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BMC Cancer Nov 2019Myeloid sarcoma (MS), also known as chloroma, is an extramedullary manifestation of malignant primitive myeloid cells. Previously, only small studies investigated...
BACKGROUND
Myeloid sarcoma (MS), also known as chloroma, is an extramedullary manifestation of malignant primitive myeloid cells. Previously, only small studies investigated clinical and imaging features of MS. The purpose of this study was to elucidate clinical and imaging features of MS based upon a multicenter patient sample.
METHODS
Patient records of radiological databases of 4 German university hospitals were retrospectively screened for MS in the time period 01/2001 and 06/2019. Overall, 151 cases/76 females (50.3%) with a mean age of 55.5 ± 15.1 years and 183 histopathological confirmation or clinically suspicious lesions of MS were included into this study. The underlying hematological disease, localizations, and clinical symptoms as well as imaging features on CT and MRI were investigated.
RESULTS
In 15 patients (9.9% of all 151 cases) the manifestation of MS preceded the systemic hematological disease. In 43 cases (28.4%), first presentation of MS occurred simultaneously with the initial diagnosis of leukemia, and 92 (60.9%) patients presented MS after the initial diagnosis. In 37 patients (24.5%), the diagnosis was made incidentally by imaging. Clinically, cutaneous lesions were detected in 35 of 151 cases (23.2%). Other leading symptoms were pain (n = 28/151, 18.5%), neurological deficit (n = 27/151, 17.9%), swelling (n = 14/151, 9.3%) and dysfunction of the affected organ (n = 10/151, 6.0%). Most commonly, skin was affected (n = 30/151, 16.6%), followed by bone (n = 29/151, 16.0%) and lymphatic tissue (n = 21/151, 11.4%). Other localizations were rare. On CT, most lesions were homogenous. On T2-weighted imaging, most of the lesions were hyperintense. On T1-weighted images, MS was hypointense in n = 22/54 (40.7%) and isointense in n = 30/54 (55.6%). A diffusion restriction was identified in most cases with a mean ADC value of 0.76 ± 0.19 × 10 mm/s.
CONCLUSIONS
The present study shows clinical and imaging features of MS based upon a large patient sample in a multicenter design. MS occurs in most cases meta-chronous to the hematological disease and most commonly affects the cutis. One fourth of cases were identified incidentally on imaging, which needs awareness of the radiologists for possible diagnosis of MS.
Topics: Adult; Aged; Diagnostic Imaging; Female; Germany; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Proportional Hazards Models; Retrospective Studies; Sarcoma, Myeloid; Symptom Assessment; Tomography, X-Ray Computed
PubMed: 31775680
DOI: 10.1186/s12885-019-6357-y -
Current Opinion in Virology Oct 2022Kaposi's sarcoma-associated herpesvirus (KSHV) causes primary effusion lymphoma (PEL). Here, we review what is known about human gene essentiality in PEL-derived cell... (Review)
Review
Kaposi's sarcoma-associated herpesvirus (KSHV) causes primary effusion lymphoma (PEL). Here, we review what is known about human gene essentiality in PEL-derived cell lines. We provide an updated list of PEL-specific human gene dependencies, based on the improved definition of core essential genes across human cancer types. The requirements of PEL cell lines for interferon regulatory factor 4 (IRF4), basic leukine zipper ATF-like transcription factor (BATF), G1/S cyclin D2 (CCND2), CASP8 and FADD like apoptosis regulator (CFLAR), MCL1 apoptosis regulator (MCL1), and murine double minute 2 (MDM2) have been confirmed experimentally. KSHV co-opts IRF4 and BATF to drive superenhancer (SE)-mediated expression of IRF4 itself, MYC, and CCND2. IRF4 dependency of SE-mediated gene expression is shared with Epstein-Barr virus-transformed lymphoblastoid cell lines (LCLs) and human T-cell leukemia virus type 1-transformed adult T-cell leukemia/lymphoma (ATLL) cell lines, as well as several B-cell lymphomas of nonviral etiology. LCLs and ATLL cell lines similarly share dependencies on CCND2 and CFLAR with PEL, but also have distinct gene dependencies. Genetic dependencies could be exploited for therapeutic intervention in PEL and other cancers.
Topics: Adult; Humans; Animals; Mice; Lymphoma, Primary Effusion; Leukemia-Lymphoma, Adult T-Cell; Epstein-Barr Virus Infections; Myeloid Cell Leukemia Sequence 1 Protein; Herpesvirus 4, Human; Herpesvirus 8, Human; Neoplasms
PubMed: 36182745
DOI: 10.1016/j.coviro.2022.101270 -
Annals of Global Health 2023Haemolymphoreticular neoplasias (HLRNs) from the Ramazzini Institute (RI) carcinogenicity studies on Aspartame (APM) in rats and mice were heterogeneously grouped over...
BACKGROUND
Haemolymphoreticular neoplasias (HLRNs) from the Ramazzini Institute (RI) carcinogenicity studies on Aspartame (APM) in rats and mice were heterogeneously grouped over the years and different statistical methods were applied.
OBJECTIVE
We report all the detailed HLRN diagnoses of all the RI rats and mice studies on APM and the related statistics.
METHODS
Histological subtypes and lineage (myeloid or lymphoid) are reported in males (MM) and females (FF) in line with the International Harmonization of Nomenclature and Diagnostic Criteria for Lesions (INHAND) for rodents and the World Health Organization (WHO) Classification of Tumours of Haematopoietic and Lymphoid Tissues. Statistical analyses included Fisher's Exact test and Cochran-Armitage trend test.
FINDINGS
Results from the post-natal bioassay on Sprague-Dawley (SD) rats (BT6008) showed statistically significant increases in lymphomas (all types) (MM, FF), leukemias (all types) (FF), immunoblastic lymphomas (MM, FF), total lymphoid tumours (MM, FF), monocytic leukemia (FF), myeloid leukemia (FF), histiocytic sarcoma (FF), and total myeloid tumours (FF). Results from the prenatal experiment on SD rats (BT6009), showed statistically significant increases in lymphomas (all types) (FF), leukemias (all types) (FF), total lymphoid tumours (FF), myeloid leukemia (FF), and total myeloid tumours (FF). Finally, results from the prenatal bioassay on Swiss mice (BT6010) showed statistically significant increases in leukemias (all types) (MM, FF), lymphoblastic leukemia (MM, FF), monocytic leukemia (MM) and total myeloid tumours (MM).
CONCLUSIONS
Our analyses, performed in line with international recommended guidelines for statistics and pathology, confirm and reinforce our previous findings of statistically significant increases of HLRNs in rodents exposed to APM.
Topics: Male; Female; Pregnancy; Rats; Mice; Animals; Aspartame; Rats, Sprague-Dawley; Neoplasms; Lymphoma; Leukemia
PubMed: 37362827
DOI: 10.5334/aogh.4163 -
World Journal of Clinical Oncology Oct 2021Myeloid sarcoma (MS) is a rare hematologic malignancy defined as an extramedullary tumor of immature granulocytic cells. It can occur as primary or and be associated...
BACKGROUND
Myeloid sarcoma (MS) is a rare hematologic malignancy defined as an extramedullary tumor of immature granulocytic cells. It can occur as primary or and be associated with myelodysplasia or myeloproliferative neoplasms. The most frequent locations are the skin, lymph nodes and bones. The case of a patient with a diagnosis of primary granulocytic gastric MS is reported.
CASE SUMMARY
A 19-year-old female patient with MS, whose abdominal computed tomography showed a bulky tumor of 16.5 cm in the gastric chamber with infiltration in the retroperitoneal, pancreatic and bile duct region; the histological study showed gastric mucosa diffusely infiltrated by mononucleated cells and the immunohistochemistry expressed myeloperoxidase. After receiving induction chemotherapy based on the 3 + 7 regimen (daunorubicin/cytarabine), the patient developed severe hematological toxicity and neutropenic typhlitis which required a prolonged medical treatment. She presented a rapid disease progression. Although she received supportive treatment, the patient died.
CONCLUSION
Gastric primary MS is a rare and aggressive course neoplasm, fostering knowledge is very important to decide its management and to promote more approaches focused on understanding this pathology and its particularities in our population.
PubMed: 34733617
DOI: 10.5306/wjco.v12.i10.960 -
Journal of Hematology & Oncology May 2022Extramedullary manifestations (EM) are rare in acute myeloid leukemia (AML) and their impact on clinical outcomes is controversially discussed.
BACKGROUND
Extramedullary manifestations (EM) are rare in acute myeloid leukemia (AML) and their impact on clinical outcomes is controversially discussed.
METHODS
We retrospectively analyzed a large multi-center cohort of 1583 newly diagnosed AML patients, of whom 225 (14.21%) had EM.
RESULTS
AML patients with EM presented with significantly higher counts of white blood cells (p < 0.0001), peripheral blood blasts (p < 0.0001), bone marrow blasts (p = 0.019), and LDH (p < 0.0001). Regarding molecular genetics, EM AML was associated with mutations of NPM1 (OR: 1.66, p < 0.001), FLT3-ITD (OR: 1.72, p < 0.001) and PTPN11 (OR: 2.46, p < 0.001). With regard to clinical outcomes, EM AML patients were less likely to achieve complete remissions (OR: 0.62, p = 0.004), and had a higher early death rate (OR: 2.23, p = 0.003). Multivariable analysis revealed EM as an independent risk factor for reduced overall survival (hazard ratio [HR]: 1.43, p < 0.001), however, for patients who received allogeneic hematopoietic cell transplantation (HCT) survival did not differ. For patients bearing EM AML, multivariable analysis unveiled mutated TP53 and IKZF1 as independent risk factors for reduced event-free (HR: 4.45, p < 0.001, and HR: 2.05, p = 0.044, respectively) and overall survival (HR: 2.48, p = 0.026, and HR: 2.63, p = 0.008, respectively).
CONCLUSION
Our analysis represents one of the largest cohorts of EM AML and establishes key molecular markers linked to EM, providing new evidence that EM is associated with adverse risk in AML and may warrant allogeneic HCT in eligible patients with EM.
Topics: Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Mutation; Nucleophosmin; Prognosis; Retrospective Studies; fms-Like Tyrosine Kinase 3
PubMed: 35562747
DOI: 10.1186/s13045-022-01267-7 -
Cells Aug 2021Ewing sarcoma (EwS) is an aggressive pediatric cancer of bone and soft tissues characterized by scant T cell infiltration and predominance of immunosuppressive myeloid...
Ewing sarcoma (EwS) is an aggressive pediatric cancer of bone and soft tissues characterized by scant T cell infiltration and predominance of immunosuppressive myeloid cells. Given the important roles of extracellular vesicles (EVs) in cancer-host crosstalk, we hypothesized that EVs secreted by EwS tumors target myeloid cells and promote immunosuppressive phenotypes. Here, EVs were purified from EwS and fibroblast cell lines and exhibited characteristics of small EVs, including size (100-170 nm) and exosome markers CD63, CD81, and TSG101. Treatment of healthy donor-derived CD33 and CD14 myeloid cells with EwS EVs but not with fibroblast EVs induced pro-inflammatory cytokine release, including IL-6, IL-8, and TNF. Furthermore, EwS EVs impaired differentiation of these cells towards monocytic-derived dendritic cells (moDCs), as evidenced by reduced expression of co-stimulatory molecules CD80, CD86 and HLA-DR. Whole transcriptome analysis revealed activation of gene expression programs associated with immunosuppressive phenotypes and pro-inflammatory responses. Functionally, moDCs differentiated in the presence of EwS EVs inhibited CD4 and CD8 T cell proliferation as well as IFNγ release, while inducing secretion of IL-10 and IL-6. Therefore, EwS EVs may promote a local and systemic pro-inflammatory environment and weaken adaptive immunity by impairing the differentiation and function of antigen-presenting cells.
Topics: Adaptive Immunity; B7-1 Antigen; Cell Differentiation; Cell Line; Dendritic Cells; Extracellular Vesicles; Fibroblasts; Humans; Interleukin-10; Interleukin-6; Lymphocyte Activation; Monocytes; Sarcoma, Ewing; T-Lymphocytes; Transcriptome; Tumor Microenvironment
PubMed: 34440851
DOI: 10.3390/cells10082081 -
Archives of Iranian Medicine Jun 2021The heterogeneous nature of hematopoietic sarcoma has restricted the diagnosis and treatment of this disease to the extent that annually, several patients lose their...
BACKGROUND
The heterogeneous nature of hematopoietic sarcoma has restricted the diagnosis and treatment of this disease to the extent that annually, several patients lose their lives. Given the lack of comprehensive epidemiologic information on the incidence of hematopoietic sarcoma in the Iranian population, we designed the present study to evaluate the distribution pattern of this disease.
METHODS
In this national population-based cancer registry study, we collected data from patients diagnosed with hematopoietic sarcoma who were registered in the Iran National Cancer Registry (INCR) between 2009 and 2013. For each patient, the variables of age, sex, province, year of diagnosis, site of involvement and morphology were collected.
RESULTS
In 45 cases from 18 provinces of Iran, we found that the incidence rate of the disease was 0.60 (95% CI: 0.44-0.80) per million persons. Among all provinces, Ilam had the highest incidence of hematopoietic sarcoma with a rate of 2 (95% CI: 0.05- 11.14) per million persons, while Isfahan had the lowest incidence with a rate of 0.21 (95% CI: 0.01-1.16) per million persons. The incidence rate of the disease increased with age and the disease was slightly more common in men (0.63 [95% CI: 0.41-0.94] vs. 0.56 [95% CI: 0.35-0.86] per million persons). The frequency of hematopoietic sarcoma in connective and soft tissues was higher than other anatomical sites and we found that myeloid morphology was the most prevalent morphology.
CONCLUSION
The resulting data provided a valuable perspective on the distribution pattern of hematopoietic sarcoma in Iran; however, further studies are required to confirm these results.
Topics: Humans; Incidence; Iran; Male; Registries; Sarcoma
PubMed: 34488308
DOI: 10.34172/aim.2021.66 -
Modern Pathology : An Official Journal... Sep 2021Myeloid/lymphoid neoplasms (M/LN) with 13q12/FLT3 rearrangement have been suggested as candidates for possible inclusion in the World Health Organization classification...
Myeloid/lymphoid neoplasms (M/LN) with 13q12/FLT3 rearrangement have been suggested as candidates for possible inclusion in the World Health Organization classification group of M/LN with eosinophilia (M/LN-eo). We report 12 patients with confirmed FLT3 rearrangement, six with t(12;13)/ETV6-FLT3; one with ins(13;22)/BCR-FLT3; and five with an unconfirmed partner gene located on chromosome bands 2p16, 3q27, 5q15, 5q35, and 7q36. Disease presentations were heterogeneous, including lymphoblastic leukemia/lymphoma, myeloid sarcoma, chronic eosinophilic leukemia, chronic myelomonocytic leukemia, and myelodysplastic syndrome. However, some common features were observed, such as extramedullary involvement (n = 7, 58%), associated eosinophilia in blood, bone marrow, or tissue (n = 8, 67%), multilineage involvement, either as biphasic myeloid/lymphoid neoplasms (n = 2) or mixed phenotype acute leukemia (n = 2). Mutations were detected in 4/8 (50%) patients by next-generation sequencing. None (0/10) had FLT3 or KIT mutations. Eleven patients received disease-based chemotherapy or hypomethylating agents, three received FLT3 inhibitors, and five patients proceeded to hematopoietic stem cell transplant. Together with a review of 16 cases published in the literature, it is apparent that M/LNs with FLT3 rearrangement show disease features reminiscent of members in the category of M/LN-eo with PDGFRA, PDGFRB, FGFR1, and PCM1/JAK2 rearrangement, characterized by a specific gene rearrangement, frequent eosinophilia, multi-lineage involvement and therapeutic benefit from kinase inhibitors.
Topics: Adult; Aged; Aged, 80 and over; Child, Preschool; Female; Gene Rearrangement; Hematologic Neoplasms; Humans; Male; Middle Aged; Oncogene Fusion; Young Adult; fms-Like Tyrosine Kinase 3
PubMed: 33990705
DOI: 10.1038/s41379-021-00817-7 -
Case Reports in Gastroenterology 2021Myeloid sarcoma (MS) is a rare solid neoplasm that consists of extramedullary myeloid precursor cells. Generally, it is associated with underlying acute myeloid leukemia...
Myeloid sarcoma (MS) is a rare solid neoplasm that consists of extramedullary myeloid precursor cells. Generally, it is associated with underlying acute myeloid leukemia (AML) or AML yet to manifest clinically. It can present as isolated, also known as primary MS without evidence of AML or other myeloproliferative neoplasms. We present the case of a previously healthy 36-year-old male, who was admitted to hospital with new-onset painful obstructive jaundice and final diagnosis of isolated MS was made after through investigations. We are pleased to report that he had favorable response to the treatment and remains well.
PubMed: 34594168
DOI: 10.1159/000514528 -
Frontiers in Immunology 2023Myeloid derived suppressor cells (MDSCs) are a heterogenous population of myeloid cells derived from monocyte and granulocyte precursors. They are pathologically... (Review)
Review
Myeloid derived suppressor cells (MDSCs) are a heterogenous population of myeloid cells derived from monocyte and granulocyte precursors. They are pathologically expanded in conditions of ongoing inflammation where they function to suppress both innate and adaptive immunity. They are subdivided into three distinct subsets: monocytic (M-) MDSC, polymorphonuclear (or neutrophilic) (PMN-) MDSC and early-stage (e-) MDSC that may exhibit differential function in different pathological scenarios. However, in cancer they are associated with inhibition of the anti-tumour immune response and are universally associated with a poor prognosis. Seven human viruses classified as Group I carcinogenic agents are jointly responsible for nearly one fifth of all human cancers. These viruses represent a large diversity of species, including DNA, RNA and retroviridae. They include the human gammaherpesviruses (Epstein Barr virus (EBV) and Kaposi's Sarcoma-Associated Herpesvirus (KSHV), members of the high-risk human papillomaviruses (HPVs), hepatitis B and C (HBV, HCV), Human T cell leukaemia virus (HTLV-1) and Merkel cell polyomavirus (MCPyV). Each of these viruses encode an array of different oncogenes that perturb numerous cellular pathways that ultimately, over time, lead to cancer. A prerequisite for oncogenesis is therefore establishment of chronic infection whereby the virus persists in the host cells without being eradicated by the antiviral immune response. Although some of the viruses can directly modulate the immune response to enable persistence, a growing body of evidence suggests the immune microenvironment is modulated by expansions of MDSCs, driven by viral persistence and oncogenesis. It is likely these MDSCs play a role in loss of immune recognition and function and it is therefore essential to understand their phenotype and function, particularly given the increasing importance of immunotherapy in the modern arsenal of anti-cancer therapies. This review will discuss the role of MDSCs in viral oncogenesis. In particular we will focus upon the mechanisms thought to drive the MDSC expansions, the subsets expanded and their impact upon the immune microenvironment. Importantly we will explore how MDSCs may modulate current immunotherapies and their impact upon the success of future immune-based therapies.
Topics: Humans; Myeloid-Derived Suppressor Cells; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Neoplasms; Carcinogenesis; Viruses; Tumor Microenvironment
PubMed: 37033972
DOI: 10.3389/fimmu.2023.1161848