Testicular Relapse of Primary Diffuse Large B-cell Lymphoma of the Central Nervous System - a Rare Occurrence.

Among diffuse large b-cell lymphoma (DLBCL) subtypes, primary testicular lymphoma (PTL) has one of the highest risks of central nervous system (CNS) relapse. The converse, primary CNS lymphoma (PCNSL) relapse outside the CNS is rare. Molecular analysis has illustrated a genetic similarity between PTL and PCNSL.

Transcriptomics of acute myeloid leukaemia core bone marrow biopsies reveals distinct therapy response-specific osteo-mesenchymal profiles.

While the bone marrow (BM) microenvironment is significantly remodelled in acute myeloid leukaemia (AML), molecular insight into AML-specific alterations in the microenvironment has been historically limited by the analysis of liquid marrow aspirates rather than core biopsies that contain solid-phase BM stroma. We assessed the effect of anthracycline- and cytarabine-based induction chemotherapy on both haematopoietic and non-haematopoietic cells directly in core BM biopsies using RNA-seq and histological analysis. We compared matched human core BM biopsies at diagnosis and 2 weeks after cytarabine- and anthracycline-based induction therapy in responders (<5% blasts present after treatment) and non-responders (≥5% blasts present after treatment).

Clinical activity of 9-ING-41, a small molecule selective glycogen synthase kinase-3 beta (GSK-3β) inhibitor, in refractory adult T-Cell leukemia/lymphoma.

GSK-3β is a serine/threonine kinase implicated in tumorigenesis and chemotherapy resistance. GSK-3β blockade downregulates the NF-κB pathway, modulates immune cell PD-1 and tumor cell PD-L1 expression, and increases CD8 + T cell and NK cell function. We report a case of adult T-cell leukemia/lymphoma (ATLL) treated with 9-ING-41, a selective GSK-3β inhibitor in clinical development, who achieved a durable response.

Detection of clonotypic DNA in the cerebrospinal fluid as a marker of central nervous system invasion in lymphoma.

The diagnosis of parenchymal central nervous system (CNS) invasion and prediction of risk for future CNS recurrence are major challenges in the management of aggressive lymphomas, and accurate biomarkers are needed to supplement clinical risk predictors. For this purpose, we studied the results of a next-generation sequencing (NGS)-based assay that detects tumor-derived DNA for clonotypic immunoglobulin gene rearrangements in the cerebrospinal fluid (CSF) of patients with lymphomas. Used as a diagnostic tool, the NGS-minimal residual disease (NGS-MRD) assay detected clonotypic DNA in 100% of CSF samples from 13 patients with known CNS involvement.

Aggressive CD4/CD8 Double-Negative Primary Cutaneous T-Cell Lymphoma With Dural Invasion: A Rare Presentation of Mycosis Fungoides?

Mycosis fungoides (MF) is primarily characterized by epidermotropic CD3+/CD4+/CD45RO+ memory T cells. CD4/CD8 double-negative MF is an uncommon variant with no presumed prognostic significance. Despite the variability in the clinical course and presentation of MF, most cases behave indolently.

Bone marrow-specific loss of induces myeloproliferative neoplasm with features resembling human myelofibrosis.

Although the pathogenesis of primary myelofibrosis (PMF) and other myeloproliferative neoplasms (MPNs) is linked to constitutive activation of the JAK-STAT pathway, JAK inhibitors have neither curative nor MPN-stem cell-eradicating potential, indicating that other targetable mechanisms are contributing to the pathophysiology of MPNs. We previously demonstrated that Abelson interactor 1 (Abi-1), a negative regulator of Abelson kinase 1, functions as a tumor suppressor. Here we present data showing that bone marrow-specific deletion of in a novel mouse model leads to development of an MPN-like phenotype resembling human PMF.

Overexpression of Tpl2 is linked to imatinib resistance and activation of MEK-ERK and NF-κB pathways in a model of chronic myeloid leukemia.

The introduction of tyrosine kinase inhibitors (TKI) has transformed chronic myeloid leukemia (CML) into a chronic disease with long-term survival exceeding 85%. However, resistance of CML stem cells to TKI may contribute to the 50% relapse rate observed after TKI discontinuation in molecular remission. We previously described a model of resistance to imatinib mesylate (IM), in which K562 cells cultured in high concentrations of imatinib mesylate showed reduced Bcr-Abl1 protein and activity levels while maintaining proliferative potential.

Heterozygous Hemoglobin Sherwood Forest Causing Polycythemia.

Hemoglobin (Hb) Sherwood Forest is a rare high-affinity hemoglobin first described in 1977, arising from an Arg to Thr substitution at codon 104 of the beta chain. This hemoglobin variant has been identified in few individuals and has been associated with a compensatory erythrocytosis in the homozygous state. Prior scarce case reports have noted that heterozygotes for this variant are phenotypically normal.

Primary Cutaneous Follicle Centre Lymphoma with Hodgkin and Reed-Sternberg Like Cells: A Case Report and Review of the Literature.

An elderly woman with a complex medical history presented with a left forearm mass that slowly developed for several months. The excisional biopsy of this skin mass was remarkable for involvement by a follicle centre cell derived lymphoma with a nodular and diffuse pattern associated with a subset of scattered Hodgkin and Reed-Sternberg like cells. Fluorescence in situ hybridization studies did not detect the presence of IgH-bcl2 fusion transcript, and molecular studies were negative for immunoglobulin heavy chain gene rearrangements and EBV DNA sequences.

Infiltrative Rash Secondary to Leukemic-Phase Diffuse Large B-Cell Lymphoma With t(14;18), CDKN2A and MLL Deletion.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous and highly aggressive subtype of non-Hodgkin's lymphoma. It commonly presents as rapidly-growing, painless lymphadenopathy (LAD). DLBCL presenting in leukemic-phase is rare, with fewer than 40 cases published.

Primary Spinal Epidural CIC-DUX4 Undifferentiated Sarcoma in a Child.

Primitive round- or spindle-cell EWSR1-negative undifferentiated sarcomas harboring CIC-DUX4 gene fusion are the most common form of Ewing-like sarcomas. These tumors primarily occur in peripheral soft tissues, but examples have been described within viscera and the brain. As far as we are aware, CIC-DUX4 positive primary epidural spinal sarcoma has not been reported.

Long-Term Exposure to Imatinib Mesylate Downregulates Hippo Pathway and Activates YAP in a Model of Chronic Myelogenous Leukemia.

Despite the success of tyrosine kinase inhibitor (TKI) therapy in chronic myelogenous leukemia (CML), leukemic stem/progenitor cells remain detectable even in the state of deep molecular remission. Mechanisms that allow them to persist despite continued kinase inhibition remain unclear. We have previously shown that prolonged exposure to imatinib mesylate (IM) results in dysregulation of Akt/Erk 1/2 signaling, upregulation of miR-181a, enhanced adhesiveness, and resistance to high IM.

TAFRO Syndrome Associated with EBV and Successful Triple Therapy Treatment: Case Report and Review of the Literature.

TAFRO syndrome is a rare constellation of symptoms: thrombocytopenia, anasarca, reticulin fibrosis of the bone marrow, renal dysfunction, and organomegaly. Its pathogenesis involves an excessive and inappropriate cytokine storm, most notably from IL-6, causing multiorgan failure; however, its etiology is undetermined. Starting in 2012, TAFRO syndrome was first identified in Japan as an atypical variant of Castleman's disease.

Fatal Sepsis in a Patient With Celiac Disease-Associated Hyposplenism.

We present a 59-year-old male with poorly controlled celiac disease (CD) and fatal sepsis, describe the morphologic findings, and stress the need for monitoring splenic function and pneumococcal vaccination in these patients.

Compressive spinal epidural mass caused by Propionibacterium acnes.

Background Context: Propionibacterium acnes is a gram-positive and facultative anaerobe bacillus that is found within sebaceous follicles of the human skin and recognized as a cause of infections after spinal surgery. To our knowledge, there has been no previously reported case of symptomatic compressive chronic inflammatory epidural mass caused by P. acnes in a patient with no prior spinal procedures.

Unusual blasts with basophilic granules in 2 cases of de novo acute myeloid leukemia with inv3(q21q26.2) and monosomy 7 and coexpression of CD2 and CD31.

Acute myeloid leukemia with inv3(q21q26.2)/t(3,3)(q21;q26.2) is a subtype of acute myeloid leukemia associated with significant dysmyelopoiesis and a poor prognosis.

Similar outcomes in Asian and Western patients with diffuse large B-cell lymphoma treated with R-CHOP.

Background: Little is known on racial differences in patients with diffuse large B-cell lymphoma (DLBCL). The aim of this retrospective study is to compare characteristics, prognostic factors and outcomes of Asian and Western patients with DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP).

Methods: Patient-level data was collected from 8 centers.

Spontaneous regression of chronic lymphocytic leukemia to a monoclonal B-lymphocytosis or to a normal phenotype.

Spontaneous remission of chronic lymphocytic leukemia (CLL) is an unusual and poorly characterized event. We performed a search for spontaneous remission in patients with CLL. Cases must have had a pathological diagnosis of CLL with disease duration > 6 months.

Acute Myeloid Leukemia Evolving from JAK 2-Positive Primary Myelofibrosis and Concomitant CD5-Negative Mantle Cell Lymphoma: A Case Report and Review of the Literature.

Primary myelofibrosis (formerly known as chronic idiopathic myelofibrosis), has the lowest incidence amongst the chronic myeloproliferative neoplasms and is characterized by a rather short median survival and a risk of progression to acute myeloid leukemia (AML) noted in a small subset of the cases, usually as a terminal event. As observed with other chronic myeloproliferative neoplasms, the bone marrow biopsy may harbor small lymphoid aggregates, often assumed reactive in nature. In our paper, we present a 70-year-old Caucasian male who was diagnosed with primary myelofibrosis, and after 8 years of followup and therapy developed an AML.