1. CASE SUBMISSION 2016 EAHP BM Workshop
Raymond E Felgar MD PhD
Professor, Department of Pathology
Director, Hematopathology Fellowship
Co-Director, Flow Cytometry Laboratory
University of Pittsburgh School of Medicine
University of Pittsburgh Medical Center
Pittsburgh, PA

2. Clinical History
84 year old man with history of chronic obstructive lung disease and now with a mass at the base of the tongue (no biopsy obtained), now with progressive weakness and fatigue, 11.4 kg unplanned weight loss, “petechial” rash, shortness of breath, anemia (hgb = 9.2 gm/dL), slight macrocytosis (MCV = 97.7 fL), and thrombocytopenia (platelets = 32,000 per microliter). Bone marrow aspiration and biopsy was obtained.

3. Morphologic Findings
Bone marrow evaluation shows 76% blast-like cells (see images) that superficially resemble lymphoblasts and replaced most normal marrow elements. Images from the aspirate, representative flow cytometric scatter plots, immunohistochemical stains, and cytogenetic results follow.

4. Bone Marrow Aspirate
Wright Giemsa stain – 100x oil objective

5. Bone Marrow Aspirate- Cytospin Preparation from sample for flow cytometry analysis
Wright Giemsa stain – 100x oil objective

6. Bone Marrow Biopsy
H&E – 50x objective

7. Immunostains –Bone Marrow Biopsy
CD123
CD20
CD3
Myeloperoxidase (MPO)

8. Flow Cytometry
Abnormal Dim CD45+ cells = 81% of total mononuclear cells.

9. Flow Cytometry-Representative Plots (Abnormal Population in Pink)

10. Flow Cytometry-Representative Plots (Mononuclear Cells in Red)

11. Flow Cytometry-Summary Phenotype
Abnormal blastic cell population comprising 81% of total events based on dim CD45 staining. Blastic cells have an immunophenotype summarized as follows:
Dim CD45+, CD34-, CD117-, moderate to bright HLA-DR+, bright CD123+, moderate CD33+, CD13-, CD14-, CD36-, CD64-, CD11b-, CD16-, CD15-, moderate CD56+, moderate CD4 + on a subset of cells, CD7+, CD8-, CD2-, surface and cytoplasmic CD3-, CD16/57-, CD19-, probable dim CD38+, CD20-, CD10-, surface kappa/lambda-, CD30-, surface T-cell receptor negative (both alpha-beta and gamma-delta type), myeloperoxidase negative, and TdT negative.

12. Cytogenetic Studies 46,XY,i(7)(q10),del(11)(q21q25)[10]/46,XY[9]

13. Cytogenetic Studies-Representative Karyotype

14. Cytogenetic Studies
FISH for 7q31 (red) and centromere of 7 (green) demonstrates abnormal cells with
Extra 7q31 signal consistent with the isochromosome 7q seen in the karyotype.
[89 of 104 (85.6%) nuclei examined showed this pattern. ]
A representative normal cell is seen on the left and abnormal one on the right.

15. Molecular Findings Not performed.

16. Proposed Diagnosis Blastic plasmacytoid dendritic cell tumor.

17. Interesting Features of the Case
This case has immunophenotypic and morphologic findings characteristic of blastic plasmacytoid dendritic cell neoplasm, but with somewhat unusual cytogenetic findings, namely the presence of an isochromosome 7q and deletion involving 11q. However, one could argue that the isochromosome 7q essentially represents loss of 7p. Loss of 7p12.2 (IKZF1 locus) has been documented in blastic plasmacytoid dendritic cell neoplasms previously (Blood 2011;118: ). The presence of a deletion involving 11q21q25 suggests that loss of KMT2A (MLL) may play a role. In at least 2 recent reports (Leuk Res 2012;36: ; Cancer Genetics 2015;208: ), genetic translocations involving disruption of KMT2A (MLL) have been documented and implicated as a potentially contributing factor in the pathogenesis.