Persistent plasmacytoid dendritic cell proliferation in the bone marrow Submitted by Hebeda and MacKenzie EAHP 2016 Bone Marrow Workshop EAHP16-BMWS-303

Clinical history July 2013: suspected Lyme disease, antibiotics. August 2013: febrile illness with neutropenia, leukocytes 1,1 x10*9/l granulocytes 0,34x10*9/l , trombocytes 87x10*9/l , Hb 8.1 mmol/l. No etiology established. October 2013: persistent neutropenia, tiredness, artralgia, intermittent fever and muscle ache. Splenomegaly (14 cm). No skin lesions. Infectious causes excluded. PETscan shows multiple active lymph nodes throughout the body, polyartritis and an enlarged spleen. BM biopsy, BM cytology, immunoflowcytometry, cytogenetics Karyotyping: 46,XY[20] Interfase FISH: no MLL (11q23) or ETV6 (12p13) rearrangement, 2 signals for ETV6 (12p13), EGR1 (5q31), LSI D5S23- D5S721(5p15.2), RB1 (13q14), TP53 (17p13.1) [200]

Biopsy T14-12034 19-05-2014

2014 BM CD123 CD123 CD123 TCL-1

Follow up October 2013: plasmacytoid dendritic cell neoplasia. No response to antibiotic treatment for Lyme disease. Patient refuses chemotherapy and/or bone marrow transplant. Supportive treatment (antibiotics if required) Last follow-up BM biopsy May 2014: stable number of PDC’s. December 2015: persistent neutropenia (leukocytes 1,3 x10*9/l, granulocytes 0,52x10*9/l). Persistent 5-10% PDC's in BM smears and flowcytometry. Stable clinical disease without treatment.

Hb mm/L 15-10-2013 16-03-2014 15-10-2013 15-08-2014 13-01-2015 15-10-2013 T 10*9/L

Interesting features the alignment of the PDC's along sinuses the very indolent nature need to establish a "normal" range of quantity, morphology and distribution of the PDC's BDCA-2

PDC’s in staging and MDS BMB Method: * Histology BMB: 18 NHLstaging, 20 MDS - anti-BDCA-2, specific for PDC’s. - average number of positive cells per high power field (HPF) , distribution (scattered or clustered). * flowcytometric immunofenotyping BM aspirate: 19 NHLstaging BMB, 41 MDS - CD123 and HLA-DR Results: The number of cases with aggregates > 6 PDC’s was equal, but the aggregates in MDS were in general much larger >15 PDC’s in 7/7 cases with MDS, and in 3/7 normal BM. Average number of PDC’s / HPF: Staging: 4.6, range 2.0-9.9 MDS: 9.1, range 0.3-35.3 IFT % PDC’s: Staging: range 0.16-0.89% MDS: 0.03%-4.97% In non-neoplastic BM the distribution of PDC’s shows a much more homogeneous pattern than in MDS. The latter shows extremes to both ends in number and aggregation of PDC’s.

BDCA-2