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Hematopathology
Monday, March 9, 7:30 PM
Convention Center BRB




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



Unusual Manifestations of Well-Defined Lymphoid/Histiocytic Proliferations
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Moderator:
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MARSHA C. KINNEY University of Texas Health Science Center, San Antonio, TX
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Disclosure:
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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.
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Panelists:
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ELIAS CAMPO, University of Barcelona, Barcelona,Spain
LETICIA M. QUINTANILLA-FEND, Eberhard Karls University of Tubingen, Tubingen, Germany
RONALD JAFFE, University of Pittsburgh School of Medicine, Pittsburgh, PA
ROBERT MCKENNA, University of Minnesota, Twin Cities, MN
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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.




for Text and References

Submitted by: Ronald Jaffe - University of Pittsburgh Medical Center, Pittsburgh, PA


A female patient first presented at age 42 with a 1.7cm raised, nodular, ulcerated lesion on the right knee. The pathological diagnosis was benign and no further therapy was given. A year later, biopsy of a raised 1.3cm nodule on the cheek proved to be the same process. Over the next few years, she developed additional lesions in the small and large bowel and was treated with surgery and chemotherapy. She died 8 years after first presentation with progressive tumors that involved skin, soft tissue, thyroid, lung, liver, bone and brain, including the posterior pituitary. The slide is from a liver mass at autopsy, some days after death.

 Case 1 - Slide 1
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 Case 1 - Figure 1 H&E x 20. Liver. Diffuse proliferation of cells that have a "histiocytic" appearance
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 Case 1 - Figure 2 H&E x 40. Liver. The nuclear morphology holds a clue. The nucleus is more than coffee-bean shaped or grooved but displays a complex folded appearance.
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 Case 1 - Figure 3 H&E x 40. Liver. There is variation in nuclear size, pleomorphism, and a high mitotic rate that includes atypical mitoses.
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 Case 1 - Figure 4 Leukocyte Common Antigen. Liver. There is little to no staining of the histiocytic population.
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 Case 1 - Figure 5 Vimentin. Liver. All cells stain strongly.
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 Case 1 - Figure 6 CD163. Liver. Interspersed macrophages stain strongly but cells with the signature nucleus are unstained.
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 Case 1 - Figure 7 S100. Liver. There is uneven cytoplasmic staining but little nuclear staining.
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 Case 1 - Figure 8 Ki-67. Liver. The very high proliferative rate is highlighted, including atypical forms.
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 Case 1 - Figure 9 CDla. Liver. The staining is universal. The quality of the membrane stain in this example is compromised by delayed fixation.
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 Case 1 - Figure 10 Langerin. Liver. Many of the cells in this field, but not all, stain for the presence of Langerin.
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 Case 1 - Figure 11 H&E x 10. Lymph node. The node is largely replaced with only residual follicles but the sinus pattern is not evident on H&E.
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 Case 1 - Figure 12 H&E x 40. Lymph node. Sinuses are filled with the Langerhans type cells that have cytologic pleomorphism and evident mitoses.
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 Case 1 - Figure 13 S100. Lymph node. The pattern of staining highlights the sinus component and paracortical spill-over.
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 Case 1 - Figure 14 CDla. Lymph node. The sharp membrane quality of the staining is evident.
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 Case 1 - Figure 15 Langerin. Lymph node. The lesional cells are universally positive.
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for Text and References

Submitted by: Robert McKenna - University of Minnesota, Twin Cities, MN


The patient is an 81 year-old female who presented with pancytopenia. Blood counts were as follows:
- WBC-0.8X109/L

- Hematocrit-27.2%

- MCV-92fL

- RDW-14.5

- Platelet count-16X109/L
A blood smear (images 1 and 2) and bone marrow specimen (images 3 to 5) were obtained. Immunohistochemical stains were performed on marrow particle sections (images 6 to 10).

Flow cytometry was performed on the bone marrow specimen. The predominant cells showed the following immunophenotype: CD19(-), CD20(+), CD5(-), CD10(-), (s)kappa(-), (s)lambda(-) CD56(-).

 Case 2 - Slide 1
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 Case 2 - Figure 1 Blood smear showing marked pancytopenia.
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 Case 2 - Figure 2 Higher magnification of the blood smear showing a small plasma cell or plasmacytoid lymphocyte.
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 Case 2 - Figure 3 Bone marrow aspirate smear showing small, relatively mature appearing plasma cells.
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 Case 2 - Figure 4 Normocellular bone marrow particle section for the patient's age with decreased hematopoietic cells replaced by a monomorphic cell infiltrate.
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 Case 2 - Figure 5 A higher magnification of figure 4 showing a predominance of plasmacytic cells
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 Case 2 - Figure 6 CD138 immunohistochemical stain of the marrow section. The majority of the cells are CD138 positive.
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 Case 2 - Figure 7 Immunohistochemical stain for kappa light chain. Nearly all of the plasmacytic cells express kappa light chain.
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 Case 2 - Figure 8 Immunohistochemical stain for lambda light chain. The plasmacytic cells are negative.
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 Case 2 - Figure 9 CD20 immunohistochemical stain. Nearly all of the plasmacytic cells express surface CD20.
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 Case 2 - Figure 10 Cyclin D1 stain--There is nuclear cyclin D1 expression in most of the plasmacytic cells.
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for Text and References

Submitted by: Elias Campo - University of Barcelona, Barcelona, Spain

 78 year-old female with a 10-year history of a low grade, leukemic, B-cell neoplasm, initially diagnosed in 1995 as chronic lymphocytic leukemia [stage A(0)]. In December 2003, a stage I renal cell adenocarcinoma was resected without complication. At the end of 2004, she developed progressive lymphocytosis, anemia, and thrombocytopenia and was referred to our hospital for splenectomy. Physical examination was normal with the exception of the splenomegaly. Laboratory tests demonstrated normal LDH levels, B2 microglobulin 6.2 mg/L (normal 0-2.3) WBC 123.40 x103/µL (lymphocytes 85%), RBC 2.88 x106/µL, Hgb 8.7 g/dL, HCT 29%, MCV 89.7 fL, platelets 119 x103/µL. Flow cytometry of the peripheral blood showed a clonal lymphoid proliferation positive for CD19, CD79b, CD20 (bright), CD22, CD23 (66% of all B-lymphocytes), FMC7, IgM/IgD, kappa (bright) and negative for CD5, CD43, CD10. The general status of the patient improved after the splenectomy, but the lymphocytosis persisted. She did not receive additional treatment for two years, until July 2007, when because of progressive lymphocytosis she again received cyclophosphamide for 6 months. The patient is currently alive with clinically stable disease.

 Case 3 - Slide 1
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 Case 3 - Figure 1 The histological section of the spleen shows an expansion of the white pulp with a diffuse lymphoid infiltrate in the red pulp
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 Case 3 - Figure 2 Some nodules of the white pulp had a hyalinized aspect. The nodules were not very well demarcated, and the lymphoid cells of merged with the infiltrate of the red pulp.
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 Case 3 - Figure 3 A small reactive germinal center could be recognized in occasional white pulp nodules.
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 Case 3 - Figure 4 The tumor cell infiltrate was composed of small lymphoid cells with round nuclei, dense chromatin and scant cytoplasm.
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 Case 3 - Figure 5 The tumor cells had a monotonous morphology with round nuclei and dense chromatin without prominent nucleoli. No plasmacytoid differentiation could be seen.
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 Case 3 - Figure 6 The tumor cells were strongly positive for CD20 with a similar intensity in all the areas.
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 Case 3 - Figure 7 CD3 staining revealed few scattered lymphoid cells, but the tumor cells were negative.
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 Case 3 - Figure 8 CD5 staining was positive only in few lymphocytes with a similar distribution to that of the CD3 positive cells. Some of these cells tended to be at the periphery of the white pulp nodules. The tumor cells were negative.
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 Case 3 - Figure 9 CD5 positivity is present in residual lymphoid cells, but tumor cells are negative.
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for Text and References

Submitted by: Leticia M. Quintanilla-Fend - Eberhard Karls University of Tubingen, Tubingen, Germany

 A 31 year-old Mexican women presented with an approximately 2 cm hyperpigmented, firm, painful lesion on the upper left thigh and inguinal lymphadenopathy on the same side. Biopsies of the skin and of one inguinal lymph node were performed.

 Case 4 - Slide 1
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 Case 4 - Slide 2
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 Case 4 - Figure 1 Skin lesion. The lymphoid infiltrate involves the epidermis, dermis and subcutaneous tissue.
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 Case 4 - Figure 2 Skin lesion. At higher magnification the lymphomatous infiltrate has an angiocentric angiodestructive quality with extensive coagulative necrosis of the subcutaneous tissue.
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 Case 4 - Figure 3 Subcutaneous tissue. Cytologically, the tumor is composed predominantly of medium-sized cells admixed with some pleomorphic large cells. Focally the neoplastic cells surround the fat cells.
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 Case 4 - Figure 4 Skin lesion. The tumor cells are strongly positive for CD3
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 Case 4 - Figure 5 Subcutaneous tissue. Immunohistochemical staining for CD56 highlights the rimming of individual fat spaces by tumor cells.
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 Case 4 - Figure 6 The neoplastic cells are strongly positive for granzyme B
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 Case 4 - Figure 7 The neoplastic cells are strongly positive for TIA-1
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 Case 4 - Figure 8 In situ hybridization for EBV-encoded RNA (EBER) is positive in practically all neoplastic cells.
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If there are glass slides for a conference, they will be available for study in the microscope room in the Convention Center Room 313 for participants who wish to review them prior to the evening session.

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