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Veterinary Pathology Sep 2021Tumor grading is a method to quantify the putative clinical aggressiveness of a neoplasm based on specific histological features. A good grading system should be simple,... (Review)
Review
Tumor grading is a method to quantify the putative clinical aggressiveness of a neoplasm based on specific histological features. A good grading system should be simple, easy to use, reproducible, and accurately segregate tumors into those with low versus high risk. The aim of this review is to summarize the histological and, when available, cytological grading systems applied in veterinary pathology, providing information regarding their prognostic impact, reproducibility, usefulness, and shortcomings. Most of the grading schemes used in veterinary medicine are developed for common tumor entities. Grading systems exist for soft tissue sarcoma, osteosarcoma, multilobular tumor of bone, mast cell tumor, lymphoma, mammary carcinoma, pulmonary carcinoma, urothelial carcinoma, renal cell carcinoma, prostatic carcinoma, and central nervous system tumors. The prognostic relevance of many grading schemes has been demonstrated, but for some tumor types the usefulness of grading remains controversial. Furthermore, validation studies are available only for a minority of the grading systems. Contrasting data on the prognostic power of some grading systems, lack of detailed instructions in the materials and methods in some studies, and lack of data on reproducibility and validation studies are discussed for the relevant grading systems. Awareness of the limitations of grading is necessary for pathologists and oncologists to use these systems appropriately and to drive initiatives for their improvement.
Topics: Animals; Carcinoma, Transitional Cell; Kidney Neoplasms; Neoplasm Grading; Prognosis; Reproducibility of Results; Urinary Bladder Neoplasms
PubMed: 33769136
DOI: 10.1177/0300985821999831 -
Oncotarget Oct 2016Mast cell sarcoma (MCS) is a rare form of mastocytosis characterized by the presence of solid tumor(s) comprising malignant mast cells that harbor destructive... (Review)
Review
Mast cell sarcoma (MCS) is a rare form of mastocytosis characterized by the presence of solid tumor(s) comprising malignant mast cells that harbor destructive infiltration capability and metastatic potential. Here, we present an extensive literature review and report on 23 cases of MCS, including 3 new cases from the French National Reference Center for Mastocytosis. From our analysis, it appears that MCS can occur at any age. It can manifest de novo or, to a lesser extent, may evolve from a previously established mastocytosis. Bone tumor is a frequent manifestation, and symptoms of mast cell activation are rare. Histological diagnosis can be difficult because MCS is frequently composed of highly atypical neoplastic mast cells and can thus mimic other tumors. Unexpectedly, the canonical KIT D816V mutation is found in only 21% of MCS; therefore, complete KIT gene sequencing is required. The prognosis of patients with MCS is poor, with a median survival time of less than 18 months, and progression to mast cell leukemia is not unusual. Because conventional chemotherapies usually fail, the role of targeted therapies and bone marrow transplantation warrants further investigation in such aggressive neoplasms.
Topics: Disease Progression; Humans; Mast-Cell Sarcoma; Prognosis
PubMed: 27602777
DOI: 10.18632/oncotarget.11812 -
Modern Pathology : An Official Journal... Jul 2022Mast cell sarcoma (MCS) is an exceedingly rare form of mastocytosis characterized by invasive malignant mast cell growth and metastatic potential. Diagnosis of MCS is... (Review)
Review
Mast cell sarcoma (MCS) is an exceedingly rare form of mastocytosis characterized by invasive malignant mast cell growth and metastatic potential. Diagnosis of MCS is very challenging due to its marked morphologic variations and significant immunophenotypic overlap with other neoplasms. In this study, we undertook an extensive study of 10 cases of MCS from our series, with review of additional 24 cases from the literature, to better clarify the clinicopathologic and molecular features of MCS. From the analyses of our 10 cases, MCS equally involved males and females with a median age of 54.5 years (range 1-63). The bone was the most common site of involvement, as noted in 9/10 of cases. Two patients had prior germ cell tumors (mediastinal germ cell tumor and ovarian dysgerminoma), and concurrent systemic mastocytosis was noted in one of nine patients. Serum tryptase levels were elevated in 6/7 of patients, and 3/9 of patients had mast cell activation symptoms. Morphologically, the tumor cells were typically large and pleomorphic with frequent reactive eosinophils. By immunohistochemical staining, MCS consistently expressed CD43 (8/8), CD117 (10/10), and mast cell tryptase (10/10), as well as CD13 (3/3) and CD33 (10/10), with variable positivity of CD2 (1/9), CD25 (4/9), CD30 (5/8), and CD68 (5/9). Notably, KIT D816V was not detected in nine cases in our study, although two cases had other mutations of KIT gene. Seven out of eight patients received chemotherapy with or without radiotherapy. However, the response was poor, and four out of eight patients died within a median follow-up interval of five months. Taken together, there are no standardized therapeutic regimens available for MCS at this time, and the prognosis is dismal. Therefore, it is critical to further investigate and characterize this rare entity, with the hope of improving diagnostic accuracy and providing more effective, targeted therapies.
Topics: Adolescent; Adult; Child; Child, Preschool; Female; Humans; Infant; Male; Mast Cells; Mast-Cell Sarcoma; Mastocytosis; Mastocytosis, Systemic; Middle Aged; Proto-Oncogene Proteins c-kit; Young Adult
PubMed: 35105959
DOI: 10.1038/s41379-022-01014-w -
The Journal of Allergy and Clinical... Aug 2022Mastocytosis is a myeloid neoplasm defined by expansion and focal accumulation of clonal mast cells (MCs) in one or more organs. The disease exhibits a complex pathology... (Review)
Review
Mastocytosis is a myeloid neoplasm defined by expansion and focal accumulation of clonal mast cells (MCs) in one or more organs. The disease exhibits a complex pathology and may be complicated by MC activation, bone abnormalities, neurological problems, gastrointestinal symptoms, and/or hematologic progression. The World Health Organization divides mastocytosis into cutaneous forms, systemic mastocytosis (SM) and MC sarcoma. In most patients with SM, somatic mutations in KIT are detected. Patients with indolent SM have a normal to near-normal life expectancy, whereas patients with advanced SM, including aggressive SM and MC leukemia, have a poor prognosis. In those with advanced SM, multiple somatic mutations and an associated hematologic neoplasm may be detected. Mediator-related symptoms can occur in any type of mastocytosis. Symptoms may be mild, severe, or even life-threatening. In patients with severe acute symptoms, an MC activation syndrome may be diagnosed. In these patients, relevant comorbidities include IgE-dependent and IgE-independent allergies. Management of patients with SM is an emerging challenge in daily practice and requires in-depth knowledge and a multidisciplinary and personalized approach with selection of appropriate procedures and interventions. In this article, we review the current knowledge on SM and MC activation syndrome, with emphasis on multidisciplinary aspects in diagnosis and patient-specific management. In addition, we provide a user's guide for application of markers, algorithms, prognostic scores, and treatments for use in daily practice.
Topics: Humans; Immunoglobulin E; Mast Cells; Mastocytosis; Mastocytosis, Systemic; Proto-Oncogene Proteins c-kit; Tryptases
PubMed: 35342031
DOI: 10.1016/j.jaip.2022.03.007 -
Cancers Nov 2023Mast cell disorders range from benign proliferations to systemic diseases that cause anaphylaxis and other diverse symptoms to mast cell neoplasms with varied clinical... (Review)
Review
Mast cell disorders range from benign proliferations to systemic diseases that cause anaphylaxis and other diverse symptoms to mast cell neoplasms with varied clinical outcomes. Mastocytosis is the pathologic process of the accumulation of abnormal mast cells in different organs, mostly driven by mutations, and can present as cutaneous mastocytosis, systemic mastocytosis (SM), and mast cell sarcoma. The WHO 5th edition classification divides systemic mastocytosis into bone marrow mastocytosis, indolent systemic mastocytosis, smoldering systemic mastocytosis, aggressive systemic mastocytosis, systemic mastocytosis with an associated hematologic neoplasm, and mast cell leukemia. The new ICC classifies SM slightly differently. The diagnosis of SM requires the integration of bone marrow morphologic, immunophenotypic, and molecular findings, as well as clinical signs and symptoms. Moreover, understanding the wide range of clinical presentations for patients with mast cell disorders is necessary for accurate and timely diagnosis. This review provides an updated overview of mast cell disorders, with a special emphasis on SM, including the latest approaches to diagnosis, prognostic stratification, and management of this rare disease.
PubMed: 38067330
DOI: 10.3390/cancers15235626 -
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 -
Journal of Clinical Medicine Jun 2022Mastocytosis, a heterogeneous mastcell disease, include three different entities: cutaneous mastocytosis, systemic mastocytosis (SM) and mast-cell sarcoma. Tryptase... (Review)
Review
Mastocytosis, a heterogeneous mastcell disease, include three different entities: cutaneous mastocytosis, systemic mastocytosis (SM) and mast-cell sarcoma. Tryptase levels can differentiate cutaneous mastocytosis from SM. In mastocytosis, quick onset drug hypersensitivity reactions (DHRs) that are facilitated by mastcell mediators, are investigated in adults. Due to the limited number of children with mastcell disease and increased serum tryptase levels, the role of drugs in this age group is less studied. In this review, we critically assessed relevant papers related with immediate DHRs in children with mastocytosis and discuss practical issues of the management. In childhood mastocytosis, anaphylaxis is frequently idiopathic, and elevated level of basal tryptase, and high burden of disease may increase the risk. Among drugs, antibiotics, NSAIDs and opioids can potentially induce anaphylaxis, anyway avoidance should be recommended only in case of previous reactions. Moreover, vaccinations are not contraindicated in patients with mastocytosis. The risk of severe systemic reactions after drugs intake seems to be extremely low and in general lower in children than in adults. Anyway, studies on this topic especially focusing on children, are missing to state final recommendations.
PubMed: 35683540
DOI: 10.3390/jcm11113153 -
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 -
American Journal of Hematology Oct 2022
Topics: Humans; Mast-Cell Sarcoma
PubMed: 35266568
DOI: 10.1002/ajh.26525 -
Blood Research Apr 2023Mastocytosis is a heterogeneous neoplasm characterized by accumulation of neoplastic mast cells in various organs. There are three main types: cutaneous mastocytosis... (Review)
Review
Mastocytosis is a heterogeneous neoplasm characterized by accumulation of neoplastic mast cells in various organs. There are three main types: cutaneous mastocytosis (CM), systemic mastocytosis (SM), and mast cell sarcoma. CM mainly affects children and is confined to the skin, whereas SM affects adults and is characterized by extracutaneous involvement, with or without cutaneous involvement. Most cases of SM have an indolent clinical course; however, some types of SM have aggressive behavior and a poor prognosis. Recent advances in the understanding of the molecular changes in SM have changed the diagnosis and treatment of aggressive and advanced SM subtypes. The International Consensus Classification and World Health Organization refined the diagnostic criteria and classification of SM as a result of accumulation of clinical experience and advances in molecular diagnostics. Somatic mutations in the gene, most frequently , are detected in 90% of patients with SM. Expression of CD30 and any mutation were introduced as minor diagnostic criteria after the introduction of highly sensitive screening methods. SM has a wide spectrum of clinical features, and only a few drugs are effective at treating advanced SM. Currently, the mainstay of SM treatment is limited to the management of chronic symptoms related to release of mast cell mediators. Small-molecule kinase inhibitors targeting the KIT-downstream and KIT-independent pathways were recently approved for treating advanced SM. I describe recent advances in diagnosis of SM, and review the currently available and emerging therapeutic options for SM management.
PubMed: 37105564
DOI: 10.5045/br.2023.2023024