Malignant Hematopathology

Front 1

What leukemia shows a positive DAT (autoimmunity) in 30% of cases?

Back 1

CLL

Hemolytic anemia in half of these (15%).

Front 2

What leukemia shows hypogammaglobulinemia in 50% of cases?

Back 2

CLL

Front 3

CD38 and ZAP-70

Favorable or unfavorable?
What disease is this used for?
What gene?

Back 3

Expression = bad
CLL
Expression implies unmutated IgVH status

Front 4

CD 5+, CD 19+ cell population on flow.

What is the differential dx?

Back 4

MCL
CLL
RA, hep C, post-BM transplant

Front 5

What is the most common chromosomal anomaly seen in CLL?

Back 5

del 13 > trisomy 12 > del 11q > del 14q > del 17p

Front 6

What % of prolymphocytic cell must be present to deem CLL prolympocytic transformation?

Back 6

11-55%

Front 7

Which leukemia has the strongest genetic predisposition, with familial clustering demonstrated in 5-10% of cases?

Back 7

CLL

Front 8

Which cytogenetic abnormalities in CLL are considered prognostically bad? good?

Back 8

Bad = del 11q, del 17p (p53) and 6q

Good= del 13q

Others= Trisomy 12

Front 9

Characteristic cytogenetic finding in MCL?

Back 9

t(11;14) CCND1(cyclin D1); IgH

Front 10

What is the single most important prognostic factor in MCL?

Back 10

Mitotic rate (proliferation index)

>10 mitosis per HPF = bad

Front 11

5+, 10-
FMC7+, CD23-

Back 11

Mantle cell lymphoma (MCL)

Front 12

What is the gene found at chromosome 11 in the 11;14 translocation of MCL and what is its function?

Back 12

CCND1 gene (cyclin D1)

stimulates entrance into G1-phase of cell cycle.

Front 13

Which lymphoma causes multiple lymphomatous polyposis?

Back 13

Mantle cell lymphoma (MCL)

Front 14

In addition to several types of DLBCL, what other lymphomas express BCL-6?

Back 14

Burkitt lymphoma
Follicular lymphoma

Front 15

What is the classic translocation seen in follicular lymphoma?

Back 15

t(14;18) IgH; BCL2

Front 16

What is the function of the BCL-2 molecule formed on chromosome 18?

Back 16

Inhibits cell death by heterodimerization with BAX and caspase

Front 17

What are the two types of lymphoma that commonly form paratrabecular aggregates in the bone marrow?

Back 17

Follicular lymphoma
T-cell rich B-cell lymphoma

Front 18

What is the most common type of primary cutaneous lymphoma?

Where does it usually occur?

Back 18

Primary cutaneous follicle center lymphoma

scalp, forehead or trunk

Front 19

In comparison to follicular lymphoma, what is the staining pattern of primary cutaneous follicle center lymphoma?

Back 19

BCL 6 + (positive in both)
CD10 -
BCL 2 -

Front 20

What is the associated stimuli?
Gastric MALT
Ocular MALT
Immunoproliferative small intestinal disease (IPSID)

Back 20

Helicobacter pylori
Chlamydia psittaci
Campylobacter jejuni

Front 21

What is the associated stimuli?
Cutaneous MALT
Salivary gland MALT
Thyroid gland MALT

Back 21

Borrelia burgdoferi
Sjogren syndrome (44x risk)
Hashimoto's thyroiditis (70x risk)

Front 22

What is the most common translocation seen in gastric MALT lymphoma?

Back 22

t(11;18) API2-MALT1

Front 23

What physical exam and peripheral blood findings are strongly associated with Hairy cell leukemia?

Back 23

Pancytopenia, specifically monocytopenia (almost always affects the BM, fibrosis)
Splenomegaly

Front 24

Which mature b-cell leukemia/lymphoma primarily involves the red pulp of the spleen?

Back 24

Red pulp- HCL
White pulp- FL, MCL, SMZL, CLL

Front 25

What is the most common genetic abnormality seen in 40% of cases of splenic marginal zone lymphoma

Back 25

del 7p

Front 26

What is the most specific non-IP stain for Hairy cell leukemia, especially when it stains brightly?

Back 26

Tartrate-resistant acid phosphatase (TRAP)
PLL, Waldenstrom, mast cell disease and Gauchers also stain but weakly.

Front 27

What is the most specific IP stain for Hairly cell leukemia?

Back 27

Annexin-1
-not expressed in any other b-cell lymphoma but is expressed in myeloid and some t-cells so must be compared with b-cell antigens

Front 28

Blood lakes are a characteristic finding of what disease?

Back 28

Hairy cell leukemia
-usually spleen but can be anywhere
(also peliosis)

Front 29

What is the "classic" cytogenetic finding seen in Hairy cell leukemia

Back 29

none

Front 30

What is the common characteristics on physical exam and peripheral blood in prolymphocytic leukemia?

Back 30

Splenomegaly without lymphadenopathy

WBC > 100k

Front 31

What is this?

Back 31

Dutcher body - seen in plasma cells, PAS+ accumulations of immunoglobulin forming pseudo inclusions in the nucleus.
Cytoplamic= Russel bodies
Numerous= Mott cell

Front 32

What is Waldenstrom macroglobulinemia?

Back 32

Lymphoplasmacytic lymphoma with an IgM monoclonal gammopathy and marrow involvement

Front 33

When DLBCL is CD5+, what IP stain should be done and why?

Back 33

bcl-1
bcl-1 positivity would make it blastoid mantle cell lymphoma

Front 34

What chromosomal abnormalities (2) are seen in 60%(30% and 30%) of cases of DLBCL?

Back 34

3q27 rearrangements (BCL6 gene)

t(14;18) IgH;BCL2

Front 35

What is the most common lymphoma seen in the brain?

Back 35

DLBCL
only rare example of other lymphomas have been reported

Front 36

What specific chromosomal abnormalities are specifically seen in Mediastinal DLBCL?

Back 36

gains in 9p (JAK2)

MAL gene expression

Front 37

Name the 7 hematologic diseases associated with tyrosine kinase mutation or rearrangement?

Back 37

CML, myeloid neoplasms with eosinophilia, PV, primary MF, ET and Mastocytosis and mediastinal DLBCL

Front 38

Name the associated TK mutation for following.
CML, myeloid neoplasm with eosinophilia and mastocytosis

Back 38

CML- ABL1
MN with eos- PDGFR a&b, FGFR1
Mastocytosis- KIT (cd117)

Front 39

Name the associated TK mutation for the following.
PV, PMF, and ET

Back 39

All are JAK2 mutations (9p). PMF and ET are rearrangements with the MPL gene.

Front 40

Gleevac (imatinib) inhibits what?

Back 40

TK
(ABL1 in CML)
(KIT in GIST)

Front 41

What are 2 unusual cells sometimes seen in CML?

Back 41

pseudo-gaucher cells
sea blue histiocytes

Front 42

Which drug can cause a Hodkin-like lymphoid infiltrate?

Back 42

Methotrexate

Front 43

What is the only myeloproliferative neoplasm that does not cause splenomegaly?

Back 43

Essential thrombocythemia

Front 44

Name the 2 EBV+ DLBCL's?

Back 44

Plasmablastic lymphoma
DLBCL of the elderly

Front 45

What is the status of each of the following markers in oral mucosal plasmablastic lymphoma?
CD38, CD138, CD56

Back 45

CD38, CD138 +
CD 56 -
"expression of CD56 should raise suspicion for underlying plasma cell myeloma"

Front 46

What virus is strongly associated with plasmablastic lymphoma? Where do they often occur in the body?

Back 46

HIV and EBV

Mucosal sites (often oral)

Front 47

Name the 3 malignancies associated with HHV-8 infection.

Back 47

Primary effusion lymphoma
Koposi's sarcoma
Multicentric Casteman's disease

Front 48

What demographic does this tumor affect? cutaneous, bcl-2 and bcl-6 positive. CD10 neg.

Back 48

Leg-type primary cutaneous DLBCL (cuteneous FL would be BCL-2 neg.) -- elderly women

Front 49

What is thought to be the cause of most early (<5y) post-transplant LPDs?

Back 49

EBV -increased risk if EBV negative before transplant
-most are clones from the recipient

Front 50

Where does endemic (African) Burkitt's often present and in what demographic?

Back 50

Jaw

Children, strong EBV assosication

Front 51

Where does sporadic (Western) Burkitt's often present and in what demographic?

Back 51

ileocecal valve

Children, not associated with EBV unlike endemic

Front 52

What is the classic IP of Burkitt's lymphoma?

Back 52

CD10 +
c-myc +
bcl-2 -
bcl-6 +

Front 53

What is the most commonly seen molecular rearrangements in Burkitt's?

Back 53

t(8;14) IgH (14), c-myc (8)
t(2;8) kappa (2)
t(8;22) lambda (22)

Front 54

Patient with mediastinal mass and hypercalcemia?

Back 54

T-LBL

B-LBL usually doesn't involve the mediastinum

Front 55

Which is the more common?
T-ALL vs. B-ALL
T-LBL vs. B-LBL

Back 55

B-ALL (80%)
T-LBL

Front 56

Name the two translocations with good prognosis in B-ALL?

Back 56

t(12;21) TEL-AML1
Hyperdiploid

Front 57

Name the four translocations with bad prognosis in B-ALL?

Back 57

Hypodiploid
t(9;22) BCR-Abl
11q23 (usually 4;11) MLL
t(1;19)

Front 58

Which IP marker is most sensitive for T-ALL?

Back 58

CD 7

Front 59

What is the expression of each of these marker in B-ALL and T-ALL?
CD7, CD19, CD20, surface Ig, Tdt, HLA-DR

Back 59

B-ALL- CD19+, CD20+/-, Tdt+, HLA-DR+, CD7-, surface Ig-
T-ALL- CD7+, Tdt+
HLA-DR-, surface Ig-

Front 60

What myeloid antigen is the most specific for determining lineage amoung hematopoetic cell lines?

Back 60

CD117 (100%) 80% sensitive
CD33 and CD13 are also fairly specific but not 100%

Front 61

What is the order (most common to least) of Ig paraprotein deposits in plasma cell myeloma?

Back 61

IgG - 55% IgA- 22%
light chain only (usually kappa)- 18%
IgD, IgE, IgM- 2%

Front 62

What is the most common chromosomal abnormality seen in plasma cell myeloma?

Back 62

14q32(IgH) translocations -70% esp. t(11;14)
Most have 4 or more abnormalities. del 13 -50%

Front 63

What are the good and bad prognostic groups in plasma cell myeloma regarding cytogenetics?

Back 63

t(4;14), t(14;16), t(14;20), del 17p, hyperdiploidy -bad
t(11;14), t(6;14), hyperdiploidy -good

Front 64

What is the major IP difference between plasma cell myeloma and plasma cell leukemia? Ig? cytogen?

Back 64

Plasma cell leukemia is usually CD56 neg. Also usually IgE, IgD or light chain only. usually monos. 13

Front 65

Where does extraosseous plasmacytoma usually arise and what is the prognosis?

Back 65

nasal cavity/oropharynx area

Most do not develop to plasma cell myeloma

Front 66

What does the acronym POEMS stand for; what does it usually imply?

Back 66

polyneuropathy,organomegaly,endocrinopathy, M-protein, skin changes. Implies plasmacytoma.

Front 67

What disease is POEMS syndrome associated with?

Back 67

plasma cell variant of Castleman's disease and HHV-8 infection

Front 68

What is the most common T cell neoplasm?

Back 68

Peripheral T-cell lymphoma (PTCL)

Front 69

What leukemia is caused by HTLV-1?

Back 69

Adult T-cell leukemia/lymphoma
- classically flower cells

Front 70

What is a classic symptomatic manifestation of Adult T-cell leukemia/lymphoma?

Back 70

Hypercalcemia and lytic bone lesions --> Osteoclast activating factor stimulation

Front 71

Flower cells are classic for what leukemia?

Back 71

Adult T-cell leukemia

Front 72

Where is Adult T-cell leukemia endemic?

Back 72

Southwest Japan
10% HTLV-1 infection

Front 73

Associated virus?
Angioimmunoblastic TCL
Adult TCL
Nasal type NK/TCL

Back 73

AILT -EBV (in associated b cells)
ATCL -HTLV-1
Nasal type NK - EBV
(Aggresive NK-cell leukemia - EBV)

Front 74

What are some peculiar associated findings in angioimmunoblastic TCL?

Back 74

autoimmune hemolytic anemia
Pleural effusion, anti-smooth muscle antibody, + rheumatoid factor

Front 75

What demographic group is most often affected by anaplastic large cell lymphoma?

Back 75

Young adults and children
-represents about half of all high grade childhood lymphomas

Front 76

What is the classic cell, Immunophenotype, distribution and genetics of ALCL?

Back 76

horse shoe cell, CD 4+/30+/45+ and ALK +, lymphadenopathy, t(2;5) ALK-NPM

Front 77

EBV + lymphoma that characteristically shows angio-invasion and extensive necrosis.

Back 77

Nasal-type NK/T-cell lymphomas

Front 78

Patients with Enteropathy-associated T-cell lymphoma have what classic history?

Back 78

Celiac sprue

HLADQ2 and HLADQ8

Front 79

Hepatosplenic T-cell lymphomas is assocated with what demographic group?

Back 79

If gamma-delta, young males

If alpha-beta, females(any age)

Front 80

What lymphomas can arise in children treated for Crohns

Back 80

Hepatosplenic TCL

(azathioprine and infliximab)

Front 81

What cytogenetic abnormality is associated with gamma-delta hepatosplenic TCL?

Back 81

isochrome 7q

Front 82

What are the classic histologic findings in subcutaneous panniculitic t-cell lymphoma?

Back 82

Tumor cell rim the subcutaneous fat, much apoptotic debris, histocytes (cleaning debris)

Front 83

What disease is associated with subcutaneous panniculitic t-cell lymphoma?

Back 83

SLE

Front 84

What is a feared sequela of subcutaneous panniculitic T-cell lymphoma. In which subtype is it common?

Back 84

Hemophagocytic syndrome

delta-gamma type

Front 85

What disease is this?

Back 85

This is a popcorn cell, classically seen in Nodular lymphocyte predominant hodkin lymphoma

Front 86

What IP stain is useful for staining the cells surrounding the "popcorn" cell in HLPHL?

Back 86

CD57 (and CD3)

Front 87

What is the staining pattern of classic HL vs. NLPHL?
CD30, CD15, CD45?

Back 87

============CHL/////NLPHL
CD15(Leu-M1)/////(+/-)//////( -)
CD30(Ki-1)//////////(+)///////(usually -)
CD45//////////////////(-)////////(+)

Front 88

In differentiating NLPHL from t-cell rich DLBCL, what stain is most useful?

Back 88

CD21 (dendritic meshwork)
If even slightly nodular with CD21, then is NLPHL

Front 89

What stain is usually negative in DLBC lymphomas that is usually positive in CHL?

Back 89

CD15 (Leu-M1)
CD15 positivity rules out DLBCL and NLPHL. Not 100% of NLPHL are CD15 +. If neg. do PAX5 (similar staining). ALCL is not ruled out.

Front 90

In nodular sclerosing classical hodkin lymphoma, what is the main demographic group and presentation?

Back 90

Young females, mediastinum

Front 91

NLPHL vs. CHL
Single node involvement? Distall relapses? Double peak in age? EBV association?

Back 91

Single node- NLPHL
Distall relap.- NLPHL
2 age peaks- CHL
EBV ass. - CHL (not used for diag or prognosis)

Front 92

Name the disease

Back 92

These are lacunar cells (caused by retraction artifact) and are seen in nodular sclerosing CHL

Front 93

Name the disese?

Back 93

This is a mummified cell (lacunar cell with shrunken, dark nuclei) and is seen in nodular sclerosing CHL

Front 94

Nodular sclerosis CHL most often occurs where (body site)?

Back 94

Mediastinum (80%)

Front 95

Lymphocyte depleted CHL isaggressive, seen in dev. nations and generally occurs where (body site)?

Back 95

Retroperitoneal lymph nodes
These are represented in the 2nd peak of age

Front 96

Which type of hodkin lymphoma least often show BM involvement?

Back 96

LPHL (<1%)
50% for LD and HIV associated
10% overall

Front 97

Can a myeloproliferative neoplasm show dysplasia?

Back 97

No, this would make it, by definition, MD/MPN

Front 98

Which commonly show splenomegaly? MDS, MD/MPN, MPN, AML?

Back 98

MD/MPN - Yes
MPN Yes
MDS No
AML No

Front 99

Most common chromosomal abnormality in MDS?
2nd?
3rd?

Back 99

Complex karyotype -bad
mono 7 or del 7q - bad
del 5q - good

Front 100

MDS with favorable prognosis?

bad prognosis?

Back 100

good- normal karyotype, del Y, del 5q, del 20q

Complex karyotype(3 or more), mono or del 7

Front 101

What is the usual presentation of MDS del 5q?

Back 101

Old women
hypolobated megs (plts normal or increased)
macrocytic anemia

Front 102

What is the classic morphology of MDS with del 17q?

Back 102

small vacuolated neutrophils with pseudo-Pelger-Huet anomaly

Front 103

What percent blast must be present to call something AML?

Back 103

Tricky question. Usually it is 20% however the several of the AMLs with translocations have no lower limit defined.

Front 104

Which small mature B-cell lymphoma is the most aggressive?

Back 104

Mantle cell lymphoma

Front 105

Cyclin D1 is present in what 3 lymphomas/leukemias?

Back 105

Mantle cell lymphoma (diagnostic)
Hairy cell leukemia
Plasma cell myeloma

Front 106

What is a normal cell in the LN that is a good internal control for cyclin D1?

Back 106

Histiocytes

Front 107

What is CMML?

Back 107

A MD/MPN disorder with specific features:
Monocytosis
<20% blasts
myelodysplasia (or genetic or >3 mos)

Front 108

What specific findings must be investigated and ruled out in order to label something as CMML?

Back 108

rule out a BCR-ABL1 fusion

No PDGFRa or b arrangement (esp. necessary if eosinophilia)

Front 109

What syndrome is associated with juvenile chronic myelomonocytic leukemia (JMML)?

Back 109

NF-1

Front 110

What hematologic disorder is a result of mutations involving genes of the RAS/MAPK pathway?

Back 110

JMML

Front 111

What physical finding is almost always seen in patients with JMML?

Back 111

hepatosplenomegaly

Front 112

What protein is greatly increased in many cases of JMML?

Back 112

hemoglobin F

Front 113

What is the "hallmark" clinical diagnostic feature of JMML?

Back 113

hypersensitivity of myeloid progenitor cells to GM-CSF

Front 114

CML cytogenetics?

Back 114

t(9;22) ABL-BCR

Most commonly M-BCR p210 protein

Front 115

p290 BCR fusion protein manifestations?

Back 115

CML with marked thrombocytosis

Front 116

p190 BCR fusion protein manifestations?

Back 116

CML with marked monocytosis

ph+ ALL

Front 117

What are the 3 major distinct fusion protein seen with CML?

Back 117

p210 - most common
p290- marked thrombocytosis
p190- marked monocytosis + ALL

Front 118

What are 2 unique testing abnormalities seen in CML?

Back 118

markedly elevated B12 (increased transcobalamin 1)
Impaired aggregation of plts in response to epinephrine

Front 119

Neutrophilia with basophilia is highly suggestive of what disease?

Back 119

CML

Front 120

What is the most effective drug we have for treating CML and what is its mechanism?

Back 120

Imatinib
Stops the enhanced TK activity of BCR-ABL1 (competative inhibitor with ATP at the BCR-ABL1 domain)

Front 121

What is the most important prognostic indicator in CML?

Back 121

Response to imatinib

Front 122

What is the natural history of CML?

Back 122

Progression to AML (70%) or ALL (30%) within 2-3 years.
Overall, 95% progress

Front 123

What is the most common "deadly" complication of polycythemia vera?

Back 123

Thrombosis (31%)

-Most common cause of budd-chiari syndrome

Front 124

How can one test for polycythemia vera by culturing the bone marrow?

Back 124

In PV new erythroid colonies will grow without addition of erythropoietin

Front 125

T/F JAK2 mutation is required for the diagnosis of PV?

Back 125

False, while 90% of cases have the mutation, it is not required.

Front 126

Why is assessing stainable iron helpful for diagnosing essential thrombocythemia?

Back 126

Helpful to ruleout reactive thrombocytosis due to iron deficiency

Front 127

T/F Chronic Eosinophilic leukemia is a clonal population of eosinophils without PDGFR or FGRF rearrangement?

Back 127

T, the blast count must be under 20%

Front 128

Which two AMLs with cytogenetic abnormalities are usually HLA-DR negative?

Back 128

t(15;17) - also usually negative for CD34
t(1;22)

Front 129

What two AMLs involve core binding factor?

Back 129

t(8;21) AML1/ETO
-- AML1 encodes CBFalpha
t(16;16)/inv 16 CBFbeta

Front 130

AML's with favorable prognosis?

Back 130

t(8;21)
t(16;16) / inv 16
t(15;17)

Front 131

Which AML translocation is strongly suggested with a positive CD 19 and CD 56? What characteristic morphology is also present?

Back 131

t(8;21)
Salmon-colored cytoplasmic granules.

Front 132

What is the translocation that manifests as AML with morphologically abnormal eosinophils?

Back 132

t(16;16) inv 16

MYH11 (myosin)- CBF-beta

Front 133

What three therapies can lead to therapy-related AML or MDS?

Back 133

Topoisomerase 2 inhibitors (1-5years)
alkylating agents (5+ years)
radiation (5+ years)

Front 134

What mutation (non-germline) is often seen in down syndrome patients with AML or transient myeloprolifeative disorder?

Back 134

mutations in the GATA-1 gene

Front 135

What cell line does a Leder stain identify and what specific material does it stain in these cells?

Back 135

Stains the chloracetate esterase found in myeloid cells
(Normally CAE is negative in eosinophils except curiously in the abnormal eos in inv. 16 AML/ t(16;16) where it is positive)

Front 136

Increased polyclonal Ig production is seen in which type of T-cell lymphoma?

Back 136

Angioimmunoblastic TCL
-also +Coombs, pleural effusions, cold agglutinins, +anti-smooth muscle antibody, +rheumatoid factor

Front 137

What is another name for CD25 and what two leukemias classically express it?

Back 137

IL-2 receptor
Hairy cell leukemia
Adult TCL

Front 138

What leukemia/lymphoma shows elevated soluble IL-2 receptor in the serum?

Back 138

Adult T-cell leukemia
AKA CD25
CD25 (IL-2 rec) stains adult TCL and hairy cell leukemia

Front 139

What is another name for MAC-1 IP stain and what leukemia is classically positive for it?

Back 139

CD 11b
Hairy cell leukemia

Front 140

The IgE receptor IP stain is helpful for differentiating what two leukemias?

Back 140

AKA CD23+

CLL+
MCL -

Front 141

What is another name for CD15?
CD30?

Back 141

CD 15 = Leu-M1

CD 30 = Ki-1 or Ber-H2

Front 142

Marginal zone lymphoma with circulating villous lymphocytes and hairy cell leukemia both affect the spleen; which do they involve, the white pulp or red pulp?

Back 142

MZL - white pulp
HCL - red pulp
In fact, HCL is the only mature b-cell leukemia to affect the red pulp

Front 143

PTLD in heart transplant recipients most commonly occurs where?

Back 143

Heart or lung

Front 144

Which type of hodkin disease most commonly progresses to DLBCL?

Back 144

LP HD