Document Detail

K-ras oncogene mutations in osteoclast-like giant cell tumors of the pancreas and liver: genetic evidence to support origin from the duct epithelium.
MedLine Citation:
PMID:  9777987     Owner:  NLM     Status:  MEDLINE    
Osteoclast-like giant cell tumors (OCGTs) of the pancreas and liver are enigmatic tumors. Despite their striking morphologic resemblance to certain mesenchymal tumors of bone and tendon sheath, it has been suggested that these tumors may, in fact, arise from epithelial precursors. It is also unclear whether the osteoclast-like giant cells in OCGTs are neoplastic or nonneoplastic. We identified OCGTs of the pancreas and liver that were associated with atypical intraductal epithelial proliferations or mucinous cystic neoplasms. To determine the relationship between the noninvasive epithelial proliferations and the infiltrating OCGTs, each individual component was analyzed for mutations at codon 12 of the K-ras oncogene. Four of the five-duct epithelial lesions harbored activating mutations of the K-ras oncogene. In each case, the same K-ras mutation was also present in the mononuclear cells from the paired OCGT. Moreover, these same mutations were detected when the osteoclast-like giant cells were individually microdissected and analyzed. A panel of immunohistochemical stains was performed, and the osteoclast-like giant cells demonstrated macrophage differentiation. These cells were consistently reactive for the monocyte/macrophage marker KP1, but showed absent staining for a panel of epithelial markers. The infiltrating mononuclear cells lacked strong staining for epithelial markers and monocyte/macrophage markers. These findings suggest that OCGTs of the pancreas and liver are undifferentiated carcinomas that arise directly from intraductal epithelial precursors. The finding of K-ras mutations in the osteoclast-like giant cells may reflect their propensity to phagocytize tumor cells.
W H Westra; P Sturm; P Drillenburg; M A Choti; D S Klimstra; J Albores-Saavedra; A Montag; G J Offerhaus; R H Hruban
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Publication Detail:
Type:  Case Reports; Journal Article; Research Support, U.S. Gov't, P.H.S.; Review    
Journal Detail:
Title:  The American journal of surgical pathology     Volume:  22     ISSN:  0147-5185     ISO Abbreviation:  Am. J. Surg. Pathol.     Publication Date:  1998 Oct 
Date Detail:
Created Date:  1998-10-28     Completed Date:  1998-10-28     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7707904     Medline TA:  Am J Surg Pathol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1247-54     Citation Subset:  IM    
Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
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MeSH Terms
Antigens, CD / metabolism
Antigens, Differentiation, Myelomonocytic / metabolism
Bile Ducts / metabolism,  pathology
DNA Primers / chemistry
DNA, Neoplasm / analysis
Epithelial Cells / metabolism,  pathology
Genes, ras / genetics*
Giant Cell Tumors / genetics*,  metabolism,  pathology
Giant Cells / metabolism,  pathology
Immunoenzyme Techniques
Liver Neoplasms / genetics*,  metabolism,  pathology
Macrophages / metabolism
Osteoclasts / pathology
Pancreatic Ducts / metabolism,  pathology
Pancreatic Neoplasms / genetics*,  metabolism,  pathology
Grant Support
Reg. No./Substance:
0/Antigens, CD; 0/Antigens, Differentiation, Myelomonocytic; 0/CD68 antigen, human; 0/DNA Primers; 0/DNA, Neoplasm

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