Submitting Author: Metcalf, Ryan Adams, MD
Institution: Stanford University Medical Center
Additional authors:Yaso Natkunam MD, PhD
Session: Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB, or FGFR1

87-year-old man with a provided prior diagnosis of myelodysplastic syndrome with trisomy 8 since 7/30/2009. The following were received in consultation: peripheral blood smear (7/2009); peripheral blood smear (10/2010); and peripheral blood smear, bone marrow aspirate, and bone marrow biopsy (7/2011).

Peripheral blood smear (7/2009): Normochromic, normocytic RBCs, neutrophils with significant dysplasia, and thrombocytopenia.

LABORATORY DATA (8/27/09): WBC 4.9 k/uL, Hgb 11.3 g/dL, HCT 33.4%, MCV 99fL, RDW 13.8%, PLT 48 k/uL.

Peripheral blood smear (10/2010): Normochromic, macrocytic RBCs, significant neutrophilic dysplasia, and marked thrombocytopenia.

LABORATORY DATA (10/19/10) : WBC 29.6 K/uL, RBC 3.56 M/uL, Hgb 11.8 g/dL, HCT 36.0%, MCV 101fL, RDW 16.2%, platelets 27 K/uL; Granulocytes 79.8%, lymphocytes 9%, monocytes 11.2%

Peripheral blood smear (7/2011): Normochromic, normocytic RBCs, neutrophils with significant dysplasia, thrombocytopenia, and now with mild peripheral eosinophilia.

LABORATORY DATA (7/26/11): WBC 21.1 K/uL, RBC 3.63 M/uL, Hgb 11.8 g./dL, HCT 35.6%, MCV 98fL, RDW 16%, platelets 29 K/uL; Granulocytes 36.6%, lymphocytes 33.2%, monocytes 30.2%.

Bone marrow aspirate and touch preparation (7/2011): Monotonous sheets of round eosinophilic precursors with large nuclei and abundant cytoplasm containing large, refractile eosinophilic granules. Several bilobed forms are also present. Residual trilineage hematopoiesis is markedly reduced to absent. Blasts are not increased.

Bone marrow biopsy and clot; B+ fixative, decalcified core biopsy (7/2011): Clot sections are highly cellular with monotonous sheets of eosinophilic precursors. Bone marrow biopsy sections are hypercellular for age (>90%) but are mostly subcortical, and show sheets of eosinophilic precursors. Megakaryocytes show dysplasia. Trabecular bone is not present in the specimen.

Negative immunostains: MPO, CD34, CD117, glycophorin A, and CD42b.

Flow cytometry: Predominant CD45+ population of cells with high side scatter reflecting prominent cytoplasmic granularity. Positive for CD33, CD64 (dim), and CD13 (partial, dim). They do not express CD34 or CD117.

Abnormal male karyotype with an extra copy of chromosome 8 (FISH also revealed +8).

Negative studies: PML/RARA fusion, MLL gene rearrangement, PDGFRb and FGFR1 rearrangements, t(8;21), inv16, and PDGFRa.

Negative studies: BCR/ABL transcript, CEBPA mutation, FLT3 internal tandem duplication, FLT3 D835 variant, and the NPM1 exon 12 mutation.

• Initial history of neutrophilic dysplasia without detection of the chronic phase of MPN

• The myeloproliferative component is a clonal proliferation of eosinophil precursors

• The infiltrate is comprised of a relative predominance of eosinophilic myelocytes with comparatively fewer mature eosinophils

Myelodysplastic/myeloproliferative neoplasm, unclassifiable (MDS/MPN, U)

Myelodysplastic/myeloproliferative neoplasm, unclassifiable, with marked eosinophilia

Case 393