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Acta Medica Portuguesa Apr 2020Mastocytosis is characterized by the clonal expansion of morphological and immunophenotypically abnormal mast cells in different organs. The skin is the most frequently... (Review)
Review
INTRODUCTION
Mastocytosis is characterized by the clonal expansion of morphological and immunophenotypically abnormal mast cells in different organs. The skin is the most frequently affected tissue. Virtually all children and more than 80% of adult patients with mastocytosis show cutaneous lesions.
MATERIAL AND METHODS
The present article describes the symptoms and signs in cutaneous mastocytosis, based on the review of recently published international consensus guidelines.
DISCUSSION
According to the 2016 World Health Organization classification, mastocytosis can be divided in cutaneous mastocytosis, systemic mastocytosis and mast cell sarcoma. Cutaneous mastocytosis is subclassified in three subtypes: maculopapular cutaneous mastocytosis, diffuse cutaneous mastocytosis and cutaneous astocytoma. Telangiectasia macularis eruptiva perstans is no longer considered a distinct entity.
CONCLUSION
Based on the age of onset, cutaneous manifestations of mastocytosis can be variable. The classification of cutaneous mastocytosis has recently been updated. Typically, in patients with childhood-onset mastocytosis, the disease occurs as cutaneous mastocytosis and shows spontaneous resolution around puberty. In contrast, adult patients, despite having also cutaneous lesions, often show systemic involvement and the course of the disease is usually chronic.
Topics: Adolescent; Adult; Age of Onset; Child; Humans; Mastocytosis; Mastocytosis, Cutaneous; Symptom Assessment
PubMed: 32238242
DOI: 10.20344/amp.12189 -
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 -
BMC Veterinary Research Jan 2020Traditionally, wide lateral surgical margins of 3 cm and one fascial plane deep have been recommended for resection of canine cutaneous mast cell tumor (MCT). Several...
BACKGROUND
Traditionally, wide lateral surgical margins of 3 cm and one fascial plane deep have been recommended for resection of canine cutaneous mast cell tumor (MCT). Several studies have been published assessing surgical margins of less than this traditional recommendation. The objective of this systematic review was to determine if resection MCT with lateral surgical margins < 3 cm results in low rates of incomplete resection and local tumor recurrence. Systematic searches of digital bibliographic databases were performed with two authors (AR & LES) screening abstracts to identify relevant scientific articles. Studies regarding surgical treatment of dogs with cutaneous MCT were reviewed. Data abstraction was performed and the quality of individual studies and the strength of the body of evidence for utilization of surgical margins < 3 cm for removal of MCTs was assessed.
RESULTS
From the initial 78 citations identified through the database searches, four articles were retained for data abstraction after both relevance screenings were performed. Two studies were retrospective observational studies, one was a prospective case series and one was a prospective clinical trial. Assessment of the quality level of the body of evidence identified using the GRADE system was low. Excision of MCT at 2 cm and 3 cm was associated with comparably low rates of incomplete excision and recurrence.
CONCLUSIONS
Despite the low quality of the overall body of evidence, a recommendation can be made that resection of canine cutaneous MCTs (< 4 cm) of Patnaik grade I and II with 2 cm lateral margins and 1 fascial plane deep results in low rates of incomplete excision and local tumor recurrence.
Topics: Animals; Dog Diseases; Dogs; Margins of Excision; Mast-Cell Sarcoma; Neoplasm Recurrence, Local; Skin Neoplasms; Treatment Outcome
PubMed: 31906934
DOI: 10.1186/s12917-019-2227-8 -
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 -
Aging Nov 2019Soft tissue sarcoma (STS) is one of the most challenging tumors for medical oncologists, with a high rate of recurrence after initial resection. In this study, a...
Soft tissue sarcoma (STS) is one of the most challenging tumors for medical oncologists, with a high rate of recurrence after initial resection. In this study, a recurrent STS-specific competitive endogenous RNA (ceRNA) network including seven recurrence and overall survival (OS)-associated genes (LPP-AS2, MUC1, GAB2, hsa-let-7i-5p, hsa-let-7f-5p, hsa-miR-101-3p and hsa-miR-1226-3p) was established based on the gene expression profiling of 259 primary sarcomas and 3 local recurrence samples from the TCGA database. The algorithm "cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT)" was applied to estimate the fraction of immune cells in sarcomas. Based on 5 recurrence and OS-associated immune cells (NK cells activated, dendritic cells resting, mast cells resting, mast cells activated and macrophages M1), we constructed a recurrent STS-specific immune cells network. Both nomograms were identified to have good reliabilities (Area Under Curve (AUC) of 5-year survival is 0.724 and 0.773, respectively). Then the co-expression analysis was performed to identify the potential regulation network among recurrent STS-specific immune cells and ceRNAs. Hsa-miR-1226-3p and MUC1 were significantly correlated and dendritic cells resting was related to hsa-miR-1226-3p. Additionally, the expression of MUC1 and dendritic cell marker CD11c were also verified by immunohistochemistry (IHC) assay and multidimensional databases. In conclusion, this study illustrated the potential mechanism of hsa-miR-1226-3p regulating MUC1 and dendritic cells resting might play an important role in STS recurrence. These findings might provide potential prognostic biomarkers and therapeutic targets for recurrent STS.
Topics: Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Humans; Lymphocytes, Tumor-Infiltrating; Microarray Analysis; Neoplasm Recurrence, Local; Nomograms; Sarcoma
PubMed: 31739284
DOI: 10.18632/aging.102424 -
Folia Histochemica Et Cytobiologica 2019Canine cutaneous round cell tumours (CCRCTs) include various benign and malignant neoplastic processes. Due to their similar morphology, the diagnosis of CCRCTs based on...
INTRODUCTION
Canine cutaneous round cell tumours (CCRCTs) include various benign and malignant neoplastic processes. Due to their similar morphology, the diagnosis of CCRCTs based on histopathological examination alone can be challenging, often necessitating ancillary immunohistochemical (IHC) analysis. This study presents a retrospective analysis of CCRCTs.
MATERIALS AND METHODS
This study includes 60 cases of CCRCTs, including 55 solitary and 5 multiple tumours, evaluated immunohistochemically using a basic antibody panel (MHCII, CD18, Iba1, CD3, CD79a, CD20 and mast cell tryptase) and, when appropriate, extended antibody panel (vimentin, desmin, a-SMA, S-100, melan-A and pan-keratin). Additionally, histochemical stainings (May-Grünwald-Giemsa and methyl green pyronine) were performed.
RESULTS
IHC analysis using a basic antibody panel revealed 27 cases of histiocytoma, one case of histiocytic sarcoma, 18 cases of cutaneous lymphoma of either T-cell (CD3+) or B-cell (CD79a+) origin, 5 cases of plas-macytoma, and 4 cases of mast cell tumours. The extended antibody panel revealed 2 cases of alveolar rhabdo-myosarcoma, 2 cases of amelanotic melanoma, and one case of glomus tumour.
CONCLUSIONS
Both canine cutaneous histiocytoma and cutaneous lymphoma should be considered at the beginning of differential diagnosis for CCRCTs. While most poorly differentiated CCRCTs can be diagnosed immunohis-tochemically using 1-4 basic antibodies, some require a broad antibody panel, including mesenchymal, epithelial, myogenic, and melanocytic markers. The expression of Iba1 is specific for canine cutaneous histiocytic tumours, and more sensitive than CD18. The utility of CD20 in the diagnosis of CCRCTs is limited.
Topics: Animals; Diagnosis, Differential; Dog Diseases; Dogs; Immunohistochemistry; Retrospective Studies; Skin; Skin Neoplasms
PubMed: 31553052
DOI: 10.5603/FHC.a2019.0016 -
International Journal of Molecular... Sep 2019Fibrosarcoma is an aggressive subtype of soft tissue sarcoma categorized in infantile/congenital-type and adult-type. Fibrosarcoma cells and its surrounding immune...
Fibrosarcoma is an aggressive subtype of soft tissue sarcoma categorized in infantile/congenital-type and adult-type. Fibrosarcoma cells and its surrounding immune inflammatory infiltrates overexpress or induce the expression of fibroblast growth factor-2 (FGF-2) that have a crucial role in tumor progression and angiogenesis. The inflammation-associated long pentraxin 3 (PTX3) was found to reduce FGF-2-mediated angiogenesis, but its role on fibrosarcoma immune inflammatory infiltrate is still unknown. In this study, we have evaluated the PTX3 activity on immune infiltrating mast cells, macrophages and T-lymphocytes by immunohistochemistry on murine MC-TGS17-51 fibrosarcoma cells and on transgenic TgN(Tie2-hPTX3) mouse. In these fibrosarcoma models we found a reduced neovascularization and a significant decrease of inflammatory infiltrate. Indeed, we show that PTX3 reduces the level of complement 3 (C3) deposition reducing fibrosarcoma progression. In conclusion, we hypothesize that targeting fibrosarcoma microenvironment by FGF/FGFR inhibitors may improve treatment outcome.
Topics: Animals; C-Reactive Protein; Cell Line, Tumor; Disease Models, Animal; Fibrosarcoma; Gene Expression; Immunohistochemistry; Immunomodulation; Inflammation; Male; Mice; Neovascularization, Pathologic; Serum Amyloid P-Component; Tumor Microenvironment
PubMed: 31533326
DOI: 10.3390/ijms20184599 -
Molecular Cancer Therapeutics Dec 2019Neurofibromatosis Type 1 (NF1) is one of the most common genetic tumor predisposition syndromes in humans. Mutant results in dysregulated RAS allowing neoplasms...
Neurofibromatosis Type 1 (NF1) is one of the most common genetic tumor predisposition syndromes in humans. Mutant results in dysregulated RAS allowing neoplasms throughout the neuroaxis. Plexiform neurofibromas (pNF) afflict up to 50% of patients with NF1. They are complex tumors of the peripheral nerve that cause major morbidity via nerve dysregulation and mortality via conversion to malignant sarcoma. Genetically engineered mouse models (GEMM) of NF1 provide valuable insights for the identification of therapies that have utility in people with pNF. Preclinical studies in GEMMs implicate mast cells and the c-Kit/Kit ligand pathway in pNF tumorigenesis. Kit ligand is a potent chemokine secreted by tumorigenic, -deficient Schwann cells. Ketotifen is an FDA-approved drug for the treatment of allergic conjunctivitis and asthma that promotes mast cell stabilization and has been used in prior case studies to treat or prevent pNFs. This study investigated the effect of ketotifen on mast cell infiltration and degranulation in the presence and absence of Kit ligand provocation and the effect of ketotifen on shrinking or preventing pNF formation in the ; GEMM. Ketotifen decreased mast cell infiltration in response to exogenous Kit ligand administration, but did not affect mast cell degranulation. Importantly, ketotifen did not reduce mast cells numbers or activity in pNF and did not prevent pNF formation or decrease the volume of established pNF despite administration of pharmacologically active doses. These findings suggest that ketotifen has limited use as monotherapy to prevent or reduce pNF burden in the setting of mutations.
Topics: Animals; Chemotaxis; Histamine H1 Antagonists; Ketotifen; Mast Cells; Mice; Neurofibroma; Neurofibromin 1; Stem Cell Factor
PubMed: 31527226
DOI: 10.1158/1535-7163.MCT-19-0123 -
Oncology Letters Sep 2019The present case report investigated the clinical characteristics of primary hematological malignancy of the uterine cervixin five patients. Among the five patients,...
The present case report investigated the clinical characteristics of primary hematological malignancy of the uterine cervixin five patients. Among the five patients, three patients were diagnosed with non-Hodgkin's lymphoma (NHL) and two patients with myeloid sarcoma (MS) of the uterine cervix. Biopsies of the uterine cervices demonstrated the involvement of lymphoid cells or myeloid blasts cells. Immunohistochemical staining demonstrated the expression of B-lymphoid and myeloid lineage markers. The associated lysozyme, myeloperoxidase and mast/stem cell growth factor receptor (CD117) markers were specific for the diagnosis of MS. The three patients with NHL survived, and one of the patients survived for 82 months with no evidence of disease; however, was eventually lost to follow-up. The two patients with MS succumbed to the cancer as a result of progressive disease and leukemia. Therefore, pathological examination may be important for the timely diagnosis and appropriate therapeutic regimen for primary hematological malignancy of the uterine cervix.
PubMed: 31516559
DOI: 10.3892/ol.2019.10652 -
Seminars in Cancer Biology Feb 2020The development of a myeloid neoplasm is a step-wise process that originates from leukemic stem cells (LSC) and includes pre-leukemic stages, overt leukemia and a... (Review)
Review
The development of a myeloid neoplasm is a step-wise process that originates from leukemic stem cells (LSC) and includes pre-leukemic stages, overt leukemia and a drug-resistant terminal phase. Organ-invasion may occur in any stage, but is usually associated with advanced disease and a poor prognosis. Sometimes, extra-medullary organ invasion shows a metastasis-like or even sarcoma-like destructive growth of neoplastic cells in local tissue sites. Examples are myeloid sarcoma, mast cell sarcoma and localized blast phase of chronic myeloid leukemia. So far, little is known about mechanisms underlying re-distribution and extramedullary dissemination of LSC in myeloid neoplasms. In this article, we discuss mechanisms through which LSC can mobilize out of the bone marrow niche, can transmigrate from the blood stream into extramedullary organs, can invade local tissue sites and can potentially create or support the formation of local stem cell niches. In addition, we discuss strategies to interfere with LSC expansion and organ invasion by targeted drug therapies.
Topics: Animals; Biomarkers; Bone Marrow; Cell Communication; Cell Movement; Humans; Immunophenotyping; Leukemia, Myeloid; Neoplasm Staging; Neoplastic Stem Cells; Phenotype; Recurrence; Transendothelial and Transepithelial Migration; Tumor Microenvironment
PubMed: 31408723
DOI: 10.1016/j.semcancer.2019.07.025