Approach to the Patient: From Endocrinopathy to the Diagnosis of a Histiocytic Disorder.

Endocrinopathies are frequently the initial presentation of histiocytic neoplasms, which are rare hematologic disorders affecting multiple organ systems. Langerhans cell histiocytosis and Erdheim-Chester disease are 2 such disorders known to infiltrate the hypothalamus and/or pituitary gland, leading to arginine vasopressin deficiency (AVP-D) and anterior pituitary dysfunction (APD) in 20% to 30% of cases, often as the first manifestation. Conversely, histiocytic disorders account for a notable proportion (10-15%) of all pituitary stalk lesions.

Personalized Medicine in Histiocytic Disorders: Novel Targets in Patients Without MAPK Alterations.

Purpose: BRAF and MEK inhibitors are standard treatments in histiocytic disorders, such as Erdheim-Chester disease (ECD). Some patients lack MAPK-pathway alterations, making these treatments less effective.

Methods: We describe three patients with histiocytic disorders who have novel non-MAPK pathway alterations.

Methotrexate and cytarabine in adult LCH: High risk, high reward and maintenance free?

Lin et al. report the long-term follow-up of a phase II trial involving 95 adult patients with Langerhans cell histiocytosis (LCH), investigating the combination of methotrexate and cytarabine (MA). After a median follow-up of 6.

Pathogenic Variants Resulting in Dural Based Fibroinflammatory Mass Lesions and H Syndrome Treated With Cobimetinib: A Case Report.

Objectives: Pathogenic variants are known to cause autosomal recessive disease with a spectrum of systemic involvement. We sought to expand on the spectrum of variants and describe potential treatment.

Methods: We describe a case of newly diagnosed -related disorder, also known as H syndrome or familial histiocytosis, associated with CNS inflammatory pseudotumor and spinal cord compression.

Multiomics analysis of IgM monoclonal gammopathies reveals epigenetic influence on oncogenesis via DNA methylation.

Currently, the role of DNA methylation in the immunoglobulin M (IgM) monoclonal gammopathy disease spectrum remains poorly understood. In the present study, a multiomics prospective analysis was conducted integrating DNA methylation, RNA sequencing (RNA-seq), and whole-exome sequencing data in 34 subjects (23 with Waldenström macroglobulinemia [WM], 6 with IgM monoclonal gammopathy of undetermined significance [MGUS], and 5 normal controls). Analysis was focused on defining differences between IgM gammopathies (WM/IgM-MGUS) compared with controls, and specifically between WM and IgM-MGUS.

Monocyte response to SARS-CoV-2 protein ORF8 is associated with severe COVID-19 infection in patients with chronic lymphocytic leukemia.

The open reading frame 8 (ORF8) protein, encoded by the SARS-CoV-2 virus after infection, stimulates monocytes/macrophages to produce pro-inflammatory cytokines. We hypothesized that a positive ex vivo monocyte response to ORF8 protein pre-COVID-19 would be associated with subsequent severe Coronavirus disease 2019 (COVID-19). We tested ORF8 ex vivo on peripheral blood mononuclear cells from 26 anonymous healthy blood donors and measured intracellular cytokine/ chemokine levels in monocytes by flow cytometry.

Bruton Tyrosine Kinase Inhibition: an Effective Strategy to Manage Waldenström Macroglobulinemia.

Purpose Of Review: The treatment of Waldenström macroglobulinemia (WM) has evolved over the past decade. With the seminal discoveries of MYD88 and CXCR warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) mutations in WM cells, our understanding of the disease biology and treatment has improved. The development of a new class of agents, Bruton tyrosine kinase inhibitors (BTKi), has substantially impacted the treatment paradigm of WM.

Clinical characteristics, molecular aberrations, treatments, and outcomes of malignant histiocytosis.

Malignant histiocytosis (MH) is an extremely rare neoplasm of the macrophage-dendritic cell lineage. We report the clinical characteristics, molecular aberrations, treatments, and outcomes of patients with MH seen at two referral centers from January 2000 to May 2023. We identified 43 patients with MH, of which 26 had histiocytic sarcoma (MH-H), 9 interdigitating dendritic cell sarcoma (MH-IDC), and 8 Langerhans cell sarcoma (MH-LC).

Long-term outcomes among adults with Langerhans cell histiocytosis.

Advances in the treatment of Langerhans cell histiocytosis (LCH) have resulted in a growing survivor population. There is a lack of data on long-term outcomes among adults with LCH. We conducted a retrospective record review of 219 adults (aged ≥18 years) with LCH.

Prognostic relevance of clonal hematopoiesis in myeloid neoplastic transformation in patients with follicular lymphoma treated with radioimmunotherapy.

While novel radioisotope therapies continue to advance cancer care, reports of therapy-related myeloid neoplasms (t-MN) have generated concern. The prevalence and role of clonal hematopoiesis (CH) in this process remain to be defined. We hypothesized that: (i) CH is prevalent in relapsed follicular lymphoma and is associated with t-MN transformation, and (ii) radiation in the form of radioimmunotherapy (RIT) plays a role in clonal progression.

Malignant Histiocytosis Comprises a Phenotypic Spectrum That Parallels the Lineage Differentiation of Monocytes, Macrophages, Dendritic Cells, and Langerhans Cells.

Malignant histiocytoses (MHs), or the 'M group' of the Histiocyte Society classification, are characterized by neoplastic histiocytes with large pleomorphic nuclei. MH encompasses the diagnoses of histiocytic sarcoma, interdigitating dendritic cell sarcoma, and Langerhans cell sarcoma. We aimed to define the phenotypic spectrum of MH and examine the genotypic features across this spectrum.