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Frontiers in Oncology 2020Mast cell sarcoma comprises a rare aggressive mast cell neoplasia with histological, clinical, and genetic features distinct from other mast cell neoplasm. Until now,...
Mast cell sarcoma comprises a rare aggressive mast cell neoplasia with histological, clinical, and genetic features distinct from other mast cell neoplasm. Until now, prognosis is still poor due to high rates of progression to mast cell leukemia and failure of conventional chemotherapies. Our here presented first report about successful allogeneic hematopoietic stem cell transplantation leading to remission in a case of tonsillar MCS represents a promising potential curative treatment option for this rare and often fatal disease.
PubMed: 32181155
DOI: 10.3389/fonc.2020.00219 -
Tissue Barriers 2015The barrier properties of endothelial cells are critical for the maintenance of water and protein balance between the intravascular and extravascular compartments. An...
The barrier properties of endothelial cells are critical for the maintenance of water and protein balance between the intravascular and extravascular compartments. An impairment of endothelial barrier function has been implicated in the genesis and/or progression of a variety of pathological conditions, including pulmonary edema, ischemic stroke, neurodegenerative disorders, angioedema, sepsis and cancer. The altered barrier function in these conditions is often linked to the release of soluble mediators from resident cells (e.g., mast cells, macrophages) and/or recruited blood cells. The interaction of the mediators with receptors expressed on the surface of endothelial cells diminishes barrier function either by altering the expression of adhesive proteins in the inter-endothelial junctions, by altering the organization of the cytoskeleton, or both. Reactive oxygen species (ROS), proteolytic enzymes (e.g., matrix metalloproteinase, elastase), oncostatin M, and VEGF are part of a long list of mediators that have been implicated in endothelial barrier failure. In this review, we address the role of blood borne cells, including, neutrophils, lymphocytes, monocytes, and platelets, in the regulation of endothelial barrier function in health and disease. Attention is also devoted to new targets for therapeutic intervention in disease states with morbidity and mortality related to endothelial barrier dysfunction.
PubMed: 25838983
DOI: 10.4161/21688370.2014.978720 -
European Journal of Nuclear Medicine... Dec 2015Mastocytosis is a clonal haematological disease characterized by uncontrolled proliferation and the activation of mast cells. The value of FDG-PET/CT (FDG-PET) in...
INTRODUCTION
Mastocytosis is a clonal haematological disease characterized by uncontrolled proliferation and the activation of mast cells. The value of FDG-PET/CT (FDG-PET) in mastocytosis has yet to be determined.
METHODS
We retrospectively identified patients with an established diagnosis of systemic mastocytosis (SM), according to the WHO criteria, who underwent PET using the French Reference Centre for Mastocytosis database. Semi-quantitative and visual analysis of FDG-PET was performed and compared to the clinico-biological data.
RESULTS
Our cohort included 19 adult patients, median age 65 years [range 58-74], including three with smouldering SM (SSM), three with aggressive SM (ASM), 10 with an associated clonal haematological non-mast-cell lineage disease (SM-AHNMD), and three with mast cell sarcoma (MCS). FDG-PET was performed at the time of the SM diagnosis (15/19), to evaluate lymph node (LN) activity (3/19) or the efficacy of therapy (1/19). FDG uptake was observed in the bone marrow (BM) (9/19, 47%), LN (6/19, 32%), spleen (12/19, 63%), or liver (1/19, 5%). No significant FDG uptake was observed in the SSM and ASM patients. A pathological FDG uptake was observed in the BM of 6/10 patients with SM-AHNMD, appearing as diffuse and homogeneous, and in the LN of 5/10 patients. All 3 MCS patients showed intense and multifocal BM pathological uptake, mimicking metastasis. No correlation was found between the FDG-PET findings and serum tryptase levels, BM mast cell infiltration percentage, and CD30 and CD2 expression by mast cells.
CONCLUSIONS
FDG uptake does not appear to be a sensitive marker of mast cell activation or proliferation because no significant FDG uptake was observed in most common forms of mastocytosis (notably purely aggressive SM). However, pathological FDG uptake was observed in the SM-AHNMD and in MCS cases, suggesting a role of FDG-PET in their early identification and as a tool of therapeutic assessment in this subgroup of patients.
Topics: Aged; Female; Fluorodeoxyglucose F18; France; Humans; Male; Mastocytosis, Systemic; Middle Aged; Multimodal Imaging; Positron-Emission Tomography; Radiopharmaceuticals; Tomography, X-Ray Computed
PubMed: 26140850
DOI: 10.1007/s00259-015-3117-3 -
Veterinary Sciences Sep 2022Background: Gastrointestinal masses in cats are of clinical relevance, but pathological studies with larger case numbers are lacking. Biomarkers such as miRNA have not...
Background: Gastrointestinal masses in cats are of clinical relevance, but pathological studies with larger case numbers are lacking. Biomarkers such as miRNA have not yet been investigated in feline intestinal neoplasms. Methods: A retrospective analysis of pathology reports included 860 feline gastrointestinal masses. Immunohistochemistry was performed on 91 lymphomas, 10 sarcomas and 7 mast cell tumours (MCT). Analyses of miRNA-20b and miRNA-192 were performed on 11 lymphomas, 5 carcinomas and 5 control tissues by ddPCR. Results: The pathological diagnosis identified 679 lymphomas, 122 carcinomas, 28 sarcomas, 23 polyps, 7 MCT and 1 leiomyoma. Carcinomas and polyps were most commonly found in the large intestine, lymphomas were most commonly found in the stomach and small intestine and MCT only occurred in the small intestine. Besides the well-described small-cell, mitotic count <2 T-cell lymphomas and the large-cell B-cell lymphomas with a high mitotic count, several variants of lymphomas were identified. The values of miRNA-20b were found to be up-regulated in samples of all types of cancer, whereas miRNA-192 was only up-regulated in carcinomas and B-cell lymphomas. Conclusions: The histopathological and immunohistochemical (sub-)classification of feline intestinal masses confirmed the occurrence of different tumour types, with lymphoma being the most frequent neoplasm. Novel biomarkers such as miRNA-20b and miRNA-192 might have diagnostic potential in feline intestinal neoplasms and should be further investigated.
PubMed: 36136693
DOI: 10.3390/vetsci9090477 -
Scientific Reports May 2017Circulating microRNAs in the blood may provide diagnostic and prognostic information about canine neoplastic diseases, and their profiles may be conserved between human...
Circulating microRNAs in the blood may provide diagnostic and prognostic information about canine neoplastic diseases, and their profiles may be conserved between human and canine species. We performed RT-qPCR to obtain the profiles of circulating plasma microRNA-214 and -126 in total 181 cases of canine neoplastic diseases and healthy controls. MicroRNA-214 levels were high in 2 epithelial tumours (thyroid and mammary carcinomas) and 4 non-epithelial tumours (osteosarcoma, histiocytic sarcoma, chondrosarcoma, and hemangiosarcoma). In contrast, microRNA-126 levels were high in 6 epithelial tumours (mammary, hepatocellular, squamous cell, thyroid, transitional cell carcinomas, and adenocarcinoma) and 4 non-epithelial tumours (osteosarcoma, mast cell tumour, melanoma, and hemangiosarcoma). The diagnostic potential of microRNA-214 was relatively high in sarcomas, whereas that of microR-126 was high in most types of the tumours. MicroRNA-214 and -126 were prognostic predictors in 2 groups (adenocarcinoma and non-epithelial tumours except for osteosarcoma) and 3 groups (epithelial tumours, adenocarcinoma, and melanoma), respectively. Additionally, the microRNA levels did not show a strong correlation with the other clinical parameters. In conclusion, circulating microRNA-214 and -126 have the potential to be diagnostic and prognostic biomarkers for canine neoplastic diseases. Furthermore, their profiles may be key references as well for exploring novel biomarkers for human cancers.
Topics: Animals; Biomarkers, Tumor; Circulating MicroRNA; Dog Diseases; Dogs; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Kaplan-Meier Estimate; Neoplasms; Prognosis
PubMed: 28536479
DOI: 10.1038/s41598-017-02607-1 -
European Journal of Haematology Jun 2015Mastocytosis is a term referring to a heterogeneous group of disorders characterized by abnormal mast cell (MC) accumulation in the skin and/or internal organs. In... (Review)
Review
Mastocytosis is a term referring to a heterogeneous group of disorders characterized by abnormal mast cell (MC) accumulation in the skin and/or internal organs. In children, the disease involves mostly the skin (cutaneous mastocytosis; CM), whereas in adults, the disease is usually systemic (systemic mastocytosis; SM). Advanced SM variants with end-organ damage and reduced life expectancy have also been described, but are rare. Clinical signs and symptoms in SM result from excessive mediator release by MCs and, in aggressive forms, from organ failure related to MC infiltration. As a consequence, treatment of indolent SM aims primarily at the control of symptoms caused by MC mediator release. By contrast, in advanced SM, such as aggressive SM, MC leukemia, and MC sarcoma, intensive (chemo)therapy with or without allogeneic stem cell transplantation has to be considered. In addition, activating mutations in KIT (mostly KIT D816V in adults) are found in most patients with SM, so that targeted therapies aimed at blocking mutant KIT variants or/and downstream signaling pathways are currently being developed. Other targets, such as specific surface antigens expressed on neoplastic MCs, might be considered for the development of future therapies in advanced SM.
Topics: Antineoplastic Agents; Cytokines; Disease Management; Humans; Immunotherapy; Inflammation Mediators; Mast Cells; Mastocytosis; Molecular Targeted Therapy; Stem Cell Transplantation; Transplantation, Homologous
PubMed: 25753531
DOI: 10.1111/ejh.12544 -
Human Pathology Sep 2017To the best of our knowledge, this manuscript describes clinical and pathologic findings of the first case of acute mast cell leukemia harboring t(4;5)(q21;q33),...
To the best of our knowledge, this manuscript describes clinical and pathologic findings of the first case of acute mast cell leukemia harboring t(4;5)(q21;q33), compatible with fusion of the PDGFRB gene to a rare partner, PRKG2. Translocation involving the PDGFRB gene is confirmed by fluorescence in situ hybridization study. This case presented a relatively fulminant clinical course with acute mast cell leukemia and "C" findings (cytopenia, hepatosplenomegaly, and weight loss), mast cell sarcoma, and severe basophilia. Despite aggressive presentation initially, the patient responded well to tyrosine kinase inhibitor treatment and is currently in complete remission 33 months after diagnosis. This case significantly extends the disease spectrum associated with PRKG2/PDGFRB fusion gene. Recognizing the whole spectrum of diseases associated with this fusion is critical because tyrosine kinase inhibitor treatment has been exceedingly effective in these patients.
Topics: Acute Disease; Antineoplastic Agents; Biomarkers, Tumor; Biopsy; Chromosomes, Human, Pair 4; Chromosomes, Human, Pair 5; Cyclic GMP-Dependent Protein Kinase Type II; Gene Fusion; Genetic Predisposition to Disease; Humans; Imatinib Mesylate; Immunohistochemistry; Leukemia, Mast-Cell; Male; Middle Aged; Molecular Diagnostic Techniques; Molecular Targeted Therapy; Phenotype; Protein Kinase Inhibitors; Receptor, Platelet-Derived Growth Factor beta; Remission Induction; Time Factors; Translocation, Genetic; Treatment Outcome
PubMed: 28412213
DOI: 10.1016/j.humpath.2017.03.014 -
Journal of the American Veterinary... Jan 2022To compare wound healing following planned marginal excision of cutaneous mast cell tumors (MCTs) with that of soft tissue sarcomas (STSs) and to identify risk factors...
Marginal excision of cutaneous mast cell tumors in dogs was not associated with a higher rate of complications or prolonged wound healing than marginal excision of soft tissue sarcomas.
OBJECTIVE
To compare wound healing following planned marginal excision of cutaneous mast cell tumors (MCTs) with that of soft tissue sarcomas (STSs) and to identify risk factors for wound healing complications and delay in healing.
ANIMALS
126 dogs that underwent intentional marginal excision of cutaneous MCTs (n = 77) or subcutaneous STSs (49).
PROCEDURES
Medical records of included dogs were reviewed and signalment, tumor size, tumor location, skin closure type, time to healing, reported complications, histopathological grade, and surgical margins were recorded. These variables and outcomes (complication rate and time to complete healing) were compared between dogs in the MCT and STS groups. Potential risk factors for complications and delayed healing were analyzed.
RESULTS
No significant difference between the groups was found in any of the variables. Wound healing complication rates were 29% (22/77) for the MCT group and 31% (15/49) for the STS group. The mean ± SD time to complete healing was 16.5 ± 7.5 days for the MCT group and 17.7 ± 9.3 days for the STS group. These outcomes did not differ significantly between groups. For both groups, the use of subdermal plexus flap reconstruction was associated with the development of complications and increased time to complete healing.
CLINICAL RELEVANCE
Marginal excision of cutaneous MCTs was not associated with a higher rate of complication or prolonged wound healing, compared with marginal excision of STSs. The use of flap reconstruction in skin closure may delay healing and planned adjuvant therapy. Owners should be counseled regarding these risks and where appropriate and feasible, surgery without reconstruction should be considered.
Topics: Animals; Dog Diseases; Dogs; Mast Cells; Mastocytoma, Skin; Neoplasm Recurrence, Local; Retrospective Studies; Sarcoma; Soft Tissue Neoplasms; Treatment Outcome; Wound Healing
PubMed: 35092664
DOI: 10.2460/javma.21.05.0235 -
Journal of Cutaneous Pathology Nov 2021We present a case of an adult male with a solitary mast cell tumor of the skin with unusual nuclear pleomorphism and mitotic activity. The tumor was excised, recurred...
We present a case of an adult male with a solitary mast cell tumor of the skin with unusual nuclear pleomorphism and mitotic activity. The tumor was excised, recurred within 2 years, was reexcised after 4 years and did not recur >6 years after diagnosis. The tumor showed progressive cytonuclear atypia and a high mitotic and proliferation rate by Ki67-staining from the onset. No KIT mutations were identified in the tumor and bone marrow. Serum tryptase levels and a bone marrow aspirate and trephine biopsy were normal. Although the histomorphology of the skin tumor was consistent with mast cell sarcoma, the clinical behavior without systemic progression argued against this diagnosis. The tumor was finally considered as atypical mastocytoma, borderline to mast cell sarcoma. Currently, the patient is in close follow-up and still in complete remission.
Topics: Adult; Diagnosis, Differential; Humans; Male; Mast-Cell Sarcoma; Mastocytoma, Skin
PubMed: 34152029
DOI: 10.1111/cup.14088 -
Journal of Cutaneous Pathology Oct 2019The low-fat and fat-free spindle cell lipomas (SCLs) are rare and often mistaken for other benign and malignant morphological mimics, because of the fact that the... (Review)
Review
The low-fat and fat-free spindle cell lipomas (SCLs) are rare and often mistaken for other benign and malignant morphological mimics, because of the fact that the diagnosis relies on its non-lipogenic component analysis. Here, we report the clinicopathological features of two oral SCLs (low-fat and fat-free variants). Both lesions presented clinically as an asymptomatic nodule, which initially yielded diagnostic difficulties on the morphological analysis alone. One case was diagnosed as low-fat SCL on the lower lip in a 29-year-old man, and the other as fat-free SCL on the buccal mucosa in a 46-year-old man. In both cases, immunohistochemistry showed strong positivity for CD34 and, remarkably, retinoblastoma (Rb) protein was deficient. Mast cell (MC) tryptase and toluidine blue stain highlighted numerous MCs distributed throughout all tumor stroma. Alpha-SMA and desmin were negative. S100 evidenced scarce adipocytes only in the low-fat SCL case. Conservative surgical treatment was performed and no recurrence was noticed in about 2-year of follow-up in both cases. Because of the potential pitfalls, careful morphological analysis of the tumor stroma in the low-fat/fat-free SCL diagnosis, supported by immunohistochemistry (especially CD34, Rb and MC tryptase), is strongly recommended. To the best of our knowledge, these are the first and second cases reported of fat-free and low-fat SCL in the oral cavity.
Topics: Adipocytes; Adult; Humans; Lipoma; Male; Mouth Mucosa; Mouth Neoplasms; Sarcoma
PubMed: 31115930
DOI: 10.1111/cup.13512