Osteochondroma and Multiple Hereditary Exostoses

Osteochondroma is a cartilage-capped bony projection on the external surface of a bone and is considered a non-neoplastic anomaly similar to hamartoma.

It can occur as a  solitary lesion or as multiple hereditary exostoses associated with anomalies of skeletal modeling.

Solitary osteochondroma is a developmental anomaly of bone that results in the formation of an exophytic outgrowth on the surface of the bone. It is composed of a mature bony stalk that is covered by a cartilaginous cap. Other terms applied include osteocartilaginous exostosis and simple exostosis.

Multiple hereditary exostoses is an autosomal dominant hereditary disorder transmitted by both sexes with incomplete penetrance in female patients, which results in a slight male predominance. It is characterized by the presence of multiple osteochondromas associated with bone deformities of the affected.

Multiple hereditary exostosis lesions show significant variability in size, number, and distribution.

Osteochondromas are usually classified as benign bone tumors, but they are not neoplastic in nature. They appear to results from aberrant epiphyseal development with a displacement of physeal cartilage through the perichondrial fibrous ring and subsequent growth at right angles to the long axis of the bone.

Solitary Osteochondroma

Solitary osteochondroma is the most common benign tumor-like lesion accounting for 10% of bone tumors and  35% of benign bone tumors.

They affect males, almost twice as common than females.

It affects the appendicular skeleton mostly on the surface of metaphyseal portions of major long tubular bones. 35% of the cases are seen around the knee followed by proximal femur and humerus.

Among the flat bones, it most commonly is seen in the bones ilium and scapula. They are rare in small tubular bones of the hands and feet, in the ribs, and in the vertebral column

Most of the osteochondromas are not symptomatic but symptoms can occur due to their location and pressure effects.

Though benign, malignant transformation to secondary chondrosarcoma has been in less than one percent patients. Osteochondroma is mostly seen around the knee and proximal humerus, though it can occur in any bone.

Osteochondroma grows until skeletal maturity. The growth generally stops once the growth plates fuse.

Types of Solitary Osteochondroma

Solitary Osteochondroma is of two types

• Pedunculated- the one that has a stalk
• Sessile- the one with a broad base of attachment

Cause and Pathophysiology

Majority of solitary osteochondromas are sporadic lesions that occur de novo but a small number have been reported to develop after external irradiation. These are called secondary osteochondromas and are reported in metaphyseal areas of the vertebral column and pelvis as long as up to 16 years after irradiation.

The exact cause of osteochondroma is not known. It is thought to result from herniation of the peripheral portion of the physis resulting in is an abnormal extension.

Genetic karyotyping has suggested that genetic abnormalities are associated with these benign growths.

With growth, osteochondroma grows away from the growth plate with time because they are essentially isolated growth plates. They are affected by and respond to, various growth factors and hormones in the same manner as epiphyseal growth plates and the growth stops with skeletal maturity.

Gross examination of the osteochondroma shows a lobulated cartilage cap covered by a fibrous membrane that is continuous with the periosteum covering the stalk.

The cartilage cap covers the distal part of a pedunculated osteochondroma. In the case of sessile osteochondroma, the cartilage covers the elevated surface.

The cap usually measures from 2 mm to 1 cm in thickness and shows all of the microscopic features of endochondral ossification.

Osteochondroma grows during childhood and adolescence by endochondral calcification.

The bursa that may form at the periphery of some osteochondroma and is lined by synovium.

It may show inflammatory changes and in some cases, chondroid metaplasia.

Chondroid metaplasia may cause numerous cartilaginous loose bodies. When calcified these may simulate secondary chondrosarcoma on radiographs.

Clinical Presentation

Small osteochondromas may remain unnoticed for a long time. They tend to grow with skeletal growth in the growing years and present as a hard swelling may have increased in the size over a few years.

Other presenting symptoms are a fracture of the osteochondroma or symptoms produced due to the pressure of osteochondromas on adjoining structure like vessel or nerve. A bursa may be present over the cap, which may become inflamed or accumulate synovial fluid or loose bodies, thereby producing symptoms.

Painless hard slow growing swelling is the usual complaint. Pain might occur due to pressure on adjacent tissues like tendon, muscle, or nerve or bursal inflammation or a fracture of the osteochondroma.

A palpable mass is usually the only finding on clinical examination.  Long-standing lesions may lead to angular deformities of the bone or limb-length discrepancies.

Lesions which occur near the joint may cause restriction of motion. In the spine, the osteochondroma may lead to symptoms secondary to cord or root compression.

Differential diagnosis

• Parosteal osteosarcoma [in c/o sessile osteochondroma]
• Juxtacortical myositis
• Periosteal chondroma

Imaging

On radiographs, osteochondromas can be sessile or pedunculated (have a stalk). The lesion typically arises from the metaphysis of a long bone, with a stalk that is continuous with the adjacent cortex and is oriented away from the epiphysis [the nearest joint].

Sessile lesions demonstrate a flat, plateau-like protuberance.

The rest of the bone is typically normal. Often slight localized distortion of the contour at stalk’s base end is visible [compare with changes of growth disturbance ] in multiple hereditary exostoses.

Usually, clinical examination and x-ay are sufficient to diagnose these lesions. In cases of doubt, CT and MRI are excellent imaging modalities.

MRI can help to measure the thickness of the cartilaginous cap but it is often not required.

MRI may be needed in large sessile osteochondromas difficult to distinguish from other cartilage-containing bone surface lesions.

Treatment

Osteochondromas are benign lesions with self-limited growth that ceases after skeletal maturity.

Most of the osteochondromas are left as such as they do not cause any symptoms. This lesion is almost always operated for its complications which include painful lesion, pressure effects, restriction of motion, compression on adjacent structures, deformity of the bone, fracture of osteochondroma, bursitis, and malignancy.

In such cases, complete removal of the lesion is sought. An incomplete removal may lead to recurrence.

Recurrence after surgical excision is rare but may develop when a portion of cartilage cap or attached, perichondrium is left in situ.

Osteochondromas need not routinely be removed especially in skeletally immature individuals when the lesion is in proximity to the physis.

Multiple Hereditary Exostoses

This condition is also known by the names like diaphyseal aclasia and multiple osteochondromas, Bessel-Hagen disease, diaphyseal aclasis, familial exostoses, and multiple osteochondromatosis

Multiple hereditary exostoses is an autosomal dominant hereditary disorder. It has penetrance in female patients, and as a result, there is a slight male predominance.

Mutations in the EXT1 and EXT2 genes cause hereditary multiple osteochondromas. The EXT1 and the EXT2 gene provide instructions for producing the proteins exostosin-1 and exostosin-2, respectively. These proteins form a complex in a cell structure called the Golgi apparatus and are involved in the modification of a protein called heparan sulfate.

However, it is not clear how the lack of this protein contributes to the development of osteochondromas.

When the EXT1 gene is involved, the condition is called hereditary multiple osteochondromas type 1. It accounts for 55 to 75 percent and is more severe of the two.

A mutation in the EXT2 gene causes hereditary multiple osteochondromas type 2.

The condition has been reported in people without any mutation of EXT1 or 2. These account for about 15% of the cases

Clinical Course

In multiple hereditary exostoses, there are multiple osteochondromas associated with bone deformities of the affected bones.

It can cause growth disturbances with shortening of the affected bones and bowing deformities of paired bones are frequently present.

Similar to solitary osteochondroma, multiple hereditary exostoses also have a predilection for the metaphyseal parts of the long tubular bones.

Femur and tibia are commonly affected proximal humerus are the next most common sites. The flat bones, such as the scapula and pelvis, also are frequently involved.

Often the lesions involve extremities symmetrically.

The disorder usually is diagnosed during childhood at an earlier age than is solitary osteochondroma due to the associated deformities and growth disturbances.

There is usually clubbing of long bone ends caused by altered bone remodeling. This results in the loss of the normal metaphyseal-diaphyseal flare and produces a shortened, broadened appearance of the femoral necks and other long bone metaphyses.

The gross and microscopic features are similar to osteochondromas.

Corrective surgery is often necessary to deal with the multiple secondary deformities, growth disturbances, and functional impairment.

Individual symptomatic osteochondromas are treated by surgical removal as in the management of solitary osteochondroma.

Patients need to be monitored for life as there is a  high risk for the development of malignant changes in multiple exostoses.

Malignant Changes In Osteochondroma

Malignant change in osteochondroma almost never occurs in growing age. As such malignant change is not very common but it does occur in adulthood to the incidence of 1 %.  An increase in size and pain in adulthood are common symptoms that should alert one to the possibility of malignant change in the osteochondroma.

The malignancy associated with osteochondromas is most often chondrosarcoma, although malignant fibrous histiocytoma and osteosarcoma have been reported.

High-grade sarcomas develop rarely in multiple hereditary exostoses

Osteochondromas in pelvis, scapula, ribs, spine (Central Lesions)  carry a higher risk of malignant transformation.

The reported risk for solitary osteochondromas is 1- 2%, and  5-25% for multiple osteochondromas. The malignancy that occurs is chondrosarcoma and the age of occurrence is around 30 years about 15 years earlier than de novo chondrosarcoma.

Signs suggestive of malignancy

• A sudden increase in size
• Sudden onset of pain at the site
• Radiographic signs
  • Areas of lucency
  • Calcification in overlying soft tissue mass
  • Destruction of the base or adjacent bone [Definite sign]

Radiographic changes may be difficult to ascertain in large sessile osteochondromas.

Most secondary tumors show the features of grade 1 to 2 chondrosarcoma. High-grade sarcomas may develop in the stalk or base of the lesion and invade adjacent bone and soft tissue.

Treatment is wide excision of the entire lesion with a surrounding rim of normal tissue.