WBC Disorders (Sloka) Flashcards
Name the WHO classification system of lymphoid neoplasms.
- Precursor B cells Neoplasms
- Peripheral B cell neoplasms
- Precursor T cell neoplasms
- Peripheral T cell and NK neoplasms
- Hodgkin’s Lymphoma
Know the markers (CD10 for example) by using Dillon’s quizlet!
pryo6619
MC cancer and leukemia in children less than 15 y/o. Peak age is 3 y/o
ALL (B-ALL)
Neoplastic accumulation of lymphoblasts (> 20%) in the bone marrow
Lymphoblasts are characterized by positive nuclear staining for TdT, a DNA polymerase.
TdT is absent in myeloid blasts and mature lymphocytes.
ALL
Characteristics of B-ALL
CALLA: CD10
TdT+
T(12,21) or philadelphia chromosome (9,22)
Hyperdiploidy (SS)
“Hyper kids like playing w/B-ALLS”
Prognosis of B-ALL
95% complete remission
75-85% cures
Lab findings of B-ALL?
WBC elevated but large range. Can be normal initially.
NN anemia!!!!
Thrombocytopenia!!!! (all acute leukemia’s have both)
Lymphoblasts- greater than 30% in BM (acute)
CD10 neg but TdT pos
Anterior mediastinal mass/acute leukemia found in an adolescent male.
Likely dx?
T-ALL!
MC leukemia of all?
CLL
Disorder:
Neoplastic proliferation of Bcells (CD20+); associated with EBV
Burkitt’s Lyphoma
MC leukemia of patients older than 60?
CLL
Burkitt Lymphoma is driven by translocations of _____. t(&)
C-myc. t(8,14)
Starry sky is caused by and is associated with Burkitt’s.
clear spaces with macrophages containing debris (“tingible” body macrophages)
MCC NHL?
Diffuse large B cell lymphomas
MCC of generalized lymphadenopathy?
SS
CLL
In CLL, lymphoblast count in BM?
How about:
anemia
thrombocytopenia
what characteristic cell will you see in CLL?
MCC of death in CLL?
WBC count varies “Smudge” cells NN anemia 50% Thrombocytopenia 40% Hypogammaglobulinemia- MCC of death due to infections. BM -
Disorder?
BCL2 on chromosome 18 translocates to the Ig heavy chain locus on chromosome 14.
Results in over-expression of Bcl2, which inhibits apoptosis
Follicular Lymphoma
Neoplastic proliferation of mature B-cells.
Middle-aged men B cell TRAP, BRAF Splenomegaly 90%, lymphadenopathy is rare Pancytopenia (especially monocytopenia)
Hairy Cell Leukemia
Pancytopenia is in the peripheral blood.
Increased lymphocytes and smudge cells are seen on blood smear
CLL
MCC of death in CLL?
Infections due to Hypogammaglobulinemia
Disorder?
Neoplastic proliferation of small B cells (CD20+) that form follicle-like nodules?
Follicular Lymphoma
Neoplastic proliferation of small B-cells.
Associated with chronic inflammatory states such as Hashimoto thyroiditis
Sjogren syndrome
H pylori gastritis
if in mucosal sites, called MALToma
Marginal zone lymphoma
Patient comes in with: WBC elevated NN anemia Lymphoblasts greater than 30% in BM Thrombocytopenia
Likely dx?
Leukemia
Acute.
Lymphoblastic
Patient does not have lympadenopathy, has splenomegaly, and is pancytopenic in peripheral blood.
Trap +
Most likely dx?
Hairy cell leukemia
Neoplastic proliferation of naive B cells that co-express CDS and CD20
CLL
Neoplastic proliferation of small B cells (CD20+).
Clinically presents in late adulthood with painless lymphadenopathy.
Driven by t(11;14)
Cyclin Dl gene on chromosome ll translocates to Ig heavy chain locus on chromosome 14.
Over expression of cyclin D1 promotes Gl/S transition in the cell cycle, facilitating neoplastic proliferation.
Mantle Cell Lymphoma
SS.
Disorder?
Often develop in patients with abnormal immune states (e.g. SLE, Sjogren’s’ syndrome, renal transplantation)
May occur at any age
Usually elderly adults
Diffuse Large B cell lymphoma
SS.
The MC form indolent lymphoma?
Follicular lymphoma
SS:
Most common monoclonal Plasma Cell Dyscrasia?
Monoclonal gammopathy of undetermined significance (MGUS)
What is multiple myeloma?
Malignant proliferation of plasma cells in the bone marrow. One plasma cell clone is proliferated while the others are suppressed leading to monoclonality.
Plasma Cell Dyscrasia:
Most commonly due to an increase in IgG
Other plasma cell clones are suppressed
Multiple Myeloma
Describe Lymphoplasmacytic lymphoma (Waldenstrom’s macroglobulinemia)
B-cell lymphoma with monoclonal IgM production.
Plasma Cell Dyscrasia:
Small IgG M spike in elderly patients
Plasma cells
Monoclonal gammopathy of undetermined significance (MGUS)
Characteristics of multiple myeloma?
High IgM
Bone pain with hypercalcemia
lytic bone lesions
Elevated serum protein –> Rouleaux formation
Bence Jones protein (free light chain excreted in urine; myeloma kidney: Renal failure 30-50%)
Amyloidosis- free light chains circulate in serum and deposit in tissues
Monoclonal antibody
NO generalized lymphadenopathy! (compare to Waldenstrom’s)
MCC of death in multiple myeloma?
infection due to monoclonal antibody
M spike with IgM
BJ protein is present
Generalized lymphadenopathy
Anemia and bone marrow but no lytic lesions
liver, and spleen involvement
Hyperviscosity syndrome due to increased IgM:
retinalhemorrhages, strokes, platelet aggregation defects
Lymphoplasmacytic lymphoma (Waldenstrom’s macroglobulinemia)
Which disorder?
Epidemiology MC in blacks Rare under age 40 Peak incidence at age 50-60 Increased risk with radiation exposure M-spike in 80-90%
Multiple Myeloma
SS:
Plasma Cell Dyscrasia:
Bone sites: vertebra, ribs, pelvis Slight increase in monoclonal protein No plasmablasts in bone marrow No BJ protein 75% develop multiple myeloma
Solitary Skeletal Plasmacytoma
SS:
Plasma Cell Dyscrasia:
Sites: upper respiratory tract (nasopharynx, sinuses, larynx)
Slight increase in monoclonal protein
Absence of malignant plasma cells in the bone marrow
Absence of BJ protein
Small percentage may develop multiple myeloma
Extramedullary plasmacytoma
Plasma Cell Dyscrasia:
Sheets of malignant plasma cells in biopsy
Greater than 30% plasma cells in aspirate
Multiple Myeloma
Similarities and differences between MM and Lymphoplasmacytic lymphoma (Waldenstrom’s macroglobulinemia)?
Similarities: IgM, BJ protein present.
Differences: W has no lytic bone lesions &
W has generalized lymphadenopathy unlike MM.
Plasma Cell Dyscrasia:
M protein heavy chain without light chains
Absence of BJ protein
Heavy-chain Disease
In MM, Myeloma cells release ___
interleukin 1 (osteoclast activating factor)
SS:
The two class IV lymphoid neoplasms that we covered?
Adult T cell leukemia/lymphoma
&
Mycosis Fungoides
SS: What gene is involved in Adult T cell leukemia/lymphoma?
TAX promotes secretion of pro-inflamatory NF-kB. Messes with TP53 (makes it ineffective)
Neoplastic proliferation of mature CD4 T cells associated with HTLV-1.
MC seen in Japan and Caribbeans.
Adult T cell leukemia/lymphoma
SS. Disorder?
Hematologic findings:
Normocytic anemia with rouleaux formation Thrombocytopenia Increased sed rate Prolonged bleeding time Due to a defect in platelet aggregation
rouleaux formation and increased sed rate bc of increased serum protein (IgM elevated)
MM is associated with platelet problems.
Tests to dx MM?
Diagnosis:
BM
SPE and UPE
Xray
Plasma cell disorder where:
Recurrent infections is a common cause of death
Sepsis due to Hemophilus influenzae, Streptococcus pneumoniae
MM
What lab results will you find with someone who has Adult T-Cell Leukemia/lymphoma?
TdT negative!! Because it’s a marker for pre-B/T cells!! (these are more mature T-cells: lymphoblasts!)
CD4+ lymphoblasts (Tdt negative)
Leukemia: So NN anemia & thrombocytopenia
WBC: normal to elevated
What is Mycosis Fungoides?
skin involvement progresses through three stages –> rash to ____ to ___ masses
spreads to other sites (MC _____)
Neoplastis proliferation of mature CD4+ cells that inflitrate the skin.
rash to plaque to nodular
spread MC to lymph nodes
Patient from Japan presents with:
Hepatosplenomegaly
Generalized lymphadenopathy
Skin infiltration (rash)
Lytic bone lesions with hypercalcemia
Adult T-Cell Leukemia/lymphoma
Neoplastic proliferation of _______ cells which are classically positive for CD15 and CD30.
Reed-sternberg (Hodgkin Lymphoma): Class V
Disorder:
Involve neoplastic peripheral CD4 Th cells
Adults 40-60 years (SS)
MF involves the skin and other extra-cutaneous sites
Skin involvement presents with a rash secondary to a T cell infiltration of the epidermis and formation of Pautrier’s abscesses
Mycosis Fungoides
Four classical subtypes of HL? From MC to LC.
Nodular sclerosing
Mixed cellularity
Lymphocyte rich
Lymphocyte poor
____ association in over 70% of cases of mixed cellularity
EBV
HL is more common in M/F?
Whites or blacks?
Age distribution of HL?
Males
Whites
Bimodal: most common in young adults 15 to 34 years of age and in patients older than 50
Pathogenesis of HL?
Unknown factors (? EBV, retrovirus) cause B and/or T cells to become neoplastic Reed-Sternberg cells
Clinical findings:
Describe lymph nodes in HL?
Involves localized groups of nodes and has contiguous spread
Often involves cervical or supra-clavicular nodes
Cut section has a bulging “fish-flesh” appearance
In HL, unlike NHL, the lymphocytes in the lymph nodes are __ _______
not neoplastic
T/F Reed-Sternberg cells have CD45 markers.
False . CD15 and CD30
Lacunar cells have to do with which subtype of HL?
NS
HL vs NHL:
Age: HL is more younger
Fever: HL more associated with fevers. Pel Ebstein’s fever.
Nodes: HL is more unilateral, while NHL is more likely to be bilateral.
Rarely involves Waldeyer’s ring (oropharyngeal lymphoid tissue), skin or gastrointestinal tract
most common type of HL?
NS
Which subtype of HL?
female predominant disease
most commonly involves the anterior mediastinum and neck nodes.
70% 5 year survival
NS
Lymphocyte depleted
presents in males under 40 years of age
enlarged, painless cervical or supraclavicular nodes
Classic RS cells are extremely difficult to find
90% survival 5 years
Lymphocyte predominant (not classical 4)
common in men greater than age 50
RS cells are very easy to find interspersed among plasma cells and eosinophils
Strong EBV relationship
50% 5 year survival
MC
T/F: Clinical stage more important than type of HL
True!
Describe AML
Neoplastic accumulation of immature myeloid cells (greater than 20%) in BM.
High yield subtypes of AML:
M2-
M2- Most common 30-40%.
AML w/maturation
AML:
M3-
Acute promyelocytic leukemia:
t(15;17) Primary granules = increased risk for DIC
myeloblasts characterized by + cytoplasmic staining for MPO. Crystal aggregates of MPO = AUER RODS!
AML:
M5-
Acute monocytic leukemia:
Proliferation of monoblasts; usually lacks MPO
Characteristically infiltrates gums
AML: M7-
Acute megakaryoblastic leukemia
Proliferation of megakaryoblasts; lacks MPO
associated with down syndrome (before age of 5)
Myelodystplastic Syndromes
Age bracket?
(RR pg 329/Robins: 462):
50-80 y/o
Pathogenesis of myelodysplastic syndrome?
5q;7q deletions
or
trisomy 8
Myeloblasts (neutrophil pre-cursors)
How do we know if myelodysplastic syndrome has progressed to AML?
If myeloblasts are >20% in BM.
What disorder is this:
Group of acquired clonal disorders that affects stem cells.
RBC’s are (mostly) macrocytic or microcytic
Characterstically have cytopenias in peripheral blood and normocellular/hypercellular bone marrows.
Frequently progresses to AML
Myelodysplastic syndromes
What are myeloproliferative disorders?
What types are there?
Neoplastic proliferation of MATURE myeloid cells.
(Retinas capacity for terminal differentiation)
Average age: 50-60
Can differentiate (mature) so cells of ALL myeloid lineages are increased; classified based on the dominant myeloid cell increased.
CML- increased granulocytes (basophils)
PV- increased RBCs
ET- increased megakaryocytes/platelets
Myelofibrosis
CML: Neoplastic proliferation of ____ myeloid cells, characteristically ____ are increased.
mature
basophils
SS.
Two outside factors that can cause CML?
Ionizing radiation or benzene.
Genetics of CML?
t(9:22) BCR-ABL proto-oncogene which activates tyrosine kinase activity!
Philadelphia chromosome (Ph)
PH 95%, +BCR-ABL 100%
CML is distinguished from a leukemoid reactions by?
In the neoplasm:
LAP is negative
Increased basophils
t(9;22)
CML can be converted to ALL or AML if:
AML- if >20% myeloblasts
ALL- if >20% lymphoblasts
Tx of CML?
Imatinib: blocks tyrosine kinase
Pathogenesis of PV?
Jak2 mutation.
Increases in all myeloid cell lines but especially RBCs!
Clinical findings in PV?
Splenomegaly- Increased RBC’s increases sequestration
Thrombotic events- Increased viscosity
Impaired CNS circulation- same
Increased histamine release- increased # of mast cells
Gout- bc increased turnover of cells (nucleus is degraded and end product of purine degradation - uric acid crystals)
PV increased/decreased:
Hct
RBC mass/Plasma volume
Leukocytosis/penia
Thrombocytosis/penia
EPO?
ABG values?
BM hypercellular or hypo?
Hct, RBC mass, Plasma Volume INCREASED
Leukocytosis
Thrombocytosis
Decreased EPO (have enough RBC's - feedback) Normal ABG
BM hypercellular –> fibrosis
ET pathogenesis?
Like PV:
Jak2 mutation.
ET symptoms?
increased risk of bleeding (platelets not working) or thrombosis (over active)
RBCs and granulocytes are increased
Pathogenesis of myelofibrosis?
Like PV, and ET:
Jak2 mutation
In myelofibrosis: what is increased?
Mature myeloid cells; especially megakaryocytes
Describe pathophys of meylofibrosis
Megakaryocytes produce excess PDGF causing marrow fibrosis.
Causing:
Extramedullary hematopoiesis.
- this causes leukoerythroblastic smear: increased leukocytes, increased erythrocytes, increased immature cells bc no reticulin gates in spleen (unlike BM)
Splenomegaly
-above reason
Tear drop RBC’s
- bc of marrow fibrosis
Thrombosis
-increased platelets
