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British Journal of Haematology May 2020
Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Humans; Leukemia, Mast-Cell; Mast-Cell Sarcoma; Middle Aged; Young Adult
PubMed: 32242922
DOI: 10.1111/bjh.16581 -
Pathobiology : Journal of... 2020Most cases of mastocytosis are indolent, usually cutaneous mastocytosis or indolent systemic mastocytosis (SM). Aggressive mast cell (MC) diseases are very rare and... (Review)
Review
Most cases of mastocytosis are indolent, usually cutaneous mastocytosis or indolent systemic mastocytosis (SM). Aggressive mast cell (MC) diseases are very rare and often fatal. They can develop de novo or due to progression of indolent forms and can present in different ways; either as MC sarcoma or as advanced SM which includes aggressive SM, MC leukemia, and SM with an associated hematological neoplasm. This review will describe these different aggressive forms of mastocytosis, illustrated by cases submitted to the workshop of the 18th Meeting of the European Association for Haematopathology, Basel 2016, organized by the European Bone Marrow Working Group. In addition, the diagnostic criteria for identifying myelomastocytic leukemia, an aggressive myeloid neoplasm with partial MC differentiation that falls short of the criteria for SM, and disease progression in patients with established mastocytosis are discussed.
Topics: Bone Marrow; Congresses as Topic; Diagnosis, Differential; Disease Progression; Europe; Humans; Leukemia, Mast-Cell; Mastocytosis; Mastocytosis, Systemic; Myeloproliferative Disorders
PubMed: 31802761
DOI: 10.1159/000504099 -
PloS One 2024Ewing's sarcoma (ES) is the second most common bone and soft tissue malignancy in children and adolescents with a poor prognosis. The identification of genes with...
Ewing's sarcoma (ES) is the second most common bone and soft tissue malignancy in children and adolescents with a poor prognosis. The identification of genes with prognostic value may contribute to the prediction and treatment of this disease. The GSE17679, GSE68776, GSE63155, and GSE63156 datasets were downloaded from the Gene Expression Omnibus database and qualified. Prognostic value of differentially expressed genes (DEGs) between the normal and tumor groups and immune cell infiltration were explored by several algorithms. A prognostic model was established and validated. Finally, functional analyses of the DEGs were performed. Proline rich 11 (PRR11) and mast cell infiltration were noted as the key indicators for the prognosis of ES. Kaplan-Meier and scatter plots for the training and two validation sets showed that patients in the low-PRR11 expression group were associated with better outcomes than those in the high-PRR11 expression group. The concordance indices and calibration analyses of the prognostic model indicated good predictive accuracy in the training and validation sets. The area under the curve values obtained through the receiver operating characteristic analysis for 1-, 3-, 5-year prediction were ≥ 0.75 in the three cohorts, suggesting satisfactory sensitivity and specificity of the model. Decision curve analyses suggested that patients could benefit more from the model than the other strategies. Functional analyses suggested that DEGs were mainly clustered in the cell cycle pathway. PRR11 and mast cell infiltration are potential prognostic indicators in ES. PRR11 possibly affects the prognosis of patients with ES through the cell cycle pathway.
Topics: Adolescent; Child; Humans; Algorithms; Calibration; Prognosis; Sarcoma; Sarcoma, Ewing
PubMed: 38427643
DOI: 10.1371/journal.pone.0299720 -
American Journal of Hematology Mar 2023
Topics: Humans; Mast-Cell Sarcoma; Mast Cells
PubMed: 36464921
DOI: 10.1002/ajh.26804 -
Clinical Cancer Research : An Official... Jun 2024To explore the cellular cross-talk of tumor-resident mast cells (MC) in controlling the activity of cancer-associated fibroblasts (CAF) to overcome tumor...
PURPOSE
To explore the cellular cross-talk of tumor-resident mast cells (MC) in controlling the activity of cancer-associated fibroblasts (CAF) to overcome tumor microenvironment (TME) abnormalities, enhancing the efficacy of immune-checkpoint inhibitors in sarcoma.
EXPERIMENTAL DESIGN
We used a coculture system followed by further validation in mouse models of fibrosarcoma and osteosarcoma with or without administration of the MC stabilizer and antihistamine ketotifen. To evaluate the contribution of ketotifen in sensitizing tumors to therapy, we performed combination studies with doxorubicin chemotherapy and anti-PD-L1 (B7-H1, clone 10F.9G2) treatment. We investigated the ability of ketotifen to modulate the TME in human sarcomas in the context of a repurposed phase II clinical trial.
RESULTS
Inhibition of MC activation with ketotifen successfully suppressed CAF proliferation and stiffness of the extracellular matrix accompanied by an increase in vessel perfusion in fibrosarcoma and osteosarcoma as indicated by ultrasound shear wave elastography imaging. The improved tissue oxygenation increased the efficacy of chemoimmunotherapy, supported by enhanced T-cell infiltration and acquisition of tumor antigen-specific memory. Importantly, the effect of ketotifen in reducing tumor stiffness was further validated in sarcoma patients, highlighting its translational potential.
CONCLUSIONS
Our study suggests the targeting of MCs with clinically administered drugs, such as antihistamines, as a promising approach to overcome resistance to immunotherapy in sarcomas.
Topics: Humans; Mice; Animals; Mast Cells; Tumor Microenvironment; Immune Checkpoint Inhibitors; B7-H1 Antigen; Sarcoma; Ketotifen; Cell Line, Tumor; T-Lymphocytes; Xenograft Model Antitumor Assays; Lymphocytes, Tumor-Infiltrating; Female; Cancer-Associated Fibroblasts; Doxorubicin; Osteosarcoma
PubMed: 38578281
DOI: 10.1158/1078-0432.CCR-24-0246 -
Clinical Pathology (Thousand Oaks,... 2022Mastocytosis is a rare disorder affecting both children and adults by gathering of functionally defective mast cells in the body's tissues. The World Health Organization...
Mastocytosis is a rare disorder affecting both children and adults by gathering of functionally defective mast cells in the body's tissues. The World Health Organization (WHO) classified mastocytosis into cutaneous mastocytosis, systemic mastocytosis (SM), and mast cell sarcoma (MCS). We hereby present a case of retroperitoneal MCS with concurrent systemic mastocytosis and an undisclosed associated hematological neoplasm (SM-undisclosed AHN). The diagnosis of MCS and SM was made after the second biopsy over retroperitoneal mass, lymph node, and ovary for rapidly progressive disease with the presentation of unexplained recurrent flushing, palpitation, and shock, in addition to abdominal pain. A clonal myeloid neoplasm was also suspected by the karyotype and hemogram data. Unfortunately, the patient succumbed to the disease quickly. Apart from this unique case, the previously reported cases of SM with MCS in the literature were also reviewed.
PubMed: 36119438
DOI: 10.1177/2632010X221123539 -
Heliyon Sep 2023The prognostic value of D-glucuronyl C5-epimerase ( and mast cell infiltration in Ewing sarcoma (ES) has not been well specified and highlighted, which may facilitate...
BACKGROUND
The prognostic value of D-glucuronyl C5-epimerase ( and mast cell infiltration in Ewing sarcoma (ES) has not been well specified and highlighted, which may facilitate survival prediction and treatment.
METHODS
Several qualified datasets were downloaded from the GEO website. Common differentially expressed genes between normal subjects and ES patients in GSE17679, GSE45544, and GSE68776 were identified and screened by multiple algorithms to find hub genes with prognostic value. The prognostic value of 64 infiltrating cells was also explored. A prognostic model was established and then validated with GSE63155 and GSE63156. Finally, functional analysis was performed.
RESULTS
and mast cell infiltration were screened as two indicators for a prognostic model. The Kaplan‒Meier analysis showed that patients in the low expression, mast cell infiltration and risk score groups had poorer outcomes than patients in the high expression, mast cell infiltration and risk score groups, both in the training and validation sets. Scatter plots and heatmaps also indicated the same results. The concordance indices and calibration analyses indicated a high prediction accuracy of the model in the training and validation sets. The time-dependent receiver operating characteristic analyses suggested high sensitivity and specificity of the model, with area under the curve values between 0.76 and 0.98. The decision curve analyses suggested a significantly higher net benefit by the model than the treat-all and treat-none strategies. Functional analyses suggested that glycosaminoglycan biosynthesis-heparan sulfate/heparin, the cell cycle and microRNAs in cancer were upregulated in ES patients.
CONCLUSIONS
and mast cell infiltration are potential prognostic indicators in ES. may affect the proliferation, angiogenesis and metastasis of ES by affecting the biosynthesis of heparan sulfate and heparin.
PubMed: 37662777
DOI: 10.1016/j.heliyon.2023.e19357 -
Clinical Sarcoma Research 2016A chronic inflammatory cell infiltrate is commonly seen in response to primary malignant tumours of bone. This is known to contain tumour-associated macrophages (TAMs)...
BACKGROUND
A chronic inflammatory cell infiltrate is commonly seen in response to primary malignant tumours of bone. This is known to contain tumour-associated macrophages (TAMs) and lymphocytes; dendritic cells (DCs) and mast cells (MCs) have also been identified but whether these and other inflammatory cells are seen commonly in specific types of bone sarcoma is uncertain.
METHODS
In this study we determined the nature of the inflammatory cell infiltrate in 56 primary bone sarcomas. Immunohistochemistry using monoclonal antibodies was employed to assess semiquantitatively CD45+ leukocyte infiltration and the extent of the DC, MC, TAM and T and B lymphocyte infiltrate.
RESULTS
The extent of the inflammatory infiltrate in individual sarcomas was very variable. A moderate or heavy leukocyte infiltrate was more commonly seen in conventional high-grade osteosarcoma, undifferentiated pleomorphic sarcoma and giant cell tumour of bone (GCTB) than in Ewing sarcoma, chordoma and chondrosarcoma. CD14+/CD68+ TAMs and CD3+ T lymphocytes were the major components of the inflammatory cell response but (DC-SIGN/CD11c+) DCs were also commonly noted when there was a significant TAM and T lymphocyte infiltrate. MCs were identified mainly at the periphery of sarcomas, including the osteolytic tumour-bone interface.
DISCUSSION
Our findings indicate that, although variable, some malignant bone tumours (e.g. osteosarcoma, GCTB) are more commonly associated with a pronounced inflammatory cell infiltrate than others (e.g. chondrosarcoma. Ewing sarcoma); the infiltrate is composed mainly of TAMs but includes a significant DC, T lymphocyte and MC infiltrate.
CONCLUSION
Tumours that contain a heavy inflammatory cell response, which includes DCs, TAMs and T lymphocytes, may be more amenable to immunomodulatory therapy. MCs are present mainly at the tumour edge and are likely to contribute to osteolysis and tumour invasion.
PubMed: 27482375
DOI: 10.1186/s13569-016-0053-3 -
The Canadian Veterinary Journal = La... Sep 2017Mast cell tumors (MCTs) are commonly encountered in dogs and have been reported in cutaneous, conjunctival, oral mucosal, and gastrointestinal locations, but not in an...
Mast cell tumors (MCTs) are commonly encountered in dogs and have been reported in cutaneous, conjunctival, oral mucosal, and gastrointestinal locations, but not in an intramuscular location. Medical records at 2 referral centers in the UK were examined to find cases of MCTs in this location. Seven dogs were identified as having an intramuscular MCT by a combination of fine-needle aspirate cytology and computed tomography or ultrasound. None of the dogs had evidence of local lymph node metastasis. Six dogs had no evidence of distant metastasis and surgery was carried out as the primary treatment option. Three of those dogs also had adjunctive chemotherapy due to a high Ki67 value or high mitotic index. All 6 dogs that had had surgery were alive at follow-up with a minimum elapsed time of 7 months. One dog had a course of chemotherapy due to the location, size, and evidence of biological activity of the tumor and died 23 days afterwards. The prognosis of intramuscular mast cell tumors appears to be favorable in most cases.
Topics: Animals; Dog Diseases; Dogs; Mast-Cell Sarcoma; Neoplasm Staging; Prognosis
PubMed: 28878416
DOI: No ID Found -
Gastrointestinal Tumors 2023Gastrointestinal mast cell sarcoma is a rare variant of mastocytosis. It is a unifocal tumor with high destructive capacity and metastatic potential. Diagnosis of mast...
Gastrointestinal mast cell sarcoma is a rare variant of mastocytosis. It is a unifocal tumor with high destructive capacity and metastatic potential. Diagnosis of mast cell sarcoma can be challenging and might be so delayed that unfavorable prognosis may be expected. In this case report, we will describe our experience with a case of mast cell sarcoma in the small intestine of an elderly woman, which was diagnosed early on throughout the course of her disease and successfully treated. The patient was a 59-year-old woman who presented with abdominal pain, flushing, weight loss, and vomiting. Imaging studies supported the existence of an infiltrative neoplasm in the jejunum. Then, surgical removal of the tumor was performed. The presence of mast cells in the resected tumor was confirmed by immunohistochemistry, histopathology, and Giemsa staining. After almost a year of follow-up, the patient's overall condition was fine, and no signs of recurrence were found. This is the first reported case of successfully treated gastrointestinal mast cell sarcoma. All of the previously reported cases had been diagnosed after recurrence with no response to treatment. Our case shows the significance of early diagnosis and treatment in this condition and its impact on outcome and prognosis. That could be achieved only if the pathologist has a high suspicion for this rare disease and keeps it in the back of one's mind.
PubMed: 36742415
DOI: 10.1159/000528887