Similarities Between Giant Cell Tumor of Bone, Giant Cell Tumor of Tendon Sheath, and Pigmented Villonodular Synovitis Concerning Ultrastructural Cytochemical Features of Multinucleated Giant Cells and Mononuclear Stromal Cells

Department of Orthopaedic Surgery, Keio University, School of Medicine, Tokyo, Japan.
Ultrastructural Pathology (Impact Factor: 1.08). 05/2006; 30(3):151-8. DOI: 10.1080/01913120600689707
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The authors investigated ultrastructural cytochemical features of multinucleated and mononuclear stromal cells in giant cell tumor of bone (GCTB), giant cell tumor of tendon sheath (GCTTS), and pigmented villonodular synovitis (PVNS). Specimens of each tumor, respectively numbering 4, 4, and 3, were stained for tartrate-resistant acid phosphatase (TRAP) reactions and examined with an electron microscope. In GCTB and GCTTS, multinucleated cells, including some relatively small giant cells, showed TRAP activity and cytoplasmic features characteristic of osteoclasts, and also sometimes abundant rough endoplasmic reticulum and siderosomes. A few giant cells with macrophage-like features and slight TRAP activity were demonstrated in GCCTS and PVNS. In each tumor type, mononuclear cells showing TRAP activity shared cytoplasmic features with osteoclast-like multinucleated giant cells, while some others had macrophage-like features, and still others were poorly differentiated; a few mononuclear cells showed cell-to-cell contact. Ultrastructural similarities of TRAP-positive mononuclear cells in the three tumor types, and those between TRAP-positive multinucleated cells in GCTB and GCTTS, suggest a common cell lineage capable of multinucleated giant cell formation in the 3 tumors, despite differing histogenesis.

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    • "In fact, GCTs were formerly known as " osteoclastomas, " and giant cells isolated from these tumors are often used as models for true osteoclasts [61] [62] [63] [64] [65]. Indeed, the giant cells express tartrate-resistant acid phosphatase (TRAP) [66] [67], cathepsin K [61,68–70], and carbonic anhydrase II [64] [71], as well as many receptors that are characteristic of osteoclasts, including the receptor activator of nuclear factor-κB (RANK) [72] [73] [74], the calcitonin receptor [75] [76], and the αvβ3 integrin [71] [77] [78]. Moreover, the giant cells are capable of bone resorption [12,78–80] and may occasionally show numerous infoldings under electron microscopy that resemble the ruffled membrane of true osteoclasts [79] [81]. "
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    ABSTRACT: Comprehending the pathogenesis of giant cell tumor of bone (GCT) is of critical importance for developing novel targeted treatments for this locally-aggressive primary bone tumor. GCT is characterized by the presence of large multinucleated osteoclast-like giant cells distributed amongst mononuclear spindle-like stromal cells and other monocytes. The giant cells are principally responsible for the extensive bone resorption by the tumor. However, the spindle-like stromal cells chiefly direct the pathology of the tumor by recruiting monocytes and promoting their fusion into giant cells. The stromal cells also enhance the resorptive ability of the giant cells. This review encompasses many of the attributes of GCT, including the process of giant cell formation and the mechanisms of bone resorption. The significance of the receptor activator of nuclear factor-κB ligand (RANKL) in the development of GCT and the importance of proteases, including numerous matrix metalloproteinases, are highlighted. The mesenchymal lineage of the stromal cells and the origin of the hematopoietic monocytes are also discussed. Several aspects of GCT that require further understanding, including the etiology of the tumor, the mechanisms of metastases, and the development of an appropriate animal model, are also considered. By exploring the current status of GCT research, this review accentuates the significant progress made in understanding the biology of the tumor, and discusses important areas for future investigation.
    Bone 10/2012; 52(1). DOI:10.1016/j.bone.2012.10.002 · 3.97 Impact Factor
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    • "There is now agreement that giant cells are circulating monocytes in origin which have converted into osteoclasts after acquiring some unique features and gene expressions in osseous environment. These conclusions are based on various light, ultrastructural and immunological markers [8] [9] [10] [11] [12]. On the other Figure 2 Tibia showing a lytic expansile lesion with septae consistent with aneurysmal bone cyst. "
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    ABSTRACT: Giant cell tumor of bone (GCTB) is a benign but locally aggressive bone tumor of young adults. It typically presents as a large lytic mass at the end of the epiphysis of long bones. Grossly it is comprised of cystic and hemorrhagic areas with little or no periosteal reaction. Microscopically areas of frank hemorrhage, numerous multinucleated giant cells and spindly stromal cells are present. Telomeric fusions, increased telomerase activity and karyotypic aberrations have been advanced as a proof of its neoplastic nature. However such findings are not universal and can be seen in rapidly proliferating normal cells as well as in several osseous lesions of developmental and/or reactive nature, and the true neoplastic nature of GCTB remains controversial. The ancillary studies have generally not reached to the point where these alone can be taken as sole diagnostic and discriminatory criteria. While giant cells and stromal cells have been extensively studied, little attention has been paid to the overwhelming hemorrhagic component. If examined carefully intact and partially degenerated red blood cells are almost invariably seen in many giant cells as well as in the stroma. While hemorrhage in many patients may be resolved without leaving any trace over time, in some it gives rise to giant cell formation, and in others it may lead to proliferation of fibroblasts and histiocytes. At times one sees xanthomatous cells due to intracytoplasmic cholesterol deposits and sharp cholesterol clefts. Individual genetic makeup, local tissue factors as well as the amount of hemorrhage may play a key role in the final effects and outcome. Malignancy usually does not occur in GCTB and when discover, it usually represents primary bone sarcomas missed at original diagnosis. Embolization therapy to curtail hemorrhage and insertion of cement substance to support matrix are helpful in reducing recurrences. Aneurysmal bone cyst (ABC) shares many features with GCTB. There had been unique karyotypic changes in some aneurysmal bone cysts making it distinct from GCTB. However these changes may be in the endothelial cells which are quite different from stromal or giant cells. It had been concluded that the poor matrix support to the vessels may lead to frequent and profuse intraosseous hemorrhage attracting blood-derived monocytes with active conversion into osteoclasts, resulting in GCTB formation. On the other hand, dilatation of the thin-walled blood vessels results in formation of ABCs. If hemorrhagic foci are replaced by proliferation of fibroblasts and histiocytes, then a picture of fibrous histiocytic lesion is emerged. Enhanced telomerase activity and karyotypic aberrations may be necessary for rapid division of the nuclei of the giant cells in order to be able to deal with significant in situ intraosseous hemorrhage.
    International journal of clinical and experimental pathology 02/2008; 1(6):489-501. · 1.89 Impact Factor
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    ABSTRACT: Silver-Russell syndrome consists in a rare genetic disorder. Its classical phenotype includes intra-uterus and post-natal growth delay, hemi-hypertrophy, lateral asymmetry, members' asymmetry, clinodactyly of the fifth finger and a variable number of facial dimorphisms, such as craniofacial disproportion and triangular face. The description of its speech therapeutic manifestations, besides being rare, emphasizes the presence of craniofacial and oral aspects instead of reading and writing involvement. The aim of this study was to describe the case of a 14 years old girl with Silver-Russell syndrome, who, after being submitted to Illinois Psycholinguistic Abilities Test; Phonological Consciousness Proof; Reading and Writing Test and School Performance Assessment, had the speech therapeutic diagnosis of Reading and Writing Disorder (RWD). The evaluation data evidenced the presence of impairment in the writing modality, determined mostly by phonologic processing deficit. Based in these findings, the evaluation of phonologic memories abilities, phonologic consciousness and mental lexical access are suggested to be applied in children with Silver-Russell syndrome, during the pre-school period, aiming at preventing the installment and aggravation of writing disorders.
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