Bone marrow morphology is a strong discriminator between chronic eosinophilic leukemia, not otherwise specified and reactive idiopathic hypereosinophilic syndrome

Abstract

Chronic eosinophilic leukemia, not otherwise specified can be difficult to distinguish from idiopathic hypereosinophilic syndrome according to the current World Health Organization guideline. To examine whether the morphological features of bone marrow might aid in the differential diagnosis of these two entities, we studied a total of 139 patients with a diagnosis of chronic eosinophilic leukemia, not otherwise specified (n=17) or idiopathic hypereosinophilic syndrome (n=122). As a group, abnormal bone marrow morphological features, resembling myelodysplastic syndromes, myeloproliferative neoplasm or myelodysplastic/myeloproliferative neoplasm, were identified in 40/139 (27%) patients: 16 (94%) of those with chronic eosinophilic leukemia and 24 (20%) of those with hypereosinophilic syndrome. Abnormal bone marrow correlated with older age (P<0.001), constitutional symptoms (P<0.001), anemia (P=0.041), abnormal platelet count (P=0.002), organomegaly (P=0.008), elevated lactate dehydrogenase concentration (P=0.005), abnormal karyotype (P<0.001), as well as the presence of myeloid neoplasm-related mutations (P<0.001). Patients with abnormal bone marrow had shorter survival (48.1 months versus not reached, P<0.001), a finding which was independent of other confounding factors (P<0.001). The association between abnormal bone marrow and shorter survival was also observed in hypereosinophilic syndrome patients alone. In summary, most patients with chronic eosinophilic leukemia, not otherwise specified and a proportion of those with idiopathic hypereosinophilic syndrome show abnormal bone marrow features similar to the ones encountered in patients with myelodysplastic syndromes, myelodysplastic/myeloproliferative neoplasm or BCR-ABL1-negative myeloproliferative neoplasm. Among patients who are currently considered to have idiopathic hypereosinophilic syndrome, abnormal bone marrow is a strong indicator of clonal hematopoiesis. Similar to other myeloid neoplasms, bone marrow morphology should be one of the major criteria to distinguish patients with chronic eosinophilic leukemia, not otherwise specified or clonal hypereosinophilic syndrome from those with truly reactive idiopathic hypereosinophilic syndrome.

Figure 1.

Mutations detected in 21 patients with a diagnosis of chronic eosinophilic leukemia, not otherwise specified/idiopathic hypereosinophilic syndrome.

Figure 2.

Many cases with idiopathic hypereosinophilic syndrome. show unremarkable bone marrow morphology. Bone marrow (BM) cellularity is either age-appropriate [(A) patient aged 48 years] or only slightly increased [(B) patient aged 45 years], with increased BM eosinophils and normal-appearing megakaryocytes. (C) Eosinophils in peripheral blood (PB) may show mild uneven granulation (D) but are unremarkable on BM smear. No dysgranulopoiesis or dyserythropoiesis (BM biopsy, hematoxylin & eosin, original magnification ×400; PB and BM smears Wright-Giemsa, original magnification ×1000).

Figure 3.

Morphologically abnormal bone marrow. (A, B) Bone marrow (BM) hypercellularity with increased eosinophils and neutrophilic granulocytic elements; frequent small hypolobated MDS-like megakaryocytes (A, arrows) or mixed MDS- and MPN-like megakaryocytes (B). (C) Peripheral blood (PB) shows abnormal eosinophils with multiple lobes and marked hypogranulation or agranulation. (D) The same changes are also observed in the BM from the same case. In addition, dysplastic erythroids and granulocytes (arrows) are evident. (E, F) A case with decreased megakaryocytes, hypercellularity with disrupted BM topography (E) and a BM smear showing markedly increased immature eosinophils and dyserythropoiesis (F, arrows). (BM biopsy: hematoxylin & eosin, original magnification ×400; PB and BM smears: Wright-Giemsa, original maginification ×1000)

Figure 4.

Comparison of survival of patients with chronic eosinophilic leukemia, not otherwise specified/idiopathic hypereosinophilic syndrome. (A) All patients (n=139): patients with morphologically abnormal bone marrow (ABN) had a median survival of 48.1 months, which is significantly inferior to that of patients with a normal BM (WNL) (unreached, P<0.001). (B) For patients who would otherwise be classified as having idiopathic HES (a normal karyotype and/or <5% blasts, n=122), an abnormal BM was also significantly associated with a shorter survival (P<0.001).