From hypereosinophilic syndrome to acute lymphoblastic leukemia: when eosinophilia reveals an occult neoplasia.
Introduction/Background/Significance: Background: Hypereosinophilic syndrome (HES) is defined by persistent eosinophilia ≥1.5×10^9/L, whether associated with eosinophil-mediated organ damage1. Its differential diagnosis includes reactive causes and myeloid or lymphoid neoplasms, the latter being less common but with important prognostic implications. 2
Acute lymphoblastic leukemia with eosinophilia (ALL-eo) is an entity recognized by the World Health Organization, with an incidence of < 1% of all ALL. It is characterized by marked peripheral and/or medullary eosinophilia, which may precede or accompany the detection of lymphoblasts. The pathophysiology involves, in most cases, the overproduction of interleukin-3 by neoplastic cells; however, specific genetic rearrangements that directly contribute to clonal eosinophilic proliferation have been described, among which the ETV6::ACSL6 translocation stands out, involved in the activation of super-enhancers. in addition to specific genetic alterations, such as rearrangements of PDGFRA, PDGFRB, FGFR1 or PCM1-JAK2, which lead to constitutive activation of tyrosine kinases and eosinophilic clonal proliferation5.
Materials and Methods/Case Presentation/Objective: Objective: Presentation a case of hypereosinophilic syndrome as the initial manifestation of acute lymphoblastic leukemia (ALL). standing out as a relevant differential diagnosis in persistent eosinophilia.
Results/Description/Main Outcome Measures: Clinical case: A 50-year-old male with diabetes and high blood pressure was admitted with hypotension, disorientation, and chest pain. Physical examination revealed multiple violaceous papules located on the face, chest, and upper extremities.
Initial studies reported hemoglobin 15.1 g/dL, leukocytes 26,600/uL, neutrophils 12,100/uL, lymphocytes 1,700/uL, monocytes 800/uL, eosinophils 11,000/uL and basophils 1,000/uL, platelets 163,000/uL. Cerebral CT angiography revealed an ischemic vascular event and the echocardiogram was compatible with myopericarditis, so treatment was initiated with aspirin, metoprolol, colchicine, broad-spectrum antibiotics, and vasopressor support.
A peripheral blood smear revealed dysplastic eosinophils with hyperlobulated nuclei. Rheumatologic, allergic, and parasitic. Secondary causes were ruled out. In the absence of an obvious secondary etiology, the patient was started on high-dose steroids, achieving clinical and laboratory improvement that led to discharge.
One month later, he was readmitted due to syncope, and leukocytosis with eosinophilia was again identified, now accompanied by lymphocytosis, which prompted a bone marrow aspiration. Immunophenotyping revealed 28.9% of pre-B lymphoblasts expressing CD19, CD10, CD34, CD22, and CD79a, confirming the diagnosis of ALL. Molecular studies were negative for BCR/ABL1, JAK2V617F, and FLIP1L1-PDGFRA. The karyotype reported hypodiploidy with unfavorable deletions (del(5q), del(17p)) and trisomies.
Conclusions: This case highlights the importance of considering hematologic malignancies, including lymphoid malignancies, in the workup of hypereosinophilic syndrome, particularly when there are atypical morphologic findings or unusual clinical manifestations.
References
1. Bain BJ. Blood Cells: A Practical Guide. 5th ed. Oxford: Wiley-Blackwell; 2015.
2. Wilson F, Kinsey SE, Prentice HG, Green J, Dearden CE. Acute lymphoblastic leukemia with eosinophilia: two case reports and a review of the literature. Leuk Lymphoma. 2005;46(7):1045-50.
3. WHO Classification of Tumours Editorial Board. Haematolymphoid Tumours. 5th ed. Lyon: IARC; 2022.
4. Lahfafa A, Louvrier C, Belhabri A, et al. B-acute lymphoblastic leukemia with hypereosinophilia associated with severe cardiac complications: a clinical case. J Pediatr Hematol Oncol. 2021;43(1):e51-e55.
5. Xu W, Lin Y, Zhang H, et al. ETV6::\ACSL6 translocation-driven super-enhancer activation leads to eosinophilia in acute lymphoblastic leukemia through IL-3 overexpression. Haematologica. 2024;109(8):2445-58
