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.

Systematic use of fluorescence in‐situ hybridisation and clinicopathological features in the screening of PDGFRB rearrangements of patients with myeloid/lymphoid neoplasms

“…Targeted NGS studies using panels of genes that are commonly altered in myeloid neoplasms were performed, with fresh‐frozen BM DNA samples and a 28‐gene panel, and, in April 2017, the panel was updated to a 81‐gene panel, with methods described previously 23,24 …”

Update on the classification of myeloid neoplasms: The 2016 revised World Health Organization classification of hematopoietic and lymphoid neoplasms

“…Diagnosis of chronic eosinophilic leukemia, not otherwise specified (CEL, NOS) requires the exclusion of any possible cause of reactive eosinophilia. In addition to an abnormal karyotype, the presence of marrow dysplasia and/or increased blasts may be helpful in confirming a suspected diagnosis of CEL, NOS . Besides gene rearrangements involving PDGFRA, PDGFRB, and FGFR1 , now also translocations affecting JAK2 exclude this diagnosis ( see below ).…”

The Diagnostic Work-Up of Hypereosinophilia

“…These features were similar to those seen in MDS, MDS/MPN, and/or BCR-ABL1 negative MPNs. Cytological abnormalities in eosinophils could be seen in reactive processes and HES [95], but the abnormalities are much more severe and frequent in CEL, NOS [81,85] (Fig. 3).…”

“…Morphological features of the BM have been found to be extremely valuable in identifying cases with clinical and biological features of a myeloid neoplasm and are strongly recommended to be incorporated in the diagnosis of CEL, NOS (Fig. 3) [85].…”

“…The argument is that morphological changes in eosinophils are not unique to a neoplastic eosinophilic disorder [78,79,[92][93][94]. Of note, a recent multicenter study that reviewed the BMs of 139 patients with a diagnosis of idiopathic HES or CEL, NOS [85], reported that the abnormal BM (and some PB) features are not only limited to eosinophils, but also include BM hypercellularity, abnormal megakaryocytes, dyserythropoiesis, dysgranulopoiesis, MF2 or greater fibrosis, and so on in a true neoplastic HE. These features were similar to those seen in MDS, MDS/MPN, and/or BCR-ABL1 negative MPNs.…”