2/13/2015. Hematopoiesis: Red and white marrow. Fluorescent in situ hybridization for chromosomal translocation. Hematopoiesis

Transcription

1 Fluorescent in situ hybridization for chromosomal translocation Hematopoiesis Hematopoiesis: Red and white marrow 1

2 Bone marrow aspirate and core biopsy Gartner, Color Textbook of Histology, 3 rd Edition reticulocytes elliptocytes schistocytes spheroctyes target cells acanthocytes 2

3 Basophilic stippling Howell Jolly bodies Pappenheimer bodies Rouleaux Anemias classified by MCV Ribosomal RNA Lead Thalassemia Myelodysplasia DNA remnant, splenectomy Inorganic iron granules, iron stain Paraproteinemia Hereditary spherocytosis Figure 11 1 Figure

4 Osmotic fragility test Sickle cell disease Normal Spherocytes Hemoglobin electrophoresis Hemoglobin electrophoresis 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 Hemoglobin High Performance Liquid Chromatography 4

5 Hemoglobin HPLC β globin mutations in β thalassemias Hemoglobin electrophoreses Glucose 6 phosphate dehydrogenase deficiency Paroxysmal nocturnal hemoglobinuria Anopheles mosquito 5

6 Hephaestus captures Aphrodite and Ares Iron regulation Figure 11 9 Bone marrow iron stains Hepatic hemochromatosis Microcytic hypochromic anemia Figure Figure

7 Sideroblastic anemia Megaloblastic anemia Marrow megaloblasts Giant metamyelocytes EtOH Pyroxidine (B6)deficiency with Isoniazid use Myelodysplasia Hyperlobated neutrophils Mitochondrial iron in erythroid precursors Aplastic anemia Peripheral blood Leukoerythroblastosis Epstein Barr Virus Myelophthisic marrow, metastatic carcinoma Monospot Heterophile antibody test Epstein Barr Virus Normal Lymph Node Burkitt lymphoma Hodgkin lymphoma Nasopharyngeal carcinoma 7

8 Acute nonspecific lymphadenitis Follicular hyperplasia Paracortical hyperplasia Sinus histiocytosis Bartonella henselae Stellate necrotizing granulomata 8

9 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) 2 light chains + 2 heavy chains Immunoglobulin (cell surface antigen receptor or secreted Ig) Reactive lymph node Mantle cell lymphoma Heavy chain protein production Light chain protein production 9

10 PCR assay for clonality: VDJ gene rearrangement Monoclonal IgG kappa PCR assay of VDJ gene rearrangement Fluorescent in situ hybridization for chromosomal translocation Most lymphomas resemble some stage of B or T cell differentiation B cell germinal center somatic hypermutation Figure

11 ALL: Acute lymphoblastic leukemia/lymphoma Chronic lymphocytic leukemia/ small lymphocytic lymphoma Smudge cells Diffuse nodal effacement Nodular marrow involvement Follicular lymphoma t(14;18) BCL2/IgH Mantle cell lymphoma t(11;14) cyclin D1 overexpression Cyclin D1 stain Lymphomatoid polyposis BCL2 follicular lymphoma BCL2 normal memory cells Diffuse large B cell lymphoma Burkitt lymphoma BCL6 CD19, CD20, CD10 t(8;14) t(2;8) t(8;22) Starry sky pattern Figure

12 Lytic lesions Multiple Myeloma Atypical plasma cells, Mott cell Lymphoplasmacytic Lymphoma Prof Jan Waldenström at New York Hospital, Cornell University, New York, NY, Waldenström Macroglobulinemia Hyperviscosity Syndrome Rouleaux formation Henry Bence Jones Renal tubular protein casts 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. Hodgkin lymphoma Nodular sclerosing pattern Hodgkin lymphoma, nodular sclerosis subtype Lacunar cell Thomas Hodgkin Reed Sternberg cell Figure Figure Figure Figure Extranodal marginal zone lymphoma Normal splenic marginal zone Gastric MALToma Hairy cell leukemia TRAP positive (outdated test) Splenomegaly 12

13 Mycosis Fungoides Cutaneous T Cell Lymphoma Sezary syndrome (exfoliative erythroderma) Abnormal erythroblasts Myelodysplasia Ring sideroblasts (iron stain) Pautrier microabscess (Lymphocyte epidermotropism) Circulating Sezary cells Hypolobated, hypogranulated neutrophils Abnormal megakaryocytes Acute myelogenous leukemias Acute Promyelocytic Leukemia FAB M3 ALL AML Auer rods Figure Acute Myelomonocytic Leukemia FAB M4 Chronic myelogenous leukemia Gingival infiltration Figure Splenomegaly 13

14 Myelofibrosis Dacryocytes (teardrops ), nucleated red cells ( ) Marrow fibrosis Splenomegaly Erythromelalgia Essential thrombocythemia Langerhans cell is a type of dermal dendritic cell Peripheral blood with thrombosis, giant platelets Marrow with increased megakaryocytes CD1a Birbeck granule Hemostasis Between Scylla and Charybdis Primary hemostasis Figure

15 Secondary hemostasis Figure 3 8 Platelet plug Coagulation clot Figure 3 5 Antithrombotic mechanisms Fibrinolytic system Figure 3 11 Figure

16 Platelet function analyzer Platelet aggregation studies Reptilase test for heparin Russell venom viper test for lupus anticoagulant research.org/3/pfa.htm Thrombotic Thrombocytopenia Purpura Hemolytic uremic syndrome E. Coli O157:H7 Figure vwf function Schistocytes Hyaline thrombi Von Willebrand multimer analysis 16

17 Disseminated intravascular coagulopathy Figure St. George and the dragon 17