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Peripheral Blood, Bone Marrow, and Tissue Morphology: Neoplastic Hematology

Peripheral Blood, Bone Marrow, and Tissue Morphology: Neoplastic Hematology. Charles Timmons, MD, PhD UT Southwestern Medical Center at Dallas Dallas, Texas. 1. 1.

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Peripheral Blood, Bone Marrow, and Tissue Morphology: Neoplastic Hematology

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  1. Peripheral Blood, Bone Marrow, and Tissue Morphology: Neoplastic Hematology Charles Timmons, MD, PhD UT Southwestern Medical Center at Dallas Dallas, Texas

  2. 1

  3. 1 Hx: 16 yo boy with pallor and bruising. Blood smear shows anemia, thrombocytopenia, leukocytosis (100,000/mm3, 90% immature cells). Flow cytometry on blood shows cells are TdT+, CD10+, CD3+, CD7+, CD4+, and CD8+. Interpretation: A. AML B. B-cell ALL C. T-cell ALL D. Hematogone hyperplasia E. Neuroblastoma

  4. 1 Hx: 16 yo boy with pallor and bruising. Blood smear shows anemia, thrombocytopenia, leukocytosis (100,000/mm3, 90% immature cells). Flow cytometry on blood shows cells are TdT+, CD10+, CD3+, CD7+, CD4+, and CD8+.Interpretation: A. AML B. B-cell ALL C. T-cell ALL D. Hematogone hyperplasia E. Neuroblastoma Comment: The cells are T lymphoblasts by morphology and flow cytometry. Hematogones are rarely seen in peripheral blood. High white count and large and small blasts favor T-cell ALL.

  5. 2

  6. 2 Hx: 5 yo boy with bruising and cervical lymph-adenopathy. Blood smear shows pancytopenia and 20% abnormal cells (pictured). Flow cytometry on marrow shows 90% of cells are TdT+, CD10+, CD3+ and CD7+. Interpretation: A. AML B. B-cell ALL C. T-cell ALL D. Hematogone hyperplasia E. Neuroblastoma

  7. 2 Hx: 5 yo boy with bruising and cervical lymph-adenopathy. Blood smear shows pancytopenia and 20% abnormal cells (pictured). Flow cytometry on marrow shows 90% of cells are TdT+, CD10+, CD3+ and CD7+. Interpretation: A. AML B. B-cell ALL C. T-cell ALL D. Hematogone hyperplasia E. Neuroblastoma Comment: The cells are immunophenotypically precursor T lymphoblasts. Morphologically they correspond to the old L2 designation from the FAB classification system.

  8. 3

  9. 3 Hx: 6 yo boy with bone pain. Blood smear shows pancytopenia, and 5% circulating immature cells (pictured). Flow cytometry on marrow shows 80% cells are TdT+, CD10+ and CD19+. Interpretation: A. AML B. B-cell ALL C. T-cell ALL D. Hematogone hyperplasia E. Neuroblastoma

  10. 3 Hx: 6 yo boy with bone pain. Blood smear shows pancytopenia but no blasts. Flow cytometry on marrow shows 95% cells are TdT+, CD10+ and CD19+. Interpretation: A. AML B. B-cell ALL C. T-cell ALL D. Hematogone hyperplasia E. Neuroblastoma Comment: This is a blast by morphology and is B phenotype by flow cytometry. Hematogones should show more of a spectrum of maturation and are unlikely to completely replace the normal marrow elements. Solid tumor cells tend to clump rather than cluster.

  11. 4

  12. 4 Hx: 15 yo boy with respiratory distress. Radiology shows cervical and mediastinal lymphadenopathy, which is biopsied. Flow cytometry shows a proliferation of cells that are TdT+, CD10+, CD3+, CD7+, CD4+ and CD8+. Interpretation: A. Myeloid sarcoma B. B lymphoblastic lymphoma C. T lymphoblastic lymphoma D. Hodgkin lymphoma E. Reactive process

  13. 4 Hx: 15 yo boy with respiratory distress. Radiology shows cervical and mediastinal lymphadenopathy, which is biopsied. Flow cytometry shows a proliferation of cells that are TdT+, CD10+, CD3+, CD7+, CD4+ and CD8+. Interpretation: A. Myeloid sarcoma B. B lymphoblastic lymphoma C. T lymphoblastic lymphoma D. Hodgkin lymphoma E. Reactive process Comment: By morphology and flow cytometry, the immature cells are precursor T lymphoblasts.An extramedullary mass of lymphoblasts is called lymphoblastic lymphoma, although it is part of a biologic continuum referred to as leukemia/lymphoma.

  14. 5

  15. 5 Hx: 16 yo boy with respiratory distress. Radiology shows a mediastinal mass and a pleural effusion, which is tapped. Flow cytometry shows 90% of effusion cells are TdT+, CD10+, CD3+, CD7+, CD4+ and CD8+. Interpretation: A. Myeloid sarcoma B. B lymphoblastic lymphoma C. T lymphoblastic lymphoma D. Hodgkin lymphoma E. Reactive process

  16. 5 Hx: 16 yo boy with respiratory distress. Radiology shows a mediastinal mass and a pleural effusion, which is tapped. Flow cytometry shows 90% of effusion cells are TdT+, CD10+, CD3+, CD7+, CD4+ and CD8+. Interpretation: A. Myeloid sarcoma B. B lymphoblastic lymphoma C. T lymphoblastic lymphoma D. Hodgkin lymphoma E. Reactive process Comment: By morphology and flow cytometry, the immature cells are T lymphoblasts.An extramedullary mass of lymphoblasts is called lymphoblastic lymphoma, although it is part of a biologic continuum referred to as leukemia/lymphoma.

  17. 6

  18. 6 Hx: 7 yo boy with an recent onset of vomiting and lethargy. Blood smear shows increased neutrophils with a left shift and 8% abnormal cells. Bone marrow contains 60% of the same cells. Flow cytometry shows cells are TdT-, CD10+, CD19+. Interpretation: A. AML B. B-cell ALL C. T-cell ALL D. Burkitt leukemia/lymphoma E. Reactive process

  19. 6 Hx: 7 yo boy with recent onset of vomiting and lethargy. Blood has increased neutrophils with left shift and 8% abnormal cells. Bone marrow contains 60% of the same cells. Flow cytometry shows cells are TdT-, CD10+, CD19+. Interpretation: A. AML B. B-cell ALL C. T-cell ALL D. Burkitt leukemia/lymphoma E. Reactive process Comment: Flow cytometry shows mature B-cells, and the morphology is that of Burkitt lymphoma, which occasionally can have a leukemic phase.

  20. 7

  21. 7 Hx: 12 yo boy with vomiting, abdominal pain and weight loss. Radiology shows an ileo-cecal mass. Histology of the resection specimen is shown. Flow cytometry on the mass shows cells are TdT-, CD10+ and CD19+. Interpretation: A. Myeloid sarcoma B. B lymphoblastic lymphoma C. T lymphoblastic lymphoma D. Burkitt lymphoma E. Reactive process

  22. 7 Hx: 12 yo boy with vomiting, abdominal pain and weight loss. Radiology shows an ileo-cecal mass. Histology of the resection specimen is shown. Flow cytometry on the mass shows cells are TdT-, CD10+ and CD19+. Interpretation: A. Myeloid sarcoma B. B lymphoblastic lymphoma C. T lymphoblastic lymphoma D. Burkitt lymphoma E. Reactive process Comment: The “starry-sky” histology can be seen in either lymphoblastic lymphoma or Burkitt lymphoma, but the immunophenotype is of a mature B-cell, consistent with Burkitt lymphoma, and the appearance of the cells also favors Burkitt lymphoma.

  23. 8

  24. 8 Hx: 14 yo boy with a single large cervical lymph node. Lymph node biopsy is shown. Flow cytometry and immunohistochemistry show cells are TdT-, CD19+, CD20+, CD3-. Interpretation: A. Large B-cell lymphoma B. T lymphoblastic lymphoma C. Mature (Peripheral) T-cell lymphoma D. Hodgkin lymphoma E. Reactive process

  25. 8 Hx: 14 yo boy with a single large cervical lymph node. Lymph node biopsy is shown. Flow cytometry and immunohistochemistry show cells are TdT-, CD19+, CD20+, CD3-. Interpretation: A. Large B-cell lymphoma B. T lymphoblastic lymphoma C. Mature (Peripheral) T-cell lymphoma D. Hodgkin lymphoma E. Reactive process Comment: The neoplastic cells are large and monomorphous, with the immunophenotype of mature B-cells.

  26. 9

  27. 9 Hx: 18 yo boy with abdominal pain, has hepatosplenomegaly, thrombocytopenia and anemia, without adenopathy. Flow cytometry on infiltrate shows cells are TdT-, CD3+, CD4-, CD8-. Interpretation: A. B lymphoblastic lymphoma B. Burkitt lymphoma C. T lymphoblastic lymphoma D. Mature (Peripheral) T-cell lymphoma E. Reactive process

  28. 9 Hx: 18 yo boy with abdominal pain, has hepatosplenomegaly, thrombocytopenia and anemia, without adenopathy. Flow cytometry on infiltrate shows cells are TdT-, CD3+, CD4-, CD8-. Interpretation: A. B lymphoblastic lymphoma B. Burkitt lymphoma C. T lymphoblastic lymphoma D. Mature (Peripheral) T-cell lymphoma E. Reactive process Comment: The infiltrate is monomorphous, with the immunophenotype of a mature T-cell process, specifically hepatosplenic T-cell lymphoma, which typically infiltrates parenchyma rather than forming a discrete mass.

  29. 10

  30. 10 Hx: 17 yo boy with fever and cervical lymphadenopathy. Lymph node biopsy shown. Immunohistochemistry shows cells are CD3-, CD 4+, CD8-, CD30+, EMA+, ALK+. Interpretation: A. Burkitt lymphoma B. T lymphoblastic lymphoma C. Mature (Peripheral) T-cell lymphoma D. Hodgkin lymphoma E. Reactive process

  31. 10 Hx: 17 yo boy with fever and cervical lymphadenopathy. Lymph node biopsy shown. Immunohistochemistry shows cells are CD3-, CD4+, CD8-, CD30+, EMA+, ALK+. Interpretation: A. Burkitt lymphoma B. T lymphoblastic lymphoma C. Mature (Peripheral) T-cell lymphoma D. Hodgkin lymphoma E. Reactive process Comment: The infiltrate is composed of large, anaplastic cells with a mature T-cell immunophenotype. In this setting, ALK-positivity is helpful in calling this anaplastic large cell lymphoma.

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  33. 11 Hx: 13 yo boy with fatigue, weight loss, night sweats and splenomegaly. Peripheral blood shows anemia and leukocytosis (300,000/mm3). Ancillary test results include normal fetal hemoglobin and karyotype showing t(9;22). Interpretation: A. Acute myeloid leukemia B. Acute lymphoblastic leukemia C. Chronic myelogenous leukemia D. Juvenile myelomonocytic leukemia E. Reactive process

  34. 11 Hx: 13 yo boy with fatigue, weight loss, night sweats and splenomegaly. Peripheral blood shows anemia and leukocytosis (300,000/mm3). Ancillary test results include normal fetal hemoglobin and karyotype showing t(9;22). Interpretation: A. Acute myeloid leukemia B. Acute lymphoblastic leukemia C. Chronic myeloid leukemia D. Juvenile myelomonocytic leukemia E. Reactive process Comment: Marked leukocytosis with prominent basophils without increased blasts (<10%) indicate chronic phase of CML. t(9;22)(q34;q11.2) indicates a BCR/ABL1 rearrangement.

  35. 12

  36. 12 Hx: 2 yo girl with new onset of fever and bronchitis. Has maculo-papular rash and hepatosplenomegaly. Blood smear has leukocytosis (100,000/mm3), anemia and thrombocytopenia. Ancillary tests include fetal hemoglobin of 80% and normal blood karyotype. Interpretation: A. Acute myeloid leukemia B. Acute lymphoblastic leukemia C. Chronic myeloid leukemia D. Juvenile myelomonocytic leukemia E. Reactive process

  37. 12 Hx: 2 yo girl with new onset of fever and bronchitis. Has maculopapular rash and hepatosplenomegaly. Blood smear has leukocytosis (100,000/mm3), anemia and thrombocytopenia. Ancillary tests include fetal hemoglobin of 80% and normal blood karyotype. Interpretation: A. Acute myeloid leukemia B. Acute lymphoblastic leukemia C. Chronic myeloid leukemia D. Juvenile myelomonocytic leukemia E. Reactive process Comment: Marked leukocytosis including monocytosis without increased blasts, accompanied by erythroid proliferation and elevation of fetal hemoglobin is characteristic of JMML. BCR/ABL1 fusion is not present.

  38. 13

  39. 13 Hx: 1 yo boy with pallor and a rash. Blood smear shows pan cytopenia and circulating abnormal cells. Interpretation: A. Acute myeloid leukemia B. Chronic myelogenous leukemia C. Acute lymphoblastic leukemia D. Leukoerythroblastic reaction E. Infectious mononucleosis

  40. 13 Hx: 1 yo boy with pallor and a rash. Blood smear shows pan cytopenia and circulating abnormal cells. Interpretation: A. Acute myeloid leukemia B. Chronic myelogenous leukemia C. Acute lymphoblastic leukemia D. Leukoerythroblastic reaction E. Infectious mononucleosis Comment: The large blasts with ample cytoplasm and prominent nucleoli are suggestive of AML, but the Auer rod is diagnostic.

  41. 14

  42. 14 Hx: 8 yo boy with bruising. Blood smear shows anemia, thrombocytopenia, and leukocytosis (30,000/mm3, 50% blasts). Flow cytometry on marrow shows 50% blasts with TdT+, MPO+, CD13+, CD33+, partial CD19+. Interpretation: A. Acute myeloid leukemia B. Chronic myelogenous leukemia C. Acute lymphoblastic leukemia D. Myelodysplastic syndrome E. Reactive process

  43. 14 Hx: 8 yo boy with bruising. Blood smear shows anemia, thrombocytopenia, and leukocytosis (30,000/mm3, 50% blasts). Flow cytometry on marrow shows 50% blasts with TdT+, MPO+, CD13+, CD33+. Interpretation: A. Acute myeloid leukemia B. Chronic myelogenous leukemia C. Acute lymphoblastic leukemia D. Myelodysplastic syndrome E. Reactive process Comment: The elevated blast count indicates acute leukemia. Auer rod is diagnostic of a myeloid neoplasm, and flow cytometry agrees. Morphology shows myeloid maturation and a large blunt Auer rod, which often correlates with t(8;21)(q22;q22) and RUNX1/RUNX1T1 fusion.

  44. 15

  45. 15 Hx: 8 yo girl with fever, tonsillitis and lymph-adenopathy. Blood smear shows anemia, thrombocytopenia, and leukocytosis (140,000/mm3, 60% blasts). Flow cytometry on marrow shows 60% blasts with TdT+, MPO+, CD13+, CD33+, CD11b partial+. Interpretation: A. Acute myeloid leukemia B. Chronic myelogenous leukemia C. Acute lymphoblastic leukemia D. Chediak-Higashi syndrome E. Reactive process

  46. 15 Hx: 8 yo girl with fever, tonsillitis and lympha-denopathy. Blood smear shows anemia, thrombocytopenia, and leukocytosis (140,000/mm3, 60% blasts). Flow cytometry on marrow shows 60% blasts with tdT+, MPO+, CD13+, CD33+, CD11b partial+. Interpretation: A. Acute myeloid leukemia B. Chronic myeloid leukemia C. Acute lymphoblastic leukemia D. Chediak-Higashi syndrome E. Reactive process Comment: Increased blasts mark as myelomonocytic lineage, so this is AML. The strange, darkly granulated cells are abnormal eosinophils, morphology that correlates with a karyotype of inv(16) or t(16;16).

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  48. 16 Hx: 13 yo girl with fever and swelling of one leg. Blood smear shows anemia and thrombo-cytopenia. WBC 3400/mm3 with marked left shift. Marrow has 2% blasts but 82% immature myeloid cells as shown. Flow cytometry on marrow shows MPO+, CD33+, CD13 partial+, HLA-DR-, CD34-. Interpretation: A. Acute myeloid leukemia B. Chronic myelogenous leukemia C. Acute lymphoblastic leukemia D. Mast cell leukemia E. Left shift with toxic granulation

  49. 16 Hx: 13 yo girl with fever and swelling of one leg. Blood smear shows anemia and thrombocytopenia. WBC 3400/mm3 with marked left shift. Marrow has 2% blasts but 82% immature myeloid cells as shown. Flow cytometry on marrow shows MPO+, CD33+, HLA-DR-, CD34-. Interpretation: A. Acute myeloid leukemia B. Chronic myelogenous leukemia C. Acute lymphoblastic leukemia D. Mast cell leukemia E. Left shift with toxic granulation Comment: Proliferating promyelocytes, which sometimes have multiple Auer rods, rather than myeloblasts characterize the acute promyelocytic form of AML, which is associated with t(15;17) and a PML/RARA fusion.

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