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Seminars in Diagnostic Pathology May 2023Myeloid Sarcoma (MS) is a high grade, hematological malignancy defined as an extramedullary tumor mass of myeloid blasts with or without maturation that effaces tissue... (Review)
Review
Myeloid Sarcoma (MS) is a high grade, hematological malignancy defined as an extramedullary tumor mass of myeloid blasts with or without maturation that effaces tissue architecture. It is a highly heterogenous condition that represents a variety of myeloid neoplasms. This heterogeneity of MS, together with its rarity, have greatly hampered our understanding of the condition. Diagnosis requires tumor biopsy, which should be accompanied by bone marrow evaluation for medullary disease. It is presently recommended that MS be treated similar to AML. Additionally, ablative radiotherapy and novel targeted therapies may also be beneficial. Genetic profiling has identified recurrent genetic abnormalities including gene mutations associated with MS, supporting its etiology similar to AML. However, the mechanisms by which MS homes to specific organs is unclear. This review provides an overview of pathogenesis, pathological and genetic findings, treatment, and prognosis. Improving the management and outcomes of MS patients requires a better understanding of its pathogenesis and its response to various therapeutic approaches.
Topics: Humans; Sarcoma, Myeloid; Prognosis; Myeloproliferative Disorders; Mutation; Leukemia, Myeloid, Acute
PubMed: 37149396
DOI: 10.1053/j.semdp.2023.04.009 -
Annals of Hematology Aug 2023Myeloid sarcoma (MS) is a distinct entity among myeloid neoplasms defined as a tumour mass of myeloid blasts occurring at an anatomical site other than the bone marrow,... (Review)
Review
Myeloid sarcoma (MS) is a distinct entity among myeloid neoplasms defined as a tumour mass of myeloid blasts occurring at an anatomical site other than the bone marrow, in most cases concomitant with acute myeloid leukaemia (AML), rarely without bone marrow involvement. MS may also represent the blast phase of chronic myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS). However, the clinical and molecular heterogeneity of AML, as highlighted by the 2022 World Health Organization (WHO) and International Consensus (ICC) classifications, indirectly define MS more as a set of heterogeneous and proteiform diseases, rather than a homogeneous single entity. Diagnosis is challenging and relies mainly on histopathology, immunohistochemistry, and imaging. Molecular and cytogenetic analysis of MS tissue, particularly in isolated cases, should be performed to refine the diagnosis, and thus assign prognosis guiding treatment decisions. If feasible, systemic therapies used in AML remission induction should be employed, even in isolated MS. Role and type of consolidation therapy are not univocally acknowledged, and systemic therapies, radiotherapy, or allogeneic hematopoietic stem cell transplantation (allo-HSCT) should be considered. In the present review, we discuss recent information on MS, focusing on diagnosis, molecular findings, and treatments also considering targetable mutations by recently approved AML drugs.
Topics: Humans; Sarcoma, Myeloid; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Myeloproliferative Disorders; Hematopoietic Stem Cell Transplantation
PubMed: 37286874
DOI: 10.1007/s00277-023-05288-1 -
Blood Reviews May 2021The World Health Organization classification and definition of "myeloid sarcoma" is imprecise and misleading. A more accurate term is "extramedullary acute myeloid... (Review)
Review
The World Health Organization classification and definition of "myeloid sarcoma" is imprecise and misleading. A more accurate term is "extramedullary acute myeloid leukemia tumor (eAML)." The pathogenesis of eAML has been associated with aberrancy of cellular adhesion molecules, chemokine receptors/ligands and RAS-MAPK/ERK signaling. eAML can present with or without synchronous or metachronous intramedullary acute myeloid leukemia (AML) so a bone marrow evaluation is always recommended. Accurate diagnosis of eAML requires tissue biopsy. eAML confined to one or a few sites is frequently treated with local therapy such as radiotherapy. About 75-90% of patients with isolated eAML will develop metachronous intramedullary AML with a median latency period ranging from 4 to 12 months; thus, patients with isolated eAML may also be treated with systemic anti-leukemia therapy. eAML does not appear to have an independent prognostic impact; selection of post-remission therapy including allogeneic hematopoietic cell transplant (alloHCT) is typically guided by intramedullary disease risk. Management of isolated eAML should be individualized based on patient characteristics as well as eAML location and cytogenetic/molecular features. The role of PET/CT in eAML is also currently being elucidated. Improving outcomes of patients with eAML requires further knowledge of its etiology and mechanism(s) as well as therapeutic approaches beyond conventional chemotherapy, ideally in the context of controlled trials.
Topics: Allografts; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; MAP Kinase Signaling System; Neoplasm Proteins; Positron Emission Tomography Computed Tomography; Radiotherapy; Sarcoma, Myeloid
PubMed: 33213985
DOI: 10.1016/j.blre.2020.100773 -
Blood Cancer Discovery Jan 2024NPM1-mutated acute myeloid leukemia (AML) represents the largest molecular subgroup of adult AML. NPM1-mutated AML is recognizable by molecular techniques and... (Review)
Review
UNLABELLED
NPM1-mutated acute myeloid leukemia (AML) represents the largest molecular subgroup of adult AML. NPM1-mutated AML is recognizable by molecular techniques and immunohistochemistry, which, when combined, can solve difficult diagnostic problems (including identification of myeloid sarcoma and NPM1 mutations outside exon 12). According to updated 2022 European LeukemiaNet (ELN) guidelines, determining the mutational status of NPM1 (and FLT3) is a mandatory step for the genetic-based risk stratification of AML. Monitoring of measurable residual disease (MRD) by qRT-PCR, combined with ELN risk stratification, can guide therapeutic decisions at the post-remission stage. Here, we review the criteria for appropriate diagnosis and molecular monitoring of NPM1-mutated AML.
SIGNIFICANCE
NPM1-mutated AML represents a distinct entity in the 2022 International Consensus Classification and 5th edition of World Health Organization classifications of myeloid neoplasms. The correct diagnosis of NPM1-mutated AML and its distinction from other AML entities is extremely important because it has clinical implications for the management of AML patients, such as genetic-based risk stratification according to 2022 ELN. Monitoring of MRD by qRT-PCR, combined with ELN risk stratification, can guide therapeutic decisions at the post-remission stage, e.g., whether or not to perform allogeneic hematopoietic stem cell transplantation.
Topics: Adult; Humans; Nuclear Proteins; Nucleophosmin; Leukemia, Myeloid, Acute; Mutation; Risk Factors
PubMed: 37917833
DOI: 10.1158/2643-3230.BCD-23-0144 -
Current Opinion in Hematology Mar 2020Myeloid sarcoma; also known as granulocytic sarcoma and chloroma, often occurs concomitantly with AML, and rarely without bone marrow involvement. In this article, we... (Review)
Review
PURPOSE OF REVIEW
Myeloid sarcoma; also known as granulocytic sarcoma and chloroma, often occurs concomitantly with AML, and rarely without bone marrow involvement. In this article, we review the recent literature on myeloid sarcoma, focusing on treatment approach for this rare disease, and addressing the prognostic and therapeutic role of molecular and cytogenetic aberrations.
RECENT FINDINGS
Molecular testing and cytogenetics are important adjunct to conventional diagnostic methods. The significance of cytogenetic and molecular abnormalities in myeloid sarcoma is not completely established, but testing for targetable mutations on myeloid sarcoma cells is feasible, imperative, and may guide treatment decisions. Outcomes in myeloid sarcoma largely depend on the background of its development. Almost all patients with myeloid sarcoma eventually develop AML typically in a short period after its diagnosis; therefore, remission induction treatment using AML type chemotherapy has been the standard of care. Postremission therapy is controversial; allogenic SCT, radiotherapy or consolidation chemotherapy should be considered according to patient risk.
SUMMARY
Further research is required to understand the nature of myeloid sarcoma, and inclusion of patients with this condition in clinical trials should be considered to better identify the best diagnostic, prognostic, and therapeutic approach in managing this rare disease.
Topics: Humans; Sarcoma, Myeloid
PubMed: 31904666
DOI: 10.1097/MOH.0000000000000571 -
Blood Feb 2021Mutations of the nucleophosmin (NPM1) gene, encoding for a nucleolar multifunctional protein, occur in approximately one-third of adult acute myeloid leukemia (AML)....
Mutations of the nucleophosmin (NPM1) gene, encoding for a nucleolar multifunctional protein, occur in approximately one-third of adult acute myeloid leukemia (AML). NPM1-mutated AML exhibits unique molecular, pathological, and clinical features, which led to its recognition as distinct entity in the 2017 World Health Organization (WHO) classification of myeloid neoplasms. Although WHO criteria for the diagnosis of NPM1-mutated AML are well established, its distinction from other AML entities may be difficult. Moreover, the percentage of blasts required to diagnose NPM1-mutated AML remains controversial. According to the European LeukemiaNet (ELN), determining the mutational status of NPM1 (together with FLT3) is mandatory for accurate relapse-risk assessment. NPM1 mutations are ideal targets for measurable residual disease (MRD) monitoring, since they are AML specific, frequent, very stable at relapse, and do not drive clonal hematopoiesis of undetermined significance. MRD monitoring by quantitative polymerase chain reaction of NPM1-mutant transcripts, possibly combined with ELN genetic-based risk stratification, can guide therapeutic decisions after remission. Furthermore, immunohistochemistry can be very useful in selected situations, such as diagnosis of NPM1-mutated myeloid sarcoma. Herein, we present 4 illustrative cases of NPM1-mutated AML that address important issues surrounding the biology, diagnosis, and therapy of this common form of leukemia.
Topics: Age Factors; Aged; Algorithms; Allografts; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Bridged Bicyclo Compounds, Heterocyclic; Cell Lineage; Clinical Trials as Topic; Clonal Evolution; Combined Modality Therapy; Diagnosis, Differential; Disease Management; Female; Gemtuzumab; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Molecular Targeted Therapy; Myelodysplastic Syndromes; Neoplastic Stem Cells; Nuclear Proteins; Nucleophosmin; Oncogene Proteins, Fusion; Patient Selection; Practice Patterns, Physicians'; Remission Induction; Risk Assessment; Salvage Therapy; Sulfonamides; fms-Like Tyrosine Kinase 3
PubMed: 33171486
DOI: 10.1182/blood.2020008211 -
Cureus Dec 2020Chloromas are an atypical cellular infiltrate of immature granulocytic cells that can occur specially in patients with acute myelogenous leukemia (AML), but can be...
Chloromas are an atypical cellular infiltrate of immature granulocytic cells that can occur specially in patients with acute myelogenous leukemia (AML), but can be present in nonleukemic patients. Its clinical course will be dependent on its size and location, from asymptomatic to simulating a malignant gastrointestinal neoplasia. Definitive diagnosis is made upon an immunoprofile that is similar to that present in the blasts and precursor cells of acute myeloid leukemia. Endoscopic and CT images are variable being only part of the protocol panel. Treatment is the same as to AML, but surgery and radiation must be used in order to maintain low relapse and better overall survival.
PubMed: 33489498
DOI: 10.7759/cureus.12080 -
ACG Case Reports Journal Sep 2023Most gastric cancers are adenocarcinomas, but other malignancies can arise in the stomach. Patients with leukemia may develop myeloid sarcoma (MS) in the...
Most gastric cancers are adenocarcinomas, but other malignancies can arise in the stomach. Patients with leukemia may develop myeloid sarcoma (MS) in the gastrointestinal tract. Our patient was a 68-year-old woman who was initially diagnosed with acute myeloid leukemia and underwent a matched unrelated stem cell transplantation. She was in remission for 10 years before developing a rare case of gastric MS without acute myeloid leukemia. She had partial response to chemotherapy but ultimately died because of infection. Gastric MS has an incidence of less than 1%. Gastrointestinal involvement usually involves the small intestine and rarely the stomach.
PubMed: 37674880
DOI: 10.14309/crj.0000000000001137