1. Myeloid neoplasms with eosinophilia
by Andreas Reiter, and Jason Gotlib
Blood
Volume 129(6):
February 9, 2017
©2017 by American Society of Hematology

2. Diagnostic algorithm for HE incorporating 2016 WHO categories of eosinophilia-associated neoplasms.
Diagnostic algorithm for HE incorporating 2016 WHO categories of eosinophilia-associated neoplasms. In patients presenting with HE, we recommend an initial work-up to rule out reactive (secondary) causes. If this work-up is negative, parallel or sequential testing for a primary (clonal) eosinophilia should be undertaken. Evaluation includes morphologic analysis of the peripheral blood and BM, immunohistochemistry (eg, CD117, tryptase, and CD25 in systemic mastocytosis), flow cytometric immunophenotyping to assess the presence of myeloid, B- and/or T-lymphocyte markers, and cytogenetic/molecular/genetic testing. As shown in the algorithm, this combination of clinicopathologic and molecular testing can help identify a specific neoplasm and the WHO category within which it resides (shown in blue-colored boxes). Idiopathic HES is a diagnosis of exclusion and requires the presence of organ damage. HES is considered a provisional diagnosis until a cause of HE is discovered. *The provisional variants ETV6-JAK2 and BCR-JAK2 are also included in this category. Figure modified from: Gotlib J, Cools J, Malone JM 3rd, et al. Blood. 2004;103(8):
Andreas Reiter, and Jason Gotlib Blood 2017;129:
©2017 by American Society of Hematology

3. Representative BM histomorphology of different myeloid neoplasms with eosinophilia.
Representative BM histomorphology of different myeloid neoplasms with eosinophilia. (A-B) CEL, NOS. (A) Hematoxylin and eosin (H&E). Histology of the BM shows an extremely hypercellular marrow with packed infiltrates of eosinophils. Normal blood cell precursors are absent. (B) Wright-Giemsa. Cytomorphological aspects on a BM smear also exhibit an abundance of eosinophils at all stages of maturation. Note that significant cellular atypia is absent. (C-D) KIT D816V-positive systemic mastocytosis with associated chronic eosinophilic leukemia (SM-CEL). (C) H&E. BM histology reveals a markedly hypercellular marrow with a massive increase in eosinophils. Centrally located in the marrow space, a compact infiltrate consisting of pale, mostly spindle-shaped cells is easily detected (left). (D) Higher magnification and Wright-Giemsa stain reveals that the spindle-shaped cells contain metachromatic granules, although in lesser number than normal mast cells. The presence of compact infiltrates mainly consisting of spindle-shaped cells allows prompt diagnosis of a systemic mastocytosis. (E-F) FIP1L1-PDGFRA-positive myeloid neoplasm. (E) H&E-stained BM shows massive hypercellularity with increase in eosinophils, which form narrow rows as an indirect sign of fibrosis. Normal blood cell precursors, in particular megakaryocytes, are missing. (F) ABC method. Anti-CD117 immunohistochemistry reveals an increase in spindle-shaped, mostly loosely scattered mast cells, with expression of CD117 (KIT). Note a small cohesive group of round mast cells on the right not sufficient for a diagnosis of systemic mastocytosis to be established. Mast cells display aberrant expression of CD25 (not depicted), which is seen outside the setting of mastocytosis only in FIP1L1-PDGFRA-positive myeloid neoplasms. (G-H) PCM1-JAK2-positive myeloid neoplasm. (G) H&E. (H) Wright-Giemsa. Extremely hypercellular BM with subtotal depletion of fat cells and massive increase in erythroblasts forming irregular giant erythra filling whole marrow spaces, and thus exceeding the size seen in any other myeloid neoplasm or reactive states. Images courtesy of Professor Hans-Peter Horny.
Andreas Reiter, and Jason Gotlib Blood 2017;129:
©2017 by American Society of Hematology

4. TK fusion genes in myeloid/lymphoid neoplasms with eosinophilia.
TK fusion genes in myeloid/lymphoid neoplasms with eosinophilia. As of October 2016, 72 tyrosine kinase fusion genes have been described. In conjunction with cytogenetic/fluorescence in situ hybridization and genetic testing, morphologic evaluation and flow cytometric immunophenotyping is required to identify whether such molecular abnormalities are associated with an acute or chronic myeloid neoplasm and/or a B- or T-cell lymphoblastic leukemia/lymphoma. Figure courtesy of Professor Nicholas C. P. Cross.
Andreas Reiter, and Jason Gotlib Blood 2017;129:
©2017 by American Society of Hematology