Summary: Though basophils were originally viewed as redundant blood ‘mast cells’, the implementation of flow cytometry has established basophils as unique leukocytes with critical immunomodulatory functions. Basophils play an active role in allergic inflammation, autoimmunity, and hematological malignancies. They are distinguishable from other leukocytes by their characteristic metachromatic deep-purple cytoplasmic, round granules. Mature basophils are phenotypically characterized by surface expression of IL-3Rα (CD123); IL-3 drives basophil differentiation, degranulation, and synthesis of inflammatory mediators including type 2 cytokines. Basophil degranulation is the predominant source of histamine in peripheral blood, promoting allergic responses. Basophils serve as a bridge between innate and adaptive immunity by secreting IL-4 which supports eosinophil migration, monocyte differentiation into macrophages, B-cell activation, and CD4 T-cell differentiation into Th2 cells. Further, basophilia is a key phenomenon in myeloid neoplasms, especially chronic myeloid leukemia (CML) for which it is a diagnostic criterion. Increased circulating basophils, often with aberrant immunophenotype, have been detected in patients with CML and other myeloproliferative neoplasms (MPNs). The significance of basophils’ immunoregulatory functions in malignant and non-malignant diseases is an active area of research. Ongoing and future research can inform the development of immunotherapies that target basophils to impact allergic, autoimmune, and malignant disease states. This review article aims to provide an overview of basophil biology, identification strategies, and roles and dysregulation in diseases.

Chronic myeloproliferative neoplasms (MPNs) are hematopoietic stem cell neoplasms with driver events including the BCR-ABL1 translocation leading to a diagnosis of chronic myeloid leukemia (CML), or somatic mutations in JAK2, CALR, or MPL resulting in Philadelphia-chromosome-negative MPNs with constitutive activation of the JAK-STAT signaling pathway. In the Philadelphia-chromosome-negative MPNs, modern sequencing panels have identified a vast molecular landscape including additional mutations in genes involved in splicing, signal transduction, DNA methylation, and chromatin modification such as ASXL1, SF3B1, SRSF2, and U2AF1. These additional mutations often influence prognosis in MPNs and therefore are increasingly important for risk stratification. This review focuses on the molecular alterations within the WHO classification of MPNs and laboratory testing used for diagnosis.

Objectives: Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is historically associated with Helicobacter pylori (HP) infections in more than 80% of patients. However, the incidence of HP-negative MALT lymphoma has been increasing. The clinicopathologic features have not been well studied, and optimal management strategies remain unclear. Methods: The pathology database was searched for primary gastric MALT lymphomas diagnosed from 2000 to 2017. The clinical data and the slides were reviewed. The cases were divided for analysis into those with a background of chronic gastritis with HP, chronic gastritis without HP, and without either a background of chronic gastritis or HP. Results: Of 70 gastric MALT lymphoma cases identified, 26 (37% of total) had chronic gastritis and were positive for HP histologically (n = 23) or were HP positive by additional laboratory testing (n = 3). The remaining 44 (63% of total) cases were HP negative by histology. Within the HP-negative cases, 5 (11% of HP-negative cases) showed histologic gastritis while 39 (89% of HP-negative cases) did not have sufficient evidence of gastritis through review of slides (n = 18) or based on available pathology reports (n = 21). The HP-negative cases without gastritis had higher propensities to show a mass lesion on endoscopy compared with HP-positive cases (37.5% vs 11.1%, P = .02) at the initial diagnosis. The immunophenotype and rate of positive B-cell gene rearrangement were not significantly different between the 2 groups. While all HP-positive patients received antibiotics for HP eradication, treatment in the HP-negative group varied among antibiotics, radiation, rituximab, or chemotherapy. Among HP-negative patients with available follow-up, 13 (39%) showed disease recurrence, similar to the recurrence rate in HP-positive patients; however, no individual from either group has died of the disease thus far. Conclusions: The incidence of HP-negative MALT lymphoma is increasing, and in our practice, it is currently more common than HP-associated MALT lymphomas. The pathophysiology of HP-negative MALT lymphoma without chronic gastritis remains unclear. Follow-up data in our study suggest that the prognosis of these cases is excellent despite varied management modalities.

Chronic lymphocytic leukemia (CLL) is a monoclonal B-cell lymphoproliferative disorder generally characterized by an indolent clinical course. However, some patients with CLL will have more aggressive disease progression, and identifying that subgroup may be important for early, or perhaps more aggressive, intervention. In addition, monoclonal B-cell lymphocytosis is often found on routine laboratory evaluation, and it is important to distinguish this entity from overt CLL. Moreover, since many patients with CLL are discovered incidentally and before significant disease progression, prognostic laboratory evaluation may become increasingly efficacious as therapeutic options replace the older strategy of expectant observation. Prognostication may be especially critical if it correctly identifies patients with early stage CLL who are at high risk of clonal evolution and/ or resistance to chemoimmunotherapy. Laboratory studies include surface CD38 and intracellular ZAP-70 expression by flow cytometry, serum β2-microglobulin, and immunoglobulin heavy-chain variable gene mutational status. Cytogenetics for targeted chromosome alterations may similarly aid in predicting outcome and guiding early intervention. This article concisely reviews the utility of commonly performed prognostic markers and addresses the laboratory evaluation in patients with incidentally discovered early stage CLL.

CEBPA‐mutant acute myeloid leukemia (AML) encompasses clinically and biologically distinct subtypes of AML in both adults and children. CEBPA‐mutant AML may occur with monoallelic (moCEBPA) or biallelic (biCEBPA) mutations, which can be somatic or germline, with each entity impacting prognosis in unique ways. BiCEBPA AML is broadly associated with a favorable prognosis, but differences in the type and location of CEBPA mutations as well as the presence of additional leukemogenic mutations can lead to heterogeneity in survival. Concurrent FLT3‐ITD mutations have a well‐documented negative effect on survival in adult biCEBPA AML, whereas support for a negative prognostic effect of mutations in TET2, DNMT3A, WT1, CSF3R, ASXL1, and KIT is mixed. NPM1 and GATA2 mutations may have a positive prognostic impact. MoCEBPA AML has similar survival outcomes compared to AML with wild‐type CEBPA, and risk stratification is determined by other cytogenetic and molecular findings. Germline CEBPA mutations may lead to familial biCEBPA AML after acquisition of second somatic CEBPA mutation, with variable penetrance and age. BiCEBPA AML in children is likely a favorable‐risk diagnosis as it is in adults, but the role of a single CEBPA mutation and the impact of concurrent leukemogenic mutations are not clear in this population. Laboratory evaluation of the CEBPA gene includes PCR‐based fragment‐length analysis, Sanger sequencing, and next‐generation sequencing. Phenotypic analysis using multiparameter flow cytometry can also provide additional data in evaluating CEBPA, helping to assess for the likelihood of mutation presence.