Malignant Melanoma With Osteoclast-Like Differentiation

Osteoclast-like giant cells are frequently encountered in nonskeletal malignancies; however, the evidence to date suggests that they represent a tissue response to the lesion rather than neoplastic differentiation. We describe a case of metastatic melanoma demonstrating osteoclast-like differentiation in the lung. The lung nodule was diagnosed as a metastatic melanoma by histological features and confirmed by immunohistochemistry. Resection specimen showed numerous multinucleated giant cells exhibiting osteoclast-like morphology dispersed throughout the lesion. Both the neoplastic melanocytes and giant cells were reactive for HMB-45, Melan-A, and S100. In addition, the multinucleated neoplastic giant cells were also reactive for the monocyte/macrophage lineage markers CD68 and CD163, and alkaline phosphatase, an enzyme present in normal osteoclasts. The neoplastic melanocytes and the multinucleated neoplastic giant cells were also reactive for microphthalmia-associated transcription factor, a protein required for the development of both melanocytes and osteoclasts. Collectively, a co-expression of monocyte/macrophage markers along with melanocytic markers and alkaline phosphatase in the multinucleated neoplastic giant cells in metastatic melanoma suggest that malignant melanocytes are capable of differentiating into osteoclast-like cells and consequently aid invasion into various structures and eliciting the aggressive behavior.