Cell characterization of mononuclear and giant cells constituting pigmented villonodular synovitis

Hum Pathol. 2003 Jan;34(1):65-73. doi: 10.1053/hupa.2003.52.


The aim of this study was to determine the histologic and cellular characteristics of 2 cell types, mononuclear cells (Mos) and multinuclear giant cells (GCs), that predominantly constitute pigmented villonodular synovitis (PVS). Synovial tissues examined in this study were obtained from 10 patients with PVS. Five methods were used for cell analysis: (1) enzyme-histochemistry for tartrate-resistant acid phosphatase (TRAP); (2) immunohistochemistry using antibodies for CD68, macrophage colony-stimulating factor (M-CSF), MIB-1, p53, p21, p16, and cathepsin-L (cath L); (3) TdT-mediated deoxyuridine triphosphate-biotin terminal end labeling (TUNEL) as a measure of apoptosis; (4) fluorescence-based polymerase chain reaction single-strand conformation polymorphism analyses (FPCR-SSCP) to detect p53 gene mutations; and (5) in situ hybridization using gene-specific oligoprobes for matrix metalloproteinase (MMP)-2, MMP-9, receptor activator of nuclear factor kappaB ligand (RANKL), and calcitonin receptor (CTR). Both Mos and GCs were shown to express the macrophage/histiocyte marker CD68. In GCs, TRAP and CTR, both of which are known as characteristic phenotype markers of osteoclasts, were expressed. M-CSF and RANKL, which are together essential for osteoclast differentiation, were expressed in both Mos and GCs. Mos were shown to express MIB-1, but GCs were not. Although proliferation-suppressor proteins p53, p21, and p16 were expressed in both Mos and GCs, little apoptotic phenomenon of lining Mos was detected by TUNEL. In our study, p53 gene mutations for exons 5, 7, and 8 in PVS synovial tissues were not detected by FPCR-SSCP analysis. Furthermore, both types of cells demonstrated the proteolytic enzymes MMP-2 and MMP-9 mRNA, and cath L protein. These results suggest that PVS has a hyperplastic property consisting of the CD68-positive monocytic cell lineage with differentiation of osteoclastic giant cells from monocyte and probably controlled against proliferation by wild-type p53, p21, and p16.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Phosphatase / metabolism
  • Ankle Joint / pathology
  • Ankle Joint / surgery
  • Apoptosis
  • Biomarkers / analysis
  • DNA Mutational Analysis
  • DNA Primers / chemistry
  • Giant Cells / metabolism
  • Giant Cells / pathology*
  • Humans
  • Immunoenzyme Techniques
  • In Situ Hybridization
  • In Situ Nick-End Labeling
  • Isoenzymes / metabolism
  • Knee Joint / pathology
  • Knee Joint / surgery
  • Matrix Metalloproteinase 2 / biosynthesis
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 9 / biosynthesis
  • Matrix Metalloproteinase 9 / genetics
  • Monocytes / metabolism
  • Monocytes / pathology*
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • RNA, Messenger / genetics
  • Synovial Membrane / metabolism
  • Synovial Membrane / pathology*
  • Synovitis, Pigmented Villonodular / genetics
  • Synovitis, Pigmented Villonodular / metabolism
  • Synovitis, Pigmented Villonodular / pathology*
  • Tartrate-Resistant Acid Phosphatase


  • Biomarkers
  • DNA Primers
  • Isoenzymes
  • RNA, Messenger
  • Acid Phosphatase
  • Tartrate-Resistant Acid Phosphatase
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9