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

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

2 reticulocytes elliptocytes schistocytes spheroctyes target cells acanthocytes Basophilic stippling Howell Jolly bodies Pappenheimer bodies Rouleaux Ribosomal RNA Lead Thalassemia Myelodysplasia DNA remnant, splenectomy Inorganic iron granules, iron stain Paraproteinemia Anemias classified by MCV 2

3 Hereditary spherocytosis Osmotic fragility test Normal Figure 11 1 Spherocytes Figure 11 2 Sickle cell disease Hemoglobin electrophoresis Hemoglobin electrophoresis Hemoglobin High Performance Liquid Chromatography Adult Fetal Hb S Hb C 1 = Control 2 = Hb A 3 = HBA and Hb F 4 = Hb S disease 5 = Control 6 = Hb S and Hb A trait 7 = HB S and Hb C 8 = Hb S and Hb A trait 3

4 Hemoglobin HPLC β globin mutations in β thalassemias Hemoglobin electrophoreses Glucose 6 phosphate dehydrogenase deficiency Paroxysmal nocturnal hemoglobinuria Figure 11 7 Anopheles mosquito 4

5 Iron regulation Bone marrow iron stains Hepatic hemochromatosis Figure 11 9 Microcytic hypochromic anemia Figure Figure Megaloblastic anemia Aplastic anemia Leukoerythroblastosis Megaloblasts Giant metamyelocytes Hyperlobated neutrophils Myelophthisic marrow, metastatic carcinoma Epstein Barr Virus Normal Lymph Node Burkitt lymphoma Nasopharyngeal carcinoma Hodgkin lymphoma Atypical lymphocyte 5

6 Acute nonspecific lymphadenitis Follicular hyperplasia Paracortical hyperplasia Sinus histiocytosis Bartonella henselae Stellate necrotizing granulomata Myeloid and lymphoid neoplasms Pluripotent stem cell Myeloid stem cell Lymphoid stem cell Polys, basos, eos, monos, plts, rbcs B cells T cells Myelodysplasia Acute Acute myelogenous leukemias B ALL T ALL Chronic Myeloproliferative Neoplasms Hodgkin Non Hodgkin 6

7 CD5, CD19 +, CD20+, CD23 Kappa/lambda light chain 2:1 Cyclin D1 negative Negative for t(11;14) CD5+, CD19+, CD20+, CD23 Kappa light chain restricted Cyclin D1 positive t(11;14) Reactive lymph node Mantle cell lymphoma 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 7

8 PCR assay of VDJ gene rearrangement PCR assay for clonality: VDJ gene rearrangement Fluorescent in situ hybridization for chromosomal translocation Figure 2 18 Most lymphomas resemble some stage of B or T cell differentiation CD55 neg C3 pos CD55 pos C3 neg Figure

9 B cell germinal center somatic hypermutation ALL: Acute lymphoblastic leukemia/lymphoma Chronic lymphocytic leukemia/ small lymphocytic lymphoma Follicular lymphoma t(14;18) BCL2/IgH Smudge cells Diffuse nodal effacement Nodular marrow involvement BCL2 follicular lymphoma BCL2 normal memory cells Mantle cell lymphoma t(11;14) cyclin D1 overexpression Cyclin D1 stain Diffuse large B cell lymphoma BCL6 CD19, CD20, CD10 Lymphomatoid polyposis Figure

10 Burkitt lymphoma Lytic lesions Multiple Myeloma Atypical plasma cells t(8;14) t(2;8) t(8;22) Starry sky pattern Rouleaux formation Renal tubular protein casts Lymphoplasmacytic Lymphoma Hodgkin lymphoma, Mixed cellularity type Prof Jan Waldenström at New York Hospital, Cornell University, New York, NY, Waldenström Macroglobulinemia Hyperviscosity Syndrome 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. Figure Reed Sternberg cell Figure Nodular sclerosing pattern Hodgkin lymphoma, nodular sclerosis subtype Lacunar cell Extranodal marginal zone lymphoma Normal splenic marginal zone Gastric MALToma Figure Figure

11 Hairy cell leukemia Mycosis Fungoides Cutaneous T Cell Lymphoma Sezary syndrome (exfoliative erythroderma) TRAP positive (outdated test) Splenomegaly Pautrier microabscess (Lymphocyte epidermotropism) Circulating Sezary cells Myelodysplasia Acute myelogenous leukemias Abnormal erythroblasts Ring sideroblasts (iron stain) ALL AML Auer rods Figure Hypolobated, hypogranulated neutrophils Abnormal megakaryocytes Acute Promyelocytic Leukemia FAB M3 Acute Myelomonocytic Leukemia FAB M4 Gingival infiltration 11

12 Chronic myelogenous leukemia Figure Splenomegaly Splenomegaly Erythromelalgia Myelofibrosis Essential thrombocythemia Dacryocytes (teardrops ), nucleated red cells ( ) Marrow fibrosis Peripheral blood with thrombosis, giant platelets Marrow with increased megakaryocytes Langerhans cell is a type of dermal dendritic cell Myeloid and lymphoid neoplasms CD1a Birbeck granule Pluripotent stem cell Myeloid stem cell Lymphoid stem cell Polys, basos, eos, monos, plts, rbcs B cells T cells Acute Chronic 12

13 Myeloid and lymphoid neoplasms Pluripotent stem cell Hemostasis Between Scylla and Charybdis Myeloid stem cell Lymphoid stem cell Polys, basos, eos, monos, plts, rbcs B cells T cells Acute Chronic Primary hemostasis Figure 3 7 Secondary hemostasis Conversion of factors via the extrinsic pathway Figure 3 9 Figure

14 Platelet plug Coagulation clot Figure 3 5 Antithrombotic mechanisms Fibrinolytic system Figure 3 11 Figure 3 6 Platelet function analyzer Platelet aggregation studies Thrombotic Thrombocytopenia Purpura Hemolytic uremic syndrome E. Coli O157:H7 Schistocytes Hyaline thrombi 14

15 vwf function Disseminated intravascular coagulopathy Figure Von Willebrand multimer analysis Figure St. George and the dragon 15