Immune landscape in children with X-linked retinoschisis.

Background: X-linked retinoschisis is a retinovitreal disorder primarily affecting males, starting in childhood. Over time, patients experience deterioration of vision due to the lack of retinoschisin-1 function. In clinical trials performing intravitreal gene delivery in those affected by this disorder, ocular inflammation was observed, which may have masked efficacy.

Markers of Follicular Helper T Cells Are Occasionally Expressed in T-Cell or Histiocyte-Rich Large B-Cell Lymphoma, Classic Hodgkin Lymphoma, and Atypical Paracortical HyperplasiaA Diagnostic Pitfall For T-Cell Lymphomas of T Follicular Helper Origin.

Objectives: Follicular helper T cell (TFH) markers are expressed in angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma of the TFH phenotype (PTCL-TFH). However, differential expression and coexpression of these markers in benign and other malignant lymphoid proliferations have not been well studied.

Methods: We performed programmed death-1 (PD-1), C-X-C motif chemokine ligand 13 (CXCL13), inducible costimulator (ICOS), CD10, and B-cell lymphoma 6 protein (BCL-6) immunohistochemistry on AITL, PTCL not otherwise specified (PTCL-NOS), PTCL-TFH, T-cell or histiocyte-rich large B-cell lymphoma (THRLBCL), classic Hodgkin lymphoma (CHL), atypical paracortical hyperplasia (PCH), progressive transformation of germinal centers (PTGC), and reactive follicular hyperplasia (RFH).

Utility of Flow Cytometry and Fluorescence In Situ Hybridization in Follow-up Monitoring of Plasma Cell Myeloma.

Objectives: We sought to investigate the clinical utility of flow cytometry (FC) and fluorescence in situ hybridization (FISH) in the workup of myeloma.

Methods: We retrospectively reviewed the reports of bone marrow biopsies received for myeloma evaluation between October 2015 and January 2019.

Results: A total of 1,708 biopsy specimens from 469 myeloma patients (mean age, 64.

Clinical laboratory validation of the MCL35 assay for molecular risk stratification of mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a clinically heterogeneous B cell malignancy for which a variety of prognostic factors have been proposed. Previously, a digital gene expression profiling "proliferation signature" capable of risk stratifying MCL was identified and subsequently developed into a multi-analyte prognostic assay, known as the "MCL35" assay. In this study, we sought to explore the performance characteristics of the MCL35 assay in a clinical laboratory and compare results with the Ki67 proliferation marker.

Molecular profiling reveals a hypoxia signature in breast implant-associated anaplastic large cell lymphoma.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a recently characterized T-cell malignancy that has raised significant patient safety concerns and led to worldwide impact on the implants used and clinical management of patients undergoing reconstructive or cosmetic breast surgery. Molecular signatures distinguishing BIA-ALCL from other ALCLs have not been fully elucidated and classification of BIA-ALCL as a WHO entity remains provisional. We performed RNA sequencing and gene set enrichment analysis comparing BIA-ALCLs to non-BIA-ALCLs and identified dramatic upregulation of hypoxia signaling genes including the hypoxia-associated biomarker CA9 (carbonic anyhydrase-9).

Recurrent mutations in ALK-negative anaplastic large cell lymphoma.

Anaplastic large cell lymphomas (ALCLs) represent a relatively common group of T-cell non-Hodgkin lymphomas (T-NHLs) that are unified by similar pathologic features but demonstrate marked genetic heterogeneity. ALCLs are broadly classified as being anaplastic lymphoma kinase (ALK) or ALK, based on the presence or absence of rearrangements. Exome sequencing of 62 T-NHLs identified a previously unreported recurrent mutation in the musculin gene, , exclusively in ALK ALCLs.

Early event status informs subsequent outcome in newly diagnosed follicular lymphoma.

Recent advances in follicular lymphoma (FL) have resulted in prolongation of overall survival (OS). Here we assessed if early events as defined by event-free survival (EFS) at 12 and 24 months from diagnosis (EFS12/EFS24) can inform subsequent OS in FL. 920 newly diagnosed grade 1-3A FL patients enrolled on the University of Iowa/Mayo Clinic Lymphoma SPORE Molecular Epidemiology Resource (MER) from 2002-2012 were initially evaluated.

Personalized risk prediction for event-free survival at 24 months in patients with diffuse large B-cell lymphoma.

We recently defined event-free survival at 24 months (EFS24) as a clinically relevant outcome for patients with DLBCL. Patients who fail EFS24 have very poor overall survival, while those who achieve EFS24 have a subsequent overall survival equivalent to that of the age- and sex-matched general population. Here, we develop and validate a clinical risk calculator (IPI24) for EFS24.

Primary Cutaneous Polymorphic EBV-Associated Posttransplant Lymphoproliferative Disorder After a Renal Transplant and Review of the Literature.

Importance: Posttransplant lymphoproliferative disorder (PTLD) is an uncommon complication after solid organ transplants and hematopoietic stem cell transplants. Extranodal involvement in PTLD can involve several organ systems, including the central nervous system, bone marrow, lungs, gastrointestinal tract, and skin. Isolated involvement of the skin without systemic involvement in PTLD is rare.

Relationships between chemotherapy, chemotherapy dose intensity and outcomes of follicular lymphoma in the immunochemotherapy era: a report from the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence Molecular Epidemiology Resource.

The optimal treatment of follicular lymphoma (FL) is not established. Rituximab's value potentially dilutes the impact of chemotherapy on FL. We reviewed 337 cases of FL treated initially with rituximab as monotherapy or with chemotherapy at the University of Iowa/Mayo Clinic from 2002 to 2009, investigating the association between chemotherapy delivery of cyclophosphamide or doxorubicin and survival.

Event-free survival at 24 months is a robust end point for disease-related outcome in diffuse large B-cell lymphoma treated with immunochemotherapy.

Purpose: Studies of diffuse large B-cell lymphoma (DLBCL) are typically evaluated by using a time-to-event approach with relapse, re-treatment, and death commonly used as the events. We evaluated the timing and type of events in newly diagnosed DLBCL and compared patient outcome with reference population data.

Patients And Methods: Patients with newly diagnosed DLBCL treated with immunochemotherapy were prospectively enrolled onto the University of Iowa/Mayo Clinic Specialized Program of Research Excellence Molecular Epidemiology Resource (MER) and the North Central Cancer Treatment Group NCCTG-N0489 clinical trial from 2002 to 2009.

Rates and outcomes of follicular lymphoma transformation in the immunochemotherapy era: a report from the University of Iowa/MayoClinic Specialized Program of Research Excellence Molecular Epidemiology Resource.

Purpose: This study sought to characterize transformation incidence and outcome for patients with follicular lymphoma (FL) in a prospective observational series begun after diffusion of rituximab use.

Patients And Methods: Patients with newly diagnosed FL were prospectively enrolled onto the University of Iowa/Mayo Clinic Specialized Program of Research Excellence Molecular Epidemiology Resource from 2002 to 2009. Patients were actively followed for re-treatment, clinical or pathologic transformation, and death.

Elevated serum free light chains are associated with event-free and overall survival in two independent cohorts of patients with diffuse large B-cell lymphoma.

Purpose: The serum free light chain (FLC) assay quantitates free kappa (κ) and free lambda (λ) immunoglobulin light chains. This assay has prognostic value in plasma cell proliferative disorders. There are limited data on serum FLC in B-cell malignancies.

An enhanced antigen-retrieval protocol for immunohistochemical staining of formalin-fixed, paraffin-embedded tissues.

Formalin is the most commonly used fixative for light microscopy because of its preservation of -morphological details. A major adverse effect of formalin fixation is formation of cross-linkages between epitopes (amino acid residues) and unrelated proteins by formaldehyde groups. The great majority of monoclonal and polyclonal antibodies used for immunohistochemical (IHC) staining of formalin-fixed, paraffin-embedded (FFPE) tissues necessitate unmasking antigens for antigen retrieval.

Independent diagnostic accuracy of flow cytometry obtained from fine-needle aspirates: a 10-year experience with 451 cases.

Although the topic is somewhat contentious, fine-needle aspiration (FNA) is frequently used in conjunction with flow cytometry (FC) to evaluate lymphoid proliferations. Despite the fact that the FNA and FC are often analyzed independently, no previous large-scale study has independently analyzed FC of FNA specimens. FC reports of 511 FNAs were retrospectively reviewed and FC diagnoses categorized as monoclonal, atypical, normal/reactive, or insufficient cellularity (3.

The utility of PU.1 as an immunohistochemical marker for histiocytic and dendritic lesions of the skin.

PU.1 is a transcription factor restricted to the hematopoietic system. It is expressed in myeloid lineage and B lymphocytes but is absent in mature T cells and nonhematopoietic cells.

Expression profiling of transcription factors Pax-5, Oct-1, Oct-2, BOB.1, and PU.1 in Hodgkin's and non-Hodgkin's lymphomas: a comparative study using high throughput tissue microarrays.

Analysis of B-cell-specific transcription factors is useful in understanding of the differentiation-linked phenotype in Hodgkin's as well as in non-Hodgkin's lymphomas. We analyzed the expression profiling of transcription factors Pax-5, Oct-1, Oct-2, BOB.1, and PU.

TRAIL-DISC formation is androgen-dependent in the human prostatic carcinoma cell line LNCaP.

We and others have previously described that the androgen-responsive human prostatic carcinoma cell line LNCaP is resistant to TRAIL and that TRAIL-mediated apoptosis in LNCaP is PI3K/Akt-dependent. In this study, we found that LNCaP remained resistant to treatment with TRAIL after androgen deprivation even in the presence of the PI3K/Akt pathway inhibitor wortmannin. This resistance was determined by failure to form the TRAIL-DISC and by decreased TRAIL-R1 and TRAIL-R2 levels after androgen deprivation; the capacity of TRAIL to induce DISC formation was completely restored in the presence of DHT.