Osteochondromatosis

Summary
Description

HMOCE (hereditary multiple osteochondral exostosis) is a rare, autosomal dominant inherited disease where multiple osteochondral bone tumors occur on the surfaces of the bones. The severity of the disease can vary from mild to very disabling. A small number of the tumors may develop into low grade chondrosarcomas.

People and Age
The disease is apparent within the first 10 years of life, about 1 in 50,000 are affected.
Symptoms and Presentation
Patients have noticeable bumps near their joints, especially the knees, hips and shoulders. Patients also have short stature and malalignment of joints.
Brief description of the xray
Xrays show multiple lesions on the surface of the long bones, pelvis and elsewhere.
Brief desc of tx
Treatment is required for the large, troublesome lesions, but the others may be observed. The risk of development of sarcoma requires that all patients with this disease ensure regular self-monitoring and follow-up.
Tumor Name
Osteochondromatosis
Tumor Type
Tumors of Cartilage
Benign or Malignant
Benign
Body region
located in multiple bones
Most Common Bones
tibia
humerus
femur
Periosteal reaction
absent
Tumor behavior
active
Tumor density
blastic
Complete Information on this Tumor
Introduction and Definition

HMOCE is a rare, autosomal dominant condition where an genetic error of bone growth results in the formation of multiple osteochondromas. The condition can range from a mild nuisance to a very severe, disabling, and even potentially deadly problem depending on the number and location of the lesions.

As HMOCE is an autosomal dominant condition, it is genetically heterogeneous and it has been linked to three loci including 8q24.1 (EXT1), 11p11-12 (EXT2), and 19p (EXT3). EXT1 and EXT2 are proposed tumor supressor genes which may be lost in HMOCE, resulting in the growth of the lesions.

The risk of malignant transformation to chondrosarcoma in hereditary multiple osteochondromatosis is unknown, but may be 25-30% compared to approximately 1% for a solitary osteochondromas. The risk of malignant degeneration increases as the number and size of the osteochondromas increases. In general, a sessile lesion is more likely to degenerate into sarcoma than an exostosis.

Incidence and Demographics
This disease occurs in approximately 1 out of 50,000 persons. A few spontaneous cases occur, but most are inherited. About 5% of individuals with the disease are unaffected or minimally affected. The condition can lead to both sessile and pedunculated lesions. The lesions may occur on different bones or on the same bone, and symptoms present in the first decade of life. There may be a few lesions, dozens, or hundreds. Joints adjacent to paired bones can also be affected by differential growth of the two involved bones.The lesions may often cluster at the metaphyseal ends of the bones near the joint.
Symptoms and Presentation

About 50% of affected children have identifiable lesions by age 5. Patients present with disfigurement or with pain induced by pressure on surrounding soft tissue structures. They may have short stature, limb-length discrepancies, valgus angulation of the knee and ankle, bowing of the radius with ulnar deviation of the wrist, and subluxation of the radiocapitellar joint. The ulna and fibula are more affected than the radius and the tibia. For this reason, differential growth of the paired bones it may lead to angular deformities of the forearm, wrist, leg, and ankle. Also, lesion clusters at the metaphyseal ends of the bones near the joint may lead to loss of motion, hip dysplasia, joint subluxation, nerve compression, vascular pseudo-aneurysm, cord compression, and pain.

X-Ray Appearance and Advanced Imaging Findings
Appears similar to solitary osteochondromas, although frequently the multiple lesions are more disorganized in structure and tend to have bosselated cartilage caps.
Treatment Options for this Tumor
As the risk of malignant transformation is unknown, cancer risk assessment should be performed by an orthopedic oncologist. The authors of this site pay particular attention to the large deep osteochondromas, often located on the pelvis or the spine, where malignant transformation may be more likely and much more difficult to treat.

Indications for surgical removal include persistent pain, functional impairment, joint subluxation, neuropraxia, and others. Early surgical corrections of deformities of the forearm has been advocated to improve function. However, the actual functional improvement has been questioned, and surgery may be safely delayed until after skeletal maturity. Significant angular deformities of the lower limb can be reduced or eliminated with re-alignment procedures. Surgical removal of troublesome lesions or lesions which appear to possess malignant potential is associated with a good outcome. Significant angular deformities of the lower limb can be reduced or eliminated with re-alignment procedures, which should improve function and reduce pain. Early surgical corrections of deformities of the forearm has been advocated to improve function. However, the actual functional improvement has been questioned, and surgery may be safely delayed until after skeletal maturity. Complications occur in approximately 10-12% of cases following elective excision of osteochondromas, including nerve injury, arterial laceration, and fracture. For this reason, the lesions should not be removed just because they exist. Indications for surgical removal include persistant pain, functional impairment, joint subluxation, neuropraxia, and others.
Outcomes of Treatment and Prognosis
Surgical removal of troublesome lesions or lesions which appear to possess malignant potential is associated with a good outcome. Re-alignment procedures often improve function and reduce pain.Complications occur in approximately 10-12% of cases following elective excision of osteochondromas, including nerve injury, arterial laceration, and fracture. For this reason, the lesions should not be removed just because they exist. The authors of this site recommend that patients with this disorder be evaluated by an orthopedic oncologist. An initial comprehensive evaluation is done, followed by regular scheduled follow-up exams as well as investigation of new problems or symptoms. In this way, necessary and helpful treatments are pursued and useless or dangerous procedures are avoided. Cancer risk can be assessed on an ongoing basis. The lifetime exposure to radiation for scans, radionucleotide studies, and surgical procedures needs to be managed to avoid secondary risks. Family members may need to be screened for orthopedic problems and cancer risk.
Special and Unusual Features
This disease has been studied by combining genetic linkage analysis of large numbers of affected families combined with modern molecular biological techniques of DNA analysis. Three chromosome locations 8q24.1 , 11p11-13, and 19p are invloved. The genes affected are tumor suppressor genes, and have been named EXT1, EXT2, and EXT3. EXT1 and EXT2 have been found in more than 80% of individuals with HMOCE who have been tested. These genes are involved with the system that synthesizes heparan sulfate (HS) in the cell. The reason why these gene mutations lead to the formation of multiple osteochondral tumors is not fully understood.
After surgery, patients with HMOCE form larger scars than usual, which is probably caused by the underlying HS synthesis defect in some way.
Suggested Reading and Reference
Bridge, JA et al: Cancer. 1998 May 1;82(9):1657-63

Wirganowicz, PZ Journal of Pediatric Orthopedics. 17(4):455-459, July/August 1997
Alman, BA. Multiple Hereditary Exostosis and Hedgehog Signaling: Implications for Novel Therapies JBJS -Am. 2009 :91 Suppl 4:63-7
Steiber and Dormans, J Am Acad Orthop Surg. 2005 Mar-Apr;13(2):110-20