—  SPECIALTY CONFERENCE HANDOUT  —

Hematopathology
Sunday March 21, 7:30 PM
Salon 3 and Balconies





Clinical histories are printed below.
Click on the case numbers for text and references of each case.
Click on each slide thumbnail image for an enlarged view





Lineage Infidelity, Promiscuity and Confusion: What's a Boy/Girl/Hematopathologist To Do?
Moderator: ADAM BAGG
University of Pennsylvania, Philadelphia, PA
Disclosure: In accordance with ACCME guidelines regarding disclosure, the USCAP policy requires that faculty members who have a significant financial or other relationship with a commercial company, entity, or service (which will be discussed in this Symposium) must disclose this to attendees. The Academy also requires that speakers disclose any products that are not labeled for the use under discussion. The speakers listed below have indicated they have nothing to disclose.
Panelists: ANDREW L. FELDMAN, Mayo Clinic, Rochester, MN
DAN JONES, UT-M.D. Anderson Cancer Center, Houston, TX
SIBRAND POPPEMA, University of Groningen, Groningen, Netherlands
STEVEN H. KROFT, Medical College of Wisconsin, Milwaukee, WI



Clinical Histories and Still Images are displayed below.
Click on slide thumbnail images for an enlarged view.

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




Case 1 - Click here for Text and References

Submitted by: Andrew L. Feldman - Mayo Clinic, Rochester, MN

Clinical Summary:

A 52 year-old male presented with lymphadenopathy in 2000 and underwent a right inguinal lymph node biopsy (Case 1a). Bone marrow biopsy showed involvement by the same process seen in the lymph node. The patient was treated with immunochemotherapy and had persistent, but stable, disease for the next 8 years. In 2008, at age 61, his lymphadenopathy increased and he underwent a left inguinal lymph node biopsy (Case 1b).


Case 1 - Slide 1
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Case 1 - Slide 2
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Case 1a - Figure 1
H&E, 4x. A low power view of the lymph node from the 2000 biopsy shows numerous, back-to-back follicles with thinned mantle zones.

Case 1a - Figure 2
H&E, 20x. At higher power, the follicles have a monotonous cellular composition and lack tingible body macrophages.

Case 1a - Figure 3
H&E, 100x (oil). At high power, the cells within the follicles are mostly small cleaved cells (centrocytes). Occasional larger cells with oval nuclei containing watery chromatin likely represent follicular dendritic cells.

Case 1b - Figure 1
H&E, 4x. A low power view of the lymph node from the 2008 biopsy shows nodules and small sheets of cells with focal necrosis.

Case 1b - Figure 2
H&E, 10x. At slightly higher power, there is a distinct sinusoidal pattern to the infiltrate in this field.

Case 1b - Figure 3
H&E, 20x. The atypical cells are medium to large in size, and have abundant cytoplasm. Foci of necrosis are present.

Case 1b - Figure 4
H&E, 40x. In this field the sinusoidal pattern is appreciated. The largest of the atypical cells have folded or lobated nuclei.

Case 1b - Figure 5
H&E, 100x (oil). In this high power view, the folded ("reniform") nuclei are easily appreciated.

Case 1b - Figure 6
CD79a, 10x. The tumor cells are negative for CD79a.

Case 1b - Figure 7
S100, 10x. The tumor cells are positive for S100.

Case 1b - Figure 8
CD1a, 10x. The tumor cells are positive for CD1a.

Case 1b - Figure 9
Langerin, 10x. The tumor cells are positive for langerin.




Case 2 - Click here for Text and References

Submitted by: Dan Jones - MD Anderson Cancer Center, Houston, TX

Clinical Summary:

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 (slide 1), and a lymph node biopsy (slide 2).

The patient responded to therapy but died 4 months following presentation from respiratory failure as a sequelae of treatment.

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
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Case 2 - Slide 2 - Skin, left lower abdomen, punch biopsy
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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, CD13 immunostain. Tumor clusters are strongly positive

Case 2 - Figure 10
Lymph node, TCL1 immunostain. Background B-cells are immunopositive; tumor cells are negative. Scanned slides 1-Lymph node, right inguinal, excision 2-Skin, left lower abdomen, punch biopsy




Case 3 - Click here for Text and References

Submitted by: Sibrand Poppema - University of Groningen, Groningen, Netherlands

Clinical History:

  • A 76 year old male, diagnosed with CLL three years earlier

  • Rapidly enlarging lymph nodes


Case 3 - Figure 1
H&E, 40x

Case 3 - Figure 2
H&E, 40x

Case 3 - Figure 3
H&E, 40x




Case 4 - Click here for Text and References

Submitted by: Steven H. Kroft - Medical College of Wisconsin, Milwaukee, WI

Clinical Summary:

The patient was a previously healthy Hispanic male with no significant past medical history who presented with a 4-week history of fever, weight loss, and fatigue. Physical examination revealed bilateral posterior cervical, axillary, and inguinal adenopathy, but no hepatosplenomegaly.

CBC revealed WBC 390,000/uL, hemoglobin 9.5 g/dL, and platelets 72,000/uL.


Case 4 - Figure 1
Peripheral blood demonstrating a dimorphic blast proliferation, one population resembling lymphoblasts, the other resembling myeloblasts. The dimorphism was most striking in the aspirate smears.

Case 4 - Figure 2
Peripheral blood demonstrating a dimorphic blast proliferation, one population resembling lymphoblasts, the other resembling myeloblasts. The dimorphism was most striking in the aspirate smears.

Case 4 - Figure 3
Bone marrow aspirate demonstrating a dimorphic blast proliferation, one population resembling lymphoblasts, the other resembling myeloblasts. The dimorphism was most striking in the aspirate smears.

Case 4 - Figure 4
Bone marrow aspirate demonstrating a dimorphic blast proliferation, one population resembling lymphoblasts, the other resembling myeloblasts. The dimorphism was most striking in the aspirate smears.

Case 4 - Figure 5
Bone marrow biopsy section revealing primitive-appearing blasts of varying size.

Case 4 - Figure 6
A myeloperoxidase cytochemical stain is negative in the blasts.

Case 4 - Figure 7
A non-specific (butyrate) esterase stain is negative in the blasts. non-specific (butyrate) esterase

Case 4 - Figure 8
Flow cytometry (gated on low side scatter events over a wide range of CD45 expression) reveals co-expression of B-lymphoid and myeloid antigens. Many of the antigens show a heterogeneous expression pattern. See text for details.

Case 4 - Figure 9
Flow cytometry (gated on low side scatter events over a wide range of CD45 expression) reveals co-expression of B-lymphoid and myeloid antigens. Many of the antigens show a heterogeneous expression pattern. See text for details.

Case 4 - Figure 10
Re-analysis of flow cytometry data with cluster analysis and color-eventing reveals three distinct blast population. All have B-lymphoid and myeloid antigen expression, but differ in the degree to which these lineages are expressed. See text for details.

Case 4 - Figure 11
Re-analysis of flow cytometry data with cluster analysis and color-eventing reveals three distinct blast population. All have B-lymphoid and myeloid antigen expression, but differ in the degree to which these lineages are expressed. See text for details.

Case 4 - Figure 12
Day 14 marrow showing induction failure. The blasts are still dimorphic, but now the myeloblast-like population is dominant.

Case 4 - Figure 13
Flow cytometry still shows three blast populations with similar immunophenotypic features as at diagnosis, but now a previously minor population with monocytic features is now dominant. See text for details.

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