Flashcards in Leukemias and Lymphomas Deck (168):
Acute Leukemia Types
1) Acute Myeloid Leukemia 2) Acute Lymphoblastic Leukemia
Symtoms of Acute Leukemia
Anemia (fatigue, pallor) Thrombocytopenia (easy bruising, petechiae) Neutropenia (infection)
What are the rare signs of Acute Leukemia?
Leukostasis, DIC, infiltration of WBCs in skin, gums, lymphs nodes
What is general Blast Marker?
Risk Factors of Acute Leukemia
Previous Chemo (aklylating agent, Topo II); Tobacco smoke, Radiation, Benzen, Down Syndrom, Bloom, Fanconi Anemia, ataxia-Telang
Acute Myeloid Leukemia - neoplastic accumulation of myeloblasts in BM
Acute Lymphoblastic Leukemia - neoplastic accumulation of lymphoblasts in BM
Age of Diagnosis: AML vs ALL
AML: 65 YO; ALL:
Diagnosis of AML
>20% myeloblasts in marrow and/or blood via smear or flow cytometry OR have cytogenetic abnormality
Diagnosis of ALL
Packed marrow with lymphoblasts - no set percentage
Markers for ALL vs AML
Both: CD34; AML: CD117(Ckit) or MPO; ALL: TdT
Remission/prognosis of AML
60% remission; consider HSC transplant for healthy pats with high risk of relapse
Remission/prognosis of ALL
95% remission; cure rate 80% in children; Adults 60-80% remission; 50% cure rate.
what factors decrease prognosis in ALL?
Under 1 or over 10 YO; high WBC, hypodiploidy, slow to respond to treatment
Types of AML
Congenital OR Therapy related
alpha subunit in Core Binding Factor is inactive; unable to differentiate homeostasis
Mutation in alpha CBF; good prognosis
Inv 16 or t(16:16)
Baso-Eos in BM: immature eosinophils with baso granules; mutation in CBF beta - for beta Core Binding Factor; Good prognosis
t(15:17); also known as APL
APL clinical Presentation
hypergranular with multiple Auer Rods; Retinoid Acid Receptor Alpha protein mutated (unable to differentiate); risk of DIC
All Trans Retioic Acid; not chemo
RBM15-MKL1 Clinical Presentation
Slow megakaryoblastic differentiation; seen in infants with down syndrome; good prognosis
MLL abnormalities with 11q23
Prognosis of Congenital vs. Therapy AML?
Congenital are usually good (except 11q23) while therapy is very bad prognosis
what therapies cause AML?
Alkylating agents, radiation, topo II inhibitors
What AML has 2-8 year latency?
Alkylating agents or radiation
What karyotype is associated with Alkylating Agent or radiation induced AML?
Complex karyotype with whole or partial loss of Ch5 and 7
what AML has 1-2 year latent period?
Topo II inhibitors
What karyotype is associated with Topo II inhibitor induced AML?
MLL with 11q23
Which therapy related AML has a more progressive path?
Topo II inhibitor induced
Internal Tandem Repeat; has an extremely bad prognosis of AML - trumps all other factors
Good prognosis for AML if negative for FLT3
Good prognosis for AML if negative for FLT3
What factors influence prognosis of AML?
FLT-3, NPM1, CEBPA
types of ALL?
B-ALL and T-ALL
prevalence of Congenital vs. Therapy induced AML?
Prevalence of B-ALL vs T-ALL?
B-ALL is 80-85% of ALL cases
what markers distinguish B-ALL from T-ALL?
B-ALL: CD19, CD22, CD79a, lack CD20; T-ALL have CD2, CD3, CD7 (CD2-8)
t(9:22); different fusion protein from CML (190 NTs) still on Philadelphia Chromosome
BCR-ABL Clinical Manifesation
Adults; poor prognosis
MLL - clinical manifestation
Common in neonates and infants, poor prognosis
ETV6-RUNX1 Clinical Manifestation
Mostly in children; very favorable prognosis
T-ALL clinical manifestation
More in males; adolescents and young adults; mediastinal mass; worse prognosis than B-ALL
Clonal population from hematopoietic stem cell takes over; failure to make normal cells over one of more lineages
Risks of MDS?
Increased risk of progression to AML
One persistent Cytopenia; Evidence of dysplasia, increased myeloblasts, clonal cytogenetic abnormalities (sideroblast, bilobed nuclei in nuetrophils, hypolobulated small megakaryocytes)
bilobed nuclei in neutrophils; characteristic of MDS
What causes MDS?
Primary/idiopathic or Therapy Related
Usually occurs in late adulthood with insidious onset; cytogenetic abnormalities
Cytogenetic abnormalities in primary MDS
Partial or whole deletion sof Ch5 and 7, Deletion of 5q, trisomy 8
due to non-neoplastic causes ( B12/Folate def, virus, toxin, heavy metal) or Neoplastic (chemo drugs or radiation that causes whole or partial deletions of Ch5 and/or 7)
Low Grade MDS basic definition
Myeloblasts are not increased in frequency;
High Grade MDS basic Definition
Myeloblasts increased in frequency; >5% in marrow; and/or >2% in periphery
Types of low grade MDS?
1) refractory cytopenia with unilineage dysplasia (RC_UD) 2) refractory cytosine with multilineage dysplasia (RC-MD) 3) MDS with isolated 5q deletion
Refractory cytopenia with unilineage dysplasia - low grade MDS; good prognosis; survival is >5 years with 2% progressing into AML; usually associated with refractory anemia and not thrombi or neutropenia
Refractory cytopenia with multilineage dysplasia; dysplasia in 2+ lineasge, whose prognosis than RC-UD; survival 2.5 years, 10% progression in AML
MDS with 5q deletion
anemia, increased platelets and marrow with small, round, non-lobulated nuclei in megakaryocytic
Types of high grade MDS
Refractory anemia with excess blasts-1 and 2
RAEB-1 vs. RAEB-2
both high grade MDS; 1: Blasts from 5-9% in BM and 2-4% in periphery 2: 10-19% in BM and 5-19% in periphery; 1 survival is 16 months with 25% transformation to AML; 2: survival 9 months with 33% progression to AML; 2) has small round non-lobulated nuclei
Too many (non-dysplastic) cells of one or more lineages
Age of MPS
Common signs of MPS?
high WBC, hypercellular marrow; Hepatosplenomegaly; BM fibrosis, Less able to transform into AML or MDS
What is more transformative MDS or MPN?
MDS into AML
Types of MPN?
1) Chronic myelogenous leukemia 2) polycythemia Vera 3) Primary Myelofibrosis 4) Essential Thrombocytopenia
a type of MPN; with neoplastic proliferation of neutrophils and basophils; characteristic BCR-ABL translocation (210; Philadelphia Ch)
Fatigue, weight loss, night sweats, splenomegaly, anemia occurs in 40-50 yo
Initial Phase of CML?
also called chronic; neutrophilia, basophilia, increased platelets, hypercellular marrow, small megakaryocytic with round, non-lobulated nuclei, no dysplasia
Blast Phase of CML?
>20% of blasts in marrow/blood, usually myeloblasts sometimes lymphoblasts
Treatment of CML?
Imatinib/Gleevec or Protein Tyrosine Inhibitors
Type of MPN with Increased RBC mass (associated with increase in neutrophils and platelets as well); JAK2 or V617F mutations
PV - Symptoms
Hyperviscosity of blood: Headaches, dizziness,venous and arterial thrombosis, visual problems, parasthesia, plethora, itching, hepatosplenomegaly
flushed face due to congestion in PV
why is there itching in PV?
due to increased histamine release from Mast cell overproduction
Where do thromboembolic form in PV?
Mesenteric, portal and splenic Veins
Treatment of PV?
Plebotomy to reduce clotting; aspirin, mild chemo
Prognosis of PV?
good, survival 10-20 years
type of MPN, proliferation of granulocyte and megakaryocytic lineaste (no erythrocytosis) and Marrow fibrosis; JAK2 mutation
Prefibrotic: hypercellular marrow; large megakaryocytes; fibrotic: reticulin fibrosis of BM, leukoerythroblastosis, falling blood counts, dacrocytes, extramedually hematopoiesis in spleen (enlarged spleen)
Prognosis of PMF
5 year survival, little AML transforamtion
Type of MPN, normocellular marrow, with large and bizzarre looking megakaryocytes; JAK2 mutation
usually asymptomatic, but increased risk of bleeding and thrombosis (transient ischemic attacks, digital ischemia with paresthesia, NO splenomegaly)
Indolent disease; survival of 10-15 years
what MPN is associated with neutrophils?
what MPN is associated with RBC?
what MPN is associated with Granulocytes and megakaryocytes?
PFM (both) and ET( only megakaryocytic)
what MPN does not have splenomegaly?
what MPNs have JAK2 mutations?
PV, PMF, ET (all except CML)
category of plasma neoplasms, NHL and HL?
neoplastic mature B- lymphoid cells that results in lymph node mass or extra nodal mass
types of NHL
SLL/CLL, Follicular Lymphoma, Mantel Cell lymphoma, Burkitt Lymphoma, Diffuse Large B-cell Lymphoma
SLL vs CLL
Pre or Post Germinal Center B cell. CLL: blood lymphocytosis with BM involvement, most common western society; SLL: is lymphocytosis in extrameduallary site (7% of NHL)
Clinical Presentation of SLL/CLL?
Asymptomatic or with fatigue, infection, AIHA, hepatosplenomegaly, lymphadenopathy
What population does SLL/CLL occur in?
Males and older adults
Lab findings of SLL/CLL?
Lymphocytosis, small round dense nuclei, smudge and basket cells; pro lymphocytes with effaced nodes and pale proliferation centers
large cytoplasm with round, fine nuclei found in SLL and CLL
Markers for SLL/CLL
CD5 and CD23 (most important) negative for CD10 and FMC7
Molecular Defect associated with SLL/CLL?
Follicular Lymphoma origin
Follicular lymphoma definition
Neoplastic proliferation of small B-cells that form follicle like nodules in lymph node
Follicular Lymphoma clinical signs
painless lymphadenopathy in nodes, spleen, BM, waldeyer’s ring, GI
Age of onset of Follicular lymphoma
Lab Findings of Follicular Lymphoma
Crowded follicle in cortex and medulla, no matel zone, node effacement, homogenous follicle with no tangible body macrophages
Markers of Follicular Lymphoma
Cd19, CD20, BCL2*, CD10, BCL6, negative for CD5 and CD23
Molecular Defect in Follicular Lymphoma
t(14;18) causes overexpression of BCL2 an oncogene that inhibits apoptosis in the germinal center
Mantel Cell lymphoma definition
Neoplastic Proliferation of small B-cells in mantel zone
Mantel Cell lymphoma Clinical signs
painless lymphadenopathy in nodes, spleen, MB, GI, waldey’s, hepatosplenomegaly. ITs moderately agressive compared to follicular!
Age of onset for Mantel cell lymphoma
Lab findings of mantle cell lymphoma
Effaced node with small to medial cells with irregular nuclei
Markers of Mantel Cell Lymphoma
Cd19, CD20, *CD5, *BCL1 negavie for CD10, and BCL6
Molecular Defect with Mantel Cell lymphoma
t(11;14) overexpression of BCL1 to promote phosphorylation of RB and transition of G1 to S phase
Burkitt Lymphoma definition
neoplastic proliferation of intermiate B-cells associated with EBV
Various kinds of Burkitt Lymphoma
Edemic, Sporadic, Immunodeficient
Occurs in 4-7 YO in africa, Mass on jaw and abdomen, +EBV
Children or young adults, ileoceccal mass; low association with EBC
HIV occurs with 25-40% EBV
Prognosis of Burkitt Lyphoma
Highly agressive but 60% curable
Lab findings with Burkitt Lymphoma
Medium cells with round neulei, basophilic city with lipid vacuoles, high mitotic index, starry sky appearance
Markers of Burkitt Lymphoma
CD19, CD20, CD10, BCL6, *MYC, negative for CD5 and CD23
Molecular Defect with Burkitt Lymphoma
t(8;14) to form c-myc an TF that promotes growth
Diffusion Large B-cell lymphoma Definition
neoplastic proliferation of large B-cells great than a histiocyte nucleus or small lymphocyte that grow into sheets
Clinical symptoms of Large-Bcell lymphoma
enlarged lymph or extra nodal mass; rapidly progressive; B-symtoms; potentially curable
Age of onset of Large B-cell Lymphoma
Lab Findings of large B-cell Lymphoma
Effaced nodes with necrosis and permeation into tissue, centroblasts with immunoblasts
Markers for Large Bc ell lymphoma
CD19 and CD20
Molecular Defect of Large B-cell lymphoma
sporadic mutation or transformation from lower grade lymphoma
Types of Hodgkin Lymphoma
Nodule-Lymphocyte predominate hodgkins lymphoma or Classic HL
Common characteristics of CHL
malignant cells are minority (
Reed Sternberg Cells
characteristic of CHL; large up to 100 um, multi lobed nulcue, large eosinophilic nucleolus, ample cytoplasm
Types of CHL
Nodular sclerosis, mixed cellularity, lymphocyte rich, lymphocyte depleted
Nodular Sclerosis Clinical Pres
Most common type of CHL (50-80%); in young adults and femals; EBC not common; enlarged cervical and mediastinal nodes above diaphragm
Morphology of Nodular Sclerosis
Thick lymph node with capsule and collagen sclerosis, RS in lacunar cells; background of small round lymphoctes, eos, plasma cells
Mixed Cellularity Clinical Prognossi
20-30% of CHL cases, most prevalent in kids and elderly, highly associated with EBV; B-symtoms with nodes below or on both sides of diaphragm
Morphology of Mixed Cellularity
Large cells that lack broad bands of collagen; abundant eosinophils
Lymphocyte Rich Clinical Characteristics
5% of CHL, Best prognosis, with B-symptoms, enlarged nodes below or on both sides of diaphragm
Morphology of Lymphocyte Rich
Lack broad collagen, RS cells are very rare
Lymphocyte Depleted Clinical Pres
1% of CHL, most agressive, associated with elderly and HIV+ as well as EBV+
Morphology of Lymphocyte depleted
NO lymphocytes, numerous RS cells that are anapestic and bizarre looking
clonal proliferation of plasma cells that secrete single immunoglobulin that originates in BM and can present extramedually
Types of Plasma cell Disorders
Plasma Cell myeloma, Monoclonal Gammaopathyof Undetermiend significance, Plasmcytoma
malignant proliferation of Plasma cells in bone marrow with overproduction of IgG and IgA
Clincical features of PCM
Asymptomatic to progressive; bone pain due to lesions or osteoporosis, weakness or tiredness due to anemia, hypercalcemia, increased risk of infection, AL amyloidosis
Age group for PCM
Diagnostic criteria of PCM
Elevated M protein (IgG or IgA) in serum or urine detectable by protein electrophoresis, BM clonal plasma cells, CRAB, sometimes peripheral plasma cells, Reuleaux
feature unique to PCM; Hypercalcemia, renal insufficiency, Anema/AL amyloidosis, Bone lesions
Increased serum or urine M-spike without myeloma, amyloidosis, or lymphoprolifeative disorder
MGUS Clinical Features
Most common in late adulthood; Precursor for PCM
MGUS diagnostic criteria
Increased M component, but less than with PCM, Marrow Plasmacytosis
Types of Plasmactoma
Solitary plasmacytoma of bone and Extraosseous/Extramedually plasmcytoma
Solitary Plasmacytoma of Bone Definition
Loca tumor of bone with myeloma like cells
Solitary Plasmacytoma of Bone Diagnostic Criteria
Single bone lesion, NO CRA; low to normal Mprotein
Extraosseous/Medually plasmacytoma definiation
PCM-cell mass lesions outside of bone in soft tissue; most commonly respiratory
Extraosseous/Medually plasmacytoma clinical age
2/3 are male; middle age
Extraosseous/Medually plasmacytoma Diagnostic criteria
similar to solitary: single lesion, NO CRA, low to normal Mprotein
Plasmacytoma vs. PCM?
PCM has multiple bone lesions and CRAB, Plasmacytoma has a single lesion and NO CRA
MGUS vs PCM
MGUS: no bone lesions or PCM symptomes, but increased IgG or IgA
which CHL are associated with EBV?
Mixed and lymphocyte depleted
What CHL have B-symptoms?
Mixed and Lymphocyte rich
what CHL have nodes blow diaphrgam?
Mixed and Lymphocyte rich
what NHL are positive fo CD10 and BCL6?
Follicular and Burkitt
means acute; rapidly enlarging mass, high WBC count, almost complete replacement of normal cells.
treatment of high grade leukemia
radiation, stem cell transplant, palliative treatment, rarely surgery
Low grade leukemia
chronic; midly enlarged lymph nodes for extensive period of time, increased WBC count, often will die with the disease rather than from it.
Treatment of low grade leukemia
no therapy, treat symptoms or survelliance