scholarly journals Post-Denosumab-Treated Giant Cell Tumor of Bone: A Retrospective Histomorphological and Immunohistochemical Study

2021 ◽  
Vol 42 (04) ◽  
pp. 325-332
Author(s):  
Anvesh Kamble ◽  
Monalisa Hui ◽  
K. Nageshwara Rao ◽  
N. Ramakrishna ◽  
P. Chandrasekhar ◽  
...  
Keyword(s):  
Giant Cell ◽  
Stromal Cells ◽  
Mononuclear Cells ◽  
Giant Cells ◽  
Positive Staining ◽  
Low Grade ◽  
Nuclear Staining ◽  
Giant Cell Tumors ◽  
Woven Bone ◽  
Spindle Cells

Abstract Introduction Giant cell tumors of bone (GCTBs) are treated with surgery with or without local adjuvants. Denosumab is a human monoclonal antibody that has recently emerged to be effective in treating unresectable and recurrent GCTBs. Objective In this study, we analyzed the histomorphological changes in GCTB following treatment with denosumab. The expression of histone mutation H3.3G34W by immunohistochemistry (IHC) using mutant specific antibody was also determined. Materials and Methods Of the total 109 GCTBs encountered during the study period, 14 cases with neoadjuvant denosumab therapy were analyzed retrospectively. The post-treatment changes on histopathology were examined on routine hematoxylin and eosin-stained sections. IHC was done using antihistone H3.3G34 antibodies. Statistical analysis was limited to descriptive statistics. No hypothesis testing was performed. Results All these cases except three showed fibrosis with areas of hyalinization, prominent newly formed woven bone along with spindle cells in short fascicles and storiform pattern. There was complete absence and marked reduction in osteoclast-like giant cells in six and five patients, respectively. Only three patients showed a substantial amount of residual osteoclast-like giant cells. IHC with antihistone H3.3G34W antibody showed unequivocal nuclear positivity in the mononuclear cells in nine cases. The mononuclear cells rimming and entrapped within the woven bone were also positive on IHC. The spindle cells in the benign fibrous histiocytoma-like areas and septa of aneurysmal bone cyst-like areas also retained nuclear staining. Conclusion Awareness of post-denosumab-related histopathological changes are necessary to avoid misdiagnosis as fibroosseous lesion and low-grade central osteosarcoma. Expression of mutant-specific H3.3 G34W antibody suggests that the neoplastic stromal cells are largely retained after denosumab therapy. The positive staining of cells both within and those rimming the newly formed woven bone point toward osteoblastic phenotype of the neoplastic stromal cells.

Histomorphometric Analysis of Pre- and Post-Denosumab–Treated Giant Cell Tumor of Bone

2020 ◽  
Vol 28 (8) ◽  
pp. 859-867
Author(s):  
Nasir Ud Din ◽  
Masood Umer ◽  
Yong-Koo Park
Keyword(s):  
Giant Cell Tumor ◽  
Giant Cell ◽  
Stromal Cells ◽  
Mononuclear Cells ◽  
Giant Cells ◽  
Cell Tumor ◽  
P Value ◽  
Osteoblastic Activity ◽  
Woven Bone ◽  
Hematoxylin And Eosin

Context. Denosumab is a monoclonal antibody against RANK ligand. Its administration in giant cell tumor of bone (GCTB) cases results in elimination of giant cells and new bone formation. Neoplastic stromal cells of GCTB harbor mutation of histone 3.3 and have pre-osteoblastic properties and thus express SATB2. Objectives. To (1) analyze histological changes in post-denosumab–treated GCTB, (2) analyze expression of H3.3G34W and SATB2 in pre- and post-denosumab–treated samples, and (3) to discuss why changes occur in the expression of not only H3.3G34W but also SATB2. Materials and Methods. Hematoxylin and eosin slides of 19 cases of denosumab-treated GCTB were reviewed. Immunohistochemical stains H3.3G34W and SATB2 were performed. The number of positive mononuclear cells were counted and graded. Results. Complete absence of osteoclast-like giant cells (OCLGCs) was noted in most cases along with a fibro-osseous component merging with peripheral shell of reactive bone. Irregular trabeculae of woven bone and osteoid with focal osteoblastic rimming was seen. Spindle cells were arranged predominantly in fascicular pattern. Morphometric analysis of H3.3G34W showed a mean of 68.8% positive stromal cells in pretreatment and a mean of 26.9% positive stromal cells in posttreated specimens with a statistically significant P value (.001). Mean percentage of SATB2-positive stromal cells in the pre- and posttreatment specimens was 36.46% and 20.8%, respectively. Conclusions. Our study validates that denosumab treatment results in marked reduction of OCLGCs with increased osteoblastic activity. Decreased expression of H3.3G34W in posttreatment may be a result of decreased antigenicity of neoplastic mononuclear cells. No significant change in SATB2 expression was noted.

scholarly journals Recurrent novel HMGA2-NCOR2 fusions characterize a subset of keratin-positive giant cell-rich soft tissue tumors

2021 ◽  
Author(s):  
Abbas Agaimy ◽  
Michael Michal ◽  
Robert Stoehr ◽  
Fulvia Ferrazzi ◽  
Pavel Fabian ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Giant Cell ◽  
Mononuclear Cells ◽  
Giant Cells ◽  
Soft Tissue Tumors ◽  
Low Grade ◽  
Giant Cell Tumors ◽  
Type Giant ◽  
Metaplastic Bone

AbstractGiant cell tumors of soft tissue (GCT-ST) are rare low-grade neoplasms that were at one time thought to represent the soft tissue counterparts of GCT of bone (GCT-B) but are now known to lack the H3F3 mutations characteristic of osseous GCT. We present six distinctive giant cell-rich soft tissue neoplasms that expressed keratins and carried a recurrent HMGA2-NCOR2 gene fusion. Patients were five females and one male aged 14–60 years (median, 29). All presented with superficial (subcutaneous) masses that were removed by conservative marginal (3) or wide (2) local excision. The tumors originated in the upper extremity (2), lower extremity (2), head/neck (1), and trunk (1). Five patients with follow-up (median, 21 months; range, 14–168) remained disease-free. Grossly, all tumors were well-demarcated but not encapsulated with variable lobulation. Histologically, they were composed of bland plump epithelioid or ovoid to spindled mononuclear cells admixed with evenly distributed multinucleated osteoclast-type giant cells. Foci of stromal hemorrhage and hemosiderin were seen in all cases. The mitotic activity ranged from 2 to 14/10 high power fields (median: 10). Foci of necrosis and vascular invasion were seen in one case each. The mononuclear cells were immunoreactive with the AE1/AE3 keratin cocktail and less frequently/less diffusely for K7 and K19 but lacked expression of other lineage-associated markers. RNA-based next-generation sequencing revealed an HMGA2-NCOR2 fusion in all tumors. None of the keratin-negative conventional GCT-ST showed the HMGA2-NCOR2 fusion (0/7). Metaplastic bone (4/9) and SATB2 expression (3/4) were frequent in keratin-negative conventional GCT-ST but were lacking in keratin-positive HMGA2-NCOR2 fusion-positive tumors. The distinctive immunophenotype and genotype of these tumors strongly suggest that they represent a discrete entity, differing from conventional GCT-ST and other osteoclast-rich morphologic mimics. Their natural history appears favorable, although a study of additional cases and longer follow-up are warranted.

Giant Cell Tumors: Inquiry Into Immunohistochemical Expression of CD117 (c-Kit), Microphthalmia Transcription Factor, Tartrate-Resistant Acid Phosphatase, and HAM-56

2005 ◽  
Vol 129 (3) ◽  
pp. 360-365
Author(s):  
Rolando Y. Ramos ◽  
Helen M. Haupt ◽  
Peter A. Kanetsky ◽  
Rakesh Donthineni-Rao ◽  
Carmen Arenas-Elliott ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Acid Phosphatase ◽  
Giant Cell ◽  
Stromal Cells ◽  
Mononuclear Cells ◽  
Osteoclast Differentiation ◽  
Tartrate Resistant Acid Phosphatase ◽  
Immunohistochemical Expression ◽  
Giant Cell Tumors ◽  
Microphthalmia Transcription Factor

Abstract Context.—Osteoclast-like giant cells (GCs) in giant cell tumors (GCTs) are thought to derive from a monocyte-macrophage lineage. Microphthalmia transcription factor (MITF) is necessary for osteoclast gene expression and tartrate-resistant acid phosphatase (TRAP) activation; c-Kit plays a role in regulation of MITF. Objective.—To gain insight into the differentiation of GCTs of bone (GCTBs) and GCTs tendon sheath (GCTTSs) by investigating immunohistochemical staining for c-Kit, MITF, TRAP, and HAM-56 in the GCs and stroma. Design.—Immunoreactivity for CD117 (c-Kit), MITF, TRAP, and HAM-56 was studied in 35 GCTBs, 15 GCTTSs, and 5 foreign-body GC controls. Results.—Across tumors, MITF and TRAP but not c-Kit were generally expressed in GCs; TRAP was variably expressed in stromal cells. The MITF was expressed more consistently in stromal cells of GCTTSs than GCTBs (P < .001). The GCTBs showed more intense MITF stromal (P < .001) and TRAP GC staining (P = .04) than GCTTSs. HAM-56 staining by stromal cells was associated with MITF stromal staining (r2 = 0.6, P < .001). Conclusions.—Results suggest that MITF and TRAP are expressed during osteoclast differentiation and that a proportion of mononuclear cells in GCTs express the macrophage marker HAM-56. Both GCTBs and GCTTSs show similar patterns of immunohistochemical expression.

scholarly journals Gaint cell tumour of phalynx: have you seen it?

2020 ◽  
Vol 8 (6) ◽  
pp. 2309
Author(s):  
Nuthan Jagadeesh ◽  
Sachin H. G. ◽  
Vishwanath M. S. ◽  
Arjun Mandri
Keyword(s):  
Giant Cell ◽  
Mononuclear Cells ◽  
Histopathological Examination ◽  
Giant Cells ◽  
Pain Scale ◽  
Giant Cell Tumors ◽  
Foot Function Index ◽  
Function Index ◽  
Foot Function ◽  
Scale 8

Giant cell tumors are rarely seen in the foot. Only 1-2% cases of GCT occur in the foot. They can cause a significant amount of pain and deformity due to their aggressive and recurrent nature whenever it occurs in foot. We present an unusual case of a giant cell tumor of proximal phalynx of middle toe of left foot. 26 year old male came with complaints of pain and swelling over the middle toe of left foot since 6 months. Clinical and radiological features showed features consistent with GCT. Foot Function Index revealed a) Pain scale: 29 / 50 = 58%, b) Disability scale: 56 / 90 = 62%, c) Activity limitation scale: 8 / 30 = 27%. Authors performed enbloc resection with ray amputation of 3rd toe. Histopathological examination of excised specimen revealed classic findings of mononuclear cells with interspersed fibro-collagenous strands and numerous multinucleated osteoclast-like giant cells which confirmed our diagnosis. Patient was serially followed up and at 6 months followup, there were no signs of recurrence with markedly improved foot function index.

Giant Cell Lesion of the Jaw. Case Report

1988 ◽  
Vol 74 (4) ◽  
pp. 479-484 ◽  
Author(s):  
Roberto Bondi ◽  
Carmelo Urso ◽  
Beatrice Santucci ◽  
Marco Santucci ◽  
Alessandro Marchesi ◽  
...  
Keyword(s):  
Giant Cell ◽  
Mononuclear Cells ◽  
Giant Cells ◽  
Cell Tumor ◽  
Long Bones ◽  
Giant Cell Reparative Granuloma ◽  
Giant Cell Tumors ◽  
Giant Cell Lesion ◽  
Characteristic Features ◽  
Microtubular Structures

A case is presented of a male patient affected by a giant cell lesion of the jaw, which had two recurrences in 8 years. Histologically, the lesion appeared to be composed of giant cells and mononuclear cells. Histoenzymatic study demonstrated acid phosphatase in both types of cells, and beta-glucuronidase in giant cells only. In some nuclei of giant cells, ultrastructural investigation showed filaments or microtubular structures of variable length, with irregular transverse periodicity, in addition to other expected findings. These characteristic features, found in giant cells of some giant cell tumors of the long bones, have never before been reported in a giant cell lesion of the jaw. The results are considered in order to assess the diagnosis, and the pathologic profiles of giant cell reparative granuloma, and of giant cell tumor are critically discussed.

scholarly journals Tenosynovial Giant Cell Tumor: Better molecular understanding revolutionizes treatment outcome

2016 ◽  
Vol 2 (1) ◽  
Author(s):  
Emad Shash
Keyword(s):  
Giant Cell ◽  
Mononuclear Cells ◽  
Response Rate ◽  
Inflammatory Cells ◽  
Giant Cells ◽  
High Response Rate ◽  
Giant Cell Tumors ◽  
Development Technology ◽  
Benign Nature ◽  
Stimulating Factor

<p>Tenosynovial giant cell tumors (TGCTs) are rare tumors, which are primarily treated via surgery with a low likelihood of metastasis. Although wide excision is an excellent choice for local control, tumors located within or close to major joints, along with the benign nature of the disease, make such resection impractical. An increase in local recurrences and the need for multiple surgical procedures promoted the interest in targeted-therapies for this disease. TGCTs contain a mixture of giant cells, mononuclear cells and inflammatory cells, with clonal cytogenetic abnormalities through rearrangements involving 1p11–13. Colony stimulating factor (<em>CSF1</em>) gene encodes for the ligand of CSF1 receptor (CSF1R). The <em>CSF1</em> gene is located at the chromosome 1p13 breakpoint and is found to be translocated in 63%–77% of patients with TGCTs. Selective CSF1R inhibitors yield high response rate and disease control, demonstrating the integration of a new drug development technology that could revolutionize treatment outcomes.  </p>

Giant Cell Granuloma of the Temporal Bone: A Case Report With Immunohistochemical, Enzyme Histochemical, and In Vitro Studies

2003 ◽  
Vol 127 (9) ◽  
pp. 1217-1220 ◽  
Author(s):  
Xue-Fei Tian ◽  
Tie-Jun Li ◽  
Shi-Feng Yu
Keyword(s):  
Giant Cell ◽  
Temporal Bone ◽  
Mononuclear Cells ◽  
Giant Cells ◽  
Tartrate Resistant Acid Phosphatase ◽  
Giant Cell Granuloma ◽  
Ki 67 ◽  
The Right ◽  
Histochemical Reactivity

Abstract A case of giant cell granuloma (GCG) that occurred in the right temporal bone is reported. The lesion showed histologic features identical to GCG. The multinuclear giant cells (MGCs) in the lesion showed strong reactivity with CD68, but patchy staining for myeloid/histiocyte antigen, α-1-antitrypsin, α-1-antichymotrypsine, and lysozyme. Activity of tartrate-resistant acid phosphatase was also consistently detected in the MGCs. Some of the mononuclear cells of the lesion exhibited similar immunocytochemical and histochemical reactivity as the MGCs. Ki-67 staining, however, was only detected in the mononuclear cells. The MGCs isolated from the lesion presented characteristic morphology of osteoclasts and possessed the ability to excavate bone in vitro. Thus, the MGCs in GCG appeared to express both macrophage- and osteoclast-associated phenotypes. The mononuclear cells were the major proliferative elements in the lesion and a subpopulation of these cells may represent precursors of the MGCs.

Giant Cell Poor Extra-Articular Diffuse-Type Tenosynovial Giant Cell Tumor With Extensive Desmin Expression: A Potential Diagnostic Pitfall With Cytogenetic Confirmation

2018 ◽  
Vol 27 (1) ◽  
pp. 59-61
Author(s):  
Liurka Lopez ◽  
Karen Schoedel ◽  
Ivy John
Keyword(s):  
Giant Cell Tumor ◽  
Giant Cell ◽  
Mononuclear Cells ◽  
Giant Cells ◽  
Cell Tumor ◽  
Diffuse Type ◽  
Tenosynovial Giant Cell Tumor ◽  
Diagnostic Pitfall

Diffuse-type tenosynovial giant cell tumor can rarely present as an entirely extra-articular mass, which can be misdiagnosed as a sarcoma especially when giant cells are absent, dominated by large dendritic mononuclear cells, and desmin expression is extensive.

scholarly journals Giant cell tumor stromal cells: osteoblast lineage-derived cells secrete IL-6 and IL-10 for M2 macrophages polarization

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9748
Author(s):  
Kuan Yang ◽  
Lihui Bao ◽  
Xiaoning He ◽  
Wanmin Zhao ◽  
Dongdong Fei ◽  
...  
Keyword(s):  
Giant Cell Tumor ◽  
Giant Cell ◽  
Stromal Cells ◽  
Macrophage Polarization ◽  
Giant Cells ◽  
Interleukin 10 ◽  
Cell Tumor ◽  
M2 Macrophages ◽  
M2 Polarization ◽  
Macrophages Polarization

Background The giant cell tumor (GCT) is a benign tumor which consists of three types cells: mononuclear histiocytic cells (MNHCs), multinuclear giant cells (MNGCs), and GCT stromal cells (GCTSCs). Numerous studies claim that GCTSCs have mesenchymal stem cells (MSCs) characters and play an important role in osteoclastogenesis; however, there are no research studies concerning macrophage polarization among GCT, which can be regarded as an ingredient for tumor aggression. Method We tested the effect of GCTSCs from three GCT samples which were collected from patients on proliferation, apoptosis and polarization of macrophage. Result In this article, we verified that GCTSCs expressed MSCs markers and had higher proliferation and relative lower differentiation abilities compared with BMMSCs. What’s more, we found a higher proportion of M2 macrophages among neoplasm. Co-culturing GCTSCs with macrophages resulted in prominent macrophage M2 polarization and increased the release of IL-6 (Interleukin-6) and IL-10 (Interleukin-10)from GCTSCs. In conclusion, GCTSCs, as originating from MSCs, can secret IL-6 and IL-10, which may play a significant role in macrophage M2 polarization.

Giant Cell Tumor of Tendon Sheath: Immunohistochemical Study of 20 Cases

1997 ◽  
Vol 83 (5) ◽  
pp. 841-846 ◽  
Author(s):  
Antonio Cavaliere ◽  
Angelo Sidoni ◽  
Emilio Bucciarelli
Keyword(s):  
Giant Cell Tumor ◽  
Giant Cell ◽  
Mononuclear Cells ◽  
Neuron Specific Enolase ◽  
Synovial Cell ◽  
Tendon Sheath ◽  
Giant Cells ◽  
Cell Tumor ◽  
Electron Microscopic ◽  
Filament Bundles

Aims and background Giant cell tumor of tendon sheath (GCTTS) is a common tumor occurring on the tendon sheaths of the fingers. The nature of this lesion is still controversial: some researchers consider it a reactive process arising from chronic inflammation while others regard it as a tumor of presumed synovial cell or monocytic macrophage system origin. In an effort to clarify the histogenesis we decided to further investigate the immunophenotypic profile of this tumor. Study design We studied 20 GCTTS of the fingers using a panel of 18 antibodies, 13 monoclonal and 5 polyclonal. Results The immunohistochemical investigation revealed that the mononuclear cells of this lesion can be divided into two groups. The cells of the first and more numerous group were positive for vimentin, PG-M1 and KP1 but also for muscle actin (HHF35 monoclonal antibody) and neuron-specific enolase. A second population of mononuclear cells, usually arranged around the giant cells, were positive for PG-M1, KP1, LCA and occasionally for alpha-1-antitrypsin and alpha-1-antichymotrypsin. Multinucleated giant cells were also positive for KP1, PG-M1 and LCA monoclonal antibodies. A variable but usually weak positivity for al-pha-1-antitrypsin, alpha-1-antichymotrypsin and lysozyme was also observed. Conclusions Our results suggest a synovial cell origin for GCTTS and do not support the hypothesis that it could be a neoplasm with a true histiocytic origin. The positivity of some cells for the HHF35 antibody, together with electron microscopic evidence of filament bundles with focal dense bodies, suggests that at least part of the mononuclear cells may have a myofibroblastic differentiation.

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