JAK2 p.R564 germ line variants associated with hereditary thrombocythemia and hematologic neoplasms.

The Janus kinase 2 (JAK2) V617F mutation activates the transcription pathway and has been well-characterized as a driver of myeloproliferative neoplasms (MPNs). Recently, there has been a heightened interest in understanding germline predisposition to hematological malignancies including MPN, including several reports of familial MPN. Here, we retrospectively analyzed medical records and data from genetic testing to describe twelve patients with germline variants at amino acid position 564 of JAK2.

Peripheral Blood and Bone Marrow Findings in Treatment-Naive Patients With Cytopenia(s)/Myeloid Neoplasms Harboring Both a Germline and a Somatic DDX41 Mutation.

DDX41 -associated cytopenia(s)/myeloid neoplasms ( DDX41 -C/MNs) are an emerging pathologic entity. We examined the hematopathologic findings in DDX41 -C/MNs with both a germline and somatic DDX41 mutation ( DDX41 -C/MNs-GS). We reviewed the peripheral blood and bone marrow (BM) findings from treatment-naive patients with DDX41 -C/MNs-GS.

Clonal hematopoiesis-derived therapy-related myeloid neoplasms after autologous hematopoietic stem cell transplant for lymphoid and non-lymphoid disorders.

Therapy-related myeloid neoplasms (tMN) are complications of cytotoxic therapies. Risk of tMN is high in recipients of autologous hematopoietic stem cell transplantation (aHSCT). Acquisition of genomic mutations represents a key pathogenic driver but the origins, timing and dynamics, particularly in the context of preexisting or emergent clonal hematopoiesis (CH), have not been sufficiently clarified.

MGMT Methylation and Differential Survival Impact by Sex in Glioblastoma.

: Sex differences in glioblastoma (GBM) have been observed in incidence, genetic and epigenetic alterations, and immune response. These differences have extended to the methylation of the MGMT promoter, which critically impacts temozolomide resistance. However, the association between sex, MGMT methylation, and survival is poorly understood, which this study sought to evaluate.

Predictors of clinical outcome in myeloproliferative neoplasm, unclassifiable: A Bone Marrow Pathology Group study.

Objectives: Myeloproliferative neoplasm, unclassifiable (MPN-U, revised to MPN, not otherwise specified in the fifth edition of the World Health Organization classification) is a heterogeneous category of primary marrow disorders with clinical, morphologic, and/or molecular features that preclude classification as a more specific MPN subtype due to stage at diagnosis, overlapping features between MPN subtypes, or the presence of coexisting disorders. Compared with other MPN subtypes, the contribution of the mutational landscape in MPN-U in conjunction with other clinical and morphologic biomarkers to prognosis has been less well investigated.

Methods: We performed a multicenter, retrospective study of MPN-U (94 cases) to better define the clinicopathologic features, genetic landscape, and clinical outcomes, including subgroups of early-stage, advanced-stage, and coexisting disorders.

Engraftment and Measurable Residual Disease Monitoring after Hematopoietic Stem Cell Transplantation: Comparison of Two Chimerism Test Strategies, Next-Generation Sequencing versus a Combination of Short-Tandem Repeats and Quantitative PCR.

Chimerism testing supports the study of engraftment and measurable residual disease (MRD) in patients after allogeneic hematopoietic stem cell transplant. In chimerism MRD, relapse can be predicted by increasing mixed chimerism (IMC), recipient increase ≥0.1% in peripheral blood, and proliferating recipient cells as a surrogate of tumor activity.

Identification and interpretation of TET2 noncanonical splicing site intronic variants in myeloid neoplasm patients.

: DNA hypermethylation and instability due to inactivation mutations in Ten-eleven translocation 2 () is a key biomarker of hematological malignancies. This study aims at characterizing two intronic noncanonical splice-site variants, c.3954+5_3954+8delGTTT and c.

Design and Implementation of Improved SARS-CoV-2 Diagnostic Assays To Mitigate the Impact of Genomic Mutations on Target Failure: the Xpert Xpress SARS-CoV-2 Experience.

In 2020, the U.S. Food and Drug Administration (FDA) enabled manufacturers to request emergency use authorization (EUA) to facilitate the rapid authorization of diagnostic (IVD) platforms for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Alpha to Omicron: Disease Severity and Clinical Outcomes of Major SARS-CoV-2 Variants.

Background: Four severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants predominated in the United States since 2021. Understanding disease severity related to different SARS-CoV-2 variants remains limited.

Method: Viral genome analysis was performed on SARS-CoV-2 clinical isolates circulating March 2021 through March 2022 in Cleveland, Ohio.

A Model for Design and Implementation of a Laboratory Information-Management System Specific for Molecular Pathology Laboratory Operations.

The Molecular Pathology Section, Cleveland Clinic (Cleveland, OH), has undergone enhancement of its testing portfolio and processes. An Excel 2013- and paper-based data-management system was replaced with a commercially available laboratory information-management system (LIMS) software application, a separate bioinformatics platform, customized test-interpretation applications, a dedicated sample-accessioning service, and a results-releasing software application. The customized LIMS solution manages complex workflows, large-scale data packets, and process automation.

Myeloid Sarcoma Involving the Testis in Adults: Clonal Evolution of Acute Myeloid Leukemia.

To describe the clinical, histologic, immunophenotypic, and genetic characteristics of myeloid sarcoma (MS) diagnosed in the testes of adults, 3 cases were identified, and information on their presentation, clinical features, treatment, and outcome was retrieved from the medical records. In addition, histologic, immunophenotypic, and molecular characteristics were reviewed. This showed that all patients had a previous history of acute myeloid leukemia (AML), in 2 cases diagnosed >10 years before the testicular lesions.

Designing Myeloid Gene Panels.

Context.—: Next-generation sequencing studies are increasingly used in the evaluation of suspected chronic myeloid neoplasms (CMNs), but there is wide variability among laboratories in the genes analyzed for this purpose. Recently, the Association for Molecular Pathology CMN working group recommended a core 34-gene set as a minimum target list for evaluation of CMNs.

A comprehensive analysis of cytopenias and bone marrow morphology in patients with a history of bariatric and metabolic surgery.

Introduction: Following bariatric and metabolic surgery (BMS), patients may develop persistent cytopenia(s) despite adequate micronutrient levels. A comprehensive analysis of laboratory and hematopathologic findings in BMS patients with unexplained cytopenia(s) has not been previously described.

Methods: We reviewed the clinical and laboratory data, bone marrow histology, and used ancillary testing to characterize patients with a history of BMS who had subsequent bone marrow biopsies due to unexplained cytopenia(s).

Clinically Significant CUX1 Mutations Are Frequently Subclonal and Common in Myeloid Disorders With a High Number of Co-mutated Genes and Dysplastic Features.

Objectives: CUX1 mutations have been reported in myeloid neoplasms. We aimed to characterize the mutational landscape, clonal architecture, and clinical characteristics of myeloid disorders with CUX1 variants.

Methods: We reviewed data from a targeted 62-gene panel with CUX1 variants.

Molecular and pathologic characterization of AML with double Inv(3)(q21q26.2).

The inv(3)(q21q26.2) altering a single chromosome 3 homolog is an established myeloid malignancy-associated entity. Comparatively, double inv(3) cases involving both homologs are exceedingly rare with 13 reports across AML, CML and MDS.

Establishing a Clinical Laboratory in a Tertiary/Quaternary Care Greenfield Hospital in the Middle East: Recounting the Cleveland Clinic Abu Dhabi Experience.

Context: - This review chronicles the establishment of a clinical laboratory in Cleveland Clinic Abu Dhabi, a greenfield tertiary/quaternary care hospital in the United Arab Emirates. It discusses the challenges faced, solutions sought, and lessons learned and shares insights and pitfalls that may be encountered in such an undertaking.

Objectives: - To share our experience in building a clinical laboratory in a start-up, multispecialty hospital and how we provided support and managed people, processes, and technology for building and making operational the Cleveland Clinic Abu Dhabi.

Donor skin allograft survival after bone marrow transplantation: Case report and systematic review of the literature☆.

Background: We present a case of skin allograft survival in a patient who previously received a bone marrow transplant from the same HLA-matched donor. DNA fingerprinting of skin biopsies showed mixed cellularity originating from the donor and recipient (68% and 32% donor DNA in the allograft skin and the native recipient's skin, respectively). Histologic sections demonstrated both grade 3/4 rejection and graft-versus-host-disease.

Genomic analysis of marginal zone and lymphoplasmacytic lymphomas identified common and disease-specific abnormalities.

Lymphoplasmacytic lymphomas and marginal zone lymphomas of nodal, extra-nodal and splenic types account for 10% of non-Hodgkin lymphomas. They are similar at the cell differentiation level, sometimes making difficult to distinguish them from other indolent non-Hodgkin lymphomas. To better characterize their genetic basis, we performed array-based comparative genomic hybridization in 101 marginal zone lymphomas (46 MALT, 35 splenic and 20 nodal marginal zone lymphomas) and 13 lymphoplasmacytic lymphomas.

Detection of T-regulatory cells has a potential role in the diagnosis of classical Hodgkin lymphoma.

Previous studies have demonstrated an increase in T-regulatory cells in the involved lymph nodes and peripheral blood of patients with Hodgkin lymphoma. Our study examined whether the detection of T-regulatory cells by flow cytometry could distinguish classical Hodgkin lymphoma (CHL) from benign cases and B-cell non-Hodgkin lymphomas (B-NHL). We measured CD4, CD25, and CD152 in 14 CHLs, 2 nodular lymphocyte-predominant Hodgkin lymphomas, 31 B-NHLs, and 54 benign cases.

Expression of HGAL in primary cutaneous large B-cell lymphomas: evidence for germinal center derivation of primary cutaneous follicular lymphoma.

The classification of primary cutaneous large B-cell lymphoma (PCLBCL) is based on standard morphology, immunohistochemistry, and clinical presentation. There are two major subtypes in the current WHO-EORTC classification: follicle center lymphoma and diffuse large B-cell lymphoma, leg-type (DLBCL-LT). The goals of this study were to examine a series of DLBCLs to determine (1) whether the immunohistochemical paradigm of germinal center B-cell and non-germinal center B-cell types of systemic DLBCL could be applied to PCLBCL; (2) whether application of the newly described germinal center B-cell marker, human germinal center-associated lymphoma (HGAL) also discriminates between these types as a further support for germinal center B-cell origin for primary cutaneous center lymphoma; and (3) whether any of these biologic markers were of prognostic significance.

Unusual case of calciphylaxis associated with metastatic breast carcinoma.

Calciphylaxis is a relatively rare disorder associated with calcification of small- and medium-sized blood vessels, progressive ischemic skin necrosis, and ulcerations. It is usually seen in patients with end-stage renal disease with secondary hyperparathyroidism and is occasionally seen in primary hyperparathyroidism, hypercalcemia of malignancy, and end-stage liver disease. We report an unusual case of calciphylaxis seen in association with metastatic breast carcinoma in the absence of end-stage renal or parathyroid disease.