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3/5/2013 1 Hematopoiesis Hematopoiesis: Red and white marrow Bone marrow aspirate and core biopsy Gartner, Color Textbook of Histology, 3 rd Edition

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Page 1: Hematopoietic lecture ppt - Indiana University Bloomingtonmedsci.indiana.edu/c602web/602/c602web/docs/heme/heme_slides.pdf · Hemoglobin electrophoresis Adult Fetal Hb S Hb C 1 =

3/5/2013

1

Hematopoiesis

Hematopoiesis:  Red and white marrow

Bone marrow aspirate and core biopsy

Gartner, Color Textbook of Histology, 3rd Edition

Page 2: Hematopoietic lecture ppt - Indiana University Bloomingtonmedsci.indiana.edu/c602web/602/c602web/docs/heme/heme_slides.pdf · Hemoglobin electrophoresis Adult Fetal Hb S Hb C 1 =

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reticulocytes elliptocytes schistocytes

spheroctyes target cells acanthocytes

Basophilic stippling Howell Jolly bodies Pappenheimer bodies

Ribosomal RNALead

ThalassemiaMyelodysplasia

DNA remnant,splenectomy

Inorganic iron granules,iron stain

Rouleaux

Paraproteinemia

Anemias classified by MCV

Page 3: Hematopoietic lecture ppt - Indiana University Bloomingtonmedsci.indiana.edu/c602web/602/c602web/docs/heme/heme_slides.pdf · Hemoglobin electrophoresis Adult Fetal Hb S Hb C 1 =

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Hereditary spherocytosis

Figure 11‐1

Figure 11‐2

Osmotic fragility test

Normal

Spherocytes

Sickle cell disease

Hemoglobin electrophoresis

Hemoglobin electrophoresis

AdultFetal Hb SHb C

1 = Control2 = Hb A3 = HBA and Hb F4 = Hb S disease

5 = Control6 = Hb S and Hb A trait7 = HB S and Hb C8 = Hb S and Hb A trait

Hemoglobin High Performance Liquid Chromatography

Page 4: Hematopoietic lecture ppt - Indiana University Bloomingtonmedsci.indiana.edu/c602web/602/c602web/docs/heme/heme_slides.pdf · Hemoglobin electrophoresis Adult Fetal Hb S Hb C 1 =

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Hemoglobin HPLCHemoglobin electrophoresesβ‐globin mutations in β‐thalassemias

Figure 11‐7

Glucose‐6‐phosphate dehydrogenase deficiencyParoxysmal nocturnal hemoglobinuria

Anopheles mosquito

Page 5: Hematopoietic lecture ppt - Indiana University Bloomingtonmedsci.indiana.edu/c602web/602/c602web/docs/heme/heme_slides.pdf · Hemoglobin electrophoresis Adult Fetal Hb S Hb C 1 =

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Figure 11‐9

Figure 11‐10

Microcytic hypochromicanemia

Iron regulation Bone marrow iron stains Hepatic hemochromatosis

Figure 15‐25

Megaloblasts

Giantmetamyelocytes

Hyperlobatedneutrophils

Megaloblastic anemia

Aplastic anemia

Myelophthisic marrow,metastatic carcinoma

Leukoerythroblastosis

Hodgkin lymphoma

Burkitt lymphoma Nasopharyngealcarcinoma

Atypicallymphocyte

Epstein‐Barr VirusNormal Lymph Node

Page 6: Hematopoietic lecture ppt - Indiana University Bloomingtonmedsci.indiana.edu/c602web/602/c602web/docs/heme/heme_slides.pdf · Hemoglobin electrophoresis Adult Fetal Hb S Hb C 1 =

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Acute nonspecific lymphadenitis

Follicular hyperplasia Paracortical hyperplasia Sinus histiocytosis

Bartonella henselae

Stellate necrotizinggranulomata

Myeloid and lymphoid neoplasms

Myeloid stem cell Lymphoid stem cell 

Pluripotent stem cell

Polys, basos, eos, monos, plts, rbcs B cells     T cells

Myelodysplasia

Acute Acute myelogenous leukemias

Chronic Myeloproliferative Neoplasms Hodgkin    Non‐Hodgkin 

B‐ALL       T‐ALL

Page 7: Hematopoietic lecture ppt - Indiana University Bloomingtonmedsci.indiana.edu/c602web/602/c602web/docs/heme/heme_slides.pdf · Hemoglobin electrophoresis Adult Fetal Hb S Hb C 1 =

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CD5+, CD19+, CD20+, CD23‐

Kappa light chain restricted

Cyclin D1 positive

t(11;14)

CD5 ‐, CD19 +, CD20+, CD23‐

Kappa/lambda light chain 2:1

Cyclin D1 negative

Negative for t(11;14)

Mantle cell lymphomaReactive lymph node

Heavy chain protein production

Light chain protein production

2 light chains + 2 heavy chains → Immunoglobulin(cell surface antigen receptor or secreted Ig)

Monoclonal IgG kappa →

Page 8: Hematopoietic lecture ppt - Indiana University Bloomingtonmedsci.indiana.edu/c602web/602/c602web/docs/heme/heme_slides.pdf · Hemoglobin electrophoresis Adult Fetal Hb S Hb C 1 =

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PCR assay for clonality:VDJ gene rearrangement

PCR assay of VDJ gene rearrangement 

Fluorescent in situ hybridization for chromosomal translocation 

Figure 2‐18

CD55 posC3 neg

CD55 negC3 pos

Most lymphomas resemble some stage of B or T cell differentiation

Figure 11‐13

Page 9: Hematopoietic lecture ppt - Indiana University Bloomingtonmedsci.indiana.edu/c602web/602/c602web/docs/heme/heme_slides.pdf · Hemoglobin electrophoresis Adult Fetal Hb S Hb C 1 =

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B cell germinal center somatic hypermutationALL:  Acute lymphoblastic leukemia/lymphoma

Chronic lymphocytic leukemia/small lymphocytic lymphoma

Smudge cells Diffuse nodal effacement Nodular marrow involvement

Follicular lymphomat(14;18) BCL2/IgH

BCL2 follicular lymphoma

BCL2 normal memory cells

Mantle cell lymphomat(11;14) cyclin D1 overexpression

Cyclin D1 stain

Lymphomatoid polyposis

Figure 11‐17

Diffuse large B cell lymphoma

BCL6CD19, CD20, CD10

Page 10: Hematopoietic lecture ppt - Indiana University Bloomingtonmedsci.indiana.edu/c602web/602/c602web/docs/heme/heme_slides.pdf · Hemoglobin electrophoresis Adult Fetal Hb S Hb C 1 =

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Burkitt lymphoma

t(8;14)t(2;8)t(8;22)

Starry sky pattern

Multiple Myeloma

Rouleaux formation Renal tubular protein casts

Lytic lesions Atypical plasma cells

Prof Jan Waldenström at New York Hospital, Cornell University, New York, NY, 1963.

Left: Before plasmapheresis optic disc edema (arrowheads), central retinal hemorrhages (bold arrows), and venous “sausaging” (thin arrows) were observed. Right: After plasmapheresis disc edema and retinal hemorrhages improved. Venous sausaging disappeared.

Lymphoplasmacytic Lymphoma

Waldenström MacroglobulinemiaHyperviscosity Syndrome

Hodgkin lymphoma,Mixed cellularity type

Reed Sternberg cell

Figure 11‐23

Figure 11‐20

Hodgkin lymphoma,nodular sclerosis subtype

Nodular sclerosing pattern Lacunar cell

Figure 11‐22 Figure 11‐21

Extranodal marginal zone lymphoma

Normal splenic marginal zone Gastric MALToma

Page 11: Hematopoietic lecture ppt - Indiana University Bloomingtonmedsci.indiana.edu/c602web/602/c602web/docs/heme/heme_slides.pdf · Hemoglobin electrophoresis Adult Fetal Hb S Hb C 1 =

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Hairy cell leukemia

TRAP positive(outdated test)

Splenomegaly

Mycosis FungoidesCutaneous T‐Cell Lymphoma

Pautrier microabscess(Lymphocyte epidermotropism)

Sezary syndrome(exfoliative erythroderma)

Circulating Sezary cells

Myelodysplasia

Abnormal erythroblasts Ring sideroblasts (iron stain)

Hypolobated, hypogranulated neutrophils

Abnormal megakaryocytes

Figure 11‐25

Acute myelogenous leukemias

Auer rods

ALL AML

Acute Promyelocytic LeukemiaFAB M3 Acute Myelomonocytic Leukemia

FAB M4

Gingival infiltration

Page 12: Hematopoietic lecture ppt - Indiana University Bloomingtonmedsci.indiana.edu/c602web/602/c602web/docs/heme/heme_slides.pdf · Hemoglobin electrophoresis Adult Fetal Hb S Hb C 1 =

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Figure 11‐26

Chronic myelogenous leukemia

Splenomegaly Erythromelalgia

Splenomegaly

Myelofibrosis

Dacryocytes (teardrops   ), nucleated red cells (            )  Marrow fibrosis

Essential thrombocythemia

Peripheral blood with thrombosis, giant platelets Marrow with increased megakaryocytes

Langerhans cell is a type of dermal dendritic cell

Birbeck granuleCD1a

Myeloid and lymphoid neoplasms

Myeloid stem cell Lymphoid stem cell 

Pluripotent stem cell

Polys, basos, eos, monos, plts, rbcs B cells     T cells

Acute             ____________

Chronic ________________ _____       ______

________________

____         _____

Page 13: Hematopoietic lecture ppt - Indiana University Bloomingtonmedsci.indiana.edu/c602web/602/c602web/docs/heme/heme_slides.pdf · Hemoglobin electrophoresis Adult Fetal Hb S Hb C 1 =

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Myeloid and lymphoid neoplasms

Myeloid stem cell Lymphoid stem cell 

Pluripotent stem cell

Polys, basos, eos, monos, plts, rbcs B cells     T cells

Acute             ____________

Chronic ________________ _____       ______

________________

____         _____

HemostasisBetween Scylla and Charybdis

Figure 3‐7

Primary hemostasis

Secondary hemostasis

Figure 3‐8

Conversion of factors via the extrinsic pathway

Figure 3‐9

Page 14: Hematopoietic lecture ppt - Indiana University Bloomingtonmedsci.indiana.edu/c602web/602/c602web/docs/heme/heme_slides.pdf · Hemoglobin electrophoresis Adult Fetal Hb S Hb C 1 =

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Figure 3‐5

Platelet plug Coagulation clot

Figure 3‐6

Antithrombotic mechanisms

Figure 3‐11

Fibrinolytic system

Platelet function analyzer Platelet aggregation studies Thrombotic Thrombocytopenia Purpura

SchistocytesHyaline thrombi

Hemolytic uremic syndrome

E. Coli O157:H7

Page 15: Hematopoietic lecture ppt - Indiana University Bloomingtonmedsci.indiana.edu/c602web/602/c602web/docs/heme/heme_slides.pdf · Hemoglobin electrophoresis Adult Fetal Hb S Hb C 1 =

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Von Willebrand multimer analysis

vWF function

Figure 11‐29

Disseminated intravascular coagulopathy

Figure 11‐28

St. George and the dragon