Familial History of Bone Tumors FREE

A 61-year-old man presents with progressive chronic pain of his lower extremities and episodes of dysthesia of his left foot. On physical examination, he has bowing of his extremities with prominent bony masses on both legs, particularly near his knee, that have been present since birth (Figure 1). The patient's father and sister have similar lesions. Complete blood cell count and differential are within normal limits. Plain radiograph and magnetic resonance imaging show multiple exostosis with the largest lesion arising from the posterior left tibia. There is no evidence of malignant transformation, although significant impingement on the posterior neurovascular bundle is seen.

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Hereditary osteochondroma

D. Offer genetic counseling including evaluation of family members.

The key clinical feature in this case is to recognize that multiple symmetric bone tumors in a patient with several relatives with similar presentation suggest the possibility of hereditary osteochondroma. Obtaining a thorough family history is important when evaluating the possibility of hereditary multiple exostoses.

Familial diseases leading to bone tumor formation are rare and carry an increased risk for developing malignant transformation over time to secondary chondrosarcoma and osteosarcomas; hence, periodic clinical monitoring is recommended.¹ Hereditary multiple exostoses, or hereditary osteochondroma, is an autosomal dominant disease; therefore, a good family history is critical for reaching the appropriate diagnosis.² The genetic etiology of hereditary multiple exostoses appears associated with inactivation of tumor suppressors located on chromosomes 8, 11, and 19, locus EXT1, EXT2, and EXT3, respectively.³ Radiologic imaging studies typically demonstrate cortical and medullary continuity between the osteochondroma and parent bone³ (Figure 2). Once pressure symptoms occur, surgical excision of exostosis is mandated. The treatment of large osteochondromas with vessel involvement in asymptomatic patients remains undefined.⁴

Malignant transformation, mostly to chondrosarcoma arising in the cartilaginous area of the tumor, develops in approximately 1% of solitary lesions and in 3% to 5% of the hereditary cases.³ Worsening pain or bone tumors that continue to grow after skeletal maturity has been reached should raise suspicion for malignant transformation because osteochondromas usually do not continue to enlarge during adulthood.⁵ In addition, imaging findings suggestive of malignant transformation include irregular borders of the lesions and destruction of the adjacent structures by the tumor.³ There are no guidelines regarding frequency and timing of imaging studies to rule out malignant transformation. Mutation analysis in relatives of a patient with hereditary multiple exostoses provides an opportunity for prenatal diagnosis and genetic counseling.

The differential diagnosis of hereditary multiple exostoses includes the enchondromatoses, which are a heterogeneous group of syndromes that present with multiple enchondromas associated with pathological fractures, pseudarthrosis, limb shortening, malignant transformation risk, and scoliosis.¹ Enchondromatoses, such as Ollier disease, present as asymmetric intraosseous benign cartilaginous tumors that are usually not inherited disorders.¹

Performing bone marrow aspiration, the mainstay of the diagnostic workup of several hematologic malignancies, would not contribute to diagnosing the etiology of solid bone tumors, particularly in light of the normal complete blood cell count and differential. A bone biopsy is usually not necessary for the diagnosis of multiple symmetric bone lesions that have remained stable for years, unless one of the lesions becomes unusually larger after puberty, suggesting malignant transformation. Electromyography results will likely be abnormal secondary to nerve compression depending on the anatomical location of a particular bone tumor; nevertheless, electromyography will not confirm a diagnosis of osteochondroma.

The patient declined genetic counseling or any surgical intervention for significant impingement on the posterior neurovascular bundle and was lost to follow-up. He recently returned to our clinic 5 years after his initial presentation and his osteochondromas remained clinically stable. The patient was treated supportively with pain medications.