Bhl Week 3: Lymphomas I- Non-Hodgkin Lymphomas

Front 1

What are the 2 regions of the lymph node cortex, and which cells are predominate in these regions?

Back 1

Follices--> predominantly B-cells
Paracortical (interfollicular) areas --> predominantly T cells

Front 2

How do antigens reach the lymph nodes?

Back 2

Via afferent lymphatics
(which drain into the subcapsular sinuses)

Front 3

How is the lymph node drained?

Back 3

Via efferent lymphatics which leave at the hilum of the lymph node

*This is how lymphocytes leave the lymph node

Front 4

What are the two functional regions of the lymph node?

Back 4

Cortex and medulla

Front 5

What's the difference between primary and secondary follicles?

Back 5

Primary follicles contain small lymphocytes

Secondary follicles contain germinal centers (B-cells) and are surrounded by mantle zones (memory B-cells)

Front 6

Which cells are predominantly in the superficial cortex of lymph nodes?

Back 6

B-cells

Front 7

Which cells are predominantly in the deep cortex of lymph nodes?

Back 7

T-cells

Front 8

Which cells are most prominent in the medulla of lymph nodes?

Back 8

Plasma cells

Front 9

Is nodal or extranodal involvement more common Non-Hodgkin lymphomas?

In the U.S., are B-cells or T-cells more involved?

Back 9

Nodal involvement

*B-cell more common

Front 10

Are Non-Hodgkin lymphomas typically associated with production of a monoclonal immunoglobulin protein?

Back 10

They occasionally produce Igs, but usually not.

(*Lymphoblastic lymphomas are the exception)

Front 11

What age group is more commonly associated with Non-Hodgkin lymphomas?

Back 11

Older people-- 60s - 70s.

Front 12

Is NHL more commonly seen in males are females?

Caucasians are African Americans?

Back 12

Males
Caucasians

Front 13

While in most cases of NHL, there are no obvious predisposing factors, list some possible etiologies of NHL.

Back 13

1. Genetic predisposition
2. Chemical exposure
3. Ionizing radiation
4. Immunosuppression
5. Viral infections
6. Chronic antigen stimulation
7. Autoimmune diseases

Front 14

What is the most common cytogenetic abnormality seen in B-cell NHLs?

Back 14

Reciprocal translocations
(mutation in heavy chain gene (IgH) on the long arm of chromosome 14)

*T-cell receptor gene also located on 14q and susceptible to translocations, which results in T-cell lymphomas

Front 15

What type of neoplasms have the fastest doubling times of any neoplasm that afflicts humans?

Why?

Back 15

Burkitt's lymphomas

*c-MYC is associated with cell proliferation

Front 16

Which neoplasm involves a c-MYC/IgH translocation?

Back 16

Burkitt's lymphoma

Front 17

Which neoplasm involves an IgH/BCL-2 translocation?

What is the result?

Back 17

Follicular neoplasms

*Resistance to apoptosis (grow slowly, but cells don't die)

Front 18

Which neoplasm involves cyclin D1/IgH translocation?

What is the result?

Back 18

Mantle cell lymphoma

*Cell proliferation (slower than Burkitt's lymphoma, though)

Front 19

What is the most common clinical presentation of NHL?

What are some other presentations?

Back 19

**Enlarged lymph nodes (lymphadenopathy)

Others:
1. Tumor in extranodal site
2. Systemic symptoms
3. Hematologic disease (lymphocytosis, leukopenia, anemia, thrombocytopenia)

Front 20

What is an important difference between the WHO and Working Formulation in their classification of NHL?

Back 20

The WHO does NOT divide lymphomas into broad prognostic groups

Front 21

How does the WHO attempt to classify NHL?

What are the 3 main categories?

Back 21

Classification based on cell of origin

1. B-cell (including plasma)
2. T-cell
3. Hodgkin lymphoma

Front 22

Give 2 examples of immature of B- and T-cell neoplasms.

Back 22

1. Acute lymphoblastic leukemias
2. Lymphoblastic lymphomas

Front 23

Give 3 examples of mature B- and T-cell neoplasms.

Back 23

1. Most NHL
2. Chronic lymphocytic leukemias
3. Plasma cell neoplasms

Front 24

How does the WHO classify mature B-cell and T-cell neoplasms?

List the 3 types.

Back 24

Grouped according to clinical presentation:

1. Predominantly disseminated/leukemic
2. Primarily extranodal
3. Predominantly nodal

Front 25

In the U.S., the majority of lymphoma cases consist of which 2 lymphoma TYPES?

Back 25

1. Diffuse large B-cell (30 - 40%)
2. Follicular lymphomas (20 - 30%)

Front 26

In general, which histologic characteristics indicate more aggressive clinical behavior?

Back 26

Diffuse architecture and large cell size

Front 27

Which types of indolent lymphomas are more likely to transform to aggressive large cell lymphomas?

Back 27

1. Follicular lymphomas
2. Small lymphocytic lymphomas

Front 28

How do the majority of indolent lymphomas present (localized or disseminated)?

Back 28

Majority are disseminated

Front 29

How do aggressive lymphomas present (localized or disseminated)?

Back 29

Majority are disseminated, but may also be localized at diagnosis

Front 30

Is relentless relapse typically seen in indolent or aggressive lymphomas?

Back 30

Indolent lymphomas

Front 31

How are indolent lymphomas treated?

Back 31

Palliative care
(incurable with conventional therapy. They respond to relatively gentle therapy in terms of decrease in tumor bulk-- but the tumor always comes back)

Front 32

How are aggressive lymphomas treated?

Back 32

Treated with a curative (rather than palliative) intent-- immediate, aggressive chemotherapy

*Even if they appear localized at diagnosis, they need to be treated systemically-- localized therapy usually results in systemic relapse

Front 33

Are indolent lymphomas predominantly nodal or extranodal?

Back 33

Nodal (+/- liver, spleen, and BM)

Front 34

Are aggressive lymphomas predominantly nodal or extranodal?

Back 34

The MAJORITY of cases involve lymph nodes, but aggressive lymphomas may also be extranodal--in contrast to indolent lymphomas which rarely have extranodal involvement

Front 35

What is the most common type of Non-Hodgkin lymphoma in the U.S.?

Back 35

Diffuse Large B-Cell Lymphoma (DLBCL)

Front 36

Which is a better prognosis in Diffuse Large B-cell Lymphomas-- germinal center or activated B-cell involvement?

Back 36

Germinal center B- cell --> better prognosis

Front 37

What is the second most common Non-Hodgkin lymphoma in the U.S.?

Back 37

Follicular lymphoma

Front 38

Which lymphoma results from t(14;18) translocation?

Back 38

Follicular lymphoma
IgH/BCL-2 (anti-apoptotic)

Front 39

How are follicular lymphomas graded?

Back 39

Based on numbers of large cells:
1 = fewest, 3 = most

Grades 1 and 2 considered low-grade (indolent)

Front 40

What is the most common extranodal lymphoma?

Back 40

Extranodal Marginal Zone (MALT) Lymphomas

Front 41

Are MALT lymphomas curable or must they be treated palliatively?

Back 41

Despite indolent behavior, they are potentially curable-- if they are localized

Front 42

Where are MALT lymphomas often located in the body?

Back 42

Half are found in the GI tract, mostly the stomach

Front 43

Marginal zones are more prominent in which lymphoid tissues?

Back 43

Peyer's patches and the spleen
(much less apparent in lymph nodes)

Front 44

Many Gastric MALT lymphomas are associated with...?

Back 44

Chronic gastritis caused by H.pylori

Front 45

Which type of lymphoma can be treated with antibiotics?

Back 45

Gastric MALT lymphoma
(eradication of H.pylori)

Front 46

Small Lymphocytic Lymphoma is essentially identical to which other neoplasm?

How are they distinguished from each other?

Back 46

B-cell chronic lymphocytic leukemia (B-CLL)

*Distinguished by presence or absence of lymphocytosis

Front 47

Is the behavior of Small Lymphocytic Lymphoma (SLL) indolent or aggressive?

Back 47

Indolent
(typically long survival)

Front 48

Which neoplasm is associated with t(11;14) translation?

Back 48

Mantel Cell lymphoma
(CCND1/IgH)

CCND1 = gene for cyclin D1--> protein associated with passage through cell cycle

Front 49

Which lymphomas have a relatively short survival, but are considered incurable with conventional therapy?

Back 49

Mantle cell lymphomas

Front 50

"Endemic Burkitt's" is common on which continent?

Back 50

Africa

Front 51

In Africa, Burkitt's lymphoma is commonly associated with which virus in?

Back 51

EBV, with Malaria as a co-factor (to suppress immune system)

(In the U.S., though, Burkitt's is more commonly due to sporadic etiology rather than viral)

Front 52

Which neoplasm is associated with t(8;14) translocation?

Back 52

Burkitt's lymphoma
(c-MYC/IgH)

Front 53

"Starry sky" histologic pattern is associated with which neoplasm?

Back 53

Burkitt's lymphoma

Front 54

Which prognosis is worse-- T or B-cell lymphomas?

Back 54

T-cell lymphomas --> worse prognosis

Front 55

While most T-cell lymphomas are aggressive, give an example of an indolent type.

Back 55

Mycosis fungoides (cutaneous lymphoma)

Front 56

What is the most common T-cell lymphoma?

Back 56

Peripheral T-cell lymphoma (PTCL)

Front 57

Describe the different stages of the Ann Arbor Staging system.

Back 57

Stage I = single site (lymph node)
Stage II = More than one site; SAME SIDE of diaphragm
Stage III = Disease on BOTH SIDES of diaphragm
Stage IV = Liver, bone marrow, or disseminated extranodal

Front 58

What's the difference between the Ann Arbor Stages IIIA and IIIB?

Back 58

Stage IIIA --> symptoms absent
Stage IIIB --> symptoms present

Front 59

List 3 systemic symptoms used for staging in the Ann Arbor system.

Back 59

1. Unexplained fever > 38*C
2. Night sweats
3. Unexplained weight loss (>10% in 6 months)

Front 60

Which imaging studies are critical in staging lymphomas?

Back 60

1. Radiographs and/or CT scans of chest or abdomen
2. PET-CT scan

Front 61

Which immunotherapy medication is used to treat NHLs?

Back 61

Rituxan
(anti-CD20 antibody)

Rituxan is often used together with chemotherapy-- CHOP plus Rituxan (R-CHOP) is a very common combination used for aggressive B-cell NHLs

*CD20 = B-cell antigen

Front 62

What's the difference between treatment initiation with indolent and aggressive NHLs?

Back 62

Indolent lymphomas may not be treated immediately if the patient is asymptomatic

Aggressive lymphomas are treated immediately with curative intent

Front 63

What type of prognostic state does an elevated LDH indicate?

Back 63

Worse prognosis

Front 64

How does LDH relate to NHLs?

Back 64

LDH levels correlate with tumor bulk and aggressiveness

Front 65

Which type of lymphomas are more common in HIV-positive patients?

Back 65

Aggressive, high-grade types
(Burkitt's, DLBCL, Large cell immunoblastic)

Front 66

How do lymphomas in HIV-(+) patients differ from HIV(-) patients?

Back 66

1. Clinically aggressive
2. Frequently extranodal
3. CNS common

Front 67

Which virus is involved in the pathogenesis of HIV-related lymphomas?

Back 67

EBV

Front 68

HIV-related lymphomas may respond to what type of therapy?

Back 68

Chemotherapy +/- HAART

Front 69

How are post-transplant lymphoproliferative disorders (PTLD) treated based on whether their histologic appearance?

Back 69

Relatively benign appearing --> may respond to decrease in immunosuppresive therapy

Overtly malignant --> treated with aggressive chemotherapy

Front 70

What are the two main options to diagnose lymphomas?

What are some additional options?

Back 70

1. Fine needle aspirate cytology (FNA)
2. Excisional biopsy

Additional tests:
1. Immunophenotyping by flow cytometry
2. Cytogenetics
3. Molecular diagnostic test

Front 71

Is fine needle aspirate cytology better for diagnosing non-lymphoid malignancies or Hodgkin lymphomas?

Back 71

Non-lymphoid malignancies

Front 72

If the FNA isn't diagnostic, how should you proceed in diagnosing a lymphadenopathy?

Back 72

Excisional biopsy

Front 73

What is the best option for diagnosing a deep-seated lymphadenopathy?

Back 73

Fine needle aspiration cytology