Recurrent Chondromas: Causes And Management Strategies

Introduction

Chondromas are a relatively rare type of benign (non-cancerous) tumour. They are formed by the abnormal growth and division of cells to form a mass called a neoplasm, and in chondromas, they are specifically formed from cartilage cells.

They are most often located on the inside (enchondroma) or outside (osteochondroma) of the bones, particularly the phalanges, which are the small bones making up the fingers and toes. Additionally, they can be located in the surrounding soft tissue (soft part chondroma) or blood vessel membrane (periosteal chondroma) of the bones, though this is less common. Although chondromas tend to have limited growth potential, there is a small risk of malignant transformation, meaning the tumour can spread and become cancerous, forming a chondrosarcoma.¹

Significance of recurrent chondromas

Although surgical removal of the tumour tends to treat chondromas, in around 10% of cases residual tumour can cause recurrence.² The impact of chondromas can therefore increase, meaning that they are more likely to develop malignancy and cause harm. Additionally, when chondromas occur as multiple lesions, where there are multiple tumours near each other, this can also increase their risk of becoming cancerous. Once in their malignant state (chondrosarcoma), recurrence is even more likely.³

For example, grade 1 chondrosarcomas, which are the least rapidly dividing form of a cancerous tumour, have been linked with a 13% local recurrence following treatment. Of these 13%, around 30% of cases end up spreading to other parts of the body (metastasis), resulting in more serious disease, which is not seen in benign chondroma types.³

Types and characteristics

Enchondroma

Enchondromas are the benign type of chondroma and are typically known by their location on the inner side of the bone, within the marrow cavity. Due to their inward location and slow growth, they are most often found incidentally during X-ray examinations and rarely develop beyond 5cm.⁴

Although typically asymptomatic, signs and symptoms can vary depending on their location. 50% of enchondromas involve the phalanges of the hand and feet.⁵ In this instance, the tumours can cause thinning of the cortex, the outermost layer of the bone, allowing an easier fracture of the bone. Enchondromas can also often be found on the upper arm (proximal humerus) or on the hips (proximal femur) but are rarely located in the ribs and vertebrae (spine).⁴ In fact, if a chondroma is found in these areas, it is more likely to be a low-grade chondrosarcoma.

Enchondromas are typically found on their own, but in some cases, there can be multiple in one area. This is known as Ollier’s disease, and when coupled with soft tissue hemangiomas, benign tumours involving the abnormal growth of blood vessels in soft tissues, it can also result in Maffucci syndrome, which may present additional risks.⁶

Osteochondroma

Osteochondromas are known as the most common type of benign bone tumour, accounting for around 40% of cases.⁷ They are mainly characterised by their formation on the outside of the bone, displayed as an outgrowth that is attached to the bone either with a broad base (sessile) or a narrow base that hangs like a stalk (pedunculated). Therefore, unlike enchondromas, they tend to be located on the ends of the long bones, such as the thigh bone (distal femur), or lower leg bone (proximal tibia).⁷

They are speculated to occur as cartilage cells are displaced from their normal location in the bone, resulting in the growth plate pushing through the outer layer of the bone at an abnormal angle. Such defects may occur due to a childhood injury of the growth plate or even radiation exposure.⁸ When bone growth stops in adulthood, these tumours also cease to develop unless they develop malignancy which only occurs in less than 1% of cases.⁷ Therefore, these tumours are most often found in 10-30-year-old individuals, most often during or after the skeletal growth period has settled.⁷

When multiple osteochondromas are present, this may be a sign of multiple hereditary exostoses (HME), which is a rare genetic disorder. HME increases the chances of malignant transformation by around 9%.⁷

Chondrosarcoma

Chondrosarcomas are the most dangerous type of chondroma as they display malignancy, meaning they are cancerous and can grow and spread throughout the body. This type of tumour accounts for 20% of malignant bone tumours.⁹ Additionally, within this category, 85-90% are primary chondrosarcomas, meaning that they randomly arise on normal bone, whereas 10% arise from pre-existing bone conditions, such as enchondromas, osteochondromas or Ollier’s and Maffucci’s.¹⁰

Chondrosarcomas mainly impact the long bones, including the arms and legs, as well as the ribs and pelvis. Unlike benign chondromas, chondrosarcomas are more common at later stages in life, between 50-70 years old.¹¹ Chondrosarcomas have varying biological behaviours depending on their malignancy ‘grade’. This refers to the level of abnormality of the tumour cells in comparison with the normal cells. Grade 1 chondrosarcomas grow slowly, whilst grade 2 and 3 chondrosarcomas grow locally in an aggressive manner.¹¹ The higher the grade, the more likely the tumour is to spread and cause debilitating effects for the patient.

Causes

Genetic factors

Although the precise cause for the occurrence of chondromas is still unclear, the isocitrate dehydrogenase genes IDH1 and IDH2 have been most associated with chondroma cases in the last decade. A study by Amary and his fellow researchers discovered that around 56% of cartilaginous tumour samples consisted of a mutation in either IDH1 or IDH2. The prevalence of this gene was also significantly higher in tumours of the hand and feet (90%) as opposed to the long and flat bones (~50%).¹²

Additionally, there have been some associations of osteochondromas with mutations in the tumour suppressor exostine (EXT) gene. Multiple hereditary exostoses (HME), the disorder in which several osteochondromas are present, is linked with the heterozygous loss-of-function mutations in the EXT-1 and EXT-2 genes in 90% of cases.¹³ This means that the HME-affected individual has inherited a malfunction of these genes from one of the two copies of the inherited version of that gene from their parents.

Environmental factors

Some, but not all, types of chondromas can arise due to certain environmental factors throughout bone development. In particular, the onset of osteochondromas has been associated with radiation exposure. Additionally, bone injuries during childhood can affect how the bone’s growth plate matures.

Clinical presentation and diagnosis

Signs and symptoms

Chondromas are most commonly asymptomatic, especially those located within the bone (enchondromas). Therefore, enchondromas are usually detected by chance during an X-ray for an alternative problem. In some cases, enchondromas may present with pain or be detected due to a fracture.

Osteochondromas are also largely asymptomatic, and if they do present with symptoms, this tends to be a painless bump on the affected bone. It is also possible that the tumour can get in the way of other structures of the body, putting pressure on a nerve and therefore reducing blood flow, resulting in a numbing and tingling sensation.⁷

Other types of chondromas may present more obvious symptoms. For example, chondrosarcomas can cause expansion of the tumour into the soft tissue, which typically manifests into aching pains along with swelling.¹⁴ Symptom severity increases based on the grade of chondrosarcoma.

Diagnostic imaging

For the diagnosis of bone tumours, images from the inside of the body are usually obtained via X-ray (2-D images), CT scans (3-D images) or MRI scans (using magnets and radio waves). Simply put, chondromas tend to appear as a distinct abnormal area on the inner or outer surface of the bone, containing small calcium deposits that appear as tiny dots or specks (punctate calcifications).¹⁵

Enchondromas usually don't show thickening or damage of the outer bone layer (cortical thickening or destruction), changes in the covering around the bone (periosteal reaction), or any abnormal soft-tissue growth. Chondrosarcomas, on the other hand, do tend to display these features. Osteochondromas are most often identified by a certain ‘cortical medullary continuity’, which means that the outer layer of the bone expands into the outer layer of the osteochondroma.¹⁶

It is sometimes difficult to differentiate between enchondromas and low-grade chondrosarcomas due to their visual similarities. It is therefore important to assess chondromas through multiple diagnostic imaging studies and histological assessments.

Biopsy and histopathology

The histologic assessment of chondromas refers to the visual differences of the tumours under a microscope, which vary largely depending on the type and grade of chondroma. This is done following a biopsy of the tumour, which can then be studied under a microscope.

Enchondromas tend to form lobes, and the cells are contained within small spaces called lacunae. These cells are spread out and separated by a material called matrix. In enchondromas, the cells look relatively similar, with little variation in their appearance, and there are no signs of rapid cell division (mitotic figures).¹⁷

A key way to differentiate between chondrosarcomas and enchondromas under a microscope is by looking for trapped pre-existing bone structures within the chondrosarcoma tumour, which is a clinical feature of malignancy. Chondrosarcomas can then be graded based on how abnormal their cells look under the microscope¹⁴:

• Grade 1 – these chondrosarcomas have few abnormal cells, and the cells look relatively similar in shape
• Grade 2 – the number of abnormal cells increases, and they appear larger and more varied in shape
• Grade 3 – the are many abnormal cells that look very different to normal. The cartilage matrix becomes sparse, and the cells may look like spindles. There is also evidence of rapid cell division via the presence of mitotic figures

Management strategies

Non-surgical interventions

In the majority of benign chondroma cases, treatment is often unnecessary as there are little to no symptoms. However, some patients may opt for treatment for cosmetic reasons or if the tumour is affecting nearby nerves, tendons, or blood vessels, leading to pain and numbness. Aside from these cases, it's essential to keep a close watch on the tumour for any changes that could indicate its progression. Regular observation and monitoring help ensure early detection and appropriate action if the chondroma shows any signs of evolving.

Surgical interventions

Surgery is the main treatment for most chondroma types and can range from simple excision (removal of the tumour) to full amputations (loss of a more extensive part of the body). Enchondromas, particularly those of the phalanges, are normally treated by simple excision via curettage, which involves the removal of the tumour along with a small portion of surrounding healthy tissue.¹⁸

In more serious cases, particularly in the case of chondrosarcomas, patients receive treatment to save the limb by completing a larger tumour removal called a wide en bloc or radical resection, in which the tumour is removed as well as some of the surrounding area. If the tumour is significantly large, it may require amputation. The affected area is then usually filled via autologous bone grafting, which involves inserting a piece of healthy bone obtained from somewhere else in the patient’s body to promote healing.¹⁹

Chemotherapy and radiation are not very effective for chondrosarcomas and so are rarely the best treatment option.

Prevention and lifestyle

There is no clear evidence on how to prevent the onset of chondromas. However, prevention of chondroma recurrence is mainly attributed to the inclusion of significant margins of healthy surrounding tissue during surgical removal of tumours to ensure there is no residue. Additionally, performing diagnostic imaging of any affected areas can ensure the discovery of chondromas as soon as possible.

Summary

Chondromas are rare non-cancerous tumours that happen because of the abnormal growth of cartilage tissue, either on the inside or outside of bones, and are usually harmless. Occasionally, especially when there are multiple or recurrent chondromas, they can become cancerous and form chondrosarcomas, which are more highly symptomatic. Surgery is usually the most effective way of treating most chondroma types. Although there are some specific gene mutations linked with chondromas, including IDH and EXT genes, there is still little known on how chondromas are caused.