Enchondroma

“Chondroma” is the broad, general term for any benign cartilage tumor. Enchondromas are a specific, common type of chondroma, namely one in which the cartilage tumor grows inside the medullary cavity of bones. That is, a chondroma is classified as an enchondroma when it is found centrally in a bone, or as a periosteal chondroma when seen on the surface of a bone. Enchondroma is the far more commonly encountered form. It is the second-most common benign cartilage tumor after osteochondroma. Enchondromas occur commonly in the long bones of the upper and lower extremities and in the tubular bones of the hands and feet but they can be found in the ribs, but rarely in the spine, scapula, and pelvis. In about 1% of cases, enchondromas can transform into chondrosarcoma, usually low grade.

Multiple enchondromas, so-called enchondromatosis can be seen in Ollier Disease or Maffucci Syndrome, both of which as associated with mutations in the IDH1 or IDH2 genes. In patients with these conditions, the risk of malignant transformation to chondrosarcoma is markedly increased. Notably, IDH1 mutations are also found in approximately 40% of solitary enchondromas.

Epidemiology

Enchondromas typically occur as solitary lesions and are usually diagnosed in adulthood. The most common locations for enchondromas are the hands and feet followed by the other long bones, especially in the proximal or distal femur and proximal humerus. Many are found incidentally on imaging studies performed for other diagnoses. Enchondroma is the most common primary bone tumor of the hand.

Clinical Features

Enchondromas have no specific clinical features as they are almost always asymptomatic, and for that reason are typically discovered incidentally.

Enchondromas, one might say, “do not know what bone they are located in”; that is, they expand to the same size whether they originate in a small or large bone. Thus, enchondromas tend to be silent and asymptomatic when they occur in large bones, but when they occur in small bones such as the digits, proximal fibula, or scapula, they can cause cortical thinning and expansion and subsequent mechanical pain.

Enchondromas are not expected to change in size or shape after adulthood, but most will demonstrate increased calcification over time. Enchondromas sit in the medullary portion of a bone and do not actively destroy bone. Chondrosarcomas, on the other hand, do destroy bone and this progressive bone destruction is associated with intra-lesional lysis, endosteal scalloping, cortical thinning and expansion or destruction, and pain. Progressive expansion or intra-lesional lysis of a lesion in a skeletally mature patient should raise the suspicion of underlying chondrosarcoma. Likewise, pain in the area of an enchondroma that is not attributable to pathology within an adjacent joint (e.g., arthritis, rotator cuff disease, etc) should also be suspicious for malignant transformation. Again, malignant transformation of an enchondroma is typically associated with characteristic signs of chondrosarcoma growth in a central bony lesion: intra-lesional lysis, endosteal scalloping, cortical thinning and expansion, and pain, especially at night.

Solitary enchondromas have a reported malignant transformation rate of roughly 1% throughout the patient’s lifetime. A somewhat higher risk is associated with more proximal lesions, while more distal lesions have a lower risk. As such, enchondromas of the hands and feet seldom develop malignant transformation. Enchondromas vary in size, especially in the large, long bones, with some lesions approaching up to 12 cm in length. There is no good data to document different rates of malignant transformation based on the size of the lesion. There is no size beyond which excision should be advised and no agreement on the prophylactic treatment of large lesions to prevent subsequent malignant transformation.

Ollier Disease and Maffucci Syndrome are the two forms of enchondromatosis. Ollier Disease is a non-hereditary condition characterized by the presence of multiple enchondromas with great variability in the number of lesions present. The lesions can occur diffusely throughout the skeleton or may be unilateral. Within a particular bone, the lesions are most commonly metaphyseal. Because of the extent of skeletal involvement and resultant deformity, the disease presents earlier than solitary enchondromas, with most diagnoses made during childhood. Compared to the 1% rate of malignant transformation of solitary enchondromas, patients with Ollier Disease experience a roughly 25% risk that one of their enchondromas will undergo malignant transformation throughout their lifetime. In light of this, the development of multiple separate chondrosarcomas over the life of an individual is occasionally encountered.

Maffucci Syndrome is an unusual disease characterized by the presence of multiple enchondromas in association with multiple soft tissue hemangiomas (angiomatosis). These lesions are usually not present at birth, but become obvious throughout childhood. The hemangiomas most commonly involve the skin and subcutaneous tissue but also involve other viscera. The risk of malignant transformation in patients with this disease approaches 100% over the lifetime of the patient, and they are also at increased risk of developing visceral malignancies.

Radiographic Features

Enchondromas can be seen on plain x-rays, but the degree to which they can be visualized depends on the degree of calcification within the lesion.

Well-calcified enchondromas give the typical appearance of a central intramedullary lobulated lesion with chondroid matrix, frequently described as “popcorn calcification,” “stippled calcification,” or “rings and arcs of calcification” (Figure 1). A sclerotic rim does not surround enchondromas as normal bone does not view them as foreign and so does not react to them. Enchondromas which demonstrate little or no calcification may be difficult to diagnose without a biopsy. As such, enchondromas without calcification often appear as nonspecific marrow-replacing lesions and mimic primary or secondary malignancies within the bone. Because radiographs are dependent on calcification to fully define enchondromas, MRI scans will more precisely visualize the lesion (Figure 2).

Figure 1: AP radiograph of the right proximal humerus, demonstrating an enchondroma with typical benign features including “stippled calcifications”.

Figure 2A-C: Coronal T1 MRI of the left shoulder (A), Coronal STIR of the left distal femur (B), and Axial STIR of the right proximal humerus (C) demonstrating enchondromas. T1 sequences demonstrate that they are marrow-replacing and hypointense. Fluid-sensitive sequences such as T2 and STIR demonstrate hyperintense lesions, with dark dots representing stippled calcification.

There are three radiographic features that suggest malignant degeneration to chondrosarcoma: intra-lesional lysis or lucency, endosteal scalloping, and cortical thinning and expansion (Figure 3).

Figure 3: AP radiograph of the left proximal femur, demonstrating an enchondroma that has developed malignant degeneration. The intralesional lysis, endosteal scalloping, and cortical thinning/expansion can be appreciated in the distal lucent portion of the lesion, which is beside the well-calcified enchondroma at the superior aspect.

The presence of an underlying enchondroma within a chondrosarcoma is not always clear, and occasionally, the underlying benign enchondroma is only diagnosed on pathologic examination of the resected specimen.

All enchondromas “light up” on technetium-99 bone scans, that is, have increased uptake and concentration of the radioactive tracer. As such, this imaging study is less useful for determining whether a lesion is biologically aggressive. Despite this, enchondromas are usually “warm” while chondrosarcomas are usually “hot” on bone scan images.

CT as the best modality for evaluating endosteal erosion, arguably the most important imaging feature distinguishing enchondroma from chondrosarcoma.

Pathology

Enchondromas are composed of chondroid tissue which appears similar to non-neoplastic hyaline cartilage. While the degree of cellularity within these lesions may vary somewhat, these lesions are typically hypocellular (Figure 4). The cartilage usually presents with a lobular appearance with benign-appearing chondrocytes, each with a small crescent-shaped hyperchromatic nucleus. Typically, there is one cell per lacunar space, and these lacunae sit in a normal-appearing uniform chondroid matrix. Greater hyper-cellularity can be associated with enchondromas of the small bones of the hands and feet. In contrast, the same finding in a large bone would raise the suspicion of low-grade chondrosarcoma.

Figure 4: H&E histology slide of an enchondroma, demonstrating the hallmarks of a benign cartilage tumor: hypocellularity, cartilage matrix between cells, cells with a single small nucleus, and one cell per lacuna (Courtesy of Dr. Gord Zhu)

Features such as increased cellularity, plump nuclei, binucleate cells, more than one cell per lacuna and cells outside lacunae are worrisome findings that suggest low-grade malignant transformation. However, these findings, in the presence of normal, high quality chondroid matrix only takes the pathologist to the transition between normal and “low-grade” cartilage. The issue here is that the presence of low-grade cartilage histologically does not necessarily predict aggressive behavior which is actually better predicted by the appearance of radiographic changes. As such, when pathologists find borderline low-grade histologic change in cartilage tumors, they usually refer to these lesions as a “low-grade cartilage tumor” or “atypical cartilaginous tumor” and it is left to the clinician to decide on appropriate treatment or follow-up.

Maffucci Syndrome and Ollier Disease are associated with a mutation in the gene IDH1 and, less commonly, the gene IDH2. These are somatic mutations that occur after fertilization. As such, these diseases occur randomly in patients lacking any family history.

Differential Diagnosis

The major diagnostic question with any central cartilaginous tumor is whether it represents an enchondroma or a chondrosarcoma. In general, enchondromas typically do not harm the bone (except when present in small bones and cause expansion), whereas chondrosarcomas are actively growing lesions associated with local damage.

Another lesion which can be confused with an enchondroma is a bone infarct. Bone infarcts are usually peripherally calcified, as the bone walls off the infarcted area from the surrounding normal marrow. This radiographic finding has been called “Coast of Maine” calcification and in its early stages has a “smoke up the chimney” appearance. MRI and CT scans are useful to demonstrate these findings when this differential diagnosis is being considered.

Disease Course: Treatment and Prognosis

As solitary enchondromas are often incidental findings that do not grow, they typically require no treatment. On the other hand, given the 1% risk of malignant transformation, periodic imaging studies are frequently recommended. Plain x-rays are effective when lesions are visible on the x-ray. MRI scans are more precise but a more expensive imaging modality.

Secondary chondrosarcoma in a pre-existing benign enchondroma is treated with the same treatment protocols used for primary chondrosarcomas. The vast majority of secondary chondrosarcomas are low-grade, being either grade 1 or 2 on a 3 point scale. If a central cartilage tumor demonstrates signs of malignant transformation and a biopsy establishes a diagnosis of grade 1 chondrosarcoma, many surgeons will perform an extended intralesional curettage with bone grafting or cementation of the defect. This intralesional treatment has been found to be adequate for grade 1 chondrosarcomas but is not acceptable for grade 2 or 3 lesions. As for most bone tumors, a biopsy is usually performed prior to definitive treatment.

The multiple lesions in patients with Ollier Disease may significantly impact limb length or cause significant bone deformity. This bone deformity and limb length inequality are the most common indications for surgery in young patients with this disease (Figure 5).

Figure 5: AP radiograph of the right upper extremity of a skeletally-immature child with Ollier Disease demonstrating enchondromas of the proximal humerus and distal ulna.

Treatment of Maffucci Syndrome centers on addressing the specific functional problems or symptoms of the affected individual. Skeletal deformities may require surgical intervention. Symptomatic lesions may require excision. Chondrosarcomas developing in this disease are treated with the standard chondrosarcoma protocols. In light of the high rate of malignant transformation in this disease, monitoring patients with this disease is advisable, although no specific regimen of imaging studies is widely accepted.

Key Test Topics

Benign radiographic characteristics of enchondromas show typical chondroid calcification in a central lesion with no signs of malignancy such as intra-lesional lysis, endosteal scalloping or cortical expansion or destruction.
Remember that enchondromas in small bones will frequently cause cortical thinning and expansion.

Observation is the treatment of choice for asymptomatic enchondromas which have a malignant transformation rate of 1% over the lifetime of the patient.

Enchondroma is the most common primary bone tumor of the hand