We present a case of a 73-year-old male with a five-month history of progressive dyspnea on exertion, cough, and worsening hypoxemia. Initial lab work did not identify peripheral eosinophilia. Chest computed tomography identified extensive ground-glass opacities in the mid-basilar. Diagnostic bronchoscopy showed an eosinophilic-rich bronchoalveolar lavage representing 63% of the total white blood cell count, confirming the diagnosis of chronic eosinophilic pneumonia. No etiology was identified despite extensive diagnostic workup. Our patient had a prolonged course of prednisone taper treatment complicated by frequent hospitalizations, osteopenia, and insomnia. Additionally, his chronic eosinophilic pneumonia relapsed shortly after stopping steroids. In our patient, off-label treatment with mepolizumab, an interleukin-5-inhibiting monoclonal antibody, was associated with symptomatic relief, imaging findings resolution, and remission maintenance without systemic steroids.

Eosinophilia is a feature of multiple conditions, both hematologic and non-hematologic, and may be associated with organ damage. The pathogenesis of eosinophilia can follow two distinct pathways. Primary eosinophilia is caused by a cell-intrinsic mechanism originating from clonal expansion of eosinophils through acquisition of a somatic mutation, such as FIP1L1-PDGFRA. In recent years, great progress has been made in the field of pathogenesis and molecularly targeted therapy of neoplastic eosinophilia. The diagnostic procedure should include, among other things, morphologic analysis of blood and bone marrow samples, cytogenetics and fluorescence in situ-hybridization tests to detect evidence of an acute or chronic myeloid or lymphoid disorder. Secondary eosinophilia follows a cell-extrinsic mechanism as a response to exogenous cytokines. In most clinical cases, peripheral blood eosinophilia is reactive and typically associated with non-hematological disorders such as infections, allergic conditions, connective tissue disorders, vasculitis, malignancy, or endocrinopathies. Nonetheless, the cause of most cases of hypereosinophilic syndrome remains unknown. In this article, we present a short review focused on differential diagnosis of eosinophilia and eosinophilic disorders. The diagnosis of eosinophilia is a challenge for physicians; thus this review may be useful in clinical practice.

Eosinophilic myocarditis (EM) is a rare but potentially fatal complication of sustained eosinophilia that is characterized by eosinophilic infiltration into myocardial tissue. There are various etiologies of EM that can be classified into general categories: reactive, clonal, and idiopathic. We present a case of EM caused by chronic eosinophilic leukemia, a rare myeloproliferative neoplasm that frequently presents with sustained peripheral eosinophilia. This case displays several serious complications of EM, including recurrent ventricular tachycardia storm, cardiogenic shock, and mural thrombus formation despite anticoagulation. Diagnosis of EM can be difficult as formal diagnosis requires an endomyocardial biopsy. Once EM is suspected, identifying the underlying etiology of eosinophilia is critical for timely implementation of disease-specific therapy.

Chronic Eosinophilic Leukemia (CEL), a rare and intricate hematological disorder characterized by uncontrolled eosinophilic proliferation, presents clinical challenges owing to its infrequency. This study aimed to investigate epidemiology and develop a prognostic nomogram for CEL patients. Utilizing the Surveillance, Epidemiology and End Results database, CEL cases diagnosed between 2001 and 2020 were analyzed for incidence rates, clinical profiles, and survival outcomes. Patients were randomly divided into training and validation cohorts (7:3 ratio). LASSO regression analysis and Cox regression analysis were performed to screen the prognostic factors for overall survival. A nomogram was then constructed and validated to predict the 3- and 5-year overall survival probability of CEL patients by incorporating these factors. The incidence rate of CEL was very low, with an average of 0.033 per 100,000 person-years from 2001 to 2020. The incidence rate significantly increased with age and was higher in males than females. The mean age at diagnosis was 57 years. Prognostic analysis identified advanced age, specific marital statuses, and secondary CEL as independent and adverse predictors of overall survival. To facilitate personalized prognostication, a nomogram was developed incorporating these factors, demonstrating good calibration and discrimination. Risk stratification using the nomogram effectively differentiated patients into low- and high-risk groups. This study enhances our understanding of CEL, offering novel insights into its epidemiology, demographics, and prognostic determinants, while providing a possible prognostication tool for clinical use. However, further research is warranted to elucidate molecular mechanisms and optimize therapeutic strategies for CEL.

Leukemia is a systemic malignancy that can compromise various physiological functions, including vision. We report a case of a 37-year-old male presenting with worsening bilateral central vision loss, fatigue, shortness of breath, and ankle edema. Ophthalmic examination revealed extensive retinal hemorrhages, Roth spots, and subhyaloid hemorrhages, consistent with leukemic retinopathy. Further hematologic workup confirmed chronic eosinophilic leukemia. The patient showed systemic and visual improvement after prompt treatment with imatinib. This case highlights the importance of ophthalmological assessment in diagnosing leukemia, as ocular manifestations may often be the first sign of hematological disease.

Chronic neutrophilic leukemia (CNL) is a clonal disorder that is characterized by increasing mature neutrophils. Colony stimulating factor 3 receptor (CSF3R) T618I mutation was frequently identified in patients with CNL and is defined as a molecular marker of the disease. Ruxolitinib, a JAK2 inhibitor, provided a promising therapeutic effect in a phase II study. In particular, ruxolitinib was more efficient for patients with CSF3R mutation. Allogeneic stem cell transplantation (Allo-SCT) may be a curative treatment for CNL. On the other hand, further studies are needed to define the optimal method of transplantation, source of donor, conditioning therapy, and timing of transplantation. Chronic eosinophilic leukemia (CEL) is a clonal disorder that is characterized by increasing eosinophils. In the World Health Organization Classification 5th edition, diagnostic criteria for CEL are renewed. Because the new criteria will be more specific for CEL than criteria in the older edition, \"not otherwise specified (NOS) \" is removed from the name of the disease. Anti-CD52 antibody, alemtuzumab, or anti-IL-5 antibody, mepolizumab, are promising drugs to control symptoms that are associated with hypereosinophilic syndrome. Allo-SCT is anticipated as a curative treatment for CEL, but the evidence of Allo-SCT for CEL is still limited. Further study is required to define the treatment strategy.

Hypereosinophilia can be primary, including idiopathic hypereosinophilic syndrome (HES) and chronic eosinophilic leukemia, or secondary/reactive to various infective and non-infective stimuli. Chronic oro-genital ulcerations can occur due to various dermatological and non-dermatological disorders, and many times it serves as a useful indicator of an underlying systemic disorder. Hence, a case presenting with chronic oro-genital ulcerations needs a thorough evaluation. We are reporting an interesting case of a middle-aged male who had chronic oro-genital ulcerations as a presenting feature of chronic eosinophilic leukemia with FIP1L1-PDGFRA fusion (FIP1-like 1/platelet-derived growth factor receptor alpha). The patient\'s oro-genital ulcerations responded excellently to imatinib.

Myeloproliferative neoplasms (MPN) are a group of clonal hematopoietic stem cell disorders with uncontrolled proliferation of one or more hematopoietic cell types, including myeloid, erythroid and megakaryocytic lineages, and minimal defect in maturation. Most MPN are associated with well-defined molecular abnormalities involving genes that encode protein tyrosine kinases that lead to constitutive activation of the downstream signal transduction pathways and confer cells proliferative and survival advantage. Genome-wide sequencing analyses have discovered secondary cooperating mutations that are shared by most of the MPN subtypes as well as other myeloid neoplasms and play a major role in disease progression. Without appropriate management, the natural history of most MPN consists of an initial chronic phase and a terminal blast phase. Molecular aberrations involving protein tyrosine kinases have been used for the diagnosis, classification, detection of minimal/measurable residual disease, and target therapy. We review recent advances in molecular genetic aberrations in MPN with a focus on MPN associated with gene rearrangements or mutations involving tyrosine kinase pathways.

BACKGROUND: Hypereosinophilia (HE) is defined as peripheral blood (PB) eosinophil count exceeding 1.5 × 109 /L. As the causes of HE can be diverse, the work-up of patients was complicated. In this study, we aimed to categorize the underlying diseases associated with HE and demonstrate minimum diagnostic approach.
METHODS: Cases presenting with HE within 7 days of bone marrow (BM) examination conducted between 2008 and 2019 were selected. Cases were classified by the revised 2022 WHO and ICC classification. We also assessed morphologic features of unclassified persisting HE (>4 weeks) patients according to the morphologic criteria suggested a previous study by Wang et al. RESULTS: A total of 364 patients were included. The work-up confirmed primary HE in 38.7%, secondary HE in 48.9%, HE patients with insufficient evaluation in 13.7%. When conducted a slide review of HE patients with sustained HE more than 4 weeks among HE patients with insufficient evaluation, the morphological features showed abnormal eosinophils in PB/BM (69.0%/81.0%), hypercellularity (26.2%), myelofibrosis (7.1%), increased M:E ratio (5.3%), and dysmegakaryopoiesis (4.8%). Of these patients, 14 patients who met all morphologic criteria were suspected of CEL.
CONCLUSIONS: This study demonstrates that HE is associated with variable conditions. BM morphological assessment based on a robust criterion can help to confirm a MN irrespective of the presence of clonal markers. The work-up of patients in whom ruled out the common secondary causes of HE requires a systematic but sufficient approach including at a minimum BM karyotyping, PDGFRA testing, lymphocyte immunophenotyping and TCR gene rearrangement.

Hypereosinophilic syndromes (HES) encompass a wide range of disorders characterized by persistent peripheral blood hypereosinophilia (HE) (i.e., an eosinophil count ≥1.5 × 109/L and ≥ 10% eosinophils preferably with a minimal duration of 6 months if documentation is available) associated with organ damage and/or dysfunction attributable to tissue eosinophilic infiltrate and release of granule contents. In most cases, HE is associated with atopic conditions/allergies, parasitic infections, medications, autoimmune disorders and/or solid tumors in most cases. More rarely, it can be one of the dominant manifestations of an underlying myeloid/lymphoid neoplasm. With regard to hematological forms, in recent decades the advances in understanding the pathogenic aspects of HES have led to a growing interest in these diseases, and in the 2016 WHO classification multiple subgroups were defined according to the molecular profile with the aim of better characterizing these syndromes and establishing which patients will benefit from specific pharmacological targeted therapies. This review article will provide a comprehensive overview of possible therapeutic approaches for HES in the light of each specific molecular alteration, considering both tyrosine kinase inhibitors and monoclonal antibodies, either implemented in clinical practice or currently still under development.