^
CANCER:

Giant Cell Tumor of Bone

3d
In our opinion, the combination of relevant clinical history, radiologic imaging, appropriate immunohistochemical markers and cytogenetics are key in differentiating closely related sarcomatoid carcinomas, true sarcomas and sarcomatoid mesotheliomas
WT1 (WT1 Transcription Factor) • NKX2-1 (NK2 Homeobox 1) • CDX-2 • NAPSA (Napsin A Aspartic Peptidase) • SYP (Synaptophysin)
3d
Oncology planned to initiate chemotherapy as an outpatient, unfortunately, the patient was unstable for a PET-scan or further testing and failed treatments with Docetaxel and Gemcitabine. This case illustrates the possibility of extensive metastasis from an osteoclastic sarcoma without an obvious primary. These can be very aggressive as seen in our patient and the present therapies may not be sufficient to manage them and better understanding of the pathology and therapeutics is necessary.
Clinical
|
AFP (Alpha-fetoprotein) • CEACAM5 (CEA Cell Adhesion Molecule 5) • VIM (Vimentin) • CD68 (CD68 Molecule) • Cancer antigen 19-9
|
gemcitabine • docetaxel
6d
This is the first report about quercetin effects on giant cell tumor of bone cultured cells. Further studies in other models could be done to support the use of quercetin as a complementary treatment in giant cell tumor of bone.Abbreviations: Giant cell tumor of bone (GCTB); transmission electron microscopy (TEM); reverse transcription - polymerase chain reaction (RT-PCR); receptor interacting protein kinase 1 (RIP1K); Dulbecco's Modified Eagle's Medium (DMEM).
Journal
|
CASP3 (Caspase 3) • CASP8 (Caspase 8) • RIPK1 (Receptor Interacting Serine/Threonine Kinase 1)
13d
Pathologists can select cases for p53 testing with high sensitivity and low risk of false negativity. Molecular characterization of endometrial carcinomas has great potential to refine ESGO risk classification for a small subset but offers little value for approximately half of endometrial carcinomas, namely, EEC1/2/stage IA cases.
Journal
|
TP53 (Tumor protein P53)
15d
Based on these findings, we concluded that the PCL scaffold is an efficient model to culture GCTB cells, and the cell viability and adherence to the scaffold can be preserved for up to 14 days. Moreover, this model can also be used in subsequent studies to assess in vitro cell-cell interactions and antineoplastic efficacy of certain agents to establish a treatment against GCTB.
Journal
|
TP63 (Tumor protein 63) • VCL (Vinculin) • CTSK (Cathepsin K)
15d
We describe the disease burden and signal characteristics on MRI and correlate with the response reported in the patients' medical records. Given that the use of pexidartinib and other CSF inhibitors is likely to increase, musculoskeletal radiologists should be aware of this novel non-operative treatment and the MRI appearance of diffuse TSGCT during therapy.
Journal
|
CSF1 (Colony stimulating factor 1)
|
Turalio (pexidartinib)
20d
Importantly, blocking CD44 with a neutralizing antibody reduces the number of MGCs and suppresses tumorigenesis in vivo. Overall, our data reveal a mechanism of MGC induction in GCTB and support CD44-targeting approaches for GCTB treatment.
Journal
|
CD44
28d
To our knowledge, this is the first case of GCTST with metastasis to multiple bone and soft tissue sites. Chhabra is a consultant with ICON Medical and Treace Medical Concepts, Inc.
Clinical
|
H3F3A (H3 Histone Family Member 3A)
28d
We believe that the initial endoscopic resection may have inadvertently created iatrogenic spread of GCT via lymphovascular spaces to the liver. This phenomenon has been described in other tumors including benign metasta-sizing leiomyoma of uterus, giant cell tumor of bone, and pleomorphic adenoma of salivary glands.
CD68 (CD68 Molecule)
1m
There was no difference between aggressive and nonaggressive lesions regarding the angiogenic markers. The expression of WT1 and CD105 suggests that CGCL presents a tumoral vascular pattern with high neoangiogenic activity. The absence of histone mutation may indicate that CGCL is not a true giant cell tumor.
Journal
|
WT1 (WT1 Transcription Factor) • CD31 (Platelet and endothelial cell adhesion molecule 1) • H3F3A (H3 Histone Family Member 3A) • ENG (Endoglin)
|
CD31 expression
1m
Although p63 was present in majority of the GCLBs, its percentage positivity was significantly higher in GCTB compared to the other GCLBs. The diagnosis of GCTB is likely if cut-off value of > 50% is applied.
Journal
|
TP63 (Tumor protein 63)
2ms
The differential diagnosis of UCOGC includes other high- grade tumours with giant cells [sarcomatoid urothelial carcinoma, pleomor- phic giant cell carcinoma (PGCC) of the bladder and PGCC of the prostate]. UCOGC usually presents at an advanced stage and its prognosis is very poor.
CD68 (CD68 Molecule) • TP63 (Tumor protein 63) • GATA3 (GATA binding protein 3)
2ms
GCTB is an uncommon, usually benign neoplasm of early adulthood, showing predilection for epiphyses of long bones. Skull GCTBs are extremely rare (0.51% of all GCTBs), especially those orig- inating from the clivus. Surgery with complete resection is the current treatment of choice, though it is difficult to achieve.
Clinical
|
CD68 (CD68 Molecule) • GFAP (Glial Fibrillary Acidic Protein)
2ms
TGCT of the temporomandibular joint may present clinical- ly and radiologically as a primary parotid gland lesion. Giant cell-rich lesions are uncommon in salivary glands. It is important to keep this entity in the differential diagnosis of giant cell-rich lesions in the parotid gland.
Clinical • Review
|
ALK (Anaplastic lymphoma kinase) • CD68 (CD68 Molecule)
2ms
UPCOC is very rare. It often occurs around the sixth decade. Histological study reveals two distinct cell populations.
Clinical
|
KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation
2ms
These include new treatments with targeted therapies and immunotherapy, which today represent possible therapeutic options. It is especially important to be attentive to new and potential avenues of research, and to promote the conduct of specific clinical trials for rare sarcomas.
Review • Journal • IO biomarker
|
NTRK (Neurotrophic receptor tyrosine kinase)
|
NTRK fusion
2ms
Notably, the cytotoxic effects were dependent on a direct contact of cells and BGs and could not be observed using indirect cultivation settings. Our data suggest that BGs might represent promising materials for the treatment of GCTB in order to reduce tumor recurrence with simultaneous enhancement of bone regeneration.
Journal
|
HMGB1 (High Mobility Group Box 1)
2ms
Small molecules and antibodies targeting the CSF1/CSF1R axis have shown promise in the treatment of TGCT and cancer, with pexidartinib recently receiving Food and Drug Administration (FDA) approval for treatment of TGCT. In preclinical studies, vimseltinib durably suppressed CSF1R activity in vitro and in vivo, depleted macrophages and other CSF1R-dependent cells, and resulted in inhibition of tumor growth and bone degradation in mouse cancer models. Translationally, in a phase 1 clinical study, vimseltinib treatment led to modulation of biomarkers of CSF1R inhibition and reduction in tumor burden in initial TGCT patients.
Journal
|
FLT3 (Fms-related tyrosine kinase 3) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • CSF1R (Colony stimulating factor 1 receptor)
|
CSF1 expression
|
Turalio (pexidartinib) • vimseltinib (DCC-3014)
2ms
Pathologists can select cases for p53 testing with high sensitivity and low risk of false negativity. Molecular characterization of endometrial carcinomas has great potential to refine ESGO risk classification for a small subset but offers little value for approximately half of endometrial carcinomas, namely, EEC12/stage IA.
TP53 (Tumor protein P53)
2ms
These data indicated possible characteristics of different aspects of TGCTs, SC, and SS. Further clarification and understanding of these factors will help with differential clinical diagnosis and recurrent risk assessment.
Clinical • Journal
|
CD163 (CD163 Molecule)
|
CD163 expression
2ms
Regarding the treatment of giant cell tumor of bone, recent studies have suggested that denosumab administration is related to a higher local recurrence rate following curettage, but a lower local recurrence rate following en bloc resection...Pexidartinib seems to be a promising systemic therapy for the treatment of tenosynovial giant cell tumors for which surgery is not expected to improve the function of the affected limb. Finally, the life expectancy of patients is the most important factor in determining the optimal surgical procedure for patients with impending or pathological fractures of the long bone due to metastatic bone tumors. Elevated C-reactive protein level was found to be an independent poor prognostic factor at 1 year after surgery for long bone metastases.
Retrospective data • Review • Journal
|
CRP (C-reactive protein)
|
Prolia (denosumab) • Turalio (pexidartinib)
2ms
P2, N=818, Recruiting, National Cancer Institute (NCI) | Trial primary completion date: Aug 2021 --> Aug 2022
Clinical • Trial primary completion date
|
CD4 (CD4 Molecule)
|
PD-L1 overexpression • PD-L1 amplification
|
Opdivo (nivolumab) • Yervoy (ipilimumab)
2ms
Cell functional experiments, co-immunoprecipitation, MG132 and ginkgolic acid treatment, western blot, and ChIP-Seq were used to identify the mechanism of S100A10 nuclear location...The expression of S100A10 in the nuclei and cytoplasm of rectal cancer after neoadjuvant chemoradiation (nCRT) and liver metastases increased compared with that in rectal cancer without nCRT. Taken together, the expression and nuclear localization of S100A10 modified by SUMOylation were associated with the high proliferation and migration of PGCCs and their daughter cells, and the differentiation, metastases, and relapse of CRCs by regulating the expression of ARHGEF18, PTPRN2, and DEFA3.
Journal
|
CD133 • CD44
|
CD44 expression • CD133 expression
|
MG132
3ms
Furthermore, in the case of a 17-year-old patient suffering from GCTB, we showed that the addition of sunitinib to the standard treatment of GCTB with the monoclonal antibody denosumab resulted in the complete depletion of multinucleated giant cells and mononuclear stromal cells in the tumor tissue. To summarize, the obtained data showed that a specific receptor tyrosine kinase (RTK) signaling pattern is activated in GCTB cells and plays an important role in the regulation of cell proliferation. Thus, activated RTKs and their downstream signaling pathways represent useful targets for precision treatment with low-molecular-weight inhibitors or with other types of modern biological therapy.
Journal
|
EGFR (Epidermal growth factor receptor) • PDGFRB (Platelet Derived Growth Factor Receptor Beta)
|
Sutent (sunitinib) • Prolia (denosumab)
3ms
Immunohistochemical profile demonstrated positivity for smooth muscle actin and CD68 and negativity for desmin, myo-D1, S100, HMB-45, Melan-A, p16, and NKIC3. The unusual characteristics of this case emphasize the clinicopathologic heterogeneity of GCTST.
Clinical • Journal
|
CD68 (CD68 Molecule)
3ms
PD-L1 expression and higher SIRPα cell infiltration were significantly correlated with shorter recurrence-free survival. PD-L1 and SIRPα immune checkpoint inhibitors may provide clinical benefit in GCTB patients with recurrent lesions after denosumab therapy.
Journal • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • IDO1 (Indoleamine 2,3-dioxygenase 1) • FOXP3 (Forkhead Box P3)
|
PD-L1 expression • PD-L1 overexpression • IDO1 expression • IDO1 positive • FOXP3 expression
|
Prolia (denosumab)
3ms
Consequently, they provide metastatic cancer cells with motility, margination, transmigration, chemotaxis, phagocytosis, angiogenesis, matrix degradation, and resistance to chemotherapy. For these reasons, we think that the concept of Epithelial-Mesencyhmal-Myeloid-Transition (EMMT) will be more accurate than EMT for cancer cells with myeloid properties.
Review • Journal
|
CD163 (CD163 Molecule) • CD33 (CD33 Molecule) • CD68 (CD68 Molecule)
3ms
These were likely silenced by upregulated CDK inhibitors p15, p16, p27, p53 through its effector p21 and possibly cyclin G1, consistent with the prevention of DNA replication. In conclusion, the upregulation of known and several novel cell cycle progression markers detected here clearly verify early replication activities in GCs, which are controlled by cell cycle arresting CDK inhibitors at G1 phase, and support the functional maturation of GCs in GCTB.
Journal
|
CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • AURKA (Aurora kinase A) • CCNA2 (Cyclin A2) • CDK2 (Cyclin-dependent kinase 2) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • MCM2 (Minichromosome maintenance complex component 2)
3ms
Patients who developed edema in response to emactuzumab had elevated HA in peripheral blood. Our findings indicate that an early increase of peripheral HA can serve as a pharmacodynamic marker for edema development and suggest potential interventions based on MMP inhibition for relieving periorbital edema in patients treated with CSF1R inhibitors.
Journal
|
MMP2 (Matrix metallopeptidase 2) • MMP3 (Matrix metallopeptidase 3)
|
emactuzumab (RG7155)
3ms
New trial
|
VEGFA (Vascular endothelial growth factor A)
4ms
The patients can be treated with pharmacological agents (Denosumab), surgery with tumor excision, reconstruction or osteosynthesis, and radiotherapy...It is necessary to evaluate in a multidisciplinary team to avoid unfavorable oncological and psychiatric developments. Through its clinical, HP, and therapeutic features, GCTB has multiple connections with the psychological and psychopathological dimension.
Journal
|
IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • TNFRSF11A (TNF Receptor Superfamily Member 11a)
|
Prolia (denosumab)
4ms
ITF-2357 was the most significant compound with an IC50 lower than 0.1 uM...As PDX retain the principal histologic and genetic characteristics of the primary tumors, mad it a valuable research tool in predictive clinical efficacy. In this study, we first established a malignant GCTB PDX model, which might further accelerate the progress of drug development in malignant GCTB.
Clinical • Journal
|
H3F3A (H3 Histone Family Member 3A)
|
givinostat (ITF2357)
4ms
The likelihood of finding a NTRK fusion in bone tumours in clinical practice is extremely low. This may imply that, if more comprehensive large scale molecular studies confirm this, routine predictive NTRK testing in bone tumour patients with advanced disease may be reconsidered.
Journal
|
NTRK (Neurotrophic receptor tyrosine kinase)
|
NTRK fusion
4ms
Awareness of this entity and application of ancillary techniques is recommended for its exact diagnosis and in differentiating this rare variant from its diagnostic mimics. This case also indicates a poor chemotherapy response in this unusual variant of Ewing sarcoma, occurring in the calcaneus.
Clinical • Journal
|
EWSR1 (EWS RNA Binding Protein 1) • TP63 (Tumor protein 63)
4ms
PLX3397 treatment concurrently depleted TAMs and FOXP3+ regulatory T cells and, surprisingly, enhanced infiltration of CD8+ T cells into the microenvironments of both primary and metastatic osteosarcoma sites. Our preclinical results show that PLX3397 has strong macrophage- and T cell-modulating effects that may translate into cancer immunotherapy for bone and soft tissue sarcomas.
Journal
|
CSF1R (Colony stimulating factor 1 receptor) • FOXP3 (Forkhead Box P3)
|
Turalio (pexidartinib)
5ms
Giant cell tumor of bone should be distinguished from its mimickers due to differences in prognosis and treatment. Immunohistochemical and molecular detection of H3F3A gene mutation represents a reliable diagnostic tool.
Clinical • Journal
|
H3F3A (H3 Histone Family Member 3A)
5ms
We conclude that RNAscope CSF1 CISH may be a valuable adjunct for the diagnosis of TGCT of all types, especially those with atypical or malignant morphologic features. Detection of CSF1 mRNA expression may also have predictive significance in cases where use of the CSF1 inhibitor pexidartinib is considered.
Journal
|
CSF1 (Colony stimulating factor 1) • CSF1R (Colony stimulating factor 1 receptor)
|
CSF1 expression
|
Turalio (pexidartinib)
5ms
Arrb2 facilitates the proliferation and inhibits the apoptosis of TGCT FLS through activating the PI3K-Akt cell survival pathway, providing new insight into the molecular mechanism of TGCT.
Journal
|
CASP3 (Caspase 3)
5ms
Therefore, we believe that these GCTB without giant cells expand one end of the heterogeneous range of GCTB. Due to the lack of giant cells the correct diagnosis of GCTB is challenging or even impossible based on pure histological grounds. In these cases, detection of the characteristic H3F3A gene mutation (G34W-specific antibody RM263 or sequencing) is extremely helpful to diagnose those lesions without giant cells as a giant cell tumour of bone.
Clinical • Journal
|
CD68 (CD68 Molecule) • H3F3A (H3 Histone Family Member 3A)
|
Prolia (denosumab)
5ms
Secukinumab may play a role in bone remodeling for GCTB. Radiologists, surgeons, and pathologists should be aware of this interaction, which can cause lesional ossification. Further research is required to define the therapeutic potential of this drug for GCTB and osteolytic disease.
Clinical • Journal
|
IL17A (Interleukin 17A)
|
Prolia (denosumab) • Cosentyx (secukinumab)
6ms
This case emphasized that pancreatic UC-OGC can provide bland morphology, which is morphologically and immunohistochemically undistinguishable from GCT of the bone and soft tissue. Our study also highlights the importance of genetic analyses in properly diagnosing and managing such patients.
Clinical • Journal
|
KRAS (KRAS proto-oncogene GTPase) • CD163 (CD163 Molecule) • GNAS (GNAS Complex Locus)
|
KRAS mutation • KRAS G12V • KRAS G12 • GNAS R201C
6ms
This is the first report of proven H3F3A mutation in both the primary GCTB and the secondary osteosarcoma in the same case. Clinicians should consider secondary malignancy in patients presenting with a lesion at the site of a previously treated GCTB after a long interval.
Clinical • Review • Journal
|
H3F3A (H3 Histone Family Member 3A)
6ms
A recent insight into their molecular genetics and pathogenesis, with identification of KRAS, FGFR1 and TRPV4 mutations, allows for better diagnostic differentiation and opens the door to the use of pathway inhibitors in the treatment of recurrent or dysmorphic lesions. In this review, we provide an updated summary of the clinical and pathological features of oral cavity giant cell granulomas that help with their precise diagnosis and management.
Review • Journal
|
KRAS (KRAS proto-oncogene GTPase) • FGFR1 (Fibroblast growth factor receptor 1)
|
FGFR1 mutation
6ms
Six cases of occipital GCT have been reported in the literature with only 1 pediatric case. There have been more females than males with a median age of 21 years. The main presenting symptom was a headache with other symptoms being neck pain, difficulty swallowing, blurry vision, or localized tenderness.
Clinical • Review
|
CD68 (CD68 Molecule)
6ms
TGCT are rare in children. Surgery is the primary treatment, but especially in diffuse TGCT, can lead to poor functional outcomes and recurrence. In the near future, systemic therapies targeting the CSF-1R, such as pexidartinib, may play crucial roles as preoperative regimens to reduce surgical morbidity, postoperative therapies to reduce recurrence rates, and may even replace surgical management completely in some cases.
Clinical
|
CSF1R (Colony stimulating factor 1 receptor)
|
Turalio (pexidartinib)
7ms
Vimseltinib is currently being evaluated in Phase 1/2 clinical studies for the treatment of TGCT and other solid tumors (NCT03069469; NCT04242238). Initial pharmacodynamic and efficacy data in TGCT patients will be presented.
PD(L)-1 Biomarker • IO biomarker
|
FLT3 (Fms-related tyrosine kinase 3) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • CSF1R (Colony stimulating factor 1 receptor)
|
vimseltinib (DCC-3014)
7ms
Subrenal capsule supports the growth of TGCT tumor grafts, maintaining their original morphology and histology. This TGCT-PDTX model plus ex vivo explant cultures is a potential preclinical translational platform for locally aggressive tumors, such as TGCT.
Preclinical • Journal
|
CD163 (CD163 Molecule)
|
Turalio (pexidartinib)
7ms
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.
Journal
|
NCOR2 (Nuclear Receptor Corepressor 2) • HMGA2 (High mobility group AT-hook 2)
7ms
Additional histologic findings include extensive calcium pyrophosphate dihydrate deposition in two cases and features resembling tenosynovial giant cell tumor (TGCT). Overall, while the tumors from our series show significant morphologic overlap with chondroblastoma-like soft tissue chondroma, we describe findings that expand the morphologic spectrum of these neoplasms and therefore refer to them as "calcified chondroid mesenchymal neoplasms." These neoplasms represent a spectrum of chondroid/cartilage matrix-forming tumors harboring FN1-receptor TK fusions that include those classified as soft tissue chondroma as well as chondroid TGCT.
Clinical • Journal
|
FGFR2 (Fibroblast growth factor receptor 2) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • FGFR1 (Fibroblast growth factor receptor 1) • MERTK (MER Proto-Oncogene, Tyrosine Kinase)
|
NTRK1 fusion • FGFR2 fusion • FGFR1 fusion
7ms
eGBM is a high-grade malignant tumor and most of the cases show recurrences or deaths in a short-period time. The younger patients have a relatively better prognosis than the older ones.
Clinical • Journal
|
BRAF (B-raf proto-oncogene) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • TERT (Telomerase Reverse Transcriptase) • ATRX (ATRX Chromatin Remodeler) • GFAP (Glial Fibrillary Acidic Protein)
|
BRAF V600E • BRAF V600 • IDH2 R172 • TERT mutation
7ms
In addition, the pleomorphic sarcoma showed an AKT2 and a NRAS mutation. These data are inconclusive concerning the role denosumab plays in the event of malignant progression/transformation of GCTB and point to diverging pathways of tumor progression of GCTB associated with this treatment.
Journal
|
NRAS (Neuroblastoma RAS viral oncogene homolog) • FGFR1 (Fibroblast growth factor receptor 1) • ARID2 (AT-Rich Interaction Domain 2) • AKT2 (V-akt murine thymoma viral oncogene homolog 2)
|
NRAS mutation • FGFR1 mutation
|
Prolia (denosumab)
7ms
Our results suggest that eNOS, endostatin, HIF-1α, IL-6, CCL2/MCP-1, CCL8/MCP-2, CCL7/MCP-3, Tie and VEGF may play important roles in tumorigenesis, reveal the expression differences of tumor-associated cytokines and angiogenesis related factors, and provide clinical evidence for studying the mechanisms on the metastasis in GC, OS and ES.
Journal
|
IL6 (Interleukin 6) • HIF1A (Hypoxia inducible factor 1, alpha subunit) • CCL2 (Chemokine (C-C motif) ligand 2) • NOS3 (Nitric oxide synthase 3)
|
HIF1A expression
8ms
One of our cases is the first to clearly demonstrate chronological loss of prostate markers during dedifferentiation from prior conventional prostate carcinoma to PGCC. Herein, we present our two new cases and comprehensively review the literature on all reported cases of PGCC with critical commentary on findings in cases of this rare tumor.
Clinical • Review • Journal
|
PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
|
PIK3CA mutation
8ms
Gliosarcomas in patients under 20 comprised 13% of all gliosarcomas reported during the study period. Frequency and mean age were higher compared to other published reports. Pathological features were similar to those described in literature. Clinicopathological features and prognosis of pediatric gliosarcomas were similar to adult gliosarcomas.
Clinical • Review • Journal
|
GFAP (Glial Fibrillary Acidic Protein)
8ms
We present a case of a malignant GCTB with a KRAS G12V mutation. This mutation is a known oncogenic driver that has not previously been reported on patients with malignant GCTB.
Journal
|
KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation • KRAS G12V • KRAS G12
8ms
In conclusion, our findings reveal mutations in PFN1 as the pathological mechanism in PDB/GCT, and we successfully established Pfn1-mutated mice as a suitable animal model for studying PDB-associated pathological mechanisms. The identification of PFN1 mutations has great diagnostic value for identifying PDB individuals predisposed toward developing GCTs.
Journal
|
SQSTM1 (Sequestosome 1)
8ms
CISH for CSF1 mRNA ISH is highly sensitive and relatively specific marker of TGCT of all types, including malignant examples. The presence of very large number of CSF1-positive cells in MTGCT supports our prior hypothesis that MTGCT represent true malignancies of synoviocytes. Demonstration of CSF1 mRNA expression may be valuable in the diagnosis of challenging TGCT, in particular giant cell-poor examples and extra-articular DTGCT, and may be predictive of response to the specific CSF1 inhibitor pexidartinib.
CSF1 (Colony stimulating factor 1) • CSF1R (Colony stimulating factor 1 receptor)
|
CSF1 expression
|
Turalio (pexidartinib)
8ms
The current neoplasms represent a tumor that to the best of our knowledge has not been reported as a primary neoplasm of the lung. The cases herein described represent an unusual occurrence and should be maintained in the differential diagnosis of primary pulmonary tumors rich in multinucleated giant cells.
Clinical • Journal
|
NKX2-1 (NK2 Homeobox 1) • VIM (Vimentin) • CD68 (CD68 Molecule)
9ms
The broad-scale epigenomic and transcriptomic changes that arise from incorporation of mutant histones into chromatin provide opportunities to develop new and disease-specific therapies. In this chapter, we review how mutant histones inhibit SETD2 and NSD2 function in bone tumors and discuss how this information could lead to better treatments for these cancers.
Journal
|
SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase)
9ms
In this chapter, we summarize the pathological features of each mutation type in its respective cancer, as well as the potential mechanism of their disruption on the epigenome and genomic instability. Understanding each mutation type would provide a thorough background for a thorough understanding of the cancers and would bring new insights for future investigations and the development of new precise therapies.
Journal
|
SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase)
9ms
Our results suggested that serum EFEMP1 levels might be used to distinguish OS patients from healthy controls and as an indicator for OS lung metastasis. Serum EFEMP1 levels could serve as a new and assisted biomarker for the auxiliary diagnosis and prognosis of OS.
Journal
|
EGF (Epidermal growth factor)
9ms
Of note, the combination treatment abrogated nilotinib-induced hypercholesterolemia and did not adversely affect the liver function or body weight. Overall, the present study provided evidences that warrant further assessment of nilotinib/rosuvastatin combination as an alternative therapeutic modality for ERα-positive breast cancer.
Preclinical • Journal
|
ER (Estrogen receptor) • CASP3 (Caspase 3)
|
ER positive • ROS1 positive
|
Tasigna (nilotinib) • rosuvastatin
9ms
Administration of the c-FMS/CSF1R kinase inhibitors GW2580 and BLZ945 significantly reduced human LC migration. We also detected presence of transcripts for its ligand, CSF1, but not IL34, in all tested LCH cases. CSF1R and CSF-1 expression in LCH, and their role in LC migration and differentiation, suggests CSF1R signaling blockade as a candidate rational approach for treatment of LCH, including the BRAFV600E and wild-type forms of the disease.
Journal
|
BRAF (B-raf proto-oncogene) • CD34 (CD34 molecule) • CD14 • CSF1R (Colony stimulating factor 1 receptor)
|
BRAF mutation
|
BLZ-945 • GW-2580
9ms
Overall, we demonstrate that H3.3 G34 oncohistones selectively promote PRC2 activity by interfering with SETD2-mediated H3K36 methylation. We propose that PRC2-mediated silencing of enhancers involved in cell differentiation represents a potential mechanism by which H3.3 G34 mutations drive these tumors.
Journal
|
SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase)
10ms
Mutations in KRAS and activation of the MAPK/ERK signaling pathway were detected in brown tumors of hyperparathyroidism of the jaws, expanding the spectrum of giant cell lesions whose molecular pathogenesis involve RAS signaling.
Journal
|
KRAS (KRAS proto-oncogene GTPase) • FGFR1 (Fibroblast growth factor receptor 1)
|
KRAS mutation • KRAS G12D • KRAS G12V • KRAS G13 • KRAS G12 • KRAS A146T
10ms
There are some important imaging features of GCTB that can be used to distinguish it from breast carcinoma to reduce misdiagnosis.
Clinical • Journal
|
CD68 (CD68 Molecule)
10ms
An increase in C reactive protein (CRP) implicated an increased risk for cancer of 2.4% (OR: 1.024, 95%CI: 1.001-1.047; p = 0.041). 18F-FDG PET/CT can reveal occult cancers at an early stage with a high negative predictive value, and it is specifically beneficial in PMR/GCA patients with nonspecific symptoms.
Clinical • Journal
|
CRP (C-reactive protein)
11ms
While these morphologic findings were concerning for a possibility of a giant cell tumor of tendon sheath and/or giant cell tumor, taken together, they most likely represent a florid histiocytic reaction to wear particles. Polarizing the sections is imperative to clarify diagnosis and avoid confusion in diagnosing this entity as cellulitis, popliteal cyst, or an underlying soft tissue tumor.
CD68 (CD68 Molecule)
11ms
In addition to these, several glycolytic enzymes, immune markers, extracellular matrix (ECM), and heat shock proteins showed adverse expressions in the GCT-untreated group were identified with favorable regulations after treatment. Therefore, the identified expression profiles will provide a better picture of treatment efficacy and effect on the molecular environment of GCT.
Journal
|
TGFB1 (Transforming Growth Factor Beta 1) • MMP9 (Matrix metallopeptidase 9)
11ms
Systemic therapy of dTGCT patients with emactuzumab resulted in pronounced and durable responses associated with symptomatic improvement and a manageable safety profile.
Clinical • Journal • HEOR
|
CD163 (CD163 Molecule) • CSF1R (Colony stimulating factor 1 receptor) • CD68 (CD68 Molecule)
|
emactuzumab (RG7155)
11ms
Final diagnosis was TSGCT. Conclusion the occasional predominance of large cells may obscure the typical features of a TSGCT and lead to a diagnosis of sarcoma.
CD68 (CD68 Molecule)
11ms
Final diagnosis was TSGCT. Conclusion the occasional predominance of large cells may obscure the typical features of a TSGCT and lead to a diagnosis of sarcoma.
CD68 (CD68 Molecule)
11ms
UPS and other unclassified high-grade sarcomas occurring at unusual sites such as the axilla, inguinal area and the lateral neck should alert to the possibility of dedifferentiated melanoma, even in the absence of positive clinical history. Genotyping represents a valuable adjunct to confirm diagnosis.
Clinical
|
BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NF1 (Neurofibromin 1) • SOX10 (SRY-Box 10)
|
BRAF mutation • NF1 mutation
11ms
Final diagnosis was TSGCT. Conclusion the occasional predominance of large cells may obscure the typical features of a TSGCT and lead to a diagnosis of sarcoma.
CD68 (CD68 Molecule)
11ms
UPS and other unclassified high-grade sarcomas occurring at unusual sites such as the axilla, inguinal area and the lateral neck should alert to the possibility of dedifferentiated melanoma, even in the absence of positive clinical history. Genotyping represents a valuable adjunct to confirm diagnosis.
Clinical
|
BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NF1 (Neurofibromin 1) • SOX10 (SRY-Box 10)
|
BRAF mutation • NF1 mutation
11ms
UPS and other unclassified high-grade sarcomas occurring at unusual sites such as the axilla, inguinal area and the lateral neck should alert to the possibility of dedifferentiated melanoma, even in the absence of positive clinical history. Genotyping represents a valuable adjunct to confirm diagnosis.
Clinical
|
BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NF1 (Neurofibromin 1) • SOX10 (SRY-Box 10)
|
BRAF mutation • NF1 mutation
11ms
A comprehensive literature search was conducted in the relevant databases to identify studies published in this field during recent years Pexidartinib acts by inhibiting the colony-stimulating factor (CSF1)/CSF1 receptor pathway which leads to inhibition of the cell lines proliferation and promotes the autophosphorylation process of ligand-induced CSF1 receptor. Pexidartinib emerged as a potential drug candidate for the treatment of TGCT.
Journal
|
CSF1R (Colony stimulating factor 1 receptor)
|
Turalio (pexidartinib)
12ms
In the last 5 years, and recently stimulated by the approval of pexidartinib (Turalio™, Daiichi Sankyo) in 2019 for the treatment of tenosynovial giant cell tumors, there has been a large increase in activity (both journal articles and patent applications) around small molecule inhibitors of CSF1R...The field has developed rapidly from 2014 to the present, with many different chemotypes proving to be potent inhibitors. The range of potential utilities of CSF1R inhibitors has also expanded to include dementia, ulcerative colitis/Crohn's disease, rheumatoid arthritis inflammation, and fibrosis.
Journal
|
FLT3 (Fms-related tyrosine kinase 3) • KIT (KIT proto-oncogene, receptor tyrosine kinase)
|
Turalio (pexidartinib)
12ms
Clinical • Journal
|
PALB2 (Partner and localizer of BRCA2)
12ms
It has led to the identification of molecular interactions between CD8 T cell and rhabdomyosarcoma via Galectin3-LAG3 binding, which is a novel immune checkpoints recently identified. In conclusion, musculoskeletal tumors may be defined as immune quiescent tumors, whereby targeting Galectin-3 and/or immune infitrative agents could be crucial in these immunologically non-inflamed musculoskeletal tumors, accelerating immunotherapeutic response.
Journal
|
CD8 (cluster of differentiation 8) • LAG3 (Lymphocyte Activating 3) • CD4 (CD4 Molecule)
|
CD8 expression
12ms
The guidelines from the National Comprehensive Cancer Network (NCCN) recommend Chest CT to evaluate for lung metastasis. Despite the fact that our patient has not had a local recurrence, we plan to follow his CT closely for evidence of growing metastases.
CD68 (CD68 Molecule)
12ms
The cartilage matrix is associated with woven bone suggesting the neoplastic cells may differentiate into chondrocyte-like and osteoblast-like cells. Recognition of this neoplasm is important to prevent misdiagnosis and overtreatment of affected patients.
Clinical • Journal
|
SOX9 (SRY-Box Transcription Factor 9)
1year
↑WS depression shows evidence of distinct genetic predisposition to immune-metabolic traits and alcohol consumption. These genetic signals suggest that biological targets including immune-cardiometabolic pathways may be germane to therapies in individuals with ↑WS depression.
CRP (C-reactive protein)
1year
An extensive literature review did not reveal another similar case of OGC-rich MPNST. Our case describes a distinct morphologic presentation of MPNST in NF1 confirmed by immunohistochemistry and molecular analysis.
Clinical
|
CDKN2A (Cyclin-dependent kinase inhibitor 2A) • SOX10 (SRY-Box 10)
|
CDKN2A deletion • CDKN2A mutation • NF1 deletion
1year
These findings suggest that long-term clinical follow-up is necessary despite benign histologic features in the primary and recurrent tumor. Furthermore, elucidation of molecular alterations unique to SFTs that ultimately undergo progression may be a more prognostically informative endeavor.
Clinical
|
BCL2 (B-cell CLL/lymphoma 2) • CD34 (CD34 molecule) • STAT6 (Signal transducer and activator of transcription 6) • PAX8 (Paired box 8)
1year
Our case meets all the histological criteria of the Turin proposal for PDTC but with pleomorphic giant cells and is very different from ATC according to clinical, histological and immunohistochemical features. Pleomorphic tumour giant cells in thyroid carcinomas could be present in PDTC and do not always represent dedifferentiation and more aggressive carcinoma, thyroid neoplasm.
Clinical • Journal
|
NKX2-1 (NK2 Homeobox 1)