Hematology - Malignancies Flashcards
Discuss the epidemiology, pathophysiology, risk factors for acute myeloid leukemia
- failure of myeloid cells to differentiate beyond blast stage Epidemiology - 65yr old most common Risk Factors - Male - Older age - Smoking - MDS - Down syndrome - Previous radiation Pathophysiology - uncontrolled blasts cells resulting in suppression of all other hematopoeitic lines resulting in appearence of blasts in blood stream and accumulation in other organ sites - decreased K and Ca - tumor lysis syndrome with treatment
Discuss the presentation, investigation and management of AML
Presentation
- Anemia, thrombocytopenia, neutropenia
- infections
- constitutional symptoms
- skeletal pain from accumulation of blasts in bone marrow
- Leukostasis where large number of blasts interfere with circulation and lead to hypoxia and hemorrhage leading to CNS bleeding and respiratory distress (APML)
Investigation
- anemia, thrombocytopenia
- circulating blasts with Auer rods
- blast count >20% in bone marrow
Management
- Induction chemotherapy to allow for remission
- Consolidation chemotherapy to prevent recurrence
- Fever then require culture of orifices, CXR, and start antibiotics
Discuss the pathophysiology, presentation and management of myelodysplastic syndromes
- malignant stem cell disorders with dysplastic and ineffective blood cell production resulting in peripheral cytopenias
Pathophysiology - inffective hematopoieisis despite adequate progenitor cells
Presentation - anemia, thrombocytopenia, neutropenia
Investigation - macrocytic anemia
- WBC have bi-lobed or unsegmented nuclei
- platelets are giant hypogranular platelets
Management - EPO
- hypomethlylating agents (Decitabine)
Discuss the pathophysiology and phases of chronic myeloid leukemia
- increased proliferation of granulocytic cell line
- median 65yr
- philadelphia chromosome where have translocation between chromosomes 9 and 22 (BCR-Abl fusion and active tyrosine kinase)
Phases - chronic phase have <10% blasts in peripheral with elevated eosinophils and basophils without significant symptoms
- accelerated phase have 10-19% blasts with increase basophils, thrombocytopenia and constitutional symptoms
- blast crisis: >20% resulting in acute leukemia
Discuss the presentation and management of CML
Presentation - asymptomatic - constitutional symptoms - splenic involvement - pruritis due to basophils Investigation - elevated WBC and basophils - normal or decreased RBC and platelets - bone marrow have myeloid hyperplasia with left shift Management - prophylactic with allopurinol - Chronic phase: imatinib inhibit proliferation and inhibit tyrosine kinase activity - accelerated phase stem cell transplantation
Discuss the pathophysiology, presentation and management of polycythemia vera
- Myeloproliferative disorder with elevated RBC mass
Major Criteria - hemoglobin 165 in men or 160 in women with Hct >49% in men and 48% in women
- bone marrow biopsy showing hypercellularity with trilieneage growth
- presence of Jak2 mutation
Minor - serum EPO level below reference range
Presentation - thrombotic complications due to increased viscosity
- erythromelalgia: burning pains in hands and feet with erythema of skin due to elevated platelets
- pruritis after warm bath or shower
Management - phlebotomy to keep Hct <45%
- hydroxyurea
- low-dose aspirin
Discuss the pathophysiology, presentation and management of idiopathic myelofibrosis
- bone marrow fibrosis Pathophysiology - myeloproliferative disorder with platelets secreting fibroblast growth factors Presentation - anemia - constitutional symptoms - hepatosplenomegaly Investigation - dry tap on bone marrow - teardrop RBC - Jak2 Management - stem cell transplant - ruxolitinib (Jak2 inhibitor)
Discuss the pathophysiology, presentation and management of essential thrombocythemia
Diagnosis
- sustained platelet count >450
- bone marrow show megakaryocytic lineage
- not PV
- JAK2
Presentation
- vasomotor symptoms (headache, erythromelalgia)
- asymptomatic
- thrombosis
Management
- ASA if previous thrombotic event or cardiovascular risk factor
Discuss the pathophysiology, presentation and management of acute lymphoblastic leukemia
- early lymphoid precursors proliferate and replace normal hematopoietic cells
- present in children <6yr
Presentation - constitutional sypmtoms
- hepatosplenomegaly
- gonads
Investigation - leukocytes >10 with neutropenia, anemia, thrombocytopenia
- increased uric acid, PO4, Ca, K, LDH
- philadelphia chromosome
- CXR for mediastinal mass
- lumbar puncture prior to chemo for CNS involvement
Management - induction chemotherapy to induce remission
- consolidation and or intensification
- maintenance over 2-3yr to prevent relapse
- prophylactic CNS radiation or methotrexate
- stem cell transplantation
Discuss the Ann Arbor staging for lymphomas
Stage I:
- involvement of single lymph node region or extralymphatic organ
Stage II
- involvement of two or more lymph node regions or an extralymphatic site and one lymph node region on same side of diaphragm
Stage III
- involvement of lymph node regions on both sides of diaphragm
Stage IV
- diffuse involvement of one or more extralymphatic organs including bone marrow
Discuss the pathophysiology, presentation and management of Hodgkin Lymphoma
- malignant proliferation of lymphoid cells with Reed-Sternberg cells (germinal B cells)
- bimodal with 20yr and >50yr
Presentation - Asymptomatic lymphadenopathy
- Splenomegaly
- mediastinal mass
- constitutional symptoms
- Alcohol induced pain in nodes
Investigations - CBC: anemia, eosinophilia, lymphopenia
- PET scan
- excisional lymph node biopsy
- bone marrow biopsy if constitutional symptoms, Stage III/IV
Management - Stage I/II: chemotherapy (ABVD) then radiotherapy of involved site
- Stage III/IV: chemotherapy with XRT (can lead to cardiac disease)
Discuss the different types of non-hodgkin lymphoma
- malignant proliferation of lymphoid cells of progenitor or mature B or T cells B-Cell - Diffuse large B cell (aggresive, Bcl-2) - Follicular lymphoma - Burkitts (very aggressive, c-Myc)) - Manlte cell T-Cell - Mycosis fungioides - anaplastic large cell
Discuss the pathophysiology, presentation and management of non-hodgkin lymphoma
Presentation - superficial lymphadenopathy - widespread disease - cytopneia - retroperitoneal involvement Investigation - lymphoma cells - excisional lymph node biopsy Management - localized: radiotherapy with adjuvant chemotherapy - indolent: watchful waiting - aggressive: combination (CHOP), radiation, CNS prophylaxis - Highly aggressive (Burkitts): short bursts of intensive chemotherapy
Discuss the pathophysiology, presentation and management of chronic lymphocytic leukemia
- indolent disease characterized by clonal malignancy of mature B cells
- accumulation of mature B cells in blood, bone marrow, lymph nodes and spleen
Presentation - asymptomatic
- constitutional symptoms
- lymphadenopathy
Investigations - smudge cells
- bone marrow have lymphocytes >30%
Managmeent - indolent and incurable
- monoclonal CD20 agent
Discuss hyperviscosity syndrome as complication of hyperviscosity syndrome
- increased blood viscosity resulting from increased serum Ig
- Waldenstrom’s macroglobinemia most common (IgM monoclona)
Presentation - CHF, headache, dilutional anemia
- CNS: stroke, vertigo
- Bleeding diathesis
Management - chemotherapy
- plasmapheresis
