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We appreciate the interest and the response to our recent publication on undifferentiated carcinoma of the pancreas with osteoclast-like giant cells.1 In contrast to our study, Deckard-Janatpour et al. found that the mononuclear cells in their series of undifferentiated carcinomas stained with mesenchymal markers in virtually all their cases and with epithelial markers in 7 of 11 of their cases.2 In reviewing our Figure 7b, which is a photomicrograph of an undifferentiated carcinoma stained with CD68, they claim that "a small proportion of the mononuclear cells are in fact positive." We believe these cells are tangentially cut osteoclast-like giant cells, not mononuclear cells. Deckard-Janatpour et al. have concluded that their results support a dual epithelial-mesenchymal origin for undifferentiated carcinomas with osteoclast-like giant cells of the pancreas, perhaps from an "undifferentiated pancreatic stem cell." On the other hand, our results support an epithelial derivation for these unusual tumors and suggest that the osteoclast-like giant cells are a reactive and nonneoplastic component of the tumor. It is now believed that the multinucleated cells result from fusion of bone marrow-derived monocytes recruited into the tumor by chemotactic factors elaborated by the neoplastic mononuclear cells.3 Moreover, mutations at codon 12 of the K-ras oncogene found in over 80% of ductal pancreatic adenocarcinomas have consistently been detected in the mononuclear cells of undifferentiated carcinoma with osteoclast-like giant cells, supporting the epithelial derivation of the mononuclear cells.4 Furthermore, the existence of an undifferentiated pancreatic stem cell with an ability to give rise to tumors of both epithelial and mesenchymal origin is not consistent with the developmental anatomy of the pancreas. The epithelial components of the pancreas are derived from endoderm, whereas the connective tissue components are derived from splanchnic mesenchyme.5 However, we do believe that a primitive pancreatic epithelial cell can give rise to a tumor that has both carcinomatous and sarcomatous differentiation (i.e., carcinosarcoma). Finally, a review of our data revealed that our single long term survivor's tumor was negative for p53 and did not contain a significant population of pleomorphic cells. Kyle H. Molberg M.D.*, Ruby Delgado M.D.*, Jorge Albores-Saavedra M.D.*, Clara Heffess M.D.