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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 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 -
Nature Medicine Oct 2018Impaired immunity in patients with late-stage cancer is not limited to antitumor responses, as demonstrated by poor vaccination protection and high susceptibility to...
Impaired immunity in patients with late-stage cancer is not limited to antitumor responses, as demonstrated by poor vaccination protection and high susceptibility to infection. This has been largely attributed to chemotherapy-induced impairment of innate immunity, such as neutropenia, whereas systemic effects of tumors on hematopoiesis and adoptive immunity remain incompletely understood. Here we observed anemia associated with severe deficiency of CD8 T cell responses against pathogens in treatment-naive mice bearing large tumors. Specifically, we identify CD45 erythroid progenitor cells (CD71TER119; EPCs) as robust immunosuppressors. CD45 EPCs, induced by tumor growth-associated extramedullary hematopoiesis, accumulate in the spleen to become a major population, outnumbering regulatory T cells (Ts) and myeloid-derived suppressor cells (MDSCs). The CD45 EPC transcriptome closely resembles that of MDSCs, and, like MDSCs, reactive oxygen species production is a major mechanism underlying CD45 EPC-mediated immunosuppression. Similarly, an immunosuppressive CD45 EPC population was detected in patients with cancer who have anemia. These findings identify a major population of immunosuppressive cells that likely contributes to the impaired T cell responses commonly observed in patients with advanced cancer.
Topics: Anemia; Animals; Antigens, CD; CD8-Positive T-Lymphocytes; Disease Models, Animal; Erythroid Precursor Cells; Humans; Immune Tolerance; Immunity, Innate; Leukocyte Common Antigens; Mice; Myeloid-Derived Suppressor Cells; Neoplasm Staging; Reactive Oxygen Species; Receptors, Transferrin; Sarcoma, Myeloid; T-Lymphocytes, Regulatory; Xenograft Model Antitumor Assays
PubMed: 30297899
DOI: 10.1038/s41591-018-0205-5 -
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 -
Cureus Jun 2020Myeloid sarcoma is an isolated extramedullary tumor mass consisting of immature myeloid cells. It is characterized by highly variable outcomes and usually disrupts the...
Myeloid sarcoma is an isolated extramedullary tumor mass consisting of immature myeloid cells. It is characterized by highly variable outcomes and usually disrupts the normal architecture of the normal tissue in which it originates. It may occur de novo or be associated with other hematological malignancies. Clinical presentation of myeloid sarcomas can be highly variable based on the tumor site, size, and extent of tissue involvement. The diagnosis of myeloid sarcoma is challenging and requires a high index of suspicion. Tissue sampling followed by the use of auxiliary studies is essential for diagnosis. Moreover, bone marrow sampling is necessary to exclude morrow involvement. Currently, the recommended therapeutic regimens for myeloid sarcoma are similar to those for acute myeloid leukemia. Much work remains to be accomplished as myeloid sarcomas, if initially missed or misdiagnosed, have poor overall survival rates. Furthermore, prognostic factors for this malignancy remain poorly understood.
PubMed: 32528784
DOI: 10.7759/cureus.8462 -
EJHaem Nov 2021
PubMed: 35845198
DOI: 10.1002/jha2.306 -
Leukemia Research Reports 2019Myeloid Sarcoma (MS) is diagnosed by an extramedullary proliferation of immature granulocytic cells. Its association with chronic myeloid leukemia (CML) is rare. CML is...
Myeloid Sarcoma (MS) is diagnosed by an extramedullary proliferation of immature granulocytic cells. Its association with chronic myeloid leukemia (CML) is rare. CML is characterized by gene rearrangement and therapies with tyrosine kinase inhibitors (TKI) are very effective. However, TKI resistance may occur secondary to the development of mutations. T315I is a common mutation that accounts for ∼20% clinical resistance to TKIs. We report the first case of a patient with T315I mutated myeloid sarcoma that occurred after complete cytogenetic response with dasatinib of a chronic phase CML. The patient was successfully treated with induction chemotherapy and ponatinib.
PubMed: 31485411
DOI: 10.1016/j.lrr.2019.100184