Disclosures/COI Cases in Hematopathology Vamsi Kota Assistant Professor Department of Hematology & Medical Oncology Leukemia/BMT I have no disclosures or conflicts of interest regarding this presentation. I served on scientific advisory board for: Pfizer, Ariad, Incyte. Outline Disclaimer: I am NOT a hematopathologist Interpretation of a Peripheral Smear Normal smear Abnormal/Immature Erythrocytes/WBC s/plts Bone Marrow/Nodal Tissue Brief review of normal morphology Key abnormalities to identify Chromosomal Translocations to Know Peripheral Smear: Clinician s Approach Most interpretations occur in an emergent situation where a life threatening disease must be ruled out Use clinical information / additional information in question stem If one cell line is abnormal in CBC, that is likely the one to focus on in review of smear Normal Peripheral Smear NORMAL NEUTROPHILS Platelets Heme Path Findings Not to Miss Schistocytes Sickle cells Blasts Promyelocytes Erythrocytes 1
Erythrocyte Maturation Neutrophil Maturation Erythrocyte Abnormalities Erythrocyte Abnormalities Schistocytes: Think TTP or DIC (or Drug effect?) Schistocytes Note: Low platelets RBC fragments Thrombocytopenia Anemia High LDH Sickle Cell Disease Sickle Cells Polychromatophilic RBC Erythrocyte Abnormalities Case Presentation/Question 1 A 63 year old African American male presents to the emergency department with several weeks of low back pain. He was recently prescribed cyclobenzaprine which has only mildly improved symptoms. CBC and Metabolic Panel are obtained which demonstrate the following: WBC 5.3 with normal differential Hgb 10.1 Platelets 176,000 Cr 2.03 Ca 10.9 Electrolytes wnl 2
Question 1 Question 1 - Answer What is the most likely explanation for the patient s low back pain? a) Prostate Cancer b) Multiple Myeloma c) Hodgkin lymphoma d) Burkitt lymphoma e) Lung Cancer Any of the answers are reasonable for a middleaged male with back pain. This smear demonstrates: Rouleaux Formation Note the obvious finding here. Answer: B Multiple Myeloma Question 2 Question 2 A 24 year old female presents with fatigue and early satiety. She has a family history of anemia but has not seen a physician for some time. On exam, she has some conjunctival pallor and palpable splenomegaly but is not ill-appearing. Hgb 9.8 T Bili 2.3 Coomb s Test is Negative for a Warm Auto-antibody Question 2 What test can you order that will lead you to the most likely diagnosis? a) Vitamin B12 and Folate b) Osmotic Fragility Test c) Flow Cytometry d) Iron Panel and Ferritin e) Need more information to know which test to order Question 2- Answer Note spherocytes on peripheral smear: Hereditary Spherocytosis Diagnosed by Osmotic Fragility Test Note: 1 & 4 are reasonable, but spherocytes on smear point to spherocytosis 3
WBC Abnormalities - Leukocytosis Question 3 Note increased mature lymphocytes (same size as erythrocytes) Smudge Cells Elev WBC Predominantly lymphocytes CLL You are called to consult for a patient with leukocytosis. This 58 year old female is otherwise healthy and reports recent fatigue and early satiety. She is otherwise well-appearing. On exam, she has palpable splenomegaly. WBC 179,000 Hgb 10.1 Platelets 450 Chemistry wnl Question 3 Which of the following is correct? a) This is a leukemoid reaction and she should be evaluated for an underlying infection. b) This is acute leukemia and she requires urgent leukapheresis. c) This is acute leukemia and she should be started on hydroxyurea right away d) This is CML and she requires urgent leukapheresis e) This is CML and she should be started on a tyrosine kinase inhibitor (such as imatinib mesylate) in consultation with hematology Question 3 - Answer First, what is it? Elevated WBC, reasonable Hgb and Plts Evidence of normal maturation Splenomegaly Pt not sick Think Chronic Myelogenous Leukemia (CML) Next, how do you treat it? Not an emergency is most cases Tyrosine kinase targeting Bcr-Abl is appropriate therapy (i.e., imatinib, dasatanib et al) Answer: E Question 4 A 50 year old female presents with a 10 day history of progressive fatigue, fevers, and bruising. She now has a progressive headache and presents for evaluation. WBC 145,000 Hgb 7.5 Platelets 14 Chem wnl Question 4 What is the next step in this patient s management? a) Arrange for emergent leukapheresis b) Start high dose steroids c) Start hydroxyurea d) Administer all-trans retinoic acid (ATRA) e) Transfuse blood and platelets; refer for urgent outpatient hematology evaluation 4
Question 4 - Answer Question 4 - Answer What is the diagnosis? Acute Leukemia If auer rods, then AML BLAST A patient with acute leukemia who has leukostasis due to elevated WBC count should be pheresed emergently: Headache/neurologic findings Chest pain/shortness of breath/hypoxia Answer: A (Hydrea is reasonable if elevated WBC and no emergent findings) Blood and platelets should NOT be transfused unless other therapy is initiated as they can worsen leukostasis Question 5 Question 5 A 50 year old female presents with a 10 day history of progressive fatigue, fevers, and bruising. She now has a progressive headache and presents for evaluation. WBC 0.7 Hgb 7.5 Platelets 14 Chem wnl Fibrinogen is decreased What is the next step in this patient s management? a) Arrange for emergent leukapheresis b) Start high dose steroids c) Start hydroxyurea d) Administer all-trans retinoic acid (ATRA) e) Transfuse blood and platelets; refer for urgent outpatient hematology evaluation Question 5 - Answer This patient has acute pro-myelocytic leukemia Numerous promyelocytes with auer rods Pancytopenia Presenting with DIC Any question of APL, give ATRA. Answer: D Promyelocyte With numerous Auer rods WBC abnormalities Hypersegmented Neutrophils Think megaloblastic anemia (B12, Folate) Look at MCV (should be elevated, especially on boards) RBC s may not be obviously altered 5
Question 6 A previously healthy 56 year old male develops thrombocytopenia on day 6 s/p hip replacement. He has been doing well until this point and is nearing time for discharge. Platelets, WBC, and hemoglobin were normal on pre-op CBC. He is asymptomatic. WBC 12.3 (normal diff) Hgb 13.6 Plts 43,000 (194,000 on pre-op CBC) Chemistries within normal limits Question 6 Question 6 What is the most appropriate next course of action? a) Reassure the patient that this is likely a benign process and ask the nurse to re-draw a platelet count in a citrate tube b) Consult hematology and pathology urgently for consideration for plasmapheresis for presumed TTP c) Transfuse platelets and recheck the following morning d) Request bone marrow biopsy for possible highgrade MDS Question 6 - Answer This is an example of platelet clumping, an artifact of the test and not a sign of platelet dysfunction. Answer: A HIT is a consideration but would not pursue HIT until re-evaluating platelets Platelet transfusion would not be needed for platelets of 42K and would be inappropriate if you are considering HIT Acute change in platelets not consistent with MDS Bone Marrow Evaluation Question 7 What is typically done in a bone marrow biopsy? Aspirate Differential Morphology Flow Cytometry Cytogenetics Core biopsy Cellularity Aggregates/Geography A 24 year old female is evaluated for persistent cough and shortness of breath along with a 15 lb weight loss over the past 2 months. A chest x- ray identifies a mediastinal mass, and a core biopsy of the mass shows the following: CBC wnl Chemistry wnl ESR 54 6
Question 7 What is the most likely diagnosis? 1) Aggressive NHL such as diffuse large B-cell lymphoma 2) Hodgkin lymphoma 3) Tuberculosis 4) Benign reactive lymph node 5) Diagnosis cannot be rendered based on available information Question 7 - Answer The primary cell is classic for Hodgkin Reed- Sternberg cell. Hodgkin lymphoma commonly (but not always) presents in a young person with a mediastinal mass. TB, DLBCL and reactive node are all considerations prior to biopsy. Question 8 A 35 year old male presents with a rapidly enlarging R cervical lymph node. He has felt poorly for the past 2 weeks with drenching night sweats, fevers to 103, and a 20lb weight loss. He has an easily palpable 5cm R cervical node on exam. WBC 19.4 Hgb 9.5 Plts 85 LDH 1532 Uric Acid 12.0 Question 8 What is the most likely diagnosis? 1) Reactive lymph node 2) Burkitt lymphoma 3) Tuberculosis 4) Hodgkin lymphoma 5) Diagnosis cannot be rendered based on available information Question 8 - Answer Hemepath Pearls re: Lymphoma LDH > 1000 is a tip off for Burkitt lymphoma Rapid onset, marked constitutional symptoms Answer: Burkitt lymphoma (B) Note: Starry Sky Appearance Excisional biopsy (or at least a core needle) are almost always required and should be recommended Identification of high-grade processes (i.e, Burkitt) is critical as patients require urgent referral and therapy In addition to morphology, we rely on immunohistochemistry, flow cytometry, and cytogenetics to diagnose lymphoma 7
Heme Path Cytogenetics *Easy points to earn but require memorization* Translocation Disease Notes t(8;14) Burkitt lymphoma CMYC & immunoglobulin heavy chain gene t(15;17) t(9;22) Acute promyelocytic leukemia Chronic myelogenous leukemia PML and RARα Philadelphia Chromosome: BCR & ABL t(11;14) Mantle cell lymphoma Cyclin D1 & Immunoglobulin heavy chain gene t(14;18) Follicular lymphoma BCL2 & Immunoglobulin heavy chain gene ***ALL, AML, CLL, MDS, and Myeloma have recurrent cytogenetic and molecular alterations that are used in risk stratification*** Conclusions Hemepath questions are going to vary, but you can almost always rely on question stem/labs to narrow diagnosis Remember high risk diseases that are diagnosed by smear: TTP, AML, APL Findings are typically classic examples Lymphoma should be evaluated with an excisional biopsy Questions? Appendix/Extras Vitamin B12 deficiency Hypersegmented neutrophil. May have neuro symptoms. Consider in pts post gastric bypass or who have other problems with absorption Appendix Lead Poisoning Note basophilic stippling This will typically be diagnosed based on history with smear to confirm Appendix Malaria Diagnosed based on history Note ring structure 8
Appendix Sepsis: Toxic granulations Higher number of bands 9