Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDC)

Blastic NK-cell lymphoma

Agranular CD4+ NK cell leukaemia

Blastic NK leukaemia/lymphoma

Agranular CD4+CD56+ haematodermic neoplasm

Epidemiology and Etiology:

• Derived from precursors of plasmacytoid dendritic cells
• Aka professional type 1 interferon producing cells
• Aka plasmacytoid monocytes
• High production of alpha-interferon
• M:F = 3:1
• Elderly mostly
• 65 y. median age
• Can occur in childhood
• Association with myelodysplasia in some cases
• Associated with or develop into AML (10-20%)
• Not associated with EBV
• Distinguish from myeloid neoplasia (often CMML) with massive nodal or extranodal localization of mature plasmacytoid dendritic cells (CD56-)

Common sites:

• Skin (~100%)
• Bone marrow (60-90%)
• May be minimal at presentation but invariably develops with progression of disease
• Peripheral blood (60-90%)
• Lymph nodes (40-50%)

Gross features:

• Skin lesions
• Solitary or multiple
• Nodules, plaques, bruise-like areas
• Regional lymphadenopathy

Histologic features:

• Diffuse
• Dermis predominantly, sparing epidermis
• Eventually spreading to subcutaneous fat
• Interfollicular areas and medulla of lymph nodes
• Monomorphous
• Medium-sized blasts
• Irregular nuclei
• Fine chromatin
• One to several small nucleoli
• Scant cytoplasm
• Grey-blue and agranular on Giemsa
• Microvacuoles along the cell membrane and pseudopodia on smears maybe
• Mitoses variable
• Rarely prominent
• Angioinvasion absent
• Coagulative necrosis absent
• Dysplastic residual haematopoietic cells in BM maybe
• Esp. megakaryocytes

Immunophenotype and special stains:

Marker:	Sensitivity:	Specificity:
CD56	Rarely negative (CD4, CD123, and TCL1 must be positive)	Extranodal localization of mature plasmacytoid dendritic cells is negative
MPO (neg)
NSE (neg)
CD4
CD43
CD45RA
CD123
BDCA-2
CD303
TCL1
CLA
MxA
CD68 (small cytoplasmic dots)	50%	Typically found on normal plasmacytoid dendritic cells
Granzyme B (neg)	Mostly negative on tissue sections	Regularly found in normal plasmacytoid dendritic cells
Perforin (neg)	Mostly negative on tissue sections	Regularly found in normal plasmacytoid dendritic cells
TIA1 (neg)	Mostly negative on tissue sections	Regularly found in normal plasmacytoid dendritic cells
CD7	Relatively common
CD33	Relatively common
CD2 (neg)	Regularly
CD36 (neg)	Regularly
CD38 (neg)	Regularly
CD3 (neg)	Regularly
CD5 (neg)	Regularly
CD13 (neg)	Regularly
CD16 (neg)	Regularly
CD19 (neg)	Regularly
CD20 (neg)	Regularly
CD79a (neg)	Regularly
LAT (neg)	Regularly
Lysozyme (neg)	Regularly
TdT (10-80% of cells)	One third	Negative in normal plasmacytoid dendritic cells
CD34 (neg)
CD117 (neg)
EBER (neg)

Molecular features:

• TCR and IG genes germline usually
• A few cases showed TCR-gamma rearrangement
• Abnormal karyotype (2/3)
• Complex commonly
• 5q21 or 5q34 (72%)
• 12p13 (64%)
• 13q13-21(64%)
• 6q23-qter (50%)
• 15q (43%)
• -9 (28%)
• Deletions by CGH:
• 4q34
• 9p13-p11
• 9q12-q34
• 13q12-q31 (RB1)
• Overexpressed oncogenes:
• HES6
• RUNX2
• FLT3

Other features:

• Cytopenias
• Esp. thrombocytopenia
• aggressive
• Relapse invariable\fulminant leukaemic phase ultimately in most cases
• 12-14 months median survival

References:

• WHO blue book (2008)