Clinical history 30-years-old female EAHP 2016 Case summary BMWS- Corina Dommann-Scherrer Canton Hospital Winterthur Switzerland Clinical history 30-years-old female progressive weakness, no B-symptoms thrombocytopenia 80 G/l, leucopenia 2,24 G/l, ANC 0,92 G/l, 1% blasts diagnostic bone marrow biopsy

Slightly hypercellular bone marrow

Massive diffuse infiltration of medium-sized blast cells with scant, sometimes eccentric, slightly eosinophilic cytoplasm.

Giemsa x600: neoplastic infiltrate (70%) show slightly irregular round to oval nuclei, fine chromatin with sometimes central nucleolus; cytoplasm scant, grey-blue. Mitoses rare.

Negative: MPOX, CD34, CD117, CD20, CD3, CD5, CD1a, CD2 CD8, CD68, lysozyme EBER MPOX - CD 34 -

Positive: CD45, CD123, TCL1, CD4, CD56 (30%), TdT(50%), Ki67 50% CD4 + CD123 + TCL1 + TdT +

Flow cytometry bone marrow: CD45 (dim)

Flow cytometry bone marrow: CD4+, CD56+ CD38 +, CD135+, CD45A+, CD123+ negative: myeloid and other NK-markers

Cytogenetics: complex karyotype 46,XX,add(11)(q21),del(12)(p12p13), del(13)(q12),add(20)(p13)[11]/46,XX[3] Molecular genetics: negative: FLT3-ITD, NPM1, EVI1, HemaVision, MLL del, ETV6 del, del(13)(q14.3) WT1-overexpression

Proposed diagnosis Extracutaneous blastic plasmocytoid dendritic cell neoplasm (BPDCN) in bone marrow and peripheral blood Positive CD45, CD4, CD123, TCL1, CD56, TdT

DD of blastic neoplasia in bone marrow and peripheral blood: acute leukemias, B-cell lymphomas AML (excluded by lack of myeloid lineage specific markers, no recurring AML anormalities) ALL (excluded by lack of B-cell markers; lack of CD3, CD5, beta F1; lack of strong and uniform CD34 &/or TdT, no Ig or TcR rearrangement)

Follow-up Induction chemotherapy with complete remission Consolidation chemotherapy Allogenic-HSCT, gender different, identical HLA and ABO (2012 January) Complete remission for 3,5 y (2015 September)

Interesting features Rare non-cutaneous presentation (2012-1015 < 25cases) Thrombocytopenia and neutropenia as initial symptoms BPDCN confined to bone marrow (extensive) and periph. blood (1% blasts) Favourable outcome (3,5 y remission after HSCT): Lack of cutaneous disease? Age (30y)? TdT expression? Therapy (HSCT in first complete remisssion)?