Low-grade B-cell lymphoma of the central nervous system with plasmacytic differentiation and amyloid deposition.

A 65-year-old woman with a resolved history of epilepsy due to a motor vehicle accident and hippocampal sclerosis presented with recurrent de novo seizures. Brain imaging demonstrated enhancement in the left parieto-occipital lobe. At histopathological examination, the lesion displayed a diffuse lymphoid infiltrate comprised of small atypical lymphocytes, plasmacytoid lymphocytes, and scattered plasma cells with amyloid deposition. Pathology workup demonstrated a monotypic B-cell phenotype of the lymphoid infiltrate, expressing lambda light chain restriction and plasmacytic differentiation without MYD88 mutations. The patient had no systemic evidence of lymphoma, plasma cell dyscrasia, or amyloidosis. A diagnosis of low-grade B-cell lymphoma of the central nervous system with plasmacytic differentiation and amyloid deposition was made.

Acute Immune Thrombocytopenia Following Influenza Vaccination in a Patient With Untreated Helicobacter pylori Infection.

A 70-year-old man with previously normal comprehensive blood counts (CBCs) was referred to our hospital for acute thrombocytopenia. Following a negative workup for secondary causes, we diagnosed immune thrombocytopenia (ITP). Aside from the influenza vaccine administered six days before presentation, there was no discernable precipitant on history. His only risk factor for ITP was untreated Helicobacter â€‹â€‹â€‹â€‹â€‹â€‹pylori diagnosed over two months prior. With treatment, the patient's platelets normalized within three days. ITP following influenza vaccination has been documented in the literature and reported to regulatory bodies. Our case indicates that individuals with untreated H. pylori infection might be particularly vulnerable to such occurrences.

An 89-Year-Old Man with COVID-19-Associated Coagulopathy Presenting with a Prolonged Partial Thromboplastin Time, Lupus Anticoagulant, and a High Titer of Factor VIII Inhibitor.

BACKGROUND Coagulation abnormalities are frequently encountered in patients with coronavirus disease 2019 (COVID-19), especially in those with more severe disease. These hematologic abnormalities are suspected to occur in the context of underlying immune dysregulation and endothelial dysfunction. Elevated D-dimer levels, COVID-19-associated coagulopathy (CAC), disseminated intravascular coagulation (DIC), and positive lupus anticoagulants are the most common findings to date. Current guidelines suggest that all patients with COVID-19 should receive pharmacologic thromboprophylaxis. CASE REPORT An 89-year-old man with a medical history of hypertension, type 2 diabetes, and advanced prostate cancer in remission presented with generalized weakness. At our center, a reverse transcription-polymerase chain reaction test was positive for severe acute respiratory syndrome coronavirus 2, but the patient did not have symptoms of COVID-19. He was also found to have a prolonged activated partial thromboplastin time, secondary to both a high titer of factor VIII inhibitor and a lupus anticoagulant. He eventually developed respiratory compromise, during which his disease manifested as a bleeding rather than a prothrombotic state. CONCLUSIONS This report highlights the importance of a comprehensive evaluation of prolonged partial thromboplastin time, rather than making an assumption based on a positive lupus anticoagulant result. In the case presented, the concomitant factor VIII inhibitor caused the patient to have a greater bleeding tendency. It is imperative that physicians balance the risk of bleeding and clotting in patients with COVID-19 because patients seem to have varying presentations based on disease severity and level of immune dysregulation.

Epstein - Barr virus association with plasma cell neoplasms.

AIMS: Epstein-Barr virus (EBV) expression has been reported in several hematopoietic and non-hematopoietic disorders but its expression in plasma cell neoplasms has been largely limited to immunodeficiency-related cases such as in the setting of post-organ transplantation or human immunodeficiency virus (HIV) infection. The aim of this study is to evaluate the association of EBV with plasma cell neoplasms, mainly in immunocompetent patients. METHODS AND RESULTS: We retrospectively studied 147 cases of patients with different plasma cell neoplasms (109 plasma cell myelomas, 22 plasmacytomas, and 16 monoclonal gammopathy cases). Six patients were immunocompromised. EBV was positive in 6 cases; 3 immunocompromised (2 patients with HIV infection and 1 patient was post-renal transplant) and 3 immunocompetent patients with plasmacytoma and variable plasmablastic features. CONCLUSIONS: Our data shows that EBV was negative in all plasma cell myeloma cases in immunocompetent patients and has an overall low association with the different plasma cell neoplasms in the immunocompetent setting. When expressed, it is usually associated with variable plasmablastic features.

Specific recognition and killing of glioblastoma multiforme by interleukin 13-zetakine redirected cytolytic T cells.

The interleukin (IL) 13 receptor alpha2 (IL13Ralpha2) is a glioma-restricted cell-surface epitope not otherwise detected within the central nervous system. Here, we describe a novel approach for targeting glioblastoma multiforme (GBM) with IL13Ralpha2-specific cytolytic T cells (CTLs) by their genetic modification to express a membrane-tethered IL13 cytokine chimeric T-cell antigen receptor, or zetakine. Our prototype zetakine incorporates an IL13 E13Y mutein for selective binding to IL13Ralpha2. Human IL13-zetakine(+)CD8(+) CTL transfectants display IL13Ralpha2-specific antitumor effector function including tumor cell cytolysis, T(C)1 cytokine production, and zetakine-regulated autocrine proliferation. The E13Y amino acid substitution of the IL13 mutein of the zetakine endows CTL transfectants with the capacity to discriminate between IL13Ralpha2(+) GBM targets from targets expressing IL13Ralpha1. In vivo, the adoptive transfer of IL13-zetakine(+)CD8(+) CTL clones results in the regression of established human glioblastoma orthotopic xenografts. Pilot clinical trials have been initiated to evaluate the feasibility and safety of local-regional delivery of autologous IL13-zetakine redirected CTL clones in patients with recurrent GBM. Our IL13-zetakine is a prototype of a new class of chimeric immunoreceptors that signal through an engineered immune synapse composed of membrane-tethered cytokine muteins bound to cell-surface cytokine receptors on tumors.