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Cureus Jan 2024This case report details a rare case of small bowel myeloid sarcoma (MS) in an otherwise fit and well 49-year-old male presenting initially with vague obstructive...
This case report details a rare case of small bowel myeloid sarcoma (MS) in an otherwise fit and well 49-year-old male presenting initially with vague obstructive symptoms and weight loss. The patient ultimately required an operation for a small bowel obstruction where a laparotomy and small bowel resection were performed due to three cicatrising completely obstructing lesions in the mid-jejunum. Fewer than 1% of patients with acute myeloid leukaemia (AML) present with MS as an initial diagnosis, and only 6.5% of these are intestinal in origin. This report adds to the current body of literature on this rare condition, emphasises the diagnostic challenges resulting in delays to diagnosis, and discusses the crucial role of early and accurate identification for optimal treatment and prognosis. Surgery may be warranted in patients with complications such as obstruction; however, systemic chemotherapy tailored to AML is the primary therapeutic approach for MS patients.
PubMed: 38283782
DOI: 10.7759/cureus.52956 -
Journal of Cytology 2024
PubMed: 38282810
DOI: 10.4103/joc.joc_65_23 -
Medicine Jan 2024With the advancement of diagnostic technology, true acute undifferentiated leukemia (AUL) is becoming more rare, and AUL with extramedullary sarcoma has not been... (Review)
Review
BACKGROUND
With the advancement of diagnostic technology, true acute undifferentiated leukemia (AUL) is becoming more rare, and AUL with extramedullary sarcoma has not been reported.
CASE PRESENTATION
This article reports a case of AUL with extramedullary sarcoma. Flow cytometric analysis of the bone marrow and lymph nodes indicated that the tumor cells of both were of the same origin and mainly expressed stem cell markers and CD7, no myeloid-specific markers, T-lymphoblastic-related markers, and B-lymphoblastic-related markers. Although the priming regimen combined with azacitidine was ineffective, complete remission was achieved by switching to azacitidine combined with HIA (homoharringtonine, idarubicin plus Ara-C).
CONCLUSION
To diagnosis de novo acute leukemia with extensive and comprehensive cellular immune maker detection is available and credible, the expression of a single relatively nonspecific myeloid antigen as a immune maker to detect AUL or AUL associated with sarcoma is precise and effective in our case, which patient was benefit from HIA regiment.
Topics: Humans; Sarcoma, Myeloid; Leukemia, Myeloid, Acute; Leukemia; Bone Marrow; Acute Disease; Azacitidine
PubMed: 38277531
DOI: 10.1097/MD.0000000000036948 -
BioRxiv : the Preprint Server For... Jan 2024Radiation therapy is frequently used to treat cancers including soft tissue sarcomas. Prior studies established that the toll-like receptor 9 (TLR9) agonist...
Radiation therapy is frequently used to treat cancers including soft tissue sarcomas. Prior studies established that the toll-like receptor 9 (TLR9) agonist cytosine-phosphate-guanine oligodeoxynucleotide (CpG) enhances the response to radiation therapy (RT) in transplanted tumors, but the mechanism(s) remain unclear. Here, we used CRISPR/Cas9 and the chemical carcinogen 3-methylcholanthrene (MCA) to generate autochthonous soft tissue sarcomas with high tumor mutation burden. Treatment with a single fraction of 20 Gy RT and two doses of CpG significantly enhanced tumor response, which was abrogated by genetic or immunodepletion of CD8+ T cells. To characterize the immune response to RT + CpG, we performed bulk RNA-seq, single-cell RNA-seq, and mass cytometry. Sarcomas treated with 20 Gy and CpG demonstrated increased CD8 T cells expressing markers associated with activation and proliferation, such as Granzyme B, Ki-67, and interferon-γ. CpG + RT also upregulated antigen presentation pathways on myeloid cells. Furthermore, in sarcomas treated with CpG + RT, TCR clonality analysis suggests an increase in clonal T-cell dominance. Collectively, these findings demonstrate that RT + CpG significantly delays tumor growth in a CD8 T cell-dependent manner. These results provide a strong rationale for clinical trials evaluating CpG or other TLR9 agonists with RT in patients with soft tissue sarcoma.
PubMed: 38260522
DOI: 10.1101/2024.01.03.573968 -
Acta Neuropathologica Communications Jan 2024Erythroblastic sarcoma (ES) (previously called chloroma or granulocytic sarcoma) are rare hematological neoplams characterized by the proliferation of myeloid blasts at...
Erythroblastic sarcoma (ES) (previously called chloroma or granulocytic sarcoma) are rare hematological neoplams characterized by the proliferation of myeloid blasts at extramedullary sites, and primarily involve the skin and soft tissue of middle-aged adults. ES may be concomitant with or secondary to myeloid neoplasms (mostly acute myeloid leukemia (AML)) or in isolated cases (de novo) without infiltration of the bone marrow by blasts. ES share cytogenetic and molecular abnormalities with AML, including RUNX1T1 fusions. Some of these alterations seem to be correlated with particular sites of involvement. Herein, we report an isolated erythroblastic sarcoma with NFIA::RUNX1T1 located in the central nervous system (CNS) of a 3-year-old boy. Recently, two pediatric cases of CNS MS with complete molecular characterization have been documented. Like the current case, they concerned infants (2 and 3 years-old) presenting a brain tumor (pineal involvement) with leptomeningeal dissemination. Both cases also harbored a NFIA::RUNX1T3 fusion. ES constitutes a diagnostic challenge for neuropathologists because it does not express differentiation markers such as CD45, and may express CD99 which could be confused with CNS Ewing sarcoma. CD43 is the earliest pan-hematopoietic marker and CD45 is not expressed by erythroid lineage cells. E-cadherin (also a marker of erythroid precursors) and CD117 (expressed on the surface of erythroid lineage cells) constitute other immunhistochemical hallmarks of ES. The prognosis of patients with ES is similar to that of other patients with AML but de novo forms seem to have a poorer prognosis, like the current case. To conclude, pediatric ES with NFIA::RUNX1T1/3 fusions seem to have a tropism for the CNS and thus constitute a potential pitfall for neuropathologists. Due to the absence of circulating blasts and a DNA-methylation signature, the diagnosis must currently be made by highlighting the translocation and expression of erythroid markers.
Topics: Child, Preschool; Humans; Infant; Male; Middle Aged; Bone Marrow; Central Nervous System Neoplasms; Leukemia, Myeloid, Acute; NFI Transcription Factors; RUNX1 Translocation Partner 1 Protein; Sarcoma; Sarcoma, Myeloid
PubMed: 38243303
DOI: 10.1186/s40478-023-01708-5 -
Cancer Immunology, Immunotherapy : CII Jan 2024Vascular endothelial growth factor is associated with reduced immune response and impaired anti-tumor activity. Combining antiangiogenic agents with immune checkpoint...
BACKGROUND
Vascular endothelial growth factor is associated with reduced immune response and impaired anti-tumor activity. Combining antiangiogenic agents with immune checkpoint inhibition can overcome this immune suppression and enhance treatment efficacy.
METHODS
This study investigated the combination of ziv-aflibercept anti-angiogenic therapy with pembrolizumab in patients with advanced melanoma resistant to anti-PD-1 treatment. Baseline and on-treatment plasma and PBMC samples were analyzed by multiplex protein assay and mass cytometry, respectively.
RESULTS
In this Phase 1B study (NCT02298959), ten patients with advanced PD-1-resistant melanoma were treated with a combination of ziv-aflibercept (at 2-4 mg/kg) plus pembrolizumab (at 2 mg/kg), administered intravenously every 2 weeks. Two patients (20%) achieved a partial response, and two patients (20%) experienced stable disease (SD) as the best response. The two responders had mucosal melanoma, while both patients with SD had ocular melanoma. The combination therapy demonstrated clinical activity and acceptable safety, despite the occurrence of adverse events. Changes in plasma analytes such as platelet-derived growth factor and PD-L1 were explored, indicating potential alterations in myeloid cell function. Higher levels of circulating CXCL10 in non-responding patients may reflect pro-tumor activity. Specific subsets of γδ T cells were associated with poor clinical outcomes, suggesting impaired γδ T-cell function in non-responding patients.
CONCLUSIONS
Although limited by sample size and follow-up, these findings highlight the potential of the combination of ziv-aflibercept antiangiogenic therapy with pembrolizumab in patients with advanced melanoma resistant to anti-PD-1 treatment and the need for further research to improve outcomes in anti-PD-1-resistant melanoma.
TRIAL REGISTRATION NUMBER
NCT02298959.
Topics: Humans; Melanoma; Leukocytes, Mononuclear; Vascular Endothelial Growth Factor A; Recombinant Fusion Proteins; Receptors, Vascular Endothelial Growth Factor; Antibodies, Monoclonal, Humanized
PubMed: 38236249
DOI: 10.1007/s00262-023-03593-2 -
Histopathology Apr 2024The discovery of somatic genetic alterations established many histiocytic disorders as haematologic neoplasms. We aimed to investigate the demographic characteristics...
AIMS
The discovery of somatic genetic alterations established many histiocytic disorders as haematologic neoplasms. We aimed to investigate the demographic characteristics and additional haematologic cancers of patients diagnosed with histiocytic disorders in The Netherlands.
METHODS AND RESULTS
We retrieved data on histiocytosis patients from the Dutch Nationwide Pathology Databank (Palga). During 1993 to 2022, more than 4000 patients with a pathologist-assigned diagnosis of a histiocytic disorder were registered in Palga. Xanthogranulomas were the most common subtype, challenging the prevailing assumption that Langerhans cell histiocytosis (LCH) is the most common histiocytic disorder. LCH and juvenile xanthogranuloma (JXG) had a peak incidence in the first years of life; males were overrepresented among all histiocytosis subgroups. 118 patients had a histiocytic disorder and an additional haematologic malignancy, including 107 (91%) adults at the time of histiocytosis diagnosis. In 16/118 patients, both entities had been analysed for the same genetic alteration(s). In 11 of these 16 patients, identical genetic alterations had been detected in both haematologic neoplasms. This included two patients with PAX5 p.P80R mutated B cell acute lymphoblastic leukaemia and secondary histiocytic sarcoma, further supporting that PAX5 alterations may predispose (precursor) B cells to differentiate into the myeloid lineage. All 4/11 patients with myeloid neoplasms as their additional haematologic malignancy had shared N/KRAS mutations.
CONCLUSIONS
This population-based study highlights the frequency of xanthogranulomas. Furthermore, our data add to the growing evidence supporting clonal relationships between histiocytic/dendritic cell neoplasms and additional myeloid or lymphoid malignancies. Particularly adult histiocytosis patients should be carefully evaluated for the development of these associated haematologic cancers.
Topics: Adult; Male; Humans; Histiocytosis, Langerhans-Cell; Histiocytes; Hematologic Neoplasms; Dendritic Cells; Demography
PubMed: 38213281
DOI: 10.1111/his.15127 -
Asian Journal of Surgery Apr 2024
Topics: Humans; Sarcoma, Myeloid; Urinary Bladder; Urinary Bladder Neoplasms; Sarcoma; Pelvis
PubMed: 38212222
DOI: 10.1016/j.asjsur.2023.12.074 -
Cancer Biology & Therapy Dec 2024CD73 is a cell surface 5'nucleotidase (NT5E) and key node in the catabolic process generating immunosuppressive adenosine in cancer. Using a murine monoclonal antibody...
CD73 is a cell surface 5'nucleotidase (NT5E) and key node in the catabolic process generating immunosuppressive adenosine in cancer. Using a murine monoclonal antibody surrogate of Oleclumab, we investigated the effect of CD73 inhibition in concert with cytotoxic therapies (chemotherapies as well as fractionated radiotherapy) and PD-L1 blockade. Our results highlight improved survival in syngeneic tumor models of colorectal cancer (CT26 and MC38) and sarcoma (MCA205). This therapeutic outcome was in part driven by cytotoxic CD8 T-cells, as evidenced by the detrimental effect of CD8 depleting antibody treatment of MCA205 tumor bearing mice treated with anti-CD73, anti-PD-L1 and 5-Fluorouracil+Oxaliplatin (5FU+OHP). We hypothesize that the improved responses are tumor microenvironment (TME)-driven, as suggested by the lack of anti-CD73 enhanced cytopathic effects mediated by 5FU+OHP on cell lines . Pharmacodynamic analysis, using imaging mass cytometry and RNA-sequencing, revealed noteworthy changes in specific cell populations like cytotoxic T cells, B cells and NK cells in the CT26 TME. Transcriptomic analysis highlighted treatment-related modulation of gene profiles associated with an immune response, NK and T-cell activation, T cell receptor signaling and interferon (types 1 & 2) pathways. Inclusion of comparator groups representing the various components of the combination allowed deconvolution of contribution of the individual therapeutic elements; highlighting specific effects mediated by the anti-CD73 antibody with respect to immune-cell representation, chemotaxis and myeloid biology. These pre-clinical data reflect complementarity of adenosine blockade with cytotoxic therapy, and T-cell checkpoint inhibition, and provides new mechanistic insights in support of combination therapy.
Topics: Animals; Mice; Antibodies, Monoclonal; Sarcoma; Immunosuppressive Agents; Adenosine; Fluorouracil; Tumor Microenvironment
PubMed: 38206570
DOI: 10.1080/15384047.2023.2296048 -
BMJ Case Reports Jan 2024Myeloid sarcoma is a very rare extramedullary malignant tumour, most often associated with acute myeloid leukaemia. We report the case of a man in his early 20s who...
Myeloid sarcoma is a very rare extramedullary malignant tumour, most often associated with acute myeloid leukaemia. We report the case of a man in his early 20s who presented with chronic headache, raised intracranial pressure and progressive vision loss of 2 years duration with no systemic manifestations. He had a history of myeloid sarcoma of the left thigh 15 years ago, treated with external beam radiotherapy and in complete remission for more than 13 years. However, the progressive blindness remained unexplained for 2 years, and he was eventually diagnosed with isolated meningeal relapse without marrow or systemic involvement. Imaging revealed subarachnoid haemorrhage, diffuse leptomeningeal enhancement and involvement of lower dorsal cord and conus, and cerebrospinal fluid cytology showed myeloid blasts. He was managed with intrathecal chemotherapy and craniospinal irradiation, after which he had mild improvement in vision.
Topics: Male; Humans; Sarcoma, Myeloid; Neoplasm Recurrence, Local; Meningeal Neoplasms; Blindness; Granulocyte Precursor Cells
PubMed: 38191225
DOI: 10.1136/bcr-2023-256821