Leukemia and WBC diseases Flashcards by Rachel Muxlow

General causes of neutropenia

Reduced marrow production
Increased destruction
Peripheral pooling

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Hereditary causes of neutropenia due to reduced marrow production

Kostmann syndrome
Wiskott-Aldrich syndrome
Cyclic neutropenia

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Mutation in Kostmann syndrome

Mutation in anti-apoptosis HAX-1 gene

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Mutation in Wiskott-Aldrich syndrome

WAS gene

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Mutation in cyclic neutropenia

Neutrophil elastase

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Causes of ineffective granulopoiesis

Vit B12 deficiency
Folate deficiency
MDS

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Acquired causes of marrow suppression in neutropenia

Chemotherapy
Aplastic anemia
Infections

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Lymphopenia cut-off in children under 6

<2000

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Congenital cause of lymphopenia

DiGeorge syndrome

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Lymphopenia caused by Cushing Syndrome

cortisol excess leads to redistribution of lymphocytes

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Iatrogenic causes of neutrophilic leukocytosis

G-CSF
GM-CSF
Corticosteroids

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General causes of neutrophilic leukocytosis

Acute inflammation
Iatrogenic
Myeloproliferative disorders
Miscellaneous neoplasms
Asplenia

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Toxic granulation of neutrophils

Reactive change associated with acute inflammation

Dark, coarse granules in cytoplasm

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Dohle bodies in neutrophils

Reactive change associated with acute inflammation

Bluish cytoplasmic inclusions due to dilated ER

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General causes of eosinophilia

Allergy
Parasitic infections
Neoplasms
HES
Pulmonary eosinophilia

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Neoplasms associated with eosinophilia

Hodgkin’s lymphoma
Chronic myeloproliferative neoplasms

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Pulmonary syndromes associated with eosinophilia

Loeffler’s syndrome
Eosinophilic granulomatosis with polyangitis/EGPA/Churg-Strauss

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General causes of basophilia

Allergic reactions - hyperacute sensitivity
CML

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General causes of lymphocytosis

Infection, acute and chronic
Parasite - toxoplasmosis
Neoplasm

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Neoplasms associated with lymphocytosis

CLL
NHL

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General causes of monocytosis

Chronic bacterial infections
Protozoa - malaria
Neoplasms

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Neoplasms associated with monocytosis

Chronic myelomonocytic leukemia (CMML)
AML subtypes

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Examples of chronic bacterial infections

TB
Brucellosis
Infectious endocarditis
Typhoid

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Definition of leukemoid reactions

Increase in WBC count that mimics leukemia, but is caused by infection or another disease

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2 general types of leukemoid reaction

Myeloid Lymphoid type

General causes of myeloid type leukemoid reaction

Bacterial infections Severe hemorrhage Acute hemolysis Post op/trauma stress Splenectomy

Characteristics of neutrophils in myeloid type leukemoid reaction

Toxic granules Cytoplasmic vacuolations Dohle bodies

LAP in CML

Markedly reduced

LAP in leukemoid reactions

High

Characteristic of draining lymph nodes and related infection

Increased neutrophils - bacterial Lymphoid cell proliferation - viral Increased plasma cells - immune reaction

Definition of leukemia

Neoplasm of blood forming cells, primarily affecting bone marrow

Clinical presentation of acute leukemia

Short history Signs of bone marrow failure Organ involvement Variable leukocytosis and cytopenias

Clinical presentation of chronic leukemia

Slow progressive history or incidental finding Organ involvement Leukocytosis Marrow infiltration by mature cell types

Main cell type implicated in ALL

Lymphoblasts

Main cell types implicated in AML

Myeloblasts

Main cell types implicated in CML

Platelets Basophils Neutrophils Eosinophils Monocytes

Main cell type implicated in CLL

B lymphocytes

Method of finding chromosomal abnormalities

Karyotyping

Methods of finding molecular abnormalities

FISH PCR Sequencing

Auer rods are seen in this cell and disease

Myeloblasts in AML

General symptoms of acute leukemias

Fatigue Weight loss Anorexia Fever

Symptoms related to bone marrow failure

Anemia and pallor Leukopenia with infections and fever Thrombocytopenia with bruising, bleeding gums, and meonorrhagia

Meningeal signs of organ infiltration

Headache Blurred vision Others

Rare manifestation of acute leukemia

Extramedullary masses --> myeloid sarcomas/chloromas

Clinical manifestations of acute leukemias

Bleeding - petechiae and purpura Lymphadenopathy Hepatosplenomegaly Infections Mediastinal mass

Acute leukemia most common between 3-11 yo

B-cell ALL

Acute leukemia most common in adolescence

T-cell ALL

Acute leukemia associated with mediastinal mass

T-cell ALL

Possible effects of mediastianal/thymus mass

Respiratory distress SVC syndrome

Symptoms of SVC syndrome

Face/neck swelling Distended neck veins Cough Dyspnea

MPO negative and possibly PAS positive

Blast cells

Immature B and T cells all show what marker

TdT+

B-ALL blasts commonly express what markers

HLA-DR CD-19 CD-10 CD79a Less often: CD22 or IgM heavy chain

T-ALL blasts commonly express what markers

CD3 CD1 CD2 CD5 CD7

What is marker of T cell immaturity?

Double negative: CD4- and CD8- Double positive: CD4+ and CD8+

Leads to dysregulation of TFs required for normal B/T cell differentiation

Cytogenetic alterations

Translocations related to B cell ALL

t(12;21) t(9;22) t(11q23;variable)

t(12;21) in B cell ALL

Involves ETV6;RUNX1 Favorable prognosis

t(9;22) in B cell ALL

BCR;ABL Poor prognosis

t(11q23;variable) in B cell ALL

MLL gene rearrangement Poor prognosis Infant leukemia

Hyperdiploidy in B cell ALL prognosis

Good prognosis

Hypodiploidy in B cell ALL prognosis

Poor prognosis

Mutation associated with T cell ALL

Gain of function mutation in NOTCH1 that activates NOTCH signaling pathway

Inherited conditions related to AML

Trisomy 21 Bloom syndrome Fanconi anemia Ataxia telangiectasia Wiscott-Aldrich syndrome

Drugs associated with developing AML

Alkylating agents, particularly when combined with radiotherapy Etoposide

Manifestations typically seen in monocytic/myelomonocytic leukemia

Gum hypertrophy Skin involvement CNS involvement Bleeding

Manifestation associated with promyelocytic leukemia

DIC

Diagnosis of AML based on blasts

20% or more myeloid blasts in bone marrow or blood

MPO positive and PAS negative staining

Myeloblasts

Immunological markers of AML blasts

CD34 CD13 CD33 CD117 MPO

Immunological markers associated with monocytic AML

CD14 CD11c CD64

Immunological markers associated with erythroid AML

Glycophorin/CD235

Immunological markers associated with megakaryocytic AML

CD41 CD42 CD61

Translocations associated with AML

t(8;21) inv16 or t(16;16) t(15;17)

AML sub-type associated with t(15;17)

Acute promyelocytic leukemia

Gene associated with acute promyelocytic leukemia

t(15;17) or PML-RARalpha fusion gene

DIC and peripheral consumption may be seen in what

Acute promyelocytic leukemia

Responds to ATRA therapy

Acute promyelocytic leukemia

Mechanism of ATRA therapy in acute promyelocytic leukemia

Binds PML-RARalpha fusion protein and antagonizes its inhbitory effect

Mechanism of PML-RARalpha fusion protein

Inhibition of granulocytic maturation and uncontrolled proliferation

Morphologic characteristics associated with acute promyelocytic leukemia

Promyelocytes in blood and bone marrow Bilobed nuclei Hyper-angular with many Auer rods

AML with monocytic differentiation

Blasts and promonocytes have folded or lobulated nuclei with abundant cytoplasm

Cytochemistry of AML with monocytic differentiation

NSE positive

Clinical presentation of AML with monocytic differentiation

Generally characterized by tissue infiltration Leukemia cutis (skin) Gingival hypertrophy CNS

Chronic lymphocytic leukemia (CLL)

Neoplastic lymphocytes in the marrow and peripheral blood predominantly

Small lymphocytic leukemia (SLL)

Neoplastic lymphocytes in lymph nodes predominantly

Clinical manifestations of CLL and SLL

Asymptomatic Generalized lymphadenopathy Hepatosplenomegaly Infections Anemia

Blood count findings in CLL

Leukocytosis with absolute lymphocytosis

Smudge cells on peripheral smear

CLL

Immunophenotype in CLL

CD19+ CD5+ CD23+ Dim expression of monoclonal light chain

Cytogenetics associated with CLL

Deletions of 13q Trisomy 21

Leukemia that can be associated with autoimmune hemolytic anemia, immune thrombocytopenia, and hypogammaglobulinemia

CLL

Lymph node in SLL

Diffuse effacement Replaced primarily by small lymphocytes with round nuclei, condensed chromatin, and scant cytoplasm

Possible outcome of CLL/SLL

Transform into high-grade lymphoma (DLBCL) Richter syndrome - aggressive lymphoma

Clinical presentation in hairy cell leukemia

Splenomegaly Frequent infections with atypical mycobacteria

TRAP positive tumor cells

Hairy cell leukemia

Pancytopenia resulting from marrow involvement and splenic sequestration with unexplained monocytopenia

Hairy cell leukemia

Immunophenotype of hairy cell leukemia

Pan B cell markers - CD19 and CD20 CD103

Dry tap during marrow aspiration cause and condition

Tumor cells induce ECM production with increased reticulin fibers in bone marrow Hairy cell leukemia

Pathogenesis of hairy cell leukemia

Activating point mutations in BRAF