Leukemia/Lymphoma Path Flashcards

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1
Q

Name the cells in this bone marrow aspirate

A

(1-7 are all myeloid lineage)

  1. blast (most immature cell)
  2. promyelocyte
  3. myelocyte
  4. metamyelocyte
  5. band
  6. neutrophil (fully bilobed nucleus)
  7. Eosinophil
  8. Monocyte
  9. pronormoblast (first erythroid)
  10. basophilic normoblast (second erythroid)
  11. polychromic normoblast (third erythroid)

(9,10,11 = erythroid lineage: as mature they get smaller w. less blue eosinophilic nucleus)

  1. lymphocyte
  2. megakaryocyte
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2
Q

Differentiate the types of cells seen in a bone marrow aspirate of acute vs. chronic leukemias

A

Acute leukemia is by definition 20% blasts (immature cells)

-chronic leukemia has excess mature cells

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3
Q

What is this skin finding?

What is it indicative of?

A

Petechial rash

-indicative of microcytic damage (damage to small capillaries) commonly caused by thrombocytopenia (low platelet count)

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4
Q

What are the cytologic markers of B-cells?

A

B cell markers = CD 19, CD20, CD21

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5
Q

What are the cytologic markers of T-cells?

A

CD2, CD3, CD4, CD5, CD7

-in general CD 1-10

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6
Q

What is a cytologic markers of cell immaturity ?

A

TdT

-present on blasts

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7
Q

Diagnose:

  • 4 yo pt w/ fever, pallor, petechial rash x 4 days
  • CD19 (+)
  • No surface Ig (kappa or lambda)
  • Tdt (+)
A

= B lymphoblastic leukemia

= pre-B ALL (acute lymphocytic leukemia)

  • peripheral smear showing all blast ( > 20% blasts = acute leukemia by definition)
  • CD19 is a marker for B cells
  • No surface immunoglobulins indicates lack of mature cells
  • Tdt is a marker of immature cells
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8
Q

What is the cell marker CD34 indicative of?

A

Myeloid stem cells

-so immature cells (blasts) but of the myeloid (not lymphoid) lineage

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9
Q

What are the cytologic markers of Monocytes?

A

CD14, CD11b

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10
Q

What are the cytologic markers of promyelocytes?

A

CD33

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11
Q

Diagnose:

  • 17 yo M w/ fatigue, dry cough, night sweats, fever x 3 weeks
  • enlarged LN
  • CXR: enlargement of mediastinum
  • CD5 (+), CD7 (+), TdT (+)
A

= T lymphoblastic lymphoma

= T-ALL (T-cell acute lymphoblast leukemia)

  • CXR + enlarged LNs indicating tissue involvement (hence lymphoma over leukemia)
  • CD5/7 are T cell markers
  • Tdt indicating immature cells and peripheral smear showing blasts => acute leukemia
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12
Q

By definition distinguish leukemia and lymphoma

A
  • both are cancers of theblood cells
  • differentiated by the degree of blood/bone marrow involvement
  • by definition if > 20% is in the blood/bone marrow = leukemia
  • tissue involvement (ex: lymph nodes) indicates lymphoma
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13
Q

Diagnose:

  • 12 yo F w/ petechial rash and pallor
  • CBC: pancytopenia, thrombocytopenia
  • CD 34 (+), CD 33 (+)
A

= Acute Myelogenous Leukemia (AML)

  • CD 33 (myelogenous marker) + CD 34 (immaturity marker) indicates myelogenous leukemia
  • bone marrow aspirate showing tons of blasts (> 20%) = acute
  • also bone marrow aspirate shows ‘needle-like’ structures in the cytoplasm called ‘auer rods’ which tells you the cell is a myeloblast
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14
Q

Yellow arrow?

A

Yellow arrow indicating an auer rod (see the needle-like structures in the cytoplasm)

  • seen mostly in myeloblasts
  • pretty indicative of AML
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15
Q

What is acute promyelocytic leukemia?

(a) How to distniguish from AML

A

APL = Subtype of AML (acute myeloid leukemia) where promyelocytes accumulate

(a) Flow cytometry: CD 13 (+), CD 33 (+) but CD 34 (-)
- CD34 negative b/c these cells are no longer immature cells so they have lost their CD 34 marker

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16
Q

When you diagnose AML what do you have to further specify?

A

myeloblastic or promyelocytic

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17
Q

Say in order the stages of granulopoiesis

A

Progenitor stem cell –> myeloid stem cell –> myeloblast –> promyelocyte –> myelocyte –> metamyelocyte –> band form –> granulocyte

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18
Q

Diagnose:

  • 65 yo F w/ fatigue + bleeding gums x 2 weeks
  • WBC 65 x 10^9 / L with 36% monocytes
  • CD14 (+)
A
  • bone marrow aspirate showing tons of blasts (can vaguely tell they’re myocytic blasts)
  • crazy high white count (normal = 4.0 - 12.0 x 10^9 / L)
  • crazy high monocyte count (normal is 2-8%)
  • CD14 = monocytic marker

= Acute monocytic leukemia

= Acute myeloid leukemia w/ monocytic differentiation

-also MPO stain (myeloid peroxidase) stains specifically for an enzyme only found in myeloid cells

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19
Q

Diagnose:

25 yo F w/ heavy menses x 10 days

  • skin pallor, petechial rash
  • CBC: pancytopenia (low WBC, HB, Plt)
  • fibrinogen 100 mg/dl (low)
  • d-dimer +++
  • CD34 (-) CD 33 (+)
A
  • d-dimer +++ (3 plus) is an indication of DIC = indicating hyperactivation of the clotting cascade
  • peripheral smear showing: promyelocytes (tons of primary granules)
  • also MPO positive (stain specific for enzymes in myeloid cells)
  • CD34(-) b/c not an immature cell, CD33(+) is a myeloid marker

= Acute promyelocytic leukemia (APL)

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20
Q

What is the cytogenetic hallmark of APL

A

APL (acute promyelocytic leukemia) due to T15/17

= t (15;17)

= translocation btwn chromosome 15 and 17 = RAR alpha fusion protein

-mechanism = transfer causes cells to stop maturation at the promyelocyte stage

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21
Q

Why is d-dimer elevated in some cases of APL?

A

About 85% of pts diagnosed w/ APL will develop DIC (disseminated intravascular coagulopathy) = hypercoagulablestate triggered by release of tissue factor from the membrane of the promyelocyteblast cells (elevated in APL)

-d-dimer = fibrin degradation product- presentin the blood after a blood clot is degraded by fibrinolysis, indicative of DIC

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22
Q

Diagnose:

  • 33 yo F w/ chronic fatigue
  • Hb 9.3
  • BM aspirate attached
  • PBS (peripheral blood smear): pancytopenia w/ scattered atypical monocytes and probable blasts
  • flow cytometry: CD 13, CD33, MPO, CD34
A
  • normal Hg 13.5-17
  • probable blasts (positive for MPO) => acute leukemia
  • BM aspirate showing eosinophilic precursors (bright red granules)

= Acute myelomonocytic leukemia w/ abnormal eosinophils

-CD13 and CD33 = myelogenous

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23
Q

What is the current 5-year survival rate for AML diagnosed before 55 yao

A

About 40% 5-year survival

-so low b/c it’s so hard to get rid of the leukemic stem cell (we can’t target cancerous vs. normal stem cells) => even after treatment it reurs

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24
Q

What are the three favorable cytogenetic profiles for AML?

A

t (8;21) = M2

t (15:17) = APL = M3

inversion 16 = M4

25
Q

Describe survival of AML pts related to mutational status of NPM and FLT3

A

Best prognosis = NPM1(+) and FLT3 wild type

-worse prognosis w/ NPM1(-) and FLT3-ITD(+)

26
Q

Why is the mutational status of AML pts so critical?

A

Determines prognosis, determines treatment

27
Q

What cell surface marker would be a good target for future AML therapies?

A

Anti CD33 (myeloid cell marker)

28
Q

Treatment for APL

A

-sensitive to all-trans retinoic acid

so that + chemotherapy => about 90% curerate

29
Q

Where to ALL cells tend to spread?

A

Testes and CNS

-high incidence of testicular and CNS spread

30
Q

Does a child have a better prognosis if diagnosed w/ AML or ALL?

A

ALL has better prognosis- but of course not w/o its complications of the intense chemotherapy given

31
Q

Genetic abnormality of CML

A

t (9;22) = BCR-ABL1 translocation = super tyrosine kinase that drives proliferation

32
Q

Differentiate bone marrow biopsy findings of AML vs. CML

A

AML- just blasts, presents w/ low white count

CML- see all the stages of maturation, presents w/ high white count (see attached)

33
Q

Why do so many pts w/ CML progress to AML?

A

B/c of the presence of an unstable choromsomal compliment => increased risk of mutations

-80% of blast crises are myeloid, 20% are lymphoid

34
Q

How does a CML classically present?

A
  • no symptoms in early stage
  • then rising WBC w/ all stages of myeloid maturation
  • elevated platelets (stem cell proliferation) + splenomegaly (accumulation of excess WBC)
35
Q

Decribe the components

A

= picture is a lymph node cross section

  • outer capsule of fibrous tissue
  • cortex just under the capsule containin lymphoid follicles: B cell germinal centers (yellow arrow)
  • in the middle = medulla w/ sinusoidal spaces filled w/ lymph
  • paranodal area in teh cortex filled w/ T cells
  • also mantle and marginal zones = slightly darker around the gemrinal centers
36
Q

Explain the CD 20 stain

A
  • CD20 = B cell stain
  • heavy staining int eh germinal centers and the mantle/marginal layers
  • non-staining parafollicular area (b/c that’s where the T cells are)
37
Q

Differentiate a lymph node staining pattern for CD20 vs. CD3

A

CD20 = B-cell marker => stain the germinal centers

vs. CD 3 = T-cell marker => stain the opposite (stains the paracortex area)

38
Q

Describe how a normal lymph node would stain for BCL-2

A

BCL-2 = anti-apoptotic protein residing in the mitochondria, so when you dont wan’t the cell to do you release this and the cell lives

  • but B lymphocytes in the germinal center that doesnt get selected (doesnt match the antigen of choice) will not express BCL-2 => will undergo apoptosis
  • germinal centers are BCL-2 negative b/c once the selected B cell is choen to survive it migrates out
39
Q

What are two cytogenic markers that stain germinal centers on immunohistochemistry?

A

BCL-6

CD10

40
Q

Are malignant nodes usually

(a) Soft or firm
(b) Tender or painless

A

Malignant lymph nodes are usually

(a) Firm
(b) Painless
- so if a node is tender than it suggests against malignancy

41
Q

(a) Diagnose:

65 yo M w/ enlarged firm, painless, mobile lymph node

  • Hb 11.2
  • retroperitoneal and bilateral internal iliac lymphadenopathy
  • BCL2 overexpression shown on immunochemistry staining
    (b) Describe the LN biopsy attached
A

(a) = follicular lymphoma grade 1
- grade 1 b/c higher mag (attached) shows mostly small cells, would be higher grade if larger cells were present
(b) LN biopsy shows back to back germinal centers indicating follicular hyperplasia, then can go a step further and tell this is follciular lymphoma (not just benign hyperplasia) by looking at higher mag and BCL-2 overexpression

42
Q

Distinguish the two germinal centers shown on the folloing BCL-2 stain

A

Normal germinal centers are BCL2 (-)

So presence of BCL 2 (+) geminal centers (the dark red ones) are indicating BCL2 mutation- indicative of follicular lymphoma

-recall: BCL2 is an anti-apoptotic protein, so if the germinal centers are BCL2 (+) than the B cells in germinal center are not undergoing the normal physiologic apoptosis

43
Q

Diagnose:

  • 71 yo M w/ lymphocytosis x 2 years
  • lymphadenopathy
  • WB: 6.5 w/ 57% lymphocytes
  • (+) for CD5, CD19, CD20, CD23, Kappa only
    (a) Is this likely aggressive? Why or why not?
A

= B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (depending on presentation)

  • immunophenotypically aberrant B cells that are also presenting a T cell antigen: abnormally are (+) for CD5
    (a) Likely not aggressive b/c older pt, chronic onset (2 years), incidental finding (pt was asympatomatic)
44
Q

Differentiate B cell CLL and SLL

A
  • same disease (same underlying pathophysiology) just w/ different presentations
  • B cell chronic lymphocytic leukemia if it presents in the blood
  • small lymphocytic lymphoma (SLL) if presents w/ tissue disease
45
Q

What is the most common subtype of CLL in the Western World

A

Small B cell CLL

46
Q

Distinguish Kappa and Lambda cytogenic marker findings

A

Kappa and lambda are the two types of immunoglobulin light gains. Usually they are balanced (b/c randomly chosen), but when the K:L ratio is unbalanced it indicates active myeloma

  • one type predominating: indicating increased production of only one cell type (single cell of origin)
  • normalization of the K/L ratio is indicative of remission
47
Q

Diagnose:

26 yo F w/ enlarged axillary mass x 2 weeks

  • fatigue and daily fever
  • upon PE: 5 cm non-tender isolated axillary mass (biopsy attached)
    (a) Is this likely aggressive? Why or why not?
    (b) Describe biopsy
    (c) Diagnosis
A

(a) Likely aggressive- younger pt (w/ blood cancers younger pts usually have more aggressive disease), more acute onset (2 weeks), and firm non-tender mass
(b) Biopsy: disruption of normal architecture of LN, desmoplasticfibrosis, debris indicatin apoptosis, larger cells => large cell lymphoma
(c) Dx = Diffuse large B-cell lymphoma, GC phenotyupe (based on cell markers)

48
Q

What are diffuse large B-cell lymphomas immunologically classified?

A

CD10, MUM, and BCL6

-GC (germinal cennter) immunophenoype: CD10 (-), MUM (-), BCL6 (+) or CD(+)

49
Q

Do GC or ABC diffuse large B-cell lymphomas have a better prognosis?

A

GC (cells arising from inside the germinal center) have a slightly better prognosis than ABC lymphomas (when cell or origin is from the marginal zone, or not the germinal center)

-distinguish these by immunohistochemistry

Recall: GC-type immunophenotype CD10(-), MUM(-), BCL6(+)

50
Q

What is Ki-67 an immunohistochemical stain for?

A

Ki-67 is a protein activated during cell cycling => is a surrogate marker for cell division

-high Ki-67 percentage indicates a rapid turnover of cells (hallmark of high grade lymphoma)

51
Q

Diagnose:

  • 18 yo F w/ dry cough, weight loss, fevers,and night sweats x 3 months
  • PE: 2 cm firm LN
  • CT:7 cm anterior mediastinal mass
    (a) Is this likely aggressive? Why or why not?
    (b) Describe attached LN biopsy
A

(a) Likely aggressive: firm LN + symptoms, young age, sub-acute time scale
(b) Give-away Reed-Sternberg cells (said to be ‘looking back at you’ b/c they look like a pair of eyes) = indicative of Hodgkin’s lymphoma

Diagnosis = Hodgkin’s lymphoma

52
Q

Why is this LN biopsy not from a diffuse large B-cell lymphoma?

A

This biopsy contains some maintained normal LN architecture

-while biopsy of LN from DLBCL will have no retained normal LN architecture

53
Q

Describe the finding:

A

= Reed-Sternberg cell

  • seen in biopsies of Hodgkin’s lymphoma pts (diagnostic)
  • sometimes considred ‘cripped’ germinal center B cells (are derived from B lymphocytes)
  • said to be ‘looking back at you’ b/c it looks like a pair of eyes
  • large cells: either multinucleated or have bilobed nucleus w/ prominent eosinophilic inclusin-like nucleoli
54
Q

What is the classical immunophenotype of Hodgkin’s lymphoma

A

Only positive for CD30 and CD15

-then CD20 (-), CD3 (-), CD45 (-), EBV (-)

55
Q

Differentiate nodular lymphocyte predominant HL from classical HL

A

Nodular lymphocyte predominant HL (NLPHL) is an indolent form of Hodgkin’s lymphoma

  • different immunophenotype: CD30/15 (-) and CD20/45 (+)
  • rare subtype w/ distinct/unique clinicopathologic features
56
Q

Diagnose:

17 yo F w/ intestinal obstruction

  • Abdominal MRI: 7-cm mass in terminal ileum
  • Ki-67 100%
A
  • recall Peyer’s patch as lymphatic tissue in the intestines => lymphoma can arise in the terminal ileum
  • Ki-67 100% is indicative of Burkett’s lymphoma
57
Q

What is the genetic translocation responsible for Burkett’s Lymphoma?

A

t (8,14) = myc/IgH translocation

58
Q

What are small cleaved cells indicative of?

A

Small cleaved cells- indicative of follicular lymphoma (indolent subtype of NHL)