Posted on December 4, 2011
This entry was posted in Pathology.
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Giant cell tumor of bone (GCTB) is a relatively rare, benign but locally aggressive osteolytic skeletal neoplasm of young adults. First recognized in 1818 , it was not until 1940 that GCTB was formally distinguished from other tumors of bone, such as aneurysmal bone cyst, chondroblastoma, and nonossifying fibroma . (See “Overview of benign bone tumors in children and adolescents”.)
Although regarded as a benign tumor, GCTB represents a continuum of neoplasia, and clinical behavior is not predictable based upon clinical, radiographic, or histologic features. GCTB can be locally aggressive, and it has a propensity to recur locally after curettage alone. Furthermore, in about 2 to 3 percent of cases, distant metastases occur, most often to the lungs. However, pulmonary metastases do not carry the same connotation as metastases associated with malignant tumors, such as lung cancer or sarcoma. In most cases, clinical behavior is benign, and metastatic disease does not lead to the death of the patient, hence the designation “benign pulmonary implants”. Rarely, GCTB undergoes true malignant transformation.
Historically, there has been a lack of prospective, randomized clinical trials to guide clinical management of GCTB, partly owing to the rarity of these tumors and to their primarily surgical treatment. Retrospective data from large single-institution series has provided some degree of consensus as to optimal local management. More recently, improved understanding of the molecular and cellular biology of GCTB has led to the identification of new targeted therapies for the disease. The most promising of these is denosumab, a fully humanized monoclonal antibody directed against the osteoclast differentiation factor RANKL (Receptor Activator of Nuclear factor Kappa B (NF-kB) Ligand), a molecule that appears to be critical to the pathogenesis of GCTB.
This topic review will discuss the epidemiology, clinical and imaging features, staging, pathology and molecular pathogenesis, and treatment approaches for GCTB.
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