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MI Immuno/Heme > Blood Cancers and Lymphoma > Flashcards

Blood Cancers and Lymphoma Flashcards

1
Q

Peripheral blood smear

A

PelgerHuët cells - dysplastic change which are abnormal appearing neutrophils having only two nuclear lobes

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2
Q

Dysplasia associated with myelodysplastic syndromes

A

PelgerHuet cells
Hypersegmented PMNs
Hypo/hypergranular cells

RBCs - presence of ringed sideroblasts (seen w/ prussian blue), megaloblastoid erythroid precursors, and mishapen erythroid precursors w/ nuclear budding

Megakaryocytes may be abnormal and only have a single nuclear lobe or multiple separate nuclei (prawn ball megakaryocytes)

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3
Q

How are myelodysplastic syndromes classified?

A

Based on # of blasts present w/i marrow

WHO classification:

<5% blasts - MDS is either refractory anemia (RA) or RA w/ ring sideroblasts (RARS)

5-20% blasts in marrow - RA w/ excess blasts (RAEB)

> 20% blasts in marrow = acute leukemia

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4
Q

5q- syndrome

A

myelodysplastic syndrome which is characterized by megakaryocytes that are uniformly small and monolobated

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5
Q

Sxs of acute leukemia

A

Fever (secondary to infection), easy fatigability (due to anemia), and bleeding (due to thrombocytopenia)

Both ALL and AML are characterized by a decrease in mature forms of cells and increase in immature forms (blasts which have immature chromatin with multiple nucleoli)

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6
Q

Acute myelogenous leukemia

Epidemiology

A

Typically adults between ages of 15-39

Risk Factors:
-Akylating chemo
-Radiation
-Myelodysplastic syndromes
-Myeloproliferative neoplasms
-Down syndrome

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7
Q

CD markers for Pt w/ acute myelogenous leukemia

A

Myeloid markers:
CD13

CD33

Blast markers:

CD34

CD117

Myeloperoxidase (MPO) = stain to differentiate AML from ALL

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8
Q

Auer rods in AML

A

Abnormal lysosomal structures (primary granules) considered pathognomonic of myeloblasts

Stain red with MPO

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9
Q

Acute promyelocytic leukemia (APL)

A

APL is also characterized by the
translocation t(15;17), which results in the fusion of the retinoic acid receptor α (RARA) gene on chromosome 17 to the PML unit on chromosome 15

produces an abnormal retinoic acid receptor such that physiologic levels of retinoic acid no longer activate it.

Treatment for APL is with large doses of vitamin A derivatives, such as all-trans-retinoic acid, which inhibits the proliferation of cells of acute myeloid leukemia.

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10
Q

What subtype of acute myelogenous leukemia is associated with gingival infiltrates?

A

Acute monocytic leukemia

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11
Q

What subtype of acute myelogenous leukemia is associated with marked fibrosis of the bone marrow

A

Acute megakaryocytic leukemia is associated with acute myelofiborisis

Acute megakaryocytic leukemia is
associated in children younger than 5 years of age with Down syndrome.

Special stains for megakaryocytes include stains for von Willebrand factor and stains for GpIb/IIIa (on platelets).

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12
Q

Acute lymphoblastic leukemia (ALL)

A

Primarily disease of children and young adults

Lymphoblasts stain positively for TdT (nuclear enzyme)

ALL is associated with CNS infiltration (distinguishes from AML) where malignant lymphoblasts are protected from chemotherapy by the BBB

Pt’s with ALL may be given prophylactic radiation to head

Also, acute lymphoblastic leukemia is associated with Down syndrome after the age of 5

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13
Q

Immunologic classification of acute lymphocytic leukemia

A

Most of ALL are B-cell origin:

Lymphoblasts express CD19

Few cases are T-cell origin:

Lymphoblasts lack CD19 but instead express T-cell Ags (CD3 and CD7)

CD markers for T cells are CDs less than 10

Many cases of T-ALL involve a mediastinal mass (which may press on the esophagus causing dysphagia) and are clinically similar to cases of T-cell lymphoblastic lymphoma.

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14
Q

Pro B-cell acute lymphoblastic leukemia

A

+TdT (marker for immature cells)

Lacks CD10/cytoplasmic μ/surface Ig

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15
Q

Common B-ALL

A

+TdT and +CD10

CD10 is called CALLA - common ALL antigen

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16
Q

Pre-B-ALL

A

Characteristic translocation t(1;19)

+cytoplasmic μ chains

-TdT and -surface Ig

May be + for CD10

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17
Q

Mature B-ALL

A

Cells have surface Ig

Lack TdT/CD10/ and cytoplasmic μ

Mature B-ALL is the leukemic form of Burkitt’s lymphoma

-Similarly malignant cells have cytoplasmic vacuoles that stain positively with the oil red O lipid stain

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18
Q

Prognosis with ALL

A

The presence of CALLA (CD10) is a marker of a favorable prognosis, as is the presence of t(12;21), which is the most common chromosomal rearrangement in childhood B-ALL.

t(9;22) is associated with a poor prognosis. Most children with ALL achieve complete remission with
chemotherapy.

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19
Q

____ is the most common leukemia and is similar in may aspects to small lymphocytic lymphoma (SLL)

A

Chronic lymphocytic leukemia (CLL)

If Pt presents w/ blood findings first = CLL

If they present w/ lymph node findings first = SLL

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20
Q

What sxs are associated w/ chronic lymphocytic leukemia?

A

CLL has an indolent course - disease is associated w/ long survivial in many cases

Sxs that may develop are related to anemia or infections - malignant cells are non-functional

Lymphadenopathy or splenomegaly may be noted

Minority of Pt - disease may transform into prolymphocytic leukemia or a large cell immunoblastic lymphome (Richters syndrome)

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21
Q

Richter’s syndrome (transformation)

A

CLL transformation into immunoblastic lymphoma

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22
Q

Prolymphocytic leukemia

A

Can be transformation from CLL

Characterized by massive splenomegaly and a markedly increased leukocyte count consisting of enlarged lymphocytes having nuclei with mature chromatin and nucleoli

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23
Q

What leukemia is associated with warm AIHA?

A

CLL - warm autoimmune hemolytic anemia is characterized by finding spherocytes in the peripheral blood

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24
Q

Tx of B-CLL

A

Rituximab - mAb against CD20 (B cell marker)

Drug is associated w/ increased risk of progressive multifocal leukoencephalopathy (demyelinating disease of CNS caused destruction of oligodendrocytes secondary to reactivation of JC virus)

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25
Q

Hairy cell leukemia

A

(HCL) - indolent type of mature B-cell leukemia found most often in older males

Signs:

Pancytopenia (due to leukemic infiltration of marrow)

Splenomegaly (most common sign) - leukemic cells infiltrating red pulp (unusual because leukemias preferentially infiltrate white pulp)

These neoplastic cells proliferate in spleen = splenectomy

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26
Q

Peripheral smear of HCL Pt blood

A

Numerous lymphocytes w/ cytoplasmic projections

Cells stain for acid phosphatase and rx’n is refractory to Tx w/ tartaric acid (tartrate-resistant acid phosphatase [TRAP])

Hairy cells also express pan-B-cell markers (CD19 and CD20) and monocyte marker CD11c

Hairy cells are negative for CD5 and CD10

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27
Q

What does aspiration of marrow in Pt w/ HCL show?

A

Dry tap

But biopsy shows proliferation of malignant cells w/ fried-egg appearance

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28
Q

Tx of HCL

A

Purine analogs like cladribine (2-CDA = first-line Tx)

Also pentostatin (also purine analog)

These drugs are resistant to breakdown by adenosine deaminase (enzyme that is deficient in the AR form of SCIDs) - inhibits nucelotide metabolism and leads to the accumulation of toxic amounts of dexyadenosine

Adenosine deaminase (ADA) is an enzyme that converts adenosine to inosine. ADA inhibition results
in the metabolism of deoxyadenosine through an alternate pathway, which is toxic to lymphocytes.

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29
Q

What stain differentiates AML from ALL?

A

Myeloperoxidase

Myeloblast stain +

Lymoblasts are -

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30
Q

What translocation is associated with acute promyelocytic leukemia?

A

t(15;17)

17 - retinoic acid receptor alpha (RARA) gene

15 - promyelocytic leukemia (PML) gene

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31
Q

What increases risk for disseminated intravascular coagulation (DIC) in Pt’s w/ acute promyelocytic leukemia (APL)?

A

The abnormal promyelocytes seen in APL contain numerous primary granules - increases risk of DIC

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32
Q

Staining of lymphoblasts from Pt w/ acute lymphoblastic leukemia (ALL)

A

Stain positive for terminal deoxynucleotidyl transferase (TdT)

Negative for myeloperoxidase

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33
Q

What translocation is associated w/ a poor prognosis for Pt’s w/ acute lymphoblastic leukemia (ALL)?

A

t(9;22)

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34
Q

What factor(s) are associated w/ a favorable prognosis for Pt’s w/ acute lymphoblastic leukemia?

A

Translocation t(12;21) and presence of CD10 (CALLA)

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35
Q

Why do Pt’s w/ acute lymphoblastic leukemia sometimes receive prophylactic radiation to their head?

A

ALL is associated w/ CNS infiltration, where malignant lymphoblasts are protected from chemotherapy by the BBB

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36
Q

Peak incidence of acute lymphoblastic leukemia

A

Between ages 2-5

Also is associated in Pt’s with Down syndrome after age 5

Down syndrome before age 5 is associated with acute megakaryocytic leukemia

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37
Q

What subtype are most cases of acute lymphoblastic leukemia?

A

B-cell origin (B-ALL)

Express CD10 and CD19

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38
Q

Signs of hairy cell leukemia

A

Pancytopenia

Dry tap of marrow

Massive splenomegaly

Splenomegaly is most common sign w/ infiltration of red pulp

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39
Q

Strongest evidence of lymphoma malignancy

A

Monoclonal lymphocytic proliferation

Benign lymph node enlargement is associated w/ a polyclonal proliferation of lymphocytes

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40
Q

What is the most common indolent non-Hodgkin lymphoma?

A

Follicular lymphoma - B-Cell origin and characterized by painless waxing and waning lymphadenopathy in an older adult

41
Q

Histological characterization of follicular lymphoma

A

Neoplastic nodule that obscure (efface) the normal lymph node arhitecture

Follicle in follicular lymphoma do not contain tingible-body macrophages and are not surrounded by mantle zones

42
Q

What translocation is associated w/ follicular lymphoma?

A

t(14;18) - causes BCL2 overexpression and inhibition of apoptosis

43
Q

Most common type of non-Hodgkin lymphoma in adults

A

Diffuse large B-cell lymphoma

Agressive (high-grade) type of lymphoma w/ a poor prognosis

Tumor cells have a high proliferative index and stain positively for CD20

Also associated w/ alteration in Bcl-2 proteins

44
Q

Primary CNS lymphoma

A

Associated w/ advanced HIV infection (secondary EBV infection)

45
Q

Primary effusion lymphoma

A

Associated w/ advanced HIV infection (secondary HHV-8 infection)

46
Q

Burkitt lymphoma

A

High-grade B-cell lymphoma associated with t(8;14) resulting in MYC overexpression - produces a nuclear protein whose Fx is to activate transcription

47
Q

Histopathology of Burkitt lymphoma

A

Sheets of malignant small, non-cleaved lymphocytes forming a starry-sky appearance due to macrophages engulfing apoptotic cells

48
Q

African type of Burkitt lymphoma

A

Endemic form and typically involves the maxilla or madible - especially of the young child

Associated w/ EBV

49
Q

American type of Burkitt lymphoma

A

Nonendemic and commonly involvees the abdomen, such as bowel, ovaries, or retroperitoneum

Associated w/ EBV if Pt is immunosuppressed (i.e. HIV)

50
Q

Gastric MALT lymphoma

A

Type of marginal zone lymphoma associated w/ H. pylori infection and t(11;18)

51
Q

Marginal cells

A

Normally located in marginal zone of the spleen (area where T and B cells first enter spleen)

52
Q

Mantle cell lymphoma

A

Characteristically associated w/ t(11;14) - involves the cyclin D1 gene (on 11) and Ig heavy chain locus (on 14) - results in overexpression of cyclin D1 (CCND1 or bcl-1)

Non-Hodgkin B cell lymphoma that originates from B-cells normally found in the mantle zones (normally located immediately outside of the follicle)

Small cleaved cells that stain + for CD5. CD19, and CD20

In contrast to CLL/SLL that are negative for CD23

53
Q

Hodgkin lymphoma

A

Bimodal age group distribution: young adults and adults older than 50

sxs: fever, night sweats, and weight loss

Characterized by the proliferation of Reed-Sternberg cells - usually present w/ focal, nontender lymphadenopathy in a young adult

54
Q

Reed-Sternberg cells

A

Malignant cells in Hodgkin lymphoma

Stain positively for CD15 and CD30

Appear as large binucleated cells w/ an owl-eye appearance in a background of reactive lymphocytes in a biopsy of lymphoid tissue

55
Q

What is the most common subtype of Hodgkin lymphoma

A

Nodular sclerosis Hodgkin lymphoma

Characterized morphologically by the presence of lacunar cells (a variant of RS cells w/ a clear space surrounding the nucleus)

56
Q

Hypercalcemia in individuals w/ Hodgkin lymphoma

A

May result from paraneoplastic secretion of gamma-interferon by activated T-cells

  • activates Vit D by increasing the expression of 1alphahydroxylase in malignant lymphocytes and macrophages

This same mechanism causing hypercalcemia can be seen with sarcoidosis

57
Q

Sézary syndrome

A

The leukemic form of mycosis fungoides

characterized by finding CD4+ cells with cerebriform nuclei (Sezary cells) in the peripheral blood.

May be associated w/ a generalized pruritic erythematous rash - red-man syndrome

Mycosis fungoides is not associated w/ hypercalcemia

58
Q

Mycosis fungoides

A

Malignancy of CD4+ T-cells

Skin biopsy shows atypical lymphocytes w/ markedly convoluted nuclei infiltrating the epidermis

May form characteristic intraepidermal clusters known as Pautrier microabscesses

Sezary syndrome

59
Q

What malignancy of CD4+ T-cells is endemic in Southern Japan and parts of the Caribbean?

A

Adult T-cell leukemia/lymphoma - mostly affects CD4+ T-cell subset which have a predilection for the skin (cutaneous T-cell lymphomas)

Characterized by hypercalcemia and poor prognosis

The cause of ATLL is infection with HTLV-1, a virus that infects CD4-positive T-cells. Examination of the peripheral smear will show abnormal hyperlobated lymphocytes, called flower cells. The prognosis of ATLL is poor.

60
Q

Langerhans cells

A

APCs found in the skin - possess characteristic racquet-shaped intracytoplasmic granules known as Birbeck granules (pentilaminar bodies)

Histological markers:

CD1a (mediates Ag presentation)
S-100 (tumor marker for cells derived from the neural crest)

61
Q

Hand-Schüller-Christian disease

A

Langherhans cell histiocytosis (multifocal LCH) that is characterized by the clinic triad:

Bone lesions (particularly the calvarium and base of skull)
DM I
Exophthalmos

Lesions are result of proliferations of LC’s - lesions around hypothalamus lead to decreased ADH production and signs of DM insipidus

Poor prognosis

Usually begins between the second and sixth years of life

62
Q

Letterer-Siwe disease

A

Acute disseminated LCH

Affects young children (<3 y/o)

Cutaneous lesions that resemble seborrhea, hepatosplenomegaly, and lymphadenopathy

LC’s infiltrate the marrow which leads to anemia, throbocytopenia, and recurrent infections

Usually rapidly fatal, intensive chemotherapy 50% of Pt’s may survive 5 years

63
Q

Eosinophilic granuloma

A

Unifocal Langerhans cell histiocytosis (LCH)

Seen in older patients

Usually unifocal - most often affecting the skeletal sytem (usually ribs)

Lesions are granulomas that contain mix of lipid-laden Langerhans cells, macrophages, lymphocytes, and eosinophils

Excellent prognosis

64
Q

What lymphoma is defined by finding hallmark cells upon histological exam?

A

Anaplastic large cell lymphoma (ALCL)

T-cell lymphoma

Hallmark cells may have nuclei w/ a horsehoe-like or embryo-like appearance

Malignant cells are strongly + for CD30

65
Q

Anaplastic large cell lymphoma is associated with what gene mutation?

A

Mutations involving the ALK gene

66
Q

What is the most common cutaneous T-cell lymphoma

A

Mycosis fungoides (MF)

Primarily affects the skin - but extracutaneous spread to lymph nodes, spleen, liver, and lungs is common

67
Q

Stages in the involvement of skin w/ mycosis fungoides

A
  1. Generalized pruritic erythematous rash
  2. Formation of plaques
  3. Formation of large tumor nodules

Early in the disease a skin biopsy will reveal a bandlike infiltrate in the upper dermis composed of atypical lymphocytes with markedly convoluted nuclei. These PAS-positive cells will infiltrate the epidermis (epidermotropism) and may form characteristic intraepidermal clusters known as Pautrier’s microabscesses.

68
Q

Type of lymphoma that histologically shows popcorn-cells

A

Popcorn-cells = variant Reed-Sternberg cells called the lymphohistiocytic cells (L&H) - only seen in the lymphocyte predominant subtype

69
Q

What class of lymphoma presents with contiguos spread to adjacent node groups

A

Hodgkin lymphoma - therefore early Tx w/ radiation therapy is possible

70
Q

How is the classification of Hodgkin lymphoma defined?

A

Based on the inflammatory response

71
Q

Classic Hodgkin Lymphoma

A
  1. Nodular sclerosis HL
  2. Mixed cellularity HL
  3. Lymphocyte-rich HL
  4. Lymphocyte depletion HL (worst prognosis)

Nodular sclerosis is most common subtype of HL

Nodular slerosis is most common in females

72
Q

Which forms of Hodgkins Lymphoma are associated w/ EBV?

A
  1. Mixed cellularity HL
  2. Lymphocyte-rich HL
  3. Lymphocyte depleted HL
73
Q

Types of B-cells in normal germinal centers

A
  1. Centroblasts - large non-cleaved lymphocyte that have a nucleolus and usually lack a nuclear cleft
  2. Centrocytes - lack a nucleolus and have irregular or cleaved nuclei (small cleaved lymphocytes)
74
Q

Buttock-cells

A

Malignant centrocytes (small cleaved cells) that are found within the peripheral blood

Associated w/ non-Hodgkin’s lymphomas

75
Q

Is BCL2 expressed in reactive germinal centers?

A

No -

the product of BCL2 is located on the outer mitochondrial membrane, ER, and nuclear envelope - it inhibits apoptosis by blocking bax channels and by binding and sequestering apoptosis activating factor 1 (Apaf-1)

Interfers w/ apoptosis mechanism that involves cyt c being released from mitochondria via bax channels (cyt c binds and activates Apaf-1 which stimulates caspase cascade and promotes apoptosis)

76
Q

Follicular form of non-Hodgkin’s lymphoma

A

Nodular (follicular) nHL results from neoplastic proliferation of B-cells dervided from germinal centers

Express CD19, CD20, and CD10 (CALLA), and surface Ig

77
Q

How do nodules seen w/ follicular lymphoma histologically differ from germinal centers?

A
  1. Increased numbers (crowding) of nodules
  2. Location in both cortex and medulla
  3. Uniform size
  4. Composition (a monotonous proliferation of cells that lack tingible-body macrophages

Follicles are not surrounded by mantle zones (unlike normal reactive germinal centers)

78
Q

Lymphoblastic lymphoma

A

high-grade NHL lymphoma that frequently involves the bone marrow and peripheral blood

Malignant cells in most cases are T-cells - clinical picture similar to that of T-cell acute lymphoblastic leukemia

T-cell lymphoblastic lymphomas occurring in the thoracic cavity of young Pt’s usually arise in the mediastinum and have a particularly aggressive clinical course w/ rapid growth

79
Q

Treatment for acute promyelocytic leukemia is with large doses of what?

A

All-trans-retinoic acid

Treatment for acute promyelocytic leukemia is with large doses of all-trans-retinoic acid (a vitamin A derivative).

80
Q

What cells stain positive for terminal deoxynucleotidyl transferase (TdT) and negative for myeloperoxidase?

A

Lympoblasts

Testing for acute lymphoblastic leukemia vs acute myeloblastic leukemia

81
Q

Malignant cells of chronic lymphocytic leukemia have what markers?

A
  • The malignant cells of CLL are most often of B-cell origin and express CD19, 20, 21, and 23, along with the T-cell marker CD5.
82
Q

which is the most common type of lymphoma in adults in the United States, is characterized by malignant lymphocytes that have a high proliferative index and stain positively for CD20?

A

Diffuse large cell lymphoma

83
Q
A

Burkitt lymphoma

84
Q
A

Sezary syndrome

85
Q
A

Follicular lymphoma

86
Q

What condition would you see marginal cells in the lymph node?

A

Toxoplasmosis lymphadenitis

87
Q
A

Follicular lymphoma - resulting from overexpression of BCL2 (located on chromosome 18)

BCL2 = B-cell lymphoma protein - antiapoptotic protein

Also - the TCR gene and heavy chain genes are located on chromosome 14

88
Q
A
89
Q
A

Small cleaved lymphocyte - aka buttock cell

90
Q

Diagnosis

A

Burkitt lymphoma

Tingible macrophages - present but there is no follicle (distinguishes between follicular lymphoma/hyperplasia and Burkitt’s lymphom)

91
Q
A

Reed-Sternberg cells - characteristic of Hodgkin lymphoma

92
Q
A

Lacunar cells are diagnostic of nodular slcerosis

93
Q
A

Specifically Han-Schuller Cristian disease

Lytic lesions in the skull of a child = Langerhan cell histiocytosis

in an adult = multiple myeloma

94
Q

What type of T cells infiltrate the skin?

A

CD4+ T cells

95
Q
A
96
Q

Which one of the following is characterized histologically by neoplastic nodules that obscure the normal lymph node architecture?

A) Burkitt lymphoma
B) Follicular lymphoma

A

B) Follicular lymphoma

97
Q

Burkitt lymphoma is a high-grade B-cell lymphoma that is associated with t(8;14), which results in overexpression of what?

A

c-MYC

Burkitt lymphoma is a high-grade B-cell lymphoma that is associated with t(8;14), which results in MYC overexpression, the product of which is a nuclear protein whose function is transcription activation.

98
Q

What RBC abnormality is seen in multiple myeloma?

A

Rouleaux formation (grouped erythrocytes w/ stacked-coin appearance)

MI Immuno/Heme (35 decks)

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