Pediatric TAFRO syndrome: A multi-institution case series illustrating clinical challenges and excellent outcomes.

A rare lymphoproliferative disorder involving thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), renal dysfunction (R), and organomegaly (O), called TAFRO syndrome, was first reported in 2010. Considered a variant of idiopathic multicentric Castleman's disease, the recent discovery and rarity of this syndrome pose challenges to diagnosis and management. Herein, we review three pediatric cases, including an infant, that illustrate the heterogeneity of TAFRO syndrome.

Immunohistochemistry screening for TP53 mutation in myeloid neoplasms in AZF-fixed bone marrow biopsies.

TP53 mutational status in myeloid neoplasms is prognostic and in acute myeloid leukaemia (AML) may lead to alternative induction therapy; therefore, rapid assessment is necessary for precision treatment. Assessment of multiple prognostic genes by next generation sequencing in AML is standard of care, but the turn-around time often cannot support rapid clinical decision making. Studies in haematological neoplasms suggest p53 immunohistochemistry (IHC) correlates with TP53 mutational status, but they have used variable criteria to define TP53 overexpression.

A Primer on Gene Editing.

Context—: Gene editing-based therapies are currently in development in the areas of oncology, inherited disease, and infectious disease. These potentially life-altering therapies are derived from decades of research in both academic and industry settings that developed technologies rooted in principles and products of nature. However, with such technologic developments come many important considerations, including adverse risks, high cost, and ethical questions.

CBFA2T3-GLIS2 model of pediatric acute megakaryoblastic leukemia identifies FOLR1 as a CAR T cell target.

The CBFA2T3-GLIS2 (C/G) fusion is a product of a cryptic translocation primarily seen in infants and early childhood and is associated with dismal outcome. Here, we demonstrate that the expression of the C/G oncogenic fusion protein promotes the transformation of human cord blood hematopoietic stem and progenitor cells (CB HSPCs) in an endothelial cell coculture system that recapitulates the transcriptome, morphology, and immunophenotype of C/G acute myeloid leukemia (AML) and induces highly aggressive leukemia in xenograft models. Interrogating the transcriptome of C/G-CB cells and primary C/G AML identified a library of C/G-fusion-specific genes that are potential targets for therapy.

A case of VEXAS syndrome associated with EBV-associated hemophagocytic lymphohistiocytosis.

Vacuoles, E1, X-linked, autoimmunity, somatic (VEXAS) syndrome is characterized by a pathogenic mutation in UBA1, which leads to protean complications including autoimmunity and myelodysplasia. A 56-year-old man with steroid-dependent, later steroid-refractory cutaneous polyarteritis nodosa and Sweet syndrome developed recurrent daily fever, macrocytic anemia, thrombocytopenia, acute hypoxic respiratory failure, and anasarca. He was eventually diagnosed with Epstein-Barr virus (EBV) viremia and hemophagocytic lymphohistiocytosis (HLH).

Myeloid Sarcoma Expressing Keratins and Mimicking Carcinoma-Case Report and Literature Review.

Unusual presentations of otherwise common hematopoietic neoplasms are a well-recognized diagnostic challenge. Herein, we present a case study of a previously healthy 64 year old woman with myeloid sarcoma whose diagnosis was delayed by an unusual immunohistochemical staining pattern, including cytokeratin expression, by the neoplastic cells and by possible anchoring bias introduced by radiographic and flow cytometric immunophenotyping reports. This case study emphasizes the need to integrate clinical, radiographic, histologic, and immunophenotyping data for rapid and accurate tissue diagnoses while being wary of the lack of specificity for many common immunophenotypic markers.

High-dose AraC is essential for the treatment of ML-DS independent of postinduction MRD: results of the COG AAML1531 trial.

Myeloid leukemia in children with Down syndrome (ML-DS) is associated with young age and somatic GATA1 mutations. Because of high event-free survival (EFS) and hypersensitivity of the leukemic blasts to chemotherapy, the prior Children's Oncology Group protocol ML-DS protocol (AAML0431) reduced overall treatment intensity but lacking risk stratification, retained the high-dose cytarabine course (HD-AraC), which was highly associated with infectious morbidity. Despite high EFS of ML-DS, survival for those who relapse is rare.

Update on B-cell lymphoproliferative disorders of the gastrointestinal tract.

The gastrointestinal (GI) tract is home to a significant portion of the immune system, which interacts daily with the antigenic milieu of its contents. Therefore, the presence of white blood cells within the walls of the GI tract upon histologic examination is a familiar sight on GI biopsies-both in health and disease. The GI tract is the most common site of extranodal lymphomas, most of which are B-cell neoplasms.

Clinician-ordered peripheral blood smears have low reimbursement and variable clinical value: a three-institution study, with suggestions for operational efficiency.

Background: Peripheral blood smears are performed to evaluate a variety of hematologic and non-hematologic disorders. At the authors' institutions, clinician requests for pathologist-performed blood smear reviews have increased in recent years. Blood smears may contribute significantly to pathologists' workloads, yet their clinical value is variable, and professional reimbursement rates are low.

The Cancer Immunotherapy Biomarker Testing Landscape.

Context.—: Cancer immunotherapy provides unprecedented rates of durable clinical benefit to late-stage cancer patients across many tumor types, but there remains a critical need for biomarkers to accurately predict clinical response. Although some cancer immunotherapy tests are associated with approved therapies and considered validated, other biomarkers are still emerging and at various states of clinical and translational exploration.

Prospective Investigation of an Automated PCR/Nucleic Acid Microarray-Based Platform for Enteric Pathogen Testing.

Background: The Verigene Enteric Pathogens Test (Luminex Corporation) is a polymerase chain reaction (PCR)/nucleic acid microarray-based assay targeting 8 bacterial and viral pathogens that cause diarrhea.

Objective: To compare traditional enteric culture methods with stool testing by Verigene EP (PCR/microarray).

Methods: Tests were performed using PCR/microarray between February and August 2016.

Urinary tract blastomycosis diagnosed by urine cytology.

Urinary tract blastomycosis is an uncommon manifestation of disseminated Blastomyces infection. Here, we report a 50-year-old male with common variable immunodeficiency who presented with urinary symptoms and a renal mass concerning for a kidney neoplasm. Urine cytology revealed typical broad-based budding yeasts with thick-walled refractile capsules, leading to diagnosis of urinary tract blastomycosis.