The prognostic significance of histomorphometry and immunohistochemistry in giant cell tumors of bone

Fornasier, Victor; Protzner, K; Zhang, I; Mason, Lyman W.

doi:10.1016/s0046-8177(96)90445-1

Cited by 39 publications

(33 citation statements)

References 22 publications

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“…In addition, GCTB stromal cells can form mature bone when implanted into immunologically deficient mice (43). We report here, as others have, that limited de novo bone matrix formation is observed in primary GCTB and also in GCTB that has metastasized to the lung (9,18,19,32,44).…”

Section: Discussionsupporting

confidence: 75%

“…They also show cytogenic markers indicating transformation, including telomere associations, but fail to show consistent chromosomal changes and are reported to be polyclonal (28)(29)(30)(31). Interestingly, GCTB tumors are occasionally reported to contain scant focal areas of osteoid matrix and woven bone that is present within the tumor and separate from the tumor margins, in an incidence ranging from 22% to 52% (9,18,19,32). Our own analysis of 31 baseline samples from the phase II study and an archival set of 40 GCTB samples revealed a similar pattern in 45% to 52% of the tumors evaluated, although localization of the biopsy to the tumor margin was not established.…”

Section: Discussionmentioning

confidence: 99%

“…Many researchers have shown that the giant cell of GCTB is osteoclastic in nature (4,6,10) and that the true neoplastic cells are ovoid cells displaying markers of mesenchymal stem cells that have partially differentiated along the osteoblast lineage (14)(15)(16)(17). These tumors are frequently described to contain small areas of osteoid matrix deposition, woven bone, and occasionally new bone, which may be reactive tissue at the tumor margin or formed de novo within the tumor (9,18,19). The hallmarks of this tumor are its aggressively lytic behavior and the clear role that osteoclast-like tumor giant cells play in the lytic process.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Denosumab Induces Tumor Reduction and Bone Formation in Patients with Giant-Cell Tumor of Bone

Branstetter

Nelson

Manivel

et al. 2012

Clinical Cancer Research

379

301

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Purpose: Giant-cell tumor of bone (GCTB) is a locally aggressive, benign osteolytic tumor in which bone destruction is mediated by RANK ligand (RANKL). The RANKL inhibitor denosumab is being investigated for treatment of GCTB. We describe histologic analyses of GCTB tumor samples from a phase II study of denosumab in GCTB.Experimental Design: Adult patients with recurrent or unresectable GCTB received subcutaneous denosumab 120 mg every 4 weeks (with additional doses on days 8 and 15). The primary histologic efficacy endpoint was the proportion of patients who had a 90% or more elimination of giant cells from their tumor. Baseline and on-study specimens were also evaluated for overall tumor morphology and expression of RANK and RANKL.Results: Baseline tumor samples were typically composed of densely cellular proliferative RANKLpositive tumor stromal cells, RANK-positive rounded mononuclear cells, abundant RANK-positive tumor giant cells, and areas of scant de novo osteoid matrix and woven bone. In on-study samples from 20 of 20 patients (100%), a decrease of 90% or more in tumor giant cells and a reduction in tumor stromal cells were observed. In these analyses, thirteen patients (65%) had an increased proportion of dense fibro-osseous tissue and/or new woven bone, replacing areas of proliferative RANKL-positive stromal cells.Conclusions: Denosumab treatment of patients with GCTB significantly reduced or eliminated RANKpositive tumor giant cells. Denosumab also reduced the relative content of proliferative, densely cellular tumor stromal cells, replacing them with nonproliferative, differentiated, densely woven new bone. Denosumab continues to be studied as a potential treatment for GCTB.

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Denosumab Induces Tumor Reduction and Bone Formation in Patients with Giant-Cell Tumor of Bone

Branstetter

Nelson

Manivel

et al. 2012

Clinical Cancer Research

379

301

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“…GCRG contains much more fibrous stroma, hemosiderin deposits, infiltrative lymphocytes, and reactive bone formation compared with GCT, and the giant cells of GCRG tend to arrange focally and have a smaller number of nuclei than those of GCT. 1,5,17,22,24,34,37,41) Multinucleated giant cells of extracranial GCT and GCRG are immunohistochemically positive for CD68, 2,3,13,16,18,20,21,28,31,32,40,42) suggesting histiocytic differentiation. Similar findings are reported for GCT 7,15) and GCRG 26) of the skull.…”

Section: Discussionmentioning

confidence: 99%

Giant Cell Reparative Granuloma of the Temporal Bone: Neuroradiological and Immunohistochemical Findings. Case Report.

Yoshimura

Onda

Tanaka

et al. 2002

Neurol. Med. Chir.(Tokyo)

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A 38-year-old man presented with a giant cell reparative granuloma (GCRG) of the left temporal bone. Computed tomography showed a osteolytic middle cranial mass lesion. Magnetic resonance (MR) imaging showed the lesion as low intensity with heterogeneous enhancement by gadolinium on the T 1 -weighted images, and extremely low intensity on the T 2 -weighted images. Angiography showed the lesion as highly vascular and fed by branches of the left external carotid artery. After preoperative embolization, gross total removal of the tumor was performed. The postoperative course was uneventful and no evidence of recurrence has been found for more than 4 years. Histological examination revealed GCRG with multinucleated giant cells in the fibrous background, abundant collagen bundles, hemosiderin deposits, and trabeculae of reactive bone. Some of the mononuclear stromal cells and almost all of the giant cells were positive for CD68, suggesting histiocytic differentiation. These histological features reflect the marked decrease in signal intensity on T 2 -weighted MR images.

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“…Many histopathological and radiological characteristics have been evaluated as indicators of prognosis. 7,8 Previous studies have not found any significant difference in the proliferation of neoplastic cells between primary and recurrent GCT. 4,9,10 The present study was undertaken to evaluate whether delineation of reactive and neoplastic component of GCT using immunohistochemistry can help in deriving histopathological performance indicators which differ in primary and recurrent GCT.…”

Section: Introductionmentioning

confidence: 89%

Histopathological, immunohistochemical, and image analytic parameters characterizing the stromal component in primary and recurrent giant cell tumor of bone

Saxena

Safaya

Madan

et al. 2016

Journal of Clinical Orthopaedics and Trauma

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Immunohistochemistry Primary Recurrent a b s t r a c tGiant cell tumor (GCT) of bone is a benign locally aggressive tumor whose biological behavior is unpredictable. Currently, there are no definitive clinical, histological, biochemical, or immunological parameters that can predict its behavior. This study was undertaken to examine whether delineation of reactive and neoplastic stromal component of GCT can help in this regard. 55 cases of GCT (30 primary, 25 recurrent) were subjected to histopathological grading, immunohistochemistry, and image analysis. Spindling of stroma was more frequent in recurrent GCT with 64% cases having more than 50% spindled stroma (p < 0.001).Number of mitosis/10 HPF and higher grade were more in recurrent GCT. Mean percentage positivity for CD68 (38.36%) and a1-ACT (70.86%) was higher in primary than recurrent GCT.PCNA and MiB-1 labeling indices were higher in recurrent (42.62% and 9.18%, respectively) than in primary group (24.75% and 7.7%, respectively). A single numerical parameter encompassing stromal cell population and its proliferation was derived as ratio of PCNA/ CD68 and PCNA/a1-ACT. Both ratios were higher in recurrent (0.81 AE 0.38; 1.58 AE 1.50) than in primary GCT (0.58 AE 0.62; 0.34 AE 0.29) ( p = 0.002; 0.01). On image analysis, parameters significantly different between the two groups were nuclear area and nuclear integrated optical density. It was thus concluded that recurrent GCT shows higher grade, increased mitosis, more spindling, fewer reactive components, and higher proliferation than primary GCT.Delineation of reactive component (a1-ACT positive) and proliferating component (PCNA positive cells) using immunohistochemistry with calculation of the PCNA/ACT ratio delivers more information than image analysis.

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The prognostic significance of histomorphometry and immunohistochemistry in giant cell tumors of bone

Cited by 39 publications

References 22 publications

Denosumab Induces Tumor Reduction and Bone Formation in Patients with Giant-Cell Tumor of Bone

Denosumab Induces Tumor Reduction and Bone Formation in Patients with Giant-Cell Tumor of Bone

Giant Cell Reparative Granuloma of the Temporal Bone: Neuroradiological and Immunohistochemical Findings. Case Report.

Histopathological, immunohistochemical, and image analytic parameters characterizing the stromal component in primary and recurrent giant cell tumor of bone

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