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Veterinary Medicine and Science May 2024A 6-year-old male golden retriever presented with swelling of the left upper eyelid of 2 months duration, which did not improve following a course of antibiotics....
A 6-year-old male golden retriever presented with swelling of the left upper eyelid of 2 months duration, which did not improve following a course of antibiotics. Routine serum biochemistry, complete blood count and diagnostic imaging identified no clinically significant abnormalities. The mass was surgically excised, and histopathologic examination was performed. Eosinophilic granulocytic sarcoma (GS) was diagnosed based on the results of histopathology and immunohistochemistry. This is the first report of GS affecting the eyelid of a dog.
Topics: Animals; Dogs; Male; Dog Diseases; Sarcoma, Myeloid; Eyelid Neoplasms
PubMed: 38709141
DOI: 10.1002/vms3.1465 -
Modern Pathology : An Official Journal... May 2024Acute promyelocytic leukemia (APL) with variant RARA translocation is linked to over 15 partner genes. Recent publications encompassing 6 cases have expanded the...
Acute promyelocytic leukemia (APL) with variant RARA translocation is linked to over 15 partner genes. Recent publications encompassing 6 cases have expanded the spectrum of RARA partners to torque teno mini virus (TTMV). This entity is likely underrecognized due to the lack of clinician and pathologist familiarity, inability to detect the fusion using routine testing modalities, and informatic challenges in its recognition within next-generation sequencing (NGS) data. We describe a clinicopathologic approach and provide the necessary tools to screen and diagnose APL with TTMV::RARA using existing clinical DNA- or RNA-based NGS assays, which led to the identification of 4 cases, all without other known cytogenetic/molecular drivers. One was identified prospectively and 3 retrospectively, including 2 from custom automated screening of multiple data sets (50,257 cases of hematopoietic malignancy, including 4809 acute myeloid leukemia/myeloid sarcoma/APL cases). Two cases presented as myeloid sarcoma, including 1 with multiple relapses after acute myeloid leukemia-type chemotherapy and hematopoietic stem cell transplant. Two cases presented as leukemia, had a poor response to induction chemotherapy, but achieved remission upon reinduction (including all-trans retinoic acid in 1 case) and subsequent hematopoietic stem cell transplant. Neoplastic cells demonstrated features of APL including frequent azurophilic granules and dim/absent CD34 and HLA-DR expression. RARA rearrangement was not detected by karyotype or fluorescent in situ hybridization. Custom analysis of NGS fusion panel data identified TTMV::RARA rearrangements and, in the prospectively identified case, facilitated monitoring in sequential bone marrow samples. APL with TTMV::RARA is a rare leukemia with a high rate of treatment failure in described cases. The diagnosis should be considered in leukemias with features of APL that lack detectable RARA fusions and other drivers, and may be confirmed by appropriate NGS tests with custom informatics. Incorporation of all-trans retinoic acid may have a role in treatment but requires accurate recognition of the fusion for appropriate classification as APL.
PubMed: 38704030
DOI: 10.1016/j.modpat.2024.100509 -
Cureus Mar 2024Myeloid sarcoma (MS) is a rare extramedullary tumor of immature granulocytic cells and is most often associated with acute myeloid leukemia (AML). Myeloid sarcomas...
Myeloid sarcoma (MS) is a rare extramedullary tumor of immature granulocytic cells and is most often associated with acute myeloid leukemia (AML). Myeloid sarcomas can occur anywhere in the body but are seldom present in the testicles, especially in the pediatric population. The treatment of MS, especially testicular myeloid sarcoma (TMS) is not well defined in the literature and the role of radiation therapy in the treatment of TMS is even less well defined. In this case report, we discuss the treatment for TMS in a pediatric patient, review the literature, and discuss the role of radiation therapy in the treatment.
PubMed: 38681318
DOI: 10.7759/cureus.57029 -
Diagnostic Pathology Apr 2024MEIS1::NCOA2 is a rare fusion gene that has been recently described in a subset of spindle cell rhabdomyosarcomas and multiple low-grade undifferentiated spindle cell...
BACKGROUND
MEIS1::NCOA2 is a rare fusion gene that has been recently described in a subset of spindle cell rhabdomyosarcomas and multiple low-grade undifferentiated spindle cell sarcomas predominantly arising in the genitourinary and gynecologic tracts with no specific line of differentiation. We present the first documented case of this neoplasm arising as a lung primary tumor.
CASE PRESENTATION
A 74-year-old woman with a 40-year smoking history presented with a 2.1 × 1.7 cm lung nodule discovered on computed tomography (CT) scan. A biopsy and subsequent lobe resection were performed, as well as an extensive metastatic work up, which revealed no additional masses. No specific line of differentiation was found by immunohistochemical staining, and an RNA-based fusion panel revealed a MEIS1::NCOA2 fusion, at which point a diagnosis of Low-Grade Undifferentiated Sarcoma with MEIS1::NCOA2-Rearrangement was rendered.
CONCLUSIONS
This report represents the first diagnosis of this tumor primary to the lung, and provides additional insight into the origin and localization of these rare tumors.
Topics: Humans; Myeloid Ecotropic Viral Integration Site 1 Protein; Female; Lung Neoplasms; Aged; Sarcoma; Nuclear Receptor Coactivator 2; Gene Rearrangement; Biomarkers, Tumor
PubMed: 38678288
DOI: 10.1186/s13000-024-01484-3 -
Annals of Hematology Apr 2024
PubMed: 38676766
DOI: 10.1007/s00277-024-05778-w -
Asian Journal of Surgery Apr 2024
PubMed: 38658275
DOI: 10.1016/j.asjsur.2024.04.060 -
Pediatric Blood & Cancer Jul 2024The outcome of extramedullary infiltration (EMI) in pediatric acute myeloid leukemia (AML) is controversial, and little is known about the implications of stem cell...
Extramedullary infiltration in pediatric acute myeloid leukemia: Results from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative.
BACKGROUND
The outcome of extramedullary infiltration (EMI) in pediatric acute myeloid leukemia (AML) is controversial, and little is known about the implications of stem cell transplantation (SCT) and gemtuzumab ozogamicin (GO) treatment on patients with EMI.
METHODS
We retrieved the clinical data of 713 pediatric patients with AML from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) dataset, and analyzed the clinical and prognostic characteristics of patients with EMI at diagnosis and relapse.
RESULTS
A total of 123 patients were identified to have EMI at diagnosis and 64 presented with EMI at relapse. The presence of EMI was associated with age ≤2 years, M5 morphology, abnormal karyotype, and KMT2A rearrangements. Hyperleukocytosis and complex karyotype were more prevalent in patients with EMI at relapse. Additionally, patients with EMI at diagnosis had a reduced incidence of FLT3 ITD/NPM1, whereas those with EMI at relapse displayed a lower frequency of FLT3 ITD. Patients with EMI at diagnosis exhibited a lower complete remission (CR) rate at the end of Induction Course 1 and higher relapse incidence. Importantly, EMI at diagnosis independently predicted both shorter event-free survival (EFS) and overall survival (OS). Regarding relapse patients, the occurrence of EMI at relapse showed no impact on OS. However, relapse patients with myeloid sarcoma (MS)/no central nervous system (CNS) exhibited poorer OS compared to those with CNS/no MS. Furthermore, regarding patients with EMI at diagnosis, SCT failed to improve the survival, whereas GO treatment potentially enhanced OS.
CONCLUSION
EMI at diagnosis is an independent adverse prognostic risk factor for pediatric AML, and GO treatment potentially improves survival for patients with EMI at diagnosis.
Topics: Humans; Leukemia, Myeloid, Acute; Child; Female; Male; Child, Preschool; Infant; Gemtuzumab; Prognosis; Adolescent; Nucleophosmin; Leukemic Infiltration; Survival Rate; Follow-Up Studies
PubMed: 38644612
DOI: 10.1002/pbc.31014 -
Journal For Immunotherapy of Cancer Apr 2024Tumor-targeted therapy causes impressive tumor regression, but the emergence of resistance limits long-term survival benefits in patients. Little information is...
BACKGROUND
Tumor-targeted therapy causes impressive tumor regression, but the emergence of resistance limits long-term survival benefits in patients. Little information is available on the role of the myeloid cell network, especially dendritic cells (DC) during tumor-targeted therapy.
METHODS
Here, we investigated therapy-mediated immunological alterations in the tumor microenvironment (TME) and tumor-draining lymph nodes (LN) in the D4M.3A preclinical melanoma mouse model (harboring the V-Raf murine sarcoma viral oncogene homolog B (BRAF) mutation) by using high-dimensional multicolor flow cytometry in combination with multiplex immunohistochemistry. This was complemented with RNA sequencing and cytokine quantification to characterize the immune status of the tumors. The importance of T cells during tumor-targeted therapy was investigated by depleting CD4 or CD8 T cells in tumor-bearing mice. Tumor antigen-specific T-cell responses were characterized by performing in vivo T-cell proliferation assays and the contribution of conventional type 1 DC (cDC1) to T-cell immunity during tumor-targeted therapy was assessed using Batf3 mice lacking cDC1.
RESULTS
Our findings reveal that BRAF-inhibitor therapy increased tumor immunogenicity, reflected by an upregulation of genes associated with immune activation. The T cell-inflamed TME contained higher numbers of activated cDC1 and cDC2 but also inflammatory CCR2-expressing monocytes. At the same time, tumor-targeted therapy enhanced the frequency of migratory, activated DC subsets in tumor-draining LN. Even more, we identified a cDC2 population expressing the Fc gamma receptor I (FcγRI)/CD64 in tumors and LN that displayed high levels of CD40 and CCR7 indicating involvement in T cell-mediated tumor immunity. The importance of cDC2 is underlined by just a partial loss of therapy response in a cDC1-deficient mouse model. Both CD4 and CD8 T cells were essential for therapy response as their respective depletion impaired therapy success. On resistance development, the tumors reverted to an immunologically inert state with a loss of DC and inflammatory monocytes together with the accumulation of regulatory T cells. Moreover, tumor antigen-specific CD8 T cells were compromised in proliferation and interferon-γ-production.
CONCLUSION
Our results give novel insights into the remodeling of the myeloid landscape by tumor-targeted therapy. We demonstrate that the transient immunogenic tumor milieu contains more activated DC. This knowledge has important implications for the development of future combinatorial therapies.
Topics: Humans; Animals; Mice; Melanoma; CD8-Positive T-Lymphocytes; Proto-Oncogene Proteins B-raf; Dendritic Cells; Antigens, Neoplasm; Tumor Microenvironment
PubMed: 38631706
DOI: 10.1136/jitc-2023-008606 -
Annals of Medicine and Surgery (2012) Apr 2024Myeloid sarcoma (MS) is a rare tumour associated with acute myeloid leukaemia (AML) and occasionally occurs independently. It typically affects skin, bone, lymph nodes,...
INTRODUCTION AND IMPORTANCE
Myeloid sarcoma (MS) is a rare tumour associated with acute myeloid leukaemia (AML) and occasionally occurs independently. It typically affects skin, bone, lymph nodes, and rarely the gastrointestinal tract, with gastric cases being extremely rare. Notably, no reported instances associate pseudoachalasia with gastric myeloid sarcoma.
CASE PRESENTATION
A 20-year-old male presented with severe dysphagia, refractory vomiting, and weight loss. Diagnosed with type III achalasia via oesophageal tests, subsequent gastroscopy revealed a large gastric mass, later identified as gastric myeloid sarcoma through histopathology.
CLINICAL DISCUSSION
MS, characterized by immature blast cells, poses diagnostic challenges without typical leukaemia symptoms. Diagnosis involves immunohistochemistry, employing markers like CD33, CD34, and CD43. Optimal treatments, such as chemotherapy or stem cell transplantation, aim to delay leukaemia progression. Gastric primary de-novo myeloid sarcoma is exceedingly rare, emphasizing the need for tailored treatment strategies.
CONCLUSION
Gastric myeloid sarcoma is an exceptionally rare tumour, especially without concurrent acute myeloid leukaemia (AML), complicating its diagnosis. This case represents the first globally documented instance of gastric myeloid sarcoma causing pseudoachalasia. Documenting this unique clinical presentation is crucial for a better grasp of gastric myeloid sarcoma's diverse manifestations.
PubMed: 38576939
DOI: 10.1097/MS9.0000000000001830 -
Oncology Letters May 2024The present retrospective study investigated the clinical features and prognosis of secondary hematological malignancies (SHMs) in patients with sarcoma at Korea Cancer...
The present retrospective study investigated the clinical features and prognosis of secondary hematological malignancies (SHMs) in patients with sarcoma at Korea Cancer Center Hospital (Seoul, South Korea). Patients who had been diagnosed with SHMs after having received treatment for sarcoma between January 2000 and May 2023 were enrolled. Clinical data were collected from the patients' medical records. Clinical characteristics were analyzed, including SHM incidence, type and prognosis. Of 2,953 patients with sarcoma, 18 (0.6%) were diagnosed with SHMs. Their median age at the time of sarcoma diagnosis was 39.5 (range, 9-72) years, and 74% (n=14) of these patients were male. The histological features of sarcoma varied, with osteosarcoma diagnosed in nine patients (50%). All patients with sarcoma underwent surgical treatment, and 16 (88.8%) received chemotherapy. The most common type of SHMs was acute myeloid leukemia (n=6; 33.3%), followed by myelodysplastic syndrome (n=5; 27.7%). The median latency period between the sarcoma diagnosis and SHM identification was 30 (range, 11-121) months. A total of 13 (72.2%) patients received treatment for the SHM. The median overall survival after SHM diagnosis was 15.7 (range, 0.4-154.9) months. The incidence of SHMs in sarcoma in the present study was consistent with that reported previously. The presence of SHMs was associated with a poor patient prognosis, especially if treatment for SHMs was not administered.
PubMed: 38572064
DOI: 10.3892/ol.2024.14344