Enchondroma are cartilaginous tumors of the benign bone tumor family. The common benign bone tumors include enchondroma, osteochondroma, chondroblastoma, and chondromyxoid fibroma all of which hail from a cartilage origin. Enchondromas are medullary cavity tumors classified in an overarching category of chondromas: benign tumors of hyaline cartilage occurring in bones of endochondral origin.
Enchondromas are the most prevalent of the intraosseous cartilage tumors, accounting for approximately 3% of bone tumors and up to 13% of benign bone tumors.[rx][rx] These tumors are usually solitary, central, metaphyseal lesions of tubular bones, favoring the small bones of the hand and feet followed by the femur and humerus. Enchondromatous tumors typically begin and grow in childhood arising from rests of growth plate cartilage or chondrocytes that proliferate and enlarge, then stop growing but remain present throughout adulthood. Bone sarcomas are rarer than sarcomas of soft tissue. Some benign bone lesions do, however, have malignant potential; enchondromas and osteochondromas can transform into chondrosarcoma.
Types of Enchondroma
| Enneking Classification of Benign Lesions | |||
| Stage | Grade | Examples | |
| Stage 1 | Latent lesions | enchondroma, non-ossifying fibroma | |
| Stage 2 | Active lesions | ABC, UBC, chondromyxoid fibroma, chondroblastoma | |
| Stage 3 | Aggressive lesions | giant cell tumor of bone | |
Pathophysiology
Enchondromatosis possesses associations with somatic mutations in isocitrate dehydrogenase-1 (IDH1) and 2 (IDH2) genes. The mutations are rare and often sporadic. Isocitrate dehydrogenase is an enzymatic component of the tricarboxylic acid (TCA) cycle functioning to convert isocitrate to alpha-ketoglutarate.[rx][rx] Mutations in IDH1 and IDH2 cause malfunction of this enzyme resulting in increased levels of the oncometabolite D-2-hydroxyglutarate (D-2-HG.) D-2-HG competitively inhibits alpha-ketoglutarate dependent enzymes. DNA hypermethylation and histone modification ensue affecting differentiation.[rx] Inhibition of the osteogenic differentiation of mesenchymal stem cells occurs via elevations in D-2-HG resulting from IDH1 and IDH2 mutations. All-in-all, blocking osteogenic differentiation during the formation of the skeleton results in cartilaginous tumor formation.[rx]
Causes of Enchondroma
While the exact cause of enchondroma is not known, it is believed to occur either as an overgrowth of the cartilage that lines the ends of the bones, or as a persistent growth of original, embryonic cartilage
Enchondromas are benign, lobulated neoplasms of hyaline cartilage most commonly occurring in the short tubular bones of the hands and feet. Femur and humerus are the two most common sites for long bone involvement. These tumors can arise in any bone formed from cartilage, and are common, representing approximately 13% of benign bone tumors. Most enchondromas begin in the medullary portion of the diaphysis, arising from ectopic cartilaginous nests in the metaphysical region, and expand outward towards the cortex. Enlarging lesions may cause a pathologic fracture.[rx][rx]
Symptoms of Enchondroma
Individuals with an enchondroma often have no symptoms at all. The following are the most common symptoms of an enchondroma. However, each individual may experience symptoms differently. Symptoms may include
- Pain that may occur at the site of the tumor if the tumor is very large, or if the affected bone has weakened causing a fracture of the affected bone
- Enlargement of the affected finger
- Slow bone growth in the affected area
- Depends on location
- Most long bone enchondromas are asymptomatic and found incidentally
- Phalangeal tumors may be painful due to stress fractures
- when a patient presents with an enchondroma and pain in the adjacent joint, the cause of pain is often unrelated to the tumor
- unlike enchondroma, most chondrosarcomas have non-mechanical pain (rest pain and nocturnal pain)
The symptoms of enchondroma may resemble other medical conditions or problems. Always consult your physician for a diagnosis.
Associated conditions
An enchondroma may occur as an individual tumor or several tumors. The conditions that involve multiple lesions include the following
- Ollier disease (enchondromatosis) – when multiple sites in the body develop the tumors. Ollier disease is very rare.
- Maffucci’s syndrome – a combination of multiple tumors and angiomas (benign tumors made up of blood vessels).
Diagnosis of Enchondroma
Evidence of a lesion on a radiologic study is not definitive enough to make the diagnosis of an enchondroma. Diagnostic confirmation requires histopathologic examination of the specimen sample. Differentiation between benign and malignant lesions poses an even greater challenge. One must examine all available tissue, and even then the diagnosis may remain in question and remain based on clinical evidence and suspicion. Microscopically enchondromas appear as gray-blue, translucent, hypocellular, non-vascular tumors with abundant hyaline cartilage. The nuclei of these cells are fairly regular with few mitotic figures. Juxtacortical chondromas and enchondromas in regions such as the hands, however, may be hypercellular with atypia and still maintain a benign nature.
Conversely, long bone enchondromas often appear benign microscopically but can recur after removal. As with many tumors, staging classifications are used to classify the tumor further. The staging of bone sarcomas follows the tumor, node, metastasis (TNM) guidelines.
Histopathologically, punctate calcifications of the chondroid matrix define the appearance of enchondromas. On examination, the typical enchondroma is smaller than 3 centimeters. The enchondroma is composed of well-circumscribed nodules of benign hyaline cartilage. The nuclei of the chondrocytes are small and uniformly round with condensed chromatin. Rarely, binucleate forms are present. Foci of endochondral ossification may be present in heavily calcified enchondromas. Syndromes characterized by multiple enchondromas, Ollier’s disease and Maffucci syndrome, exhibit more cellularity and atypia than classic, single enchondromas. The increased cellularity and atypia makes distinguishing enchondroma from chondrosarcoma more difficult. Distinctions between benign cartilaginous lesions and atypical cartilaginous tumor/chondrosarcoma grade 1 (ACT/CS1) is difficult. The cartilaginous lesions are typically hypocellular while ACT/CS1 has a hypercellular appearance.
History and Physical
- The symptoms of enchondroma are often nonspecific and found as a result of a pathologic fracture/trauma or localized versus radiating pain. However, many are ultimately found incidentally on radiographic imaging.[rx] Enchondromas may present at any age although the classic presentation is in the second decade of life: 15 to 35 years of age. Enchondromatosis syndromes present earlier in life; typically before age 10.[rx]
- Enchondromas are the most common benign tumor to present in the hand. The classic location of the lesions is in the proximal metaphysis of the proximal phalanx with a predilection for the ulnar side of the bone.[rx]
Evaluation
- Radiographically – enchondromas have varied appearance based on location and extent of calcification, and they may resemble medullary bone infarcts. Enchondromas typically appear as well-defined solitary defects in the metaphysical region of bones. Their appearance depends heavily on the location and extent of calcification of the tumor. Centrally located lesions usually appear as well-circumscribed areas of rarefaction, most frequently diaphyseal, with an expanded cortex around it. Juxtacortical lesions are eccentric and beneath the periosteum in well-defined cortical defects. Small, flocculent foci of calcification are visible within the tumor. Radiographically visible calcifications appear as fine, punctate stipplings, and if pronounced, may suggest a bone infarct. The calcifications can range in size from punctate to rings. Larger lesions can cause endosteal scalloping along with expansion and thinning of the cortex.
- Computed tomography (CT) – is useful for detecting matrix mineralization and cortex integrity while MRI adds insight into the aggressive and destructive features of the tumor. Indicators of potential malignancy include large size, a large unmineralized component, significant thinning of the adjacent cortex, and bone scan activity greater than that of the anterior superior iliac spine (ASIS). Progressive destruction of the chondrite matrix by an expanding, non-mineralized component, an enlarging lesion associated with pain, or an expansile soft tissue mass strongly associated with malignant transformation of an enchondroma.
- Magnetic resonance imaging (MRI) – is an additional modality used for the evaluation of bone lesions. Enchondroma and chondrosarcoma often have a similar appearance on first pass analysis. Both exhibit low signal intensities on T1 with reciprocal high-intensity changes on the T2-weighted images with a lobular growth pattern. Both enhance with gadolinium contrast in peripheral and spatial areas. Neither dynamic contrast-enhanced MRI nor advanced techniques such as diffusion-weighted imaging and hydrogen proton spectroscopy has proved effective in differentiation enchondroma from chondrosarcoma. To differentiate the two, peritumoral edema must be assessed. Although this finding has not undergone prospective examination, case series have revealed consistency. In the case series analysis, no peritumoral edema was noted with enchondromatous lesions while chondrosarcoma lesions showed the edema. Both CT and MRI can easily distinguish bone infarct from enchondroma.[rx]
- Only two known biomarkers– exist that can distinguish enchondroma from chondrosarcoma: periostin and alpha-methyl acyl-CoA racemase (AMACR). Periostin, a stromal-related protein, is reported absent in enchondroma but is present in low-grade chondrosarcoma. AMCR, a mitochondrial and peroxisomal enzyme, is expressed in most enchondromas. Conversely, AMCR is present in a minority of chondrosarcomas.[rx] Further investigation is needed to further validate and confirm these biomarkers as reliably entities.
- Technetium bone scans – are used to determine active bone lesions and to rule out bone metastasis. However, a bone scan may be positive in specific active benign lesions, and it may be falsely negative in multiple myeloma[rx]. However, most of the time a normal bone scan is reassuring.
- Positron emission tomography (PET) – records the whole-body distribution of positron-emitting radioisotopes. In musculoskeletal tumors, PET is useful in staging, biopsy planning, response to chemotherapy, detecting recurrence, and follow-up imaging.
- Ultrasonography – is useful for differentiating solid from cystic bone lesions and better imaging of soft tissue lesions.
- Blood and urine tests – may be helpful in selected clinical situations. The complete blood count may help predict wound healing following surgery and to rule out any infection or leukemia. Erythrocyte sedimentation rate (ESR) may show as elevated in infection, metastatic carcinoma, leukemia, etc. Elevated prostate-specific antigen (PSA) is often present in prostate cancer metastasis. Hypercalcemia is a presenting feature in certain malignancies and hyperparathyroidism.
- Biopsy – should be the last step after the complete evaluation of musculoskeletal tumors for the site of the lesion, the behavior of the tumor and extent of respectability. Type of biopsy, placement of biopsy incision, and histopathological workup of biopsy tissue requires planning. MRI and bone scans can be adversely affected by biopsy and postoperative changes in the tissue; hence they are generally obtained preoperatively.
- Radionuclide bone scan – a nuclear imaging method to evaluate any degenerative and/or arthritic changes in the joints; to detect bone diseases and tumors; to determine the cause of bone pain or inflammation. This test is to rule out any infection or fractures.
Treatment of Enchondroma
Specific treatment for enchondroma is determined by a physician based on the age, overall health, and medical history of the patient. Other considerations include:
- the extent of the disease
- tolerance for specific medications, procedures, or therapies
- expectations for the course of the disease
- opinion or preference of the patient
Management of enchondroma lesions typically requires simple curettage with bone grafting. The bone graft used may be allogeneic bone, autogenous, or synthetic bone substitutes. The impact of the type of graft on healing, recurrence, complications, and malignant transformation is unknown. Currently, no standardized algorithm for surgical treatment of this kind of tumor exists. The necessity of curettage with grafting remains unproven. The timing of surgical intervention has also not been shown to have significant benefits. Early and delayed surgical intervention was shown to have similar functional outcomes.[rx]
Needle biopsy is not required and is actually discouraged by pathologists.[rx] When treating bone lesions non-surgically, bone structure and integrity can undergo compromise following the treatment. Pathologic fracture risk increases with the size of the lesion. Lesions in weight-bearing bones with a diameter greater than 25 millimeters or that involve over 50% of the diameter of the boney cortex have the highest risk of fracture.
Prophylactic intervention aiming to prevent impending fracture via internal fixation methods is unknown and controversial. Retrospective studies have formed a basis to guide the indications, but limits of these guidelines are the use of plain radiographs, subjective patient information, and inadequate understanding of the biomechanical factors involved in the neoplastic process. The Mirels criteria were developed to quantify the risks of fracture pertaining to bone neoplasms. These criteria take into account the location, pain, lesion type, and lesion size. A score greater than 8 dictates a significant risk of fracture and a need for a prophylactic internal fixation. A bone tumor with a scoreless than seven can undergo observation according to these criteria. In applying these criteria, the defined fracture risk uses the load-bearing requirement of the bone divided by its load-bearing capacity. The parameters for load-bearing requirements and capacity were also stipulated and analyzed. The patient’s age, weight, activity level, and ability to protect the site dictate the load-bearing requirement. The load-bearing capacity depends on the amount of bone loss, modulus of the remaining bone, and location of the defect with respect to the type of load applied. The graphic representation of the Mirels criteria is depicted below.
Characteristics of a more aggressive tumor or malignant chondrosarcoma include:
- Thickening of the bone’s outer cortex
- Reactive bone growth on the outer surface of the bone
- Destruction of the bone by the tumor
- Soft-tissue mass
- Large amounts of bone erosion
- Bone erosion that is growing
- Erosion surrounded by reactive bone
References
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