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3812 Biological Description of 109 Cases of Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) from the French Network of BPDCN

Acute Myeloid Leukemia: Biology, Cytogenetics and Molecular Markers in Diagnosis and Prognosis
Program: Oral and Poster Abstracts
Session: 617. Acute Myeloid Leukemia: Biology, Cytogenetics and Molecular Markers in Diagnosis and Prognosis: Poster III
Monday, December 7, 2015, 6:00 PM-8:00 PM
Hall A, Level 2 (Orange County Convention Center)

Eve Poret1*, Fanny Angelot Delettre1*, Sabeha Biichle2*, Anne Roogy1*, Louis Benazet3*, Maider Pagadoy3*, Chrystelle Vidal3*, Franck Leroux3*, Véronique Harrivel4*, Christophe Ferrand, PhD5, Veronique Salaun6*, Zehaira Benseddik7*, Julien Guy8*, Marie Christine Jacob9*, Christophe Roumier10*, Jean Feuillard11*, Liliana Vila12*, Lucile Baseggio13*, Adriana Plesa14*, Christine Arnoulet15*, B Benet16*, Bernard Drenou, MD17*, Veronique Latger Cannard18*, Marie-Christine Bene, MD19*, Michel Ticchioni20*, Daniel Lusina21*, Valerie Bardet22*, Magalie LE Garff Tavernier23*, Elizabeth Macintyre, MD, PhD24, Vahid Asnafi, MD PhD25*, Maria Elena Noguera23*, Sabrina Bouyer26*, Carine Lecoq Lafon27*, Mikael Roussel, MD, PhD28*, Fabrice Jardin29*, Francoise Solly, MD30*, Lydia Campos, MD, PhD31, Anne Galoisy32*, Anne Arnaud33*, Sylvie Daliphard34*, Franck Genevieve, MD, PhD35*, Romaric Lacroix36*, Françoise Schillinger37*, Estelle Seilles1*, Delphine Binda3*, Eric Deconinck38, Philippe Saas, PhD39 and Francine Garnache Ottou, PhD5*

1EFS BFC, INSERM UMR1098, Besançon cedex, France
2INSERM UMR 1098/Université Bourgogne Franche-Comté/EFS BFC, Besancon, France
3Inserm CIC1431, CHRU de Besançon, Besançon cedex, France
4CHU Amiens, AMIENS, France
5EFS BFC, Inserm UMR1098, University hospital Besancon, University Franche Comte, Besancon, France
6CHU CAEN, CAEN, France
7CH CHARTRES, CHARTRES, France
8CHU DIJON, DIJON, France
9CHU GRENOBLE, GRENOBLE, France
10CHRU LILLE, LILLE, France
11Laboratoire d'hématologie, CHU, Limoges, France
12HOSPITAL LYON EDOUARD HERRIOT, LYON, France
13HOSPITAL LYON SUD, LYON Pierre Benite, France
14HOSPITAL LYON SUD, LYON, France
15IPC, MARSEILLE, France
16CHR METZ, METZ, France
17CH MULHOUSE, MULHOUSE, France
18CHU NANCY, NANCY, France
19Hopital Hotel Dieu, Laboratoire d'Hematologie, Nantes, France
20CHU NICE, NICE, France
21Hematology Laboratory, CHU Avicenne, Paris, France
22Department of Hematology, Imagine Institute, Hôpital Universitaire Necker -Enfants Malades Paris, Paris, France
23APHP, PARIS, France
24Université Paris Descartes Sorbonne Cité, Institut Necker-Enfants Malades (INEM), Institut national de recherche médicale (INSERM) U1151, and Laboratory of Onco-Hematology, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Necker Enfants-Malades, Paris, France
25Université Paris Descartes Sorbonne Cité, Institut Necker-Enfants Malades (INEM), Institut national de recherche médicale (INSERM) U1151, and Laboratory of Onco-Hematology, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Necker Enfants-Malades, Paris, Paris, France
26CHU POITIERS, POITIERS, France
27CHU REIMS, REIMS, France
28INSERM U917 - CHU de Rennes, Rennes, France
29Centre Henri Becquerel, Rouen, France
30Saint-Etienne University Hospital, Saint-Etienne, France
31Laboratoire Hematologie, Hopital Nord, Saint-Etienne, France
32CHU STRASBOURG, STRASBOURG, France
33CHU NIMES, NIMES, France
34CHU ROUENS, ROUENS, France
35CHU ANGERS, ANGERS, France
36APHM, MARSEILLE, France
37EFSBFC, Besançon cedex, France
38Hematology, INSERM UMR1098 - CHU Jean Minjoz, Besancon, France
39EFS BFC, INSERM UMR 1098/Université Bourgogne Franche-Comté/ EFS BFC/LabEx lispSTIC, Besancon, France

Blastic plasmacytoid dendritic cell neoplasm is a clonal disease derived from precursors of plasmacytoid dendritic cells (pDC). It is a rare neoplasm involving the skin which may or may not be associated from the outset with a leukemic component. The disease invariably progresses to aggressive leukemic dissemination, leading to a differential diagnosis with acute leukemia.

In 2004, we set up a French network to recruit biological data at diagnosis. Diagnosis was according to recommendations (Swerdlow et al, 2008), with, in addition, a mandatory panel of pDC markers (Garnache-Ottou et al, 2009) detected by flow cytometry or by immunohistochemistry on infiltrated blood, bone marrow or cutaneous lesions.

In total, 109 cases of BPDCN were included in 35 hospitals (2000-2013). BPDCN is more prevalent in men (sex ratio 4.4/1) and in elderly subjects (median age: 63 years; 7 patients were <20 yo). Skin lesions are very prevalent (85%) with variable lesion types. Blood cell counts show variable leukocytosis (figure 1A) with presence of blasts in 65% of cases. Anemia and thrombopenia were present in 59% and 76% of cases respectively. Bone marrow aspiration showed blastic infiltration in 94% of cases. Indeed, in 7 cases, there was isolated cutaneous involvement at diagnosis, with neither blood nor bone marrow infiltration. Morphologies of blast cells were heterogeneous. Typical morphologies were the most frequent, including medium-sized cells with a blastic round or irregular nucleus, cytoplasm displayed faint and irregular basophilia and no granulation. In a contingent of the blastic populations, we observed small vacuoles in a peculiar arrangement under the cytoplasmic membrane (42%) or the presence of large pseudopodia (28%) or both (17%) (Figure 1B, C, D). Some cases showed a more immature morphology with larger cells, higher nucleo-cytoplasmic ratio, very visible nucleoli and reinforced basophilia (28%) or a pseudomonoblastic morphology (5%) (Figure 1E). Rare cases presented a pseudolymphocytic form (7%, figure 1F) or large granulations in the cytoplasm (2%). Peroxidase and esterase were negative in all cases. Dysplasia of hematopoietic lineages was observed in 29% (figure 1G). For 8% of patients, myelodysplastic syndrome was diagnosed before the diagnosis of BPDCN.

Immunophenotype showed that HLA-DR and CD4 were expressed in all cases, but 4 cases did not express CD56 (confirmed using 3 different antibodies). Expression of markers of others hematopoietic lineages was frequent. Among myeloid markers, the most frequent was CD33 (46%), followed by CD117 (23%), whereas CD13, CD11c, CD15 and CD65 were rarely expressed. Monocyte markers (CD14, CD64, CD11b) and myeloperoxidase were never expressed. For the T lineage, CD2 and CD7 were the most frequent (62% and 58% respectively) whereas CD5 was rare (7%). No cytoplasmic or surface CD3 were detected. For the B lineage, CD22 was expressed in 16%, and low levels of cCD79a in 5%. Both were never expressed together, and no CD19, CD20 and immunoglobulins were found. Generally, we observed one of these antigens (Ags) per case, but in 44% of cases, there was a combination of 2 or 3 Ags from 2 or 3 different lineages. Immature Ags such as CD34 and CD133 were never found, and Tdt was found in 14% of cases.

Cytogenetic analysis revealed abnormal caryotype in 65% of the 78 caryotypes evaluated, with 20 cases having a complex caryotype. The frequency of the chromosomal abnormalities involved are shown in Figure 1H.

In conclusion, we describe the largest series of BPDCN to date in the literature. Detailed clinical and biological data at presentation allow improved recognition of this rare form of acute and aggressive leukemia, enabling early initiation of appropriate management.


Figure 1. A: Blood cell count in 109 BPDCN patients at diagnosis. Bars represent the median. B: Typical BPDCN morphology. C: In this case, the nuclei were peripheral, cytoplasm presented heterogenous basophilia, vacuoles were rare but large pseudopodia are frequent. D: Typical morphology with frequent microvacuoles under the cytoplasmic membrane. E : Immature morphology. F: Pseudolymphocytic morphology. G: Presence of dysplasia in myeloid cells with Auer Rods in the granulocytes. The morphology of the Blastic cells is typical. H. Chromosomal abnormalities in 78 caryotypes evaluated: The histogram represents the number of cases in which each chromosome was involved (deletion, gain, translocations).

Disclosures: Bardet: Celgene: Research Funding . Deconinck: CHUGAI: Other: Travel for international congress ; PFIZER: Research Funding ; ROCHE: Research Funding ; NOVARTIS: Other: Travel for international congress ; ALEXION: Other: Travel for international congress ; JANSSEN: Other: Travel for international congress ; LFB loboratory: Consultancy .

*signifies non-member of ASH