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CD4-negative Blastic Plasmacytoid Dendritic Cell Neoplasm, Involving Bone Marrow, Skin, and Lymph Node, with Immunophenotypic Variability/Differentiation at Different Sites
Dan Jones
MD Anderson Cancer Center
Houston, TX
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Clinical History:
59 year old man who noted skin lumps for approximately two months followed by
enlargement of lymph nodes in the right groin that reportedly regressed somewhat without any therapy. A
bone marrow biopsy/aspirate was done (slide 1), followed by a skin biopsy (slide 2), and a lymph node
biopsy (slide 3). The patient responded to therapy but died 4 months following presentation from
respiratory failure as a sequelae of treatment.
Pertinent Laboratory Data:
CBC at presentation was Hgb 14.3g/dL, MCV 93 fL, Plt 72 (x 10E9/L), WBC
3.3 (x 10E9/L) with 54% grans, 37% lymphs, 6% monos, and 1% eos. Flow cytometry on disaggregated cells
from lymph node showed tumor cells were uniformly positive for CD45, HLA- DR, and CD7 and negative for
surface CD3, CD4, CD5, CD8, CD10, CD19, CD20, CD23, and immunoglobulin light chains. Immunostain for CD3
on paraffin section was negative. Cytogenetic analysis performed on short-term cultures of lymph node
revealed 45,XY,+8 in 2 of 30 analyzed metaphases. Immunoperoxidase staining of frozen sections of the
skin biopsy shows negative staining of most tumor cells for CD2 (T11), CD3 (Leu-4), and CD7 (Leu-9), with
weak staining for CD3 and CD7 in some cells. Flow cytometry on disaggregated cells on skin show tumors
cells are positive for CD16 and CD56, negative for CD3, CD4, CD5, and B-cell markers. Immunoperoxidase
staining done on paraffin sections shows uniform and strong positive staining of neoplastic cells for
CD56. Flow cytometry on bone marrow aspirate with gating on the "blasts" show cells are positive for
cytoplasmic CD3 and CD56, negative for CD1, CD2, surface CD3, CD5, CD10, CD34, CD64, CD117,
TCR-alpha/beta and TCR-gamma/delta.
Slide 1 - Lymph node, right inguinal, excision
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Slide 2 - Skin, left lower abdomen, punch biopsy
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Figure 1
Bone marrow, loose aggregate of blastoid tumor cells at top, adjacent erythropoiesis is megaloblastoid |
Figure 2
Bone marrow, loose aggregate of blastoid tumor cells |
Figure 3
Skin, superficial perivascular dermal infiltrate of tumor cells with focal epitheliotropism |
Figure 4
Skin, blastoid neoplastic cells infiltrate adnexae |
Figure 5
Lymph node, subtotal diffuse replacement by sheets of neoplastic cells |
Figure 6
Lymph node, neoplastic cells with a small "lymphoid blast" appearance. |
Figure 7
Lymph node, neoplastic cells including with prominent nucleoli and abundant cytoplasm. Some showed lysozyme expression (not shown) |
Figure 8
Lymph node, TdT immunostain, areas with dense positivity adjacent to areas with only rare positive cells, correlating with phenotypic variation seen with other markers |
Figure 9
Bone marrow, CD123 immunostain. Tumor clusters are strongly positive |
Figure 10
Lymph node, TCL1 immunostain. Background B-cells are immunopositive; tumor cells are negative. |
Introduction:
59 year old man who noted skin lumps for approximately two months followed by
enlargement of lymph nodes in the right groin that reportedly regressed somewhat without any therapy. A
bone marrow biopsy/aspirate was done, followed by a skin biopsy, and a lymph node biopsy. The patient
responded to therapy but died 4 months following presentation from respiratory failure as sequelae of
treatment.
Pathological/Microscopic Findings and any Immunohistochemical or Other Studies:
Bone marrow biopsy:
Multiple interstitial clumps of immature-appearing mononuclear cells with folded nuclear contours.
Surrounding hematopoiesis is erythroid- predominant with minimal dysplastic changes. CBC at presentation
was Hgb 14.3g/dL, MCV 93 fL, Plt 72 (x 10E9/L), WBC 3.3 (x 10E9/L) with 54% grans, 37% lymphs, 6% monos,
and 1% eos. Skin: Superficial and mid-dermal predominantly perivascular infiltrate of
immature-appearing mononuclear cells with lymphoid appearance. Focal involvement of the epidermis and
infiltration into adnexa is observed.
Lymph node:
Partially to complete diffuse effacement by blastoid
mononuclear cells, including some areas with tumor cells with more abundant cytoplasm and more prominent
nucleoli. Flow cytometry on disaggregated cells from lymph node showed tumor cells were uniformly
positive for CD45, HLA- DR, and CD7 and negative for CD3, CD4, CD5, CD8, CD10, CD19, CD20, CD23, and
immunoglobulin light chains. Immunostain for CD3 on paraffin section was negative. Cytogenetic analysis
performed on short-term cultures of lymph node revealed 45,XY,+8 in 2 of 30 analyzed metaphases.
Immunoperoxidase staining of frozen sections of the skin biopsy shows negative staining of most tumor
cells for CD2 (T11), CD3 (Leu-4), and CD7 (Leu-9), with weak staining for CD3 and CD7 in some cells.
Flow cytometry on disaggregated cells on skin show tumors cells are positive for CD16 and CD56, negative
for CD3, CD4, CD5, and B-cell markers. Immunoperoxidase staining done on paraffin sections shows uniform
and strong positive staining of neoplastic cells for CD56. Flow cytometry on bone marrow aspirate with
gating on the blast gate show cells are positive for cytoplasmic CD3 and CD56, negative for CD1, CD2,
surface CD3, CD4 (partial), CD5, CD10, CD34, CD64, CD117, TCR-alpha/beta and TCR- gamma/delta.
Additional tie-breaker studies performed:
CD123 immunostain (BM): Strongly positive
BDCA-2 immunostain (LN): Focally positive
TCL1 immunostain (skin/LN): Negative
CD45RA (skin): Positive
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Non-specific esterase (BM cyto): Negative
Lysozyme immunostain (LN): Focal positive
Epstein-Barr virus EBER (skin/LN): Negative
TdT immunostaining:
Bone marrow: 85%
Lymph node: 25%, positive to mostly negative
Skin: 50% Ki-67(skin): 95%
Differential Diagnoses:
CD56 blastoid tumors could represent true NK-cell malignancies, AML, ALL,
poorly differentiated carcinomas (e.g. Merkel cell carcinoma) or neuroendocrine tumors.
Final Diagnosis:
CD4-negative blastic plasmacytoid dendritic cell neoplasm, involving bone marrow,
skin, and lymph node, with immunophenotypic variability/differentiation at different sites
Case Discussion:
Review of the Literature/Treatment Options (if applicable):
Conclusion(s):
BPDCN is closely related to myelomonocytic leukemia and often requires a panel of
immunomarkers for definitive diagnosis and distinction from AML and NK-cell neoplasms.
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