Case 2 -

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

Virtual Slides as well as Still Images are displayed below.
For the fastest viewing of virtual slides, click:



under each thumbnail image below. You must have Aperio ImageScope installed on your PC.

If you do not already have Aperio ImageScope, Windows users with administrator privileges may download and install a free version in order to view USCAP Virtual Slides. Click the icon on the right to get your free copy:

Or, click on slide thumbnail images to view each slide
in a Web-based slide viewer, which is somewhat slower.

If you have any difficulties viewing these slides, email or call George Clay at +1.724.449.1137.

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. Case 2 - Slide 1 - Lymph node, right inguinal, excision Click to view with ImageScope Click to view with a Web-Based Viewer Case 2 - Slide 2 - Skin, left lower abdomen, punch biopsy Click to view with ImageScope Click to view with a Web-Based Viewer Case 2 - Figure 1 Bone marrow, loose aggregate of blastoid tumor cells at top, adjacent erythropoiesis is megaloblastoid Case 2 - Figure 2 Bone marrow, loose aggregate of blastoid tumor cells Case 2 - Figure 3 Skin, superficial perivascular dermal infiltrate of tumor cells with focal epitheliotropism Case 2 - Figure 4 Skin, blastoid neoplastic cells infiltrate adnexae Case 2 - Figure 5 Lymph node, subtotal diffuse replacement by sheets of neoplastic cells Case 2 - Figure 6 Lymph node, neoplastic cells with a small "lymphoid blast" appearance. Case 2 - Figure 7 Lymph node, neoplastic cells including with prominent nucleoli and abundant cytoplasm. Some showed lysozyme expression (not shown) Case 2 - 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 Case 2 - Figure 9 Bone marrow, CD123 immunostain. Tumor clusters are strongly positive Case 2 - 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 --------------------------------------------------- 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.