Submitting Author: Li, Shaoying, MD
Institution: Vanderbilt University School of Medicine
Additional authors:Aaron Shaver, MD, PhD, David Head, MD
Session: Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB, or FGFR1

54-year-old female with left-shifted leukocytosis and massive splenomegaly on ultrasound. CBC: WBC 211, Hb 11.6, Plt 204; Differential: Neutrophil: 70.5% Eosinophil: 0.8%

A marrow biopsy was performed on 11/2/2012 and fixed in B plus fixative. The previous outside marrow biopsy performed one month before was also reviewed. The two marrows showed virtually the same morphologic features.

The peripheral blood smear showed mild macrocytic and normochromic anemia with a few circulating nucleated red blood cells. Leukocytes were markedly increased and included neutrophilia and immature myeloids with no circulating blasts and no significant dysplasia. There was no significant eosinophilia and only rare basophils were identified. Platelets were adequate with unremarkable morphology.

Aspirate Smears and Touch Preparations showed increased myeloids with orderly maturation and a few neutrophils with hypersegmented nuclei and hypergranular cytoplasm. Blasts were not increased. Megakaryocytes were adequate with no significant atypia. Erythroid elements were decreased with orderly maturation. The M:E ratio was 96:1. Storage iron was decreased with no ring sideroblasts.

The biopsy and particle preparation were markedly hypercellular (>95% cellularity). Megakaryocytes were adequate with no significant atypia. Myeloids were increased with left-shifted maturation. Erythroids were decreased with orderly maturation. Blasts were not increased. Eosinophils were slightly increased focally.

Flow cytometry and immunostaining for CD34 demonstrated no increase in blasts.

Karyotype: 46,XX,t(8;17)(p12;q11.2)[20]

FISH for BCR/ABL: negative

FISH for abnormalities involving chromosome 5, 7, 8, 20, 11q23, and 8p11.2 (FGFR1): FGFR1 rearrangement present in all cells analyzed. All others were negative.

BCR/ABL: negative

JAK2 V617F: negative

Myeloid and lymphoid neoplasms with FGFR1 abnormalities are an established entity in the 2008 WHO Classification. They usually present with eosinophilia, either as chronic eosinophilic leukemia or as AML, T-LBL or B-LBL with accompanying eosinophilia. This case showed the following unique features:

1. Morphologic features similar to CML, chronic phase

2. A balanced translocation, t(8;17)(p12;q11.2), confirmed as involving the FGFR1 locus by FISH analysis. This translocation has not been reported previously, neither in the 2008 WHO Classification or English literature, nor in the Mitelman Database.

3. No significant eosinophilia in either the bone marrow or the peripheral smear.

Myeloproliferative neoplasm with FGFR1 abnormality [t(8;17)(p12;q11.2)]

Myeloid neoplasm with FGFR1 rearrangement, t(8;17)(p12;q11.2), presenting with myeloproliferative neoplasm and eosinophilia

Case 75