Self-Assessment in Hematology:
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1 Self-Assessment in Hematology: Cellular Morphology Karl S. Theil, M.D. Staff, Section of Hematopathology Department of Clinical Pathology The Cleveland Clinic Foundation June 3, 2012 Objectives Recognize classic morphologic features of selected entities in peripheral blood smears. Correlate morphologic findings with clinical and lb laboratory data. dt Format Ten single answer, multiple choice questions Examine image, then answer question Discuss correct and incorrect choices
2 Case #1 A 23 year old male graduate student presents to the Emergency Room with fever and chills. a. Trypanosomiasis b. Babesiosis c. Borreliosis d. Malaria e. Artifact
3 Case #1 A 23 year old male graduate student presents to the Emergency Room with fever and chills. a. Trypanosomiasis b. Babesiosis c. Borreliosis d. Malaria e. Artifact Case #1 A 23 year old male graduate student presents to the Emergency Room with fever and chills. a. Trypanosomiasis b. Babesiosis c. Borreliosis d. Malaria e. Artifact
4 Microorganisms in Blood Smears Plasmodium sp. Babesia sp. Bacteria (rod, cocci) Borrelia recurrentis Fungi (Histoplasma sp.) Microfilaria Trypanosomes
5 Malaria versus Babesiosis Feature Malaria Babesiosis Insect vector mosquito tick Trophozoite rings tetrads distinctive Pigment present absent Gametocyte round or absent banana shaped Extra-erythrocytic absent present forms
6
7 Case #2 A 32 year old asymptomatic woman had a platelet count of 50,000/uL. a. systemic lupus erythematosus b. spurious thrombocytopenia c. heparin-induced thrombocytopenia d. idiopathic thrombocytopenic purpura e. drug effect
8 Case #2 A 32 year old asymptomatic woman had a platelet count of 50,000/uL. a. systemic lupus erythematosus b. spurious thrombocytopenia c. heparin-induced thrombocytopenia d. idiopathic thrombocytopenic purpura e. drug effect Case #2 A 32 year old asymptomatic woman had a platelet count of 50,000/uL. a. systemic lupus erythematosus b. spurious thrombocytopenia c. heparin-induced thrombocytopenia d. idiopathic thrombocytopenic purpura e. drug effect
9 Platelet Satellitosis Adherence of 4 or more platelets to surface of a neutrophil or monocyte May cause spurious thrombocytopenia In vitro phenomenon requiring EDTAanticoagulated blood Platelet phagocytosis may be present No clear disease association
10 Spurious Thrombocytopenia EDTA-related platelet antibody Platelet satellitosis Platelet clumping Partially clotted specimen Platelet cold agglutinin
11 Case #3 A 42 year old male presents with a WBC of 35.5 x 10 9 /L. a. infectious mononucleosis b. leukemoid reaction c. chronic lymphocytic leukemia d. chronic myelogenous leukemia e. acute myelogenous leukemia
12 Case #3 A 42 year old male presents with a WBC of 35.5 x 10 9 /L. a. infectious mononucleosis b. leukemoid reaction c. chronic lymphocytic leukemia d. chronic myelogenous leukemia e. acute myelogenous leukemia
13 Case #3 A 42 year old male presents with a WBC of 35.5 x 10 9 /L. a. infectious mononucleosis b. leukemoid reaction c. chronic lymphocytic leukemia d. chronic myelogenous leukemia e. acute myelogenous leukemia
14 Blast Morphology Size varies m High nuclear:cytoplasmic ratio Fine granular chromatin One or more prominent nucleoli li Basophilic agranular cytoplasm ± Auer rods Auer Rods Fusion of primary granules into rod-like bundle Myeloperoxidase positive May occur in bundles (APL) Found in acute myeloid leukemia and high grade myelodysplastic syndrome (RAEB-2)
15 Case #4 A 32 year old female presented with fever and generalized pain, Hgb 9.0 g/dl, and MCV 95 fl. Electrophoresis showed no hemoglobin A. a. Hemoglobin S-HPFH b. Hemoglobin SC disease c. Hemoglobin SS disease d. Hemoglobin S trait e. Hemoglobin CC disease
16 Case #4 A 32 year old female presented with fever and generalized pain, Hgb 9.0 g/dl, and MCV 95 fl. Electrophoresis showed no hemoglobin A. a. Hemoglobin S-HPFH b. Hemoglobin SC disease c. Hemoglobin SS disease d. Hemoglobin S trait e. Hemoglobin CC disease Case #4 A 32 year old female presented with fever and generalized pain, Hgb 9.0 g/dl, and MCV 95 fl. Electrophoresis showed no hemoglobin A. a. Hemoglobin S-HPFH b. Hemoglobin SC disease c. Hemoglobin SS disease d. Hemoglobin S trait e. Hemoglobin CC disease
17 Hemoglobin SC Disease Found in 0.04% 04% of African Americans Hemoglobin S: 6 Glu Val Hemoglobin C: 6 Glu Lys Mild hemolytic anemia Splenomegaly May develop vaso-occlusive occlusive complications associated with SS homozygotes Diagnosis by hemoglobin electrophoresis
18
19 Case #5 A 58 year old male with anemia, neutropenia, thrombocytopenia and splenomegaly. a. Waldenström s macroglobulinemia b. Chronic lymphocytic leukemia c. Hairy cell leukemia d. Prolymphocytic leukemia e. Chronic myelomonocytic leukemia
20 Case #5 A 58 year old male with anemia, neutropenia, thrombocytopenia and splenomegaly. a. Waldenström s macroglobulinemia b. Chronic lymphocytic leukemia c. Hairy cell leukemia d. Prolymphocytic leukemia e. Chronic myelomonocytic leukemia Case #5 A 58 year old male with anemia, neutropenia, thrombocytopenia and splenomegaly. a. Waldenström s macroglobulinemia b. Chronic lymphocytic leukemia c. Hairy cell leukemia d. Prolymphocytic leukemia e. Chronic myelomonocytic leukemia
21 Hairy Cell Characteristics ti Ragged cytoplasmic border Small single nucleolus Immature nuclear chromatin Tartrate resistant acid phosphatase h (TRAP) CD19, CD20, CD25, CD11c, CD103, CD123 Bone marrow aspirate dry tap
22 Lymphocyte vs. Hairy cell Sharp edge Nucleolus Lymphocyte Ragged edge Hairy cell Prolymphocyte Nucleolus Plasmacytoid lymphocyte Case #6 A 35 year old male presents to the ER with fever, confusion, Hgb 7.5 g/dl, platelets 20 x 10 9 /L, and normal PT and PTT. a. idiopathic thrombocytopenic purpura b. thrombotic thrombocytopenic purpura c. autoimmune hemolytic anemia d. disseminated intravascular coagulation e. acute promyelocytic leukemia
23 Case #6 A 35 year old male presents to the ER with fever, confusion, Hgb 7.5 g/dl, platelets 20 x 10 9 /L, and normal PT and PTT. a. idiopathic thrombocytopenic purpura b. thrombotic thrombocytopenic purpura c. autoimmune hemolytic anemia d. disseminated intravascular coagulation e. acute promyelocytic leukemia
24 Case #6 A 35 year old male presents to the ER with fever, confusion, Hgb 7.5 g/dl, platelets 20 x 10 9 /L, and normal PT and PTT. a. idiopathic thrombocytopenic purpura b. thrombotic thrombocytopenic purpura c. autoimmune hemolytic anemia d. disseminated intravascular coagulation e. acute promyelocytic leukemia
25 Microangiopathic Hemolytic Anemia Disseminated intravascular coagulation Thrombotic thrombocytopenic purpura Hemolytic uremic syndrome Heart valve disease Vasculitis Metastatic carcinoma Drugs (mitomycin C, cyclosporine) Severe burns Malignant hypertension
26 Case #7 A 55 year old male with WBC 45 x 10 9 /L, Hgb 12 g/dl, and platelets 129 x 10 9 /L. a. Viral infection b. Bordatella pertussis infection c. Sézary syndrome d. Acute lymphoblastic leukemia e. Chronic lymphocytic leukemia
27 Case #7 A 55 year old male with WBC 45 x 10 9 /L, Hgb 12 g/dl, and platelets 129 x 10 9 /L. a. Viral infection b. Bordatella pertussis infection c. Sézary syndrome d. Acute lymphoblastic leukemia e. Chronic lymphocytic leukemia
28 Case #7 A 55 year old male with WBC 45 x 10 9 /L, Hgb 12 g/dl, and platelets 129 x 10 9 /L. a. Viral infection b. Bordatella pertussis infection c. Sézary syndrome d. Acute lymphoblastic leukemia e. Chronic lymphocytic leukemia
29 Chronic Lymphocytic Leukemia Mature lymphocytosis Smudge cells CD19+, CD5+, CD23+, CD20+, CD79b- Dim surface immunoglobulin ( or ) ) Adverse prognosis: CD38+, ZAP-70+ Genetic markers: +12, del(13q), del(11q), del(17p) Sézary cells Convoluted cerebriform nucleus
30 Case #8 A 58 year old female with anemia and generalized lymphadenopathy. a. clotted specimen b. cold agglutinin c. cryoglobulin d. rouleaux e. artifact
31 Case #8 A 58 year old female with anemia and generalized lymphadenopathy. a. clotted specimen b. cold agglutinin c. cryoglobulin d. rouleaux e. artifact Case #8 A 58 year old female with anemia and generalized lymphadenopathy. a. clotted specimen b. cold agglutinin c. cryoglobulin d. rouleaux e. artifact
32 RBC Agglutination Clump or cluster of RBC overlapping in an irregular arrangement Most are caused by IgM antibodies Disease associations: Viral infection (infectious mononucleosis) Mycoplasma infection Lymphoproliferative disorderd Plasma cell dyscrasia Idiopathic
33
34 Case #9 A 19 year old female with fatigue, sore throat, and cervical lymphadenopathy. a. infectious mononucleosis b. idiopathic thrombocytopenic purpura c. non-hodgkin s lymphoma d. acute myeloid leukemia e. acute lymphoblastic leukemia
35 Case #9 A 19 year old female with fatigue, sore throat, and cervical lymphadenopathy. a. infectious mononucleosis b. idiopathic thrombocytopenic purpura c. non-hodgkin s lymphoma d. acute myeloid leukemia e. acute lymphoblastic leukemia Case #9 A 19 year old female with fatigue, sore throat, and cervical lymphadenopathy. a. infectious mononucleosis b. idiopathic thrombocytopenic purpura c. non-hodgkin s lymphoma d. acute myeloid leukemia e. acute lymphoblastic leukemia
36 Reactive Lymphocytes WBC count is variable Spectrum of lymphocyte morphology present Greater range of morphologic appearance More abundant cytoplasm ± vacuoles Lower nuclear:cytoplasmic ratio Irregular nuclei ± nucleoli Important to interpret morphology in the context of clinical features
37 Lymphocyte Monocyte Reactive Lymphocytosis Infectious mononucleosis Cytomegalovirus infection Viral hepatitis Other viral infections Drug reactions (may have eosinophilia) Chronic inflammatory disordersd
38 Case #10 A 20 year old male undergraduate student presented with fever, petechial rash, and platelets 25 x 10 9 /L. a. Ehrlichiosis b. Disseminated Histoplasmosis c. Candidal sepsis d. Meningococcemia e. Chediak-Higashi syndrome
39 Case #10 A 20 year old male undergraduate student presented with fever, petechial rash, and platelets 25 x 10 9 /L. a. Ehrlichiosis b. Disseminated Histoplasmosis c. Candidal sepsis d. Meningococcemia e. Chediak-Higashi syndrome Case #10 A 20 year old male undergraduate student presented with fever, petechial rash, and platelets 25 x 10 9 /L. a. Ehrlichiosis b. Disseminated Histoplasmosis c. Candidal sepsis d. Meningococcemia e. Chediak-Higashi syndrome
40 Bacteria in Blood Smear Overwhelming infection Meningococcemia Pneumococcal sepsis Infected intravascular catheter Collection from infected site (heel stick) Rule out immunocompromised host Splenectomy Correlate with clinical ca findings
41 Organisms in WBC Bacteria Ehrlichiosis Histoplasmosis Candidiasis Chediak-Higashi Syndrome Rare autosomal recessive disorder Abnormal cytoplasmic granulation Recurrent pyogenic infections
42
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