Tumors of the pancreas with osteoclast-like and pleomorphic giant cells: an immunohistochemical and ploidy study.
BACKGROUND
Tumors of the pancreas with osteoclast-like giant cells are of uncertain histogenesis and aggressiveness. Their relationship, if any, to undifferentiated (anaplastic) carcinomas of the pancreas with pleomorphic giant cells is also not clear.


METHODS
Eleven tumors with osteoclast-like giant cells were studied by immunohistochemistry for epithelial and mesenchymal markers, as well as for a proliferation marker (Ki67) and p53 protein expression. Cytometric image analysis for nuclear DNA content was also performed. K-ras mutations were investigated by DNA sequence analysis.


RESULTS
Neoplastic, predominantly spindle-shaped cells and osteoclast-like giant cells were positive for mesenchymal markers CD68, LCA, and A1ACT. These spindle-shaped cells were also positive for human muscle actin. Spindle-shaped cells of seven tumors were also positive for epithelial markers carcinoembryonic antigen, epithelial membrane antigen, or keratin. Nine tumors contained a variable number of pleomorphic giant cells in addition to osteoclast-like giant cells. Pleomorphic giant cells were much less positive for mesenchymal markers than were osteoclast-like giant cells, but they were positive for some epithelial markers. A high percentage of spindle-shaped and pleomorphic giant cells were positive for Ki67. Diploid and aneuploid populations were present in varying proportions in both spindle cells and pleomorphic giant cells. The nuclei of osteoclast-like giant cells, however, were diploid and not proliferating. Spindle-shaped and pleomorphic giant cells were positive for p53 protein in 5 of 10 cases. Five of six tumors studied were positive for K-ras mutations.


CONCLUSIONS
The distinction between tumors with osteoclast-like giant cells and undifferentiated carcinomas with pleomorphic giant cells is often not clear-cut. Both types of tumors have mesenchymal and epithelial characteristics in varying proportions and may arise from an undifferentiated pancreatic stem cell. Long-term survival of two patients suggests that some tumors with osteoclast-like giant cells may have a better prognosis than the usual pancreatic ductal adenocarcinoma.
Deckard-Janatpour
K
K
Department of Pathology, University of California Davis Medical Center, Sacramento 95817, USA.
Kragel
S
S
Teplitz
R L
RL
Min
B H
BH
Gumerlock
P H
PH
Frey
C F
CF
Ruebner
B H
BH
D002455:Cell Division / Q000502:physiology; D011905:Genes, ras / Q000235:genetics; D015726:Giant Cells / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D009154:Mutation / Q000235:genetics; D010010:Osteoclasts / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D011003:Ploidies; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53