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Current Oncology Reports Jun 2020The purpose of this review is to summarize the current literature on the presentation, diagnosis, and treatment options available for extramedullary (EM) manifestations... (Review)
Review
PURPOSE OF REVIEW
The purpose of this review is to summarize the current literature on the presentation, diagnosis, and treatment options available for extramedullary (EM) manifestations of leukemia including myeloid sarcoma (MS) and leukemia cutis (LC).
RECENT FINDINGS
Advanced imaging using 18FDG-PET/CT is an effective screening tool for EM manifestations of leukemia. The role of radiation therapy has been more clearly delineated in the treatment of both MS and LC. FDA-approved targeted agents have improved outcomes in patients with AML but have not demonstrated improvements specifically for EM; however, a checkpoint inhibitor, Ipilimumab, holds promise in impacting local control for the treatment of AML-related EM. EM manifestations of leukemia pose significant therapeutic challenges. Treatment of EM is predicated on multiple factors including the presence of concomitant bone marrow involvement, AML-risk classification, and timing of presentation at initial diagnosis or relapse following systemic therapy.
Topics: Humans; Leukemia, Myeloid, Acute; Prognosis; Sarcoma, Myeloid; Skin Neoplasms
PubMed: 32577912
DOI: 10.1007/s11912-020-00919-6 -
Cureus Jan 2022Chronic myeloid leukemia (CML) is a slow-growing type of cancer that originates in the blood-forming cells of the bone marrow and is caused by a chromosomal mutation... (Review)
Review
Chronic myeloid leukemia (CML) is a slow-growing type of cancer that originates in the blood-forming cells of the bone marrow and is caused by a chromosomal mutation that is thought to occur spontaneously. CML could potentially lead to the development of myeloid sarcoma (MS), which is a rare neoplasm composed of immature myeloid cells that could evolve into a tumor mass at any anatomical site other than the bone marrow. MS can develop spontaneously or as a result of another form of myeloid neoplasm. Most instances of CML precede blast phase (BP) within two to three years after the first diagnosis of CML chronic phase (CP) at the age of pre-tyrosine kinase inhibitor (TKI) treatment. MS developing in CML patients during the era of TKI treatment is infrequently mentioned in the literature, primarily in single-case studies. As a result, the prognostic influence of MS in CML patients has not been well investigated. In the age of TKI treatment, it is uncertain whether MS and medullary BP have comparable clinical and prognostic relevance. The precise diagnosis of MS is critical for effective treatment, which is frequently delayed due to a high risk of misdiagnosis. This review focuses on the relationship between the development of MS from CML, and it culminates with recommendations for future hematology practice. A literature search was conducted in multiple databases, and the studies were appraised based on the inclusion and exclusion criteria. Finally, studies to date have shown that the existence of CML and its possible progression to MS in individuals map out the numerous implications this disease has in hematology practice. Though occurrences are uncommon in general, the prognosis for patients is bleak, necessitating the exploration and implementation of diagnostic and therapy advancements. Because there is limited evidence in the literature on its existence in the medullary chronic phase and outcomes in the era of TKI, it must be carefully investigated because it might be the first symptom of progressive illness prior to hematological progression.
PubMed: 35036234
DOI: 10.7759/cureus.21077 -
Leukemia & Lymphoma Dec 2021Myeloid sarcoma (MS) in the setting of concomitant medullary AML is relatively well described, while much less is known about patients presenting with MS with <20% bone...
Myeloid sarcoma (MS) in the setting of concomitant medullary AML is relatively well described, while much less is known about patients presenting with MS with <20% bone marrow blasts. We conducted a retrospective analysis of 56 patients with MS with <20% marrow blasts seen at MD Anderson between 2005 and 2020. The prevalence of MS without medullary AML was 1.4% among all newly diagnosed AML patients. The majority (75%) of patients had a single known anatomic site involved, with the skin (34%) being the most frequent. The most common histologic subtype was monocytic, and 11% of patients had a known history of an antecedent hematologic disorder. The majority of patients (70%) received frontline intensive chemotherapy induction, with 75% of those evaluable attaining complete or partial responses. The median overall survival (OS) and event-free survival (EFS) were 3.41 and 3.07 years, respectively. Patients with bone marrow blasts of ≥5% or medullary relapse had inferior outcomes, while age (>60 years) was not associated with outcomes. There was a suggestion that patients with isolated leukemia cutis may have had better outcomes compared to patients with other organ involvement, but this did not reach statistical significance. Most patients who had cytogenetic analysis had a diploid karyotype within their MS and bone marrow pathway mutations were enriched in MS at diagnosis, and at time of medullary relapse. Our study provides a large dataset summarizing the clinical and molecular analysis of patients with MS with <20% BM blasts and suggests that monitoring for medullary leukemia is important for early detection of relapse.
Topics: Bone Marrow; Humans; Leukemia, Myeloid, Acute; Middle Aged; Prognosis; Recurrence; Retrospective Studies; Sarcoma, Myeloid
PubMed: 34380367
DOI: 10.1080/10428194.2021.1961235 -
Cancers Feb 2023Myeloid sarcomas (MS), commonly referred to as chloromas, are extramedullary tumors of acute myeloid leukemia (AML) with varying incidence and influence on outcomes.... (Review)
Review
Myeloid sarcomas (MS), commonly referred to as chloromas, are extramedullary tumors of acute myeloid leukemia (AML) with varying incidence and influence on outcomes. Pediatric MS has both a higher incidence and unique clinical presentation, cytogenetic profile, and set of risk factors compared to adult patients. Optimal treatment remains undefined, yet allogeneic hematopoietic stem cell transplantation (allo-HSCT) and epigenetic reprogramming in children are potential therapies. Importantly, the biology of MS development is poorly understood; however, cell-cell interactions, epigenetic dysregulation, cytokine signaling, and angiogenesis all appear to play key roles. This review describes pediatric-specific MS literature and the current state of knowledge about the biological determinants that drive MS development. While the significance of MS remains controversial, the pediatric experience provides an opportunity to investigate mechanisms of disease development to improve patient outcomes. This brings the hope of better understanding MS as a distinct disease entity deserving directed therapeutic approaches.
PubMed: 36900239
DOI: 10.3390/cancers15051443 -
Diagnostic Cytopathology Nov 2022
Topics: Cell Biology; Humans; Sarcoma, Myeloid
PubMed: 35960136
DOI: 10.1002/dc.25034 -
Frontiers in Oncology 2023
PubMed: 37434976
DOI: 10.3389/fonc.2023.1223296 -
Indian Journal of Pediatrics Jun 2022Superior mediastinal syndrome (SMS) is a relatively common emergency in the practice of Pediatric Oncology. It typically results from the compression of large airways...
Superior mediastinal syndrome (SMS) is a relatively common emergency in the practice of Pediatric Oncology. It typically results from the compression of large airways and superior vena cava by a swiftly growing mass. T-lineage acute lymphoblastic leukemia or lymphoma, neuroblastoma, and germ cell tumor are the common etiologies of SMS in children. Occasionally, SMS can be an unexpected presentation of less common childhood cancers and a surprise for the diagnostic and treating teams. The present paper reports the diagnostic and therapeutic challenge of managing a 9-y-old boy with SMS resulting from mediastinal myeloid sarcoma. The presence of a sizeable intracardiac thrombus, in addition, contributed to the SMS. The initial pleural fluid cytology and image-guided fine-needle aspiration cytology of the mediastinal mass were nondiagnostic. A thoracotomy was subsequently performed to debulk the tumor for symptomatic relief and obtain tissue for diagnosis.
Topics: Child; Humans; Male; Mediastinal Neoplasms; Sarcoma, Myeloid; Superior Vena Cava Syndrome; Thrombosis; Vena Cava, Superior
PubMed: 35092581
DOI: 10.1007/s12098-021-04056-1 -
Pediatric Hematology and Oncology Feb 2020Myeloid sarcoma (MS) is a neoplastic condition composed of immature myeloid cells involving an extramedullary site. We investigated underlying chromosomal and molecular...
Myeloid sarcoma (MS) is a neoplastic condition composed of immature myeloid cells involving an extramedullary site. We investigated underlying chromosomal and molecular alterations to assess potential molecular markers of prognosis and outcome in this rare pediatric disease. We conducted a retrospective review of clinicopathologic and cytogenetic data from 33 pediatric patients with MS (ages 1 month-18 years) at our institution over a 32 year period (1984-2016). Tissue-based cancer microarray and targeted next-generation sequencing analysis were performed on six cases. The median age at diagnosis was 2.8 years with a male-to-female ratio of 2.6:1. MS is commonly presented with concomitant marrow involvement ( = 12, 36.4%) or as a recurrence of acute myeloid leukemia (AML; = 14, 42.4%). The skin ( = 18, 54.5%) and soft tissue ( = 9, 27.3%) were the most common sites of involvement. Twenty-one of 25 samples (84.0%) harbored chromosomal aberrations; alterations ( = 10, 40.0%) or complex cytogenetics ( = 7, 28.0%) were most frequent. Mutations in RAS, tyrosine kinase, cell signaling, and chromatin remodeling genes were detected. When compared to pediatric patients with AML without extramedullary involvement (EMI), inferior overall survival (OS) was observed (18.8 months vs. 89.3 months, = .008). Pediatric patients with MS with non-favorable cytogenetics [abnormalities other than t(8;21), inv(16)/t(16;16), or t(15;17)] had a significantly lower OS compared to patients with AML with non-favorable cytogenetics and no extramedullary involvement (8.0 months vs. 28.1 months, < .001). Pediatric MS is a rare disease with diverse clinical presentations. Non-favorable cytogenetics may be a poor prognostic marker for pediatric patients with MS and molecular diagnostics can assist with risk stratification and identify potentially actionable targets.
Topics: Adolescent; Child; Child, Preschool; Female; Humans; Infant; Male; Sarcoma, Myeloid
PubMed: 31682773
DOI: 10.1080/08880018.2019.1683107 -
Human Pathology Feb 2021Myeloid sarcoma (MS) is a rare manifestation of acute myeloid leukemia (AML) characterized by extramedullary proliferation of myeloid blasts. Owing to the rarity of MS,... (Comparative Study)
Comparative Study
Myeloid sarcoma (MS) is a rare manifestation of acute myeloid leukemia (AML) characterized by extramedullary proliferation of myeloid blasts. Owing to the rarity of MS, the clonal evolution of cell populations giving rise to MS is not well understood. To study the genomic signature of MS, we used a capture-based next-generation sequencing panel targeting 479 cancer genes to interrogate the genetic variants present in MS samples and compared their genetic profiles with their paired AML samples from a cohort of seven individuals. We identified a spectrum of single-nucleotide variants (SNVs) and a spectrum of copy number alterations in MS. Our study found that variant profiles observed in MS were generally similar to AML from the same individual, supporting the notion that these tumors are derived from a common precursor, rather than de novo tumors in a susceptible host. In addition, MS cases with a higher number of SNVs show worse clinical outcomes than MS with a lower number of SNVs. Identification of these abnormalities could potentially contribute to improved prognostic classification and identify new therapeutic targets for MS.
Topics: Adult; Aged; Aged, 80 and over; DNA Copy Number Variations; Female; Gene Expression Profiling; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Polymorphism, Single Nucleotide; Sarcoma, Myeloid; Transcriptome; Young Adult
PubMed: 33232718
DOI: 10.1016/j.humpath.2020.11.005 -
Oncology Letters Jun 2020Myeloid sarcoma (MS) carries a poor prognosis, and information on epigenetic modifications in MS is currently limited. In the present study, 214 ten-eleven...
Myeloid sarcoma (MS) carries a poor prognosis, and information on epigenetic modifications in MS is currently limited. In the present study, 214 ten-eleven translocation-2 () mice were successfully constructed. In addition, 436 patients with myelodysplastic syndrome (MDS) and 354 with acute myeloid leukemia (AML) patients were recruited. The incidence of MS in mice and patients with deficiency was examined, and the efficiency of hypomethylating agents (HMAs) was also be evaluated. A total of 93% of the mice developed myeloid malignancies, 5.5% of which were accompanied by MS (n=11). The survival of these mice ranged between 3 and 25 months. No significant difference was observed between the survival of MS and non-MS mice with loss (P>0.05). In addition, MS cells were transplantable, and their recipients exhibited myeloproliferative characteristics, such as increased white blood cell counts, monocytosis, low erythrocyte counts and hepatosplenomegaly. Their median survival duration was 94.8 days. In the clinical setting, 9.7% of MDS and 11.6% of AML patients with deficiency developed MS, which was higher compared with previous reports (1.5-9.1%). The median age of the MS patients was 44 years old. 5-Aza-2'-deoxycytidine (5-Aza-dC) reduced the incidence of MS in mice, and decitabine was a suitable treatment strategy for MS patients. These data indicate that deficiency plays a key role in MS and its prognostic significance requires further investigation. HMAs may be a useful treatment for MS patients with mutations.
PubMed: 32382331
DOI: 10.3892/ol.2020.11479