Origin of giant cells in osteoclast-like giant cell tumors of the pancreas.

To clarify the origin of giant cells in osteoclast-like giant cell tumors (OGCTs) of the pancreas, we performed microscopical, immunohistochemical, and K-ras gene mutation analyses with a microdissection approach in 3 cases, featuring 4 cellular components (osteoclast-like giant cells [OGCs], pleomorphic large cells [PLCs], mononuclear cells, and ductal carcinoma cells). Two cases had abundant OGCs, and 1 case contained large number of both OGCs and PLCs. In each, none of the microdissected OGCs contained any K-ras gene mutation while they were positive for a histiocytic marker (CD-68). In contrast, PLCs, when present, frequently harbored K-ras gene mutations and were negative for CD-68. In all cases, mononuclear cells, a mixture of histiocyte-like and atypical, from microscopic and immunohistochemical viewpoints, also frequently showed K-ras alteration. Histiocyte-like mononuclear cell was equipped with a regular and oval nucleus similar to those in OGCs and was positive for CD-68. Atypical mononuclear cell showed an irregular, pleomorphic, or sometimes bizarre nucleus similar to those in PLCs and was negative for CD-68. All of the K-ras gene mutations found in PLCs and mononuclear cells were the same as in the ductal carcinoma cells within the same tumor. Thus, OGCs differ in origin from ductal cells and are strongly suggested to be nonneoplastic and of mesenchymal origin, whereas PLCs, which harbor K-ras gene mutations, are neoplastic and presumably derived from ductal carcinoma cells. Moreover, mononuclear cells may be classified into 2 types, histiocyte-like and atypical.