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Case 10 New Frontiers in Pathology, 2009 William G. Finn, M.D. University of Michigan.

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Presentation on theme: "Case 10 New Frontiers in Pathology, 2009 William G. Finn, M.D. University of Michigan."— Presentation transcript:

1 Case 10 New Frontiers in Pathology, 2009 William G. Finn, M.D. University of Michigan

2 History A 3-month-old girl was referred to the pediatric hematology-oncology service for persistent neutropenia. She had been born premature at 32 weeks gestation, with time in NICU. At birth she had a white blood cell count of 9x10 9 /L and an absolute neutrophil count of 1.5x10 9 /L (both within reference range). Over the following 3 months her neutrophil count decreased to as low as 0.5x10 9 /L. A bone marrow aspiration was performed.

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6 Findings Acquired anemia/ neutropenia in an infant Numerous immature cells in marrow Leukemia?

7 Acute Leukemia in Children Signs and symptoms (variable among patients) –Fatigue –Pallor –Petechiae –Cytopenias –Organomegaly –Lymphadenopathy

8 Leukemia? Pros –Persistent idiopathic cytopenias (neutropenia, anemia) –Marked increase in immature cells in marrow (>20%) Cons –Normal platelet count –No leukocytosis (O.K. for A.L.L. but uncommon in infant A.L.L.) –Clinically stable, not acutely ill

9 Our Patient A.L.L.

10 Flow Cytometry B-A.L.L. in children: –CD19+, CD10+, CD20+/-, CD22+/-, CD34+/-, CD38+, TdT+

11 Flow Cytometry Our patient: –CD19+, CD10+, CD20+/-, CD22+/-, CD34+/-, CD38+, TdT+

12 Flow Cytometry – A.L.L. CD45 Side Scatter CD33 CD34 CD19 CD10

13 Flow Cytometry – A.L.L. CD45 Side Scatter CD19 CD38 CD5 CD20

14 Flow Cytometry – Our Patient CD45 Side Scatter CD33 CD34 CD19 CD10

15 Flow Cytometry – Our Patient CD45 Side Scatter CD19 CD38 CD5 CD20

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17 Flow Cytometry – Our Patient CD45 Side Scatter CD33 CD34 CD19 CD10

18 Flow Cytometry – Our Patient CD45 Side Scatter CD19 CD38 CD5 CD20

19 Flow Cytometry – Our Patient Side Scatter CD45 CD33 CD34 CD19 CD10

20 Flow Cytometry – Our Patient Side Scatter CD45 CD19 CD38 CD5 CD20

21 Diagnosis Hematogone Hyperplasia

22 Hematogones Physiologic B-cell precursors –“Mystery Cells” –Normal counterpart to B-precursor lymphoblasts Substantially resemble leukemic lymphoblasts, both morphologically and immunophenotypically

23 Hematogones Proliferate in a variety of reactive states, most notably in children –Autoimmune cytopenias (ITP, etc) –Recovery from chemotherapy (including A.L.L. therapy) –Hematogone hyperplasia usually <10% of nucleated cells in marrow, but occasionally much higher, raising differential diagnosis with acute leukemia

24 Hematogones May be distinguished from leukemic lymphoblasts by a characteristic pattern of maturation, both morphologically and immunophenotypically

25 Hematogones Maturation pattern by flow cytometry very consistent and reproducible-- readily distinguishable from lymphoblasts –Analysis should be iterative, based on known patterns at each stage of maturation –Evaluate patterns not lists of markers –Avoid simple “gate and analyze” approach –Treat as data not as dot-plots

26 Hematogones-immunophenotype CD45 dim in early forms, brighter in later forms Low side angle light scatter

27 Hematogones-immunophenotype CD19 increases slightly with maturation CD10 bright in early forms, slightly dimmer in later forms, negative in mature B- cells

28 Hematogones-immunophenotype CD20 increases progressively with maturation CD34 uniformly positive in earliest forms, then negative (no gradual progression) CD38 uniformly positive in early and later forms, then variable in mature B-cells (no gradual progression)

29 Hematogones-immunophenotype TdT expression mirrors CD34 expression No expression of myeloid antigens

30 Our Patient A.L.L.

31 Summary Hematogones are physiologic B-cell precursors; normal counterpart to B- lineage lymphoblasts May become hyperplastic in numerous reactive conditions, especially in children Often seen in recovery from anti-leukemic therapy– diagnostic pitfall

32 Summary May be present in high enough percentage to mimic overt leukemia Readily distinguished from lymphoblasts by careful morphologic and immunophenotypic assessment


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