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HEME: Yetter > 3.25 STROM Hematologic Malignancies I > Flashcards

3.25 STROM Hematologic Malignancies I Flashcards

1
Q

HCT=

A

(RBC/Bld Vol)x(RBC vol/RBC)=RBCxMCV

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2
Q

Blast Criteria

A

a. Big Cell
b. Increased nuclear/cytoplasm ratio
c. Immature Chromatin
d. Big nucleolus or two
e. A bunch of cell that look a like***

–Does not have to meet all the standards to be considered a blast

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3
Q

Myelophthisic/Leuko-erythroblastic

A

What hematologic malignancies look like

-Stuff that should be in the BM is in the peripheral blood

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4
Q

Immunophenotyping

A
  • Differnent cell types express different antigens
  • use mAbs to detect
  • hint most markers for T-cells will be <10
  • Malignancies can change surface expression so not as helpful as ppl thought it would be
  • Access via flow cytometry (remember lyse RBC so will not detect poss RBC precursors)
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5
Q

B-cell and T-cell Antigens

A

B-cell: CD-20, IgG kappa/lambda, CD45(both)

T-cell: CD3, CD7, CD4 or CD8

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6
Q

CD45, CD33, CD34

A

Usually start with CD45: on almost all marrow cells and can help to ID a blast population (left ball of graft)

  • Most blast tend to express CD34
  • Maturing granulocytes tend to express CD33
  • COMBO of CD33 & CD34 indicate AML if in large population (premature myeloid cell in peripheral)
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7
Q

Immunohistochemistry

A
  • Works better for larger cells than flow cytometry
  • use enzyme conjugated abs to desired cell surface protein and then use CHROMOGENIC substrate
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8
Q

Gilman’s Hypothesis

A

Need to mutations for the AML to hurt the patients

Class I: increases proliferation

Class 2: decreases differentiation -together these will make the leukemia much more aggressive and dangerous

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9
Q

Summary of Malignancies Arising in the BM

A
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10
Q

AML

A

Rapidly proliferating clones: Blasts in marrow and often in blood stream

Can arise from 3 cell lineages:

(1) Megs
(2) Erythroid Lineage
(3) Myeloid lineage

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11
Q

Acute Lymphocytic Leukemias (ALL)

A

Arise from the lymphocyte lineage

-Rapidly proliferating clones: blasts in marrow and often blood stream

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12
Q

Typical Presentation of Acute Leukemias

A
  • Clones can take over a variety of locations, usually blood stream and BM
  • They can take over BM w/o raising the WBC count in peripheral
  • Can sometimes present as cytopenias (decreased cellularity of the blood), would not expect a rapidly proliferating population to present as cytopenia

Blasts outside of Marrow (rare): Myeloid: Myeloid Sarcoma and Lymphoid: Lymphoblastic lymphoma

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13
Q

Acute Leukemia Diagnosis

A

-Use to simply be >20% blast in marrow, not very predictive of how the leukemia will progress

Other methods:Morphology (useless by itself), Immunophenotyping (blasts can change surface expression) and genotyping

-Use an many as possible, genotyping can predict AML even if blast count is low

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14
Q

Genotyping Acute Leukemias, Specific Mutations

A

t(15:17) PML-RARA (AML Subtype)

t(8;21) RUNX1-RUNXT1 (AML Subtype)

t(12;21) FLT3 mutation(+) (AML Subtype)

-These and others give increased prognostic value, predicts response to therapy, IDs molecular targets for therapy development

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15
Q

Gililand Hyposthesis AGAIN!!

A

Class I (proliferation/survival advantage):

-FLT3-ITD, FLT3-TKD, Kit, Ras, PTPN11 Jak2 (usually dectected via sequencing)

Class II (impaired differentiation/apoptosis):

-t(15;17) PML-RARA, t(8;21) Runx-Runx1T1, (inv(16) or t(16;16)))CBFB-Myh11, MLL fusions (usually detected via cytogenetics)

BOLDED= AML diagnosed with presence even w/o blast count

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16
Q

AML with AUER RODs

A

t(8;21) Runx-1-Run1T1 Mutation

Clinical Presentation: younger patients/kids

Auer rods: crystalization of granule contents (excess myeloperoxidase production)

Immunophenotype: CD34+, CD13+, CD33weak

Prognosis: good response to chemo

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17
Q

APL: PML-RARA

A

t(15;17) fusion of PML (trans factor) with RARA (retinoic acid receptor)

  • Class II mutation: Inhibits granulocyte differentiation
  • TREATMENT: All Trans Retinoic Acid (ATRA), induces cell differentiation of the blasts to granulocytes (CLINICAL REMISSION)
  • CLINICAL PRESENTATION: DIC, SEVERE THROMBOCYTOPENIA***
  • Morphology: AUER RODS in stacks (faggot cells)*** sometimes see Bi-nuclear appearance

Immunophenotype: Weak/absent: CD34, HLA-DR, CD13+, CD33+

Prognosis: good if diagnosis is made

18
Q

AML: CBFB-MYH11

A

inv(16) or t(16;16)

  • Class II mutant, clinical presentation: younger patients/kids
  • Morphology: Myelomonocytic* (mixed granulocyte-monocyte feats), Increased Eosinophils in blood and marrow (not known why)
  • Immunophenotype: CD34+, CD117+ (blasts); CD13+, CD33+ (granulocytes); CD14+, CD11b+ (monocytes)

Prognosis: GOOD; optimal with high dose CYTARABINE

19
Q

AML w/ Normal Cytogenetics

A

40-50% of AML cases

-Any age group

Morphology: undifferentiated or variable granulocytic or monocytic/monoblastic

  • Immunophenotype: blast markers (CD34, CD117)+, can show any lineage markers
  • Prognosis: have to look at molecular genetics, pairing of mutation will determine
  • For some BM transplant doesnt help (NPMN! or CEBPA+, FLT3-ITD-, 60% 4-yr survival)
  • for other it will (FLT3-ITD+ or NPM1-, CEBPA-, FLT3-ITD-, ~29% 4-yr survival)
20
Q

ALL (Acute Lymphoblastic Leukemias)

A

TdT: important for VDJ recombination and marker of B and T cells

  • CD19,CD10 and uCD20 are markers of B cells, can also express myeloid markers (CD13, CD33)
  • Can also express CD34 (GENERAL BLAST MARKER*****)
21
Q

ALL: BCR-ABL1

A
  • t(9;22), proliferation activator (class I), diff from the mutation found in CML which is a class II mutation and prevents maturation of the cell, and have similar cytogenetics
  • Clinical Presentation: Older adults (25% of all cases)

Morphology: Big agranular blasts, hard to tell ir myeloid or lymphoid

Immunophenotype CD10+, CD19+, TdT+

Prognosis: Poor

22
Q

ALL: MLL rearranged

A

t(v;11q23), or t(11;19) Class II mutation, also found in AML

Clinical Presentation: most common leukemia in kids

Morphology: big agranular blasts

Immunophenotype: CD10-, CD19+, TdT+

Prognosis: Poor

23
Q

ALL, Mutations that made St. Jude Famous

A
  • t(12;21); TEL-AML1 (ETV6-RUNX1), class II (inhibits differentition)
  • Clinical Presentation: Kids, 25% of pediatric B-ALL

Morphology: big agranular blasts

Immunophenotype: TdT+, CD34+, CD20-

Prognosis: 90% cure rate

24
Q

ALL: T-ALL

A
  • Common motif for lymphoid malignancies: oncogene>>>>Ig or TCR promoter
  • Clinical Presentation: Kids 25% of pediatric T-ALL, often wih thymic mass**

Morphology: Big agranular blasts

Immunophenotype: TdT+, CD3+, CD5+, can express myeloid or B-cell antigens as well

Prognosis: High Risk: more intense chemotherapy regime, pretty good survival rate

25
Q

Myeloproliferative Disease

A

Definition: Chronically proliferating clones which differentiate to circulating blood cells

Chronic Myelogenous Leukemia (CML): shows blast profile

CMML (myelodysplastic/myelomonocytic): hybrid b/t myelocytes and granulocytes

-Can also see Chronic: eosinophilic, neutrophilic or mastocytosis leukemia. Need to differentiate from a Reactive condition

–Best indicator if prominence of mature to immature cells is out of order, “Myeloid Bulge” (more blasts than more mature cells)

26
Q

Myeloproliferative Diseases of Erythroid and Megs Lineages

A

Polycythemia Vera, elevated RBC count (erythroid lineage)

  • Essential thromboythaemia/Primary myelofibrosis: elevated platelet count (meg lineage)
  • Can progress to AML
27
Q

CML that is Undectable

A

Cryptic Translocation, Cannot see with Routine Cytogenetics

-Will progress to AML (can be myeloid or lymphoid)

PHASES: chronic, accelerated, acute

-Can also confuse with sepsis, get a BM

28
Q

Mastocytosis

A

–Usually presents as benign cutaneous lesions in kids (itchy) that goes away by itself

-Release of histamine can cause systemic symptoms that confuse clinician

Morphology: Aggregates of blank looking cells, round or spindle shapes, s/t with eosinophils

Immunophenotype: Tryptase+, CD117+, CD25+

Treatment: Imatinib

Prognosis: highly variable

29
Q

Polycythemia Vera

A
  • Jak2 mutation in >95% of cases-detectable in PB leukocytes
  • Clinical presentation: Thromboisis?hypertension/stroke or MI. increased RBC #

Morphology: hypercellular marrow, erythroid hyperplasia, increased Megs

-Immunophenotype: no known features

Prognosis: >10yr survival is common, can progress to myelofibrosis MDS, acute leukemia

Epo will usually be low, one way to differ between neoplastic and reactive

30
Q

Essential Thrombocythemia

A

Jak2 mutation in ~50% of cases-detectable in PB

-Clinical Presentation: Thrombosis, increased platelets, can also be due to Fe deficiancy, infecion or chronic inflammation, can also have bleeding and splenomegaly

Morphology: Increased Megs (very abnormal and tend to cluster)

Immunopheno: not known, can not put Meg through flow cytometry (too fragile)

-Prognosis: >10yr survival is common, can progress to myelofibrosis MDS, acute leukema

31
Q

Primary Myelofibrosis

A

Jak2 mutation ~50%, disputed diagnostic criteria

-Morphology: increased Megs, bizarre shapes, clusting and fibrosis (TEAR DROPS?)

No known immunopheno

Prognosis: usually shorter survival than ET, can progress to marrow failure, acute leukemia

-Cells of bone marrow will relocate to spleen and liver: Extra-medullary hematopoiesis

Treatment: supportive care, blood transfusions, splenectomy are dangerous (pts too old, will bleed) and HSCT is curative but high mortality rate b/c pts are old as hell

32
Q

Myelodyisplasias

A
  • Usually present as unexplained cytopenia, bicytopenia or pancytopenia
  • see poorly functioning clones, mostly in elderly (>70)

5 major adult forms (best to worst prognosis): (1) Refractory cytopenia with unilineage dysplasia (2) refractory anemia with ring sideroblasts (3) myelodysplastic syndrome with isolated del(5q) (4) refractory cytopenia with multilineage dysplasia (5) refractory anemia with excess blasts

-Accumulation of several mutations over time in different mutations

33
Q

Refractory Cytopenia with Unilineage Dysplasia

A

Clinical pres: unexplanined cytopenai

Morphology: weird looking precursors: binucleation or irregular nuclei, can show fibrosism high or low cellularity, megaloblastoid features

Prognosis: surival unclear, rarely progresses to AML

34
Q

Refractory Anemia with Ring Sideroblasts

A
  • Nonspecific cytogenetic abnormalities (trisomes, monosomes) may be present
  • Morphology: ring sideroblasts usually with dyspoietic feats (in red cell series only)

–Iron granules form ring around nucleus

-Prognosis: rarely progresses to AML

35
Q

MDS with Isolated del(5q)

A
  • All the Megakaryocytes are MONOCUCLEAR
  • Clinical pres: Anemia often severe, usually elderly
  • Morph: megs are mononuclear
  • Prognosis: good median survival; treatable with LENALIDOMIDE, 10% progress to AML
36
Q
A
37
Q

Refractory Cytopenia with multilineage dysplasia

A
  • Two or more lineages show dysplastic changes
  • Clinical pres: Anemia often severe: usually elderly
  • Morph: Granulocytes dont granulate normally (if affected), nuclei dont lobulate normally

Prognosis: Median survival 30 months, 10% progress to AML in 2 years

38
Q

Myelodysplastic Case Study

77y.o. man with newly diagnosed pulmonary adenocarcinoma

A
  • anemia was not worked up completely, has had for past 2 years (b/f diagnosis): Fe studies, folate, B12 levels are all normal
  • Gave chemo for initial diagnosis
  • Really had Refractory Anemia with trilineage dysplasia

BM biopsy: Myeloid hyperplasia

Poor prognosis, gave chemo that made him sick and was not going to help

39
Q
A
40
Q

ALL: T-ALL

A
  • Common motif for lymphoid malignancies: oncogene>>>>Ig or TCR promoter
  • Clinical Presentation: Kids 25% of pediatric T-ALL, often wih thymic mass**

Morphology: Big agranular blasts

Immunophenotype: TdT+, CD3+, CD5+, can express myeloid or B-cell antigens as well

Prognosis: High Risk: more intense chemotherapy regime, pretty good survival rate

HEME: Yetter (22 decks)

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