non-hodgkin lymphoma

Question 1

lymphoma

Answer 1

tumor of cells that normally reside in lymph node

Question 2

Acute lymphocytic leukemia cells appear to arise at the level of the _____________ and display none of the characteristic proteins seen in mature cells.

Answer 2

lymphoid stem cell

Question 3

present a period of vulnerability where genes are being cut and re-connected and the potential exists for recombination to occur with the wrong piece of DNA (3)

Answer 3

1. Ig Gene rearrangement: lymphoid progenitor commits to the B-cell lineage it rearranges its globulin genes to create a unique fusion gene
2. Somatic hypermutation-
3. class switching

Question 4

Chromosomal translocations involving ___________ have been implicated in the development of B-cell malignancies.

These proto-oncogenes become activated through translocations that move the genes from their normal chromosomal locations into the promoter region for Ig heavy-chain locus at 14q32. These include (3)

When translocated into the heavy-chain locus, these ___________ become overexpressed because of the strong transcriptional enhancer elements that normally drive expression of the Ig genes in B cells.
Chromosomal translocations are one mechanism by which normal cellular ____________ can be activated to become oncogenes.

Answer 4

Chromosomal translocations involving proto-oncogenes have been implicated in the development of B-cell malignancies.

These ___________ become activated through translocations that move the genes from their normal chromosomal locations into the promoter region for Ig heavy-chain locus at 14q32. These include (1) bcl-1, (2) bcl-2, and (3) c-Myc.

When translocated into the heavy-chain locus, these proto-oncogenes become overexpressed because of the strong transcriptional enhancer elements that normally drive expression of the Ig genes in B cells.
Chromosomal translocations are one mechanism by which normal cellular proto-oncogenes can be activated to become oncogenes.

Question 5

___________________ represent the 5th leading cause of cancer in the US with an expected 81000 new diagnoses and nearly 21000 deaths in 2016. It is the most common hematologic cancer accounting for about half of all diagnoses and about a third of all deaths. The majority are ____-cell in origin, the remainder are primarily ____-cell, and far fewer ______cell.

The incidence is rising/decreasing in the US at every age group

Answer 5

Non-Hodgkin’s lymphoma (NHL) represent the 5th leading cause of cancer in the US with an expected 81000 new diagnoses and nearly 21000 deaths in 2016. NHL is the most common hematologic cancer accounting for about half of all diagnoses and about a third of all deaths. The majority of NHLs are B-cell in origin, the remainder are primarily T-cell, and far fewer NK-cell.

The incidence of NHL is rising in the US at every age group with an incidence that has more than doubled since the 1970’s. The cause(s) of this rise are unknown.

Question 6

The presenting symptoms of lymphoma are determined in part by the aggressiveness of the tumor.

In general, _________ disease tends not to cause symptoms until the disease is fairly advanced. Often, the diagnosis is made incidentally, during routine health screening. More often, patients present with _____________ which may have appeared stable for some months or have been observed to grow slowly. Fatigue can be present at diagnosis, but can be difficult to appreciate unless pronounced.

In contrast, __________ lymphomas tend to present with _________symptoms which may occasionally precede diagnosis by months. Swollen lymph nodes may also prompt evaluation – often they appear suddenly and/or can grow over the course of days to weeks. Pain due to a lymph node stretching its capsule, pressing on a nerve, or infiltrating or obstructing an organ (blocking the ureters, for example) may be present at diagnosis.

Answer 6

The presenting symptoms of lymphoma are determined in part by the aggressiveness of the tumor.

In general, indolent disease tends not to cause symptoms until the disease is fairly advanced. Often, the diagnosis is made incidentally, during routine health screening. More often, patients present with painless swollen lymph node(s) which may have appeared stable for some months or have been observed to grow slowly. Fatigue can be present at diagnosis, but can be difficult to appreciate unless pronounced.

In contrast, aggressive lymphomas tend to present with systemic symptoms which may occasionally precede diagnosis by months. Swollen lymph nodes may also prompt evaluation – often they appear suddenly and/or can grow over the course of days to weeks. Pain due to a lymph node stretching its capsule, pressing on a nerve, or infiltrating or obstructing an organ (blocking the ureters, for example) may be present at diagnosis.

Question 7

Lymphomas can be classified based on (2)

By defining the subtype of lymphoma, we are able to make general predictions about their behavior – whether a patient will become sick quickly or live relatively free of symptoms for many years, for example. The treatment paradigms differ depending on subtype: those that are curable, we generally treat ____________. Classification follows specific, repeatable criteria which ensures that a mantle cell diagnosed in the U.S. is the same entity diagnosed in Europe.

Answer 7

Lymphomas can be classified based on their (1) appearance under the microscope and on the (2) proteins they display on their surface.

By defining the subtype of lymphoma, we are able to make general predictions about their behavior – whether a patient will become sick quickly or live relatively free of symptoms for many years, for example. The treatment paradigms differ depending on subtype: those that are curable, we generally treat agressively. Classification follows specific, repeatable criteria which ensures that a mantle cell diagnosed in the U.S. is the same entity diagnosed in Europe.

Question 8

rate survival rate:

mantle cell lymphoma, follicular lymphoma and diffuse large b-cell

Answer 8

follicular lymphoma (>8yr) > dffuse large b-cell (3 yr) > mantle cell lymphoma (2.5 yr)

Question 9

Approximately half of patients with NHL have the more indolent form at diagnosis, which is characterized by slow disease progression and a median survival of up to 10 years.1

Answer 9

yep

Question 10

1. Follicular lymphoma
2. Marginal zone B-cell
3. lymphoma, MALT type
4. Marginal zone B-cell
5. lymphoma, nodal type
6. Small lymphocytic
7. lymphoma
   Lymphoplasmacytic lymphoma

Answer 10

indolent

Question 11

1. Diffuse large B-cell 2. lymphoma
2. Mantle cell lymphoma
3. Peripheral T-cell lymphoma
4. Primary mediastinal large B-cell lymphoma
5. Anaplastic large cell lymphoma
6. Lymphoblastic lymphoma
7. Burkitt-like lymphoma
8. Burkitt’s lymphoma

Answer 11

aggressive

Question 12

In a patient presenting with a mass or other lesion a _______ is critical to making the diagnosis.

Biopsies can involve aspiration of a suspension of singe cells (fine needle aspiration, the least invasive), removal of a very thin sliver of tissue through a hollow core needle (core biopsy, Tru-cut, slightly more invasive in most circumstances), pinch biopsies typically taken through a fiber optic instrument (bronchoscope, endoscope, etc) or open excision (cutting a piece of tissue free through an incision in the skin, most invasive). For the purpose of diagnosing most malignancies, a ____________ is sufficient.

For suspected lymphoma, however, an FNA is never sufficient why? what is preferred?

Answer 12

In a patient presenting with a mass or other lesion a biopsy is critical to making the diagnosis.

Biopsies can involve aspiration of a suspension of singe cells (fine needle aspiration, the least invasive), removal of a very thin sliver of tissue through a hollow core needle (core biopsy, Tru-cut, slightly more invasive in most circumstances), pinch biopsies typically taken through a fiber optic instrument (bronchoscope, endoscope, etc) or open excision (cutting a piece of tissue free through an incision in the skin, most invasive). For the purpose of diagnosing most malignancies, a fine needle aspiration or core needle is sufficient.

For suspected lymphoma, however, an FNA is never sufficient because architectural information is lost in a suspension of cells – you can’t tell anymore which cells were next to which or in what proportion. An open excision is preferred when ever possible.

Question 13

the lymphoma cells growing in sheets without any consideration for the presence of their neighbors. These cells have lost the basic property of forming nodules, consistent with a more

Answer 13

aggressive phenotype.

Question 14

lymphoma cells organizing in groups which are appear similar to the germinal centers seen in normal lymph nodes. This implies that the lymphoma cells have retained some of their innate programming, a feature more likely to be seen in an

Answer 14

indolent lymphoma

Question 15

histo slides show a large, open nuclei b/cthe cells are actively moving through the cell cycle. this is consistent with

Answer 15

less mature and aggressive phenotype

Question 16

histo slides show cells that have very condensed nuclei because the chromosomes are tightly packaged and in active. These cells are not actively transcribing RNA or synthesizing new DNA, consistent with a mature phenotype

Answer 16

indolent

Question 17

CD2, CD3, CD4 or CD8, CD5

Answer 17

T-cell markers

Question 18

CD19, CD20, CD22, CD79a, Ig (immunoglobulin).

Answer 18

B-cell markers

Question 19

positive CD5 with positive CD23

Answer 19

SLL

Question 20

only positive CD5

Answer 20

MCL

Question 21

positive CD138

Answer 21

LPL

Question 22

single lymph node group stage

Answer 22

stage I

Question 23

2+ LN groups on the same side of the diaphragm stage

Answer 23

stage II

Question 24

2+ LN groups above and below the diaphragm stage

Answer 24

stage III

Question 25

involves organs outside of the lymph nodes- bone marrow, liver, lungs stage

Answer 25

stage IV

Question 26

Extensive stage disease – stage III or IV – is not amenable to treatment with ________. Treatment strategies tend to use ____________ only at these stages.

Answer 26

Extensive stage disease – stage III or IV – is not amenable to treatment with radiation. Treatment strategies tend to use chemotherapy only at these stages.

Question 27

In general, bulky disease has a better/worse prognosis

Answer 27

In general, bulky disease has a worse prognosis – possibly because the blood supply does not readily reach the center of a large tumor, decreasing delivery of oxygen and therapeutics.

Question 28

Stage I and II disease is considered ‘limited’ in extent as the involved areas can typically be incorporated in a______________

Treatment may ultimately involve radiation in those patients with limited stage disease.

Answer 28

Stage I and II disease is considered ‘limited’ in extent as the involved areas can typically be incorporated in a singe radiation therapy beam / field.

Treatment may ultimately involve radiation in those patients with limited stage disease.

Question 29

Staging is further refined with A/B designation depending on whether there are

Answer 29

symptoms of fever, night sweats or weight loss.

Question 30

Staging involves physical examination for likely sites of involvement.

Enlarged lymph nodes can easily be felt in the neck, supraclavicular fossae, axillae and groin. In addition, an enlarged spleen, liver or abdominal masses can often be palpated.

The imaging study of choice is the ________ scan encompassing the chest, abdomen and pelvis, performed with IV and oral contrast.

A ______________, which involves inserting a small needle into the posterior iliac crest or the sternum is required in most cases to establish whether a patient has stage IV disease.

In those patients with multiple extramedulary sites of disease – say, masses in the lungs or liver – they already meet criteria for stage _______ disease and bone marrow biopsy becomes less critical.

___________involvement in aggressive lymphoma is a risk factor for central nervous system involvement and full work up should include a lumbar puncture in those patients with bone marrow involvement and/or signs of CNS disease.

Answer 30

Staging involves physical examination for likely sites of involvement.

Enlarged lymph nodes can easily be felt in the neck, supraclavicular fossae, axillae and groin. In addition, an enlarged spleen, liver or abdominal masses can often be palpated.

The imaging study of choice is the CT scan encompassing the chest, abdomen and pelvis, performed with IV and oral contrast.

A bone marrow aspiration and biopsy, which involves inserting a small needle into the posterior iliac crest or the sternum is required in most cases to establish whether a patient has stage IV disease.

In those patients with multiple extramedulary sites of disease – say, masses in the lungs or liver – they already meet criteria for stage IV disease and bone marrow biopsy becomes less critical.

Bone marrow involvement in aggressive lymphoma is a risk factor for central nervous system involvement and full work up should include a lumbar puncture in those patients with bone marrow involvement and/or signs of CNS disease.

Question 31

Functional imaging with either gallium scanning or 18FDG-PET can be a useful adjunct to initial staging of patients. Areas involved with lymphoma concentrate the radiotracer and may reveal sites of disease not visible on CT scan. In cases where imaging or examination suggests extensive disease, it is important to document involvement with biopsy when ever possible.

Answer 31

yep

Question 32

Case 1:

a. no B-symptoms
b. negative bone marrow biopsy
c. PET CT- lymph node above diaphgram

Answer 32

stage IA

Question 33

case 1:

a. night sweats
b. PET scan- LN above and below diaphragm
c. positive bone marrow biopsy

Answer 33

stage IVB

Question 34

Over the years, many scoring systems have been proposed to predict outcome based on parameters measurable early in the disease course. The International Prognostic Index (IPI) has gained popularity based on its ease of use and potent ability to discriminate patients at high and low risk for death. While the scoring system was initially developed for patients with diffuse large B-cell NHL, it has proven to be widely applicable across most, if not all, histologic sub-types.

The score is determined by assigning one point for each adverse feature: (1) age ___ 60, (2) Eastern Cooperative Oncology Group (ECOG) performance status of ___, (3) lactose dehydrogenase (LDH) elevated/decreased, (4) _______ extranodal sites of involvement (bone marrow counts as one if involved), and (5) _______stage.

Answer 34

Over the years, many scoring systems have been proposed to predict outcome based on parameters measurable early in the disease course. The International Prognostic Index (IPI) has gained popularity based on its ease of use and potent ability to discriminate patients at high and low risk for death. While the scoring system was initially developed for patients with diffuse large B-cell NHL, it has proven to be widely applicable across most, if not all, histologic sub-types.

The score is determined by assigning one point for each adverse feature: (1) age >60, (2) Eastern Cooperative Oncology Group (ECOG) performance status of 2 or worse (generally this means that the patient cannot get through their day without taking a nap), (3) lactose dehydrogenase (LDH) greater than normal, 2 or (4) more extranodal sites of involvement (bone marrow counts as one if involved), and (5) advanced stage.

Question 35

IPI score of 0-1 survival rate ___

IPI score of 2 survival rate ___

IPI score of 3 survival rate ____

IPI score of 4-5 survival rate ________

Answer 35

IPI score of 0-1 survival rate 73%

IPI score of 2 survival rate 51%

IPI score of 3 survival rate 43%

IPI score of 4-5 survival rate 26%

Question 36

1. Slow growing, asymptomatic for years
2. Respond to chemotherapy, but ultimately recur
3. Emphasis on maintaining quality of life

Answer 36

indolent

Question 37

1. Grow and cause symptoms quickly
2. Response to chemotherapy can be profound, ultimately curable
3. Emphasis on curing those who can tolerate therapy

Answer 37

aggressive

Question 38

The fundamental paradigm in the management of lymphoma is revealed in what I call the treatment paradox

Answer 38

Patients with indolent disease will respond to treatment, but the lymphoma will inevitably return – low grade NHL is NOT curable. In contrast, patients with aggressive lymphoma can become sick very quickly and rapidly develop a high burden of disease – yet many, if not the majority of these patients can currently be cured with chemotherapy and/or radiation.

Question 39

As these representative survival curves show, patients with _________ histologies succumb to their lymphoma slowly over the years, with eventually all patients dying of the disease (if they live long enough – ie they don’t die of old age – ie their CAD, lung cancer, CHF, diabetes, etc – first). Treatment is not particularly toxic.

In contrast, there is a steep drop off in survival early in the course of lymphoma with ___________ histologies. Those who survive the first couple of years after diagnosis however, only rarely die of lymphoma. The early drop-off can be attributed to the ____________ of the tumors, complications from more __________ therapy, and other health related co-morbidities in older patients (don’t forget, the median age for the diagnosis of NHL is in the mid 60’s).

Answer 39

As these representative survival curves show, patients with indolent histologies succumb to their lymphoma slowly over the years, with eventually all patients dying of the disease (if they live long enough – ie they don’t die of old age – ie their CAD, lung cancer, CHF, diabetes, etc – first). Treatment is not particularly toxic.

In contrast, there is a steep drop off in survival early in the course of lymphoma with aggressive histologies. Those who survive the first couple of years after diagnosis however, only rarely die of lymphoma. The early drop-off can be attributed to the agressiveness of the tumors, complications from more aggressive therapy, and other health related co-morbidities in older patients (don’t forget, the median age for the diagnosis of NHL is in the mid 60’s).

Question 40

watch and worry vs watch and wait

Answer 40

since patients with indolent disease cannot be cured, there is no advantage in beating them over the head with treatment. Instead, treatment is reserved until there is a symptomatic need: constitutional symptoms, pain, fatigue, unsightly lymphadenopathy

Question 41

Many patients with ____________ lymphoma who are otherwise in fairly good physical condition can be cured of lymphoma with aggressive treatment. Untreated, these patients face a median survival measured in months and therefore an ___________ approach to treatment which may make patients sick can be justified.

Evaluation for diagnosis and staging should be carried out and treatment begun promptly in these patients.

Answer 41

Many patients with aggressive lymphoma who are otherwise in fairly good physical condition can be cured of lymphoma with aggressive treatment. Untreated, these patients face a median survival measured in months and therefore an aggressive approach to treatment which may make patients sick can be justified.

Evaluation for diagnosis and staging should be carried out and treatment begun promptly in these patients.

Question 42

Surgery plays no significant role in the treatment of lymphoma. Unlike many early stage solid tumors, lymphomas tend to have early dispersal of tumor and surgery only delays the initiation of effective treatment.

Answer 42

YEP

Question 43

Chemotherapy has long been the mainstay in the management of NHL. Classes of chemotherapeutics with particular activity in NHL include __________ (cyclophosphamide, chlorambucil), __________(donorubicin, mitoxantrone) and ___________(high doses of prednisone 1-2 mg/kg/day).

Combinations of these drugs have proven very effective. Finally, high dose combinations given in concert with stem cell transplantation can cure lymphomas in relapse following effective treatment.

Answer 43

Chemotherapy has long been the mainstay in the management of NHL. Classes of chemotherapeutics with particular activity in NHL include alkylators (cyclophosphamide, chlorambucil), anthracyclines (donorubicin, mitoxantrone) and steroids (high doses of prednisone 1-2 mg/kg/day).

Combinations of these drugs have proven very effective. Finally, high dose combinations given in concert with stem cell transplantation can cure lymphomas in relapse following effective treatment.

Question 44

rituximab kills tumor cells by inducing (3)

The Fab portions of the antibody bind to CD______, and the Fc portion recruits immune effector functions that mediate B-cell lysis.1

Answer 44

rituximab kills tumor cells by inducing (1) antibody-dependent cellular cytotoxicity (ADCC), (2) complement-dependent cytotoxicity (CDC), and (3) apoptosis.

The Fab portions of the antibody bind to CD20, and the Fc portion recruits immune effector functions that mediate B-cell lysis.1

Question 45

Aggressive lymphomas should be considered potentially _________ in all patients.

The health status of individual patients will determine who can tolerate treatment.

In general, chemotherapy is required to treat NHL which has already spread from the involved site(s) (ie occult disease), but treatment needs to be concentrated in the involved site(s). Patients can receive chemotherapy for 6 months which will provide sufficient treatment of the primary site, but probably over-treat occult disease, or they can receive less chemotherapy followed by radiation therapy to the involved site(s). Rare patients with a minimum of NHL may be cured with _______alone.

Answer 45

Aggressive lymphomas should be considered potentially curable in all patients.

The health status of individual patients will determine who can tolerate treatment.

In general, chemotherapy is required to treat NHL which has already spread from the involved site(s) (ie occult disease), but treatment needs to be concentrated in the involved site(s). Patients can receive chemotherapy for 6 months which will provide sufficient treatment of the primary site, but probably over-treat occult disease, or they can receive less chemotherapy followed by radiation therapy to the involved site(s). Rare patients with a minimum of NHL may be cured with radiation alone.

Question 46

CHOP and why?

Answer 46

chemo for aggressive NHL- least toxic

cyclophophamide, doxorubicin, vincristine and prednisone

Question 47

monoclonal antibody recognizing the B-cell antigen CD20 and low/limited toxic

Answer 47

rituximab

Question 48

The risk of developing lymphoma in addition to other cancers is dramatically increased/decreased in patients with compromised immune systems, whether acquired through infection (HIV), immune dysregulation (rheumatologic diseases), or iatrogenic means (immunosuppression for organ transplantation, treatment of rheumatologic disease).

In patients seropositive for _____, 25 – 40% will develop cancer during their infection and 10% will develop lymphoma.

The risk of lymphoma is tied to the degree of _____________; those with CD4 counts < 200 cells/μl, and/or high viral load (typically seen in those with advanced disease) are at particular risk (200 – 600 fold increase over general population).

Answer 48

The risk of developing lymphoma in addition to other cancers is dramatically increased in patients with compromised immune systems, whether acquired through infection (HIV), immune dysregulation (rheumatologic diseases), or iatrogenic means (immunosuppression for organ transplantation, treatment of rheumatologic disease).

In patients seropositive for HIV, 25 – 40% will develop cancer during their infection and 10% will develop lymphoma.

The risk of lymphoma is tied to the degree of immunosuppression; those with CD4 counts < 200 cells/μl, and/or high viral load (typically seen in those with advanced disease) are at particular risk (200 – 600 fold increase over general population).

Question 49

The majority of lymphomas developing in HIV patients (>80%) are of _____-cell origin and of aggressive phenotype. Most fall into one of four subtypes in three categories: systemic lymphoma (immunoblastic variant of diffuse large cell and Burkitt’s), primary central nervous system lymphoma (typically presenting with multiple enhancing brain lesions) and primary effusion / body cavity (presenting with pleural effusion or ascites without lymphadenopathy).

Indolent B-cell lymphomas and T-cell lymphomas are uncommon/also common.

Answer 49

The majority of lymphomas developing in HIV patients (>80%) are of B-cell origin and of aggressive phenotype. Most fall into one of four subtypes in three categories: systemic lymphoma (immunoblastic variant of diffuse large cell and Burkitt’s), primary central nervous system lymphoma (typically presenting with multiple enhancing brain lesions) and primary effusion / body cavity (presenting with pleural effusion or ascites without lymphadenopathy). Indolent B-cell lymphomas and T-cell lymphomas are uncommon.

Question 50

The etiology of lymphomas in these patients relates to chronic co-infection with viruses which induce sustained B-cell proliferation (2) and the acquired inability of the ____-cells to control either the proliferation or the infection itself.

Institution of highly active antiretroviral therapy (HAART) restores ___-cell immunity and has been shown to reduce the risk of lymphoma within months in population-based studies.

Answer 50

The etiology of lymphomas in these patients relates to chronic co-infection with viruses which induce sustained B-cell proliferation (1) Epstein Barr Virus and (2) human herpesvirus-8 and the acquired inability of the T-cells to control either the proliferation or the infection itself.

Institution of highly active antiretroviral therapy (HAART) restores T-cell immunity and has been shown to reduce the risk of lymphoma within months in population-based studies.

Question 51

Patients with HIV developing lymphoma tend to present with symptoms reflecting the ___________ phenotype: rapidly progressing, extensive lymphadenopathy and constitutional symptoms (fevers, night sweats, anorexia, weight loss) are common.

Note that these signs and symptoms overlap with infections and demand careful evaluation in this immunocompromised population. Patients with primary CNS lymphoma may present with mental status changes, focal neurologic deficits or seizure. Those with primary effusion lymphomas will not have lymphadenopathy, but may be symptomatic from pleural effusion or ascites.

Answer 51

Patients with HIV developing lymphoma tend to present with symptoms reflecting the aggressive phenotype: rapidly progressing, extensive lymphadenopathy and constitutional symptoms (fevers, night sweats, anorexia, weight loss) are common.

Note that these signs and symptoms overlap with infections and demand careful evaluation in this immunocompromised population. Patients with primary CNS lymphoma may present with mental status changes, focal neurologic deficits or seizure. Those with primary effusion lymphomas will not have lymphadenopathy, but may be symptomatic from pleural effusion or ascites.

Question 52

A rare subtype of Hodgkin’s lymphoma, _____________ is predominantly made up of large R-S cells and contains little of the inflammatory infiltrate seen in other subtypes. This type can be easily confused with large cell lymphoma.

Answer 52

lymphocyte depleted Hodgkin’s lymphoma

Question 53

The second most common type of Hodgkin’s lymphoma, _____________ contains RS cells with a large admixture of inflammatory cells (B- and T-cells, plasma cells, and eosinophils). Patients tend to be older with more males affected than females.

Answer 53

mixed cellularity Hodgkin’s lymphoma

Question 54

is an aggressive B-cell lymphoma. The risk of developing lymphoma is dramatically increased in patients with compromised immune systems, including those with compromise acquired through immune dysregulation as in HIV. The majority of lymphomas developing in HIV patients are B-cell in origin and of the aggressive phenotype.

Answer 54

Burkitt’s lymphoma

Question 55

is an indolent lymphoma and one of the most common types of Non-Hodgkin’s lymphoma. It is characterized by cell markers CD20, and sometimes CD10 and CD23; it can be distinguished from other, similar types of lymphoma by its pattern of growth and morphological appearence

Answer 55

Follicular lymphoma