakenly established as aneurysmal bone cyst.

As intraoperatory event we report a pathological

fracture of the right femur occured at the lesions level and a intramedually rod was inserted followed

by casting.Postoperative period was uneventful.The images are shown bellow.

The patient was followed up clinicaly and radiolo- gicaly at two months in the next six months and afterwards every one year.The rod was removed

after six months without visible shortening of the right lower limb, but with an persistent mild limping.In the following period, the patient accused minor pain at the lower limb level and also right upper limb and foot pain were associated.

At the age of four, an x-ray of the lower and upper limb and cranium were performed and revealed multiple radiolucent, homogenous lesions with an oval shape and well defined slightly thickened bony margin-enchondromas like-localized at the superior metaphyseal and diaphyseal regions of the right femur , right tibia and at the II, III,IV, V metatarsals regions(see the images bellow).No pathologicals images at the upper limb and at the cranium level were found.

A biopsy of suspicious lesions from the right tibia was performed and the diagnosis was confirmed by the histopathological exams both in our laboratory and in Centre de Pathologie from Montpellier in France.Postoperative period was uneventful.

The follow up was continued .Two years later,in 24.04.2009, the patient was admitted in our department with a pathological fracture of the right femur following a minor injury caused by a fall from the same level.An open reduction and nailing were performed and a new biopsy was prelevated, the Ollier disease being confirmed again.

At the present time, the patient is imobilized and monitorized every two months.

Prevention

Despite the universal acceptance that Ollier disease carries a high risk of malignant change the litera-

ture data about systematic screening for early diagnosis are very poor. One paper statedWe concluded that periodic surveillance of the brain and abdomen for occult malignant lesions is indicated in patients who have enchondromatosis(12)-but failed to be more specific about the recommended frequency of screening.Another statedIt is associated with an increased risk of malignancy including intracranial chondrosarcomas.Early diagnosis is crucial;screening patients with Ollier disease is recommended.(13)Again there is no guidance as to frequency or technique.It did state that the treatment of choice for intracranial cartilaginous tumors is complete surgical excision, but this is often dificult to achieve.An alternative treatment is proton-beam therapy.

Conclusions

Ollier disease is a extremely rare, non-hereditary skeletal condition.There is no medical treatment for this disease, the only treatment is surgery in case of complications. Most of the enchondromas stabilize after puberty as cartilage is replaced by bone,but around 25% of the cases will suffer malignant transformation by the age of 40.

We recommend clinicaly follow up every year until after puberty, when ossification is completed

and long term follow up until the age of 40, every one or two years for early diagnosis of malignant change.

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