Answer: Undifferentiated carcinoma with multinucleated giant

Histology: This high-grade undifferentiated neoplasm is remarkable for two cell types. High-grade spindle shaped atypical mononuclear cells are admixed with large osteoclast-like giant cells. The large osteoclast-like cells lack the nuclear atypia seen in the infiltrating mononuclear cells.

Discussion: These rare neoplasms are typically well circumscribed, yellow-pink, and fleshy. By light microscopy, they are composed of multinucleated, benign-appearing, osteoclast-like giant cells dispersed among infiltrating atypical mononuclear cells. The multinucleated giant cells in these tumors more closely resemble the osteoclast of resorbing bone than the pleomorphic giant cells of the anaplastic giant cell carcinoma. Furthermore, these giant cells are consistently reactive for monocyte/macrophage markers such as KP-1. Some osteoclast-like giant tumors of the pancreas are associated with mucinous cystic neoplasms or an adenocarcinoma, suggesting an epithelial origin to these neoplasms. Indeed, at the molecular level, these distinctive neoplasms frequently harbor activating point mutations in codon 12 of K-ras. Furthermore, the same k-ras mutations have been demonstrated in both the epithelial (that is, the mucinous cystic neoplasm or adenocarcinoma) and the infiltrating mononuclear cell components of these neoplasms, helping to establish that undifferentiated carcinomas with osteoclast-like giant cells arise from the epithelial components. These neoplasms are therefore best considered carcinomas which elicit a non-neoplastic giant cell response and not mesenchymal neoplasms. The term “undifferentiated carcinoma with osteoclast-like giant cells” is therefore preferred over “osteoclast-like giant cell tumor (11,12).”