Lymphoma

Question 1

the “B symptoms” of lymphoma (fever, malaise, night sweats, weight loss) are due to what?

Answer 1

increased inflammatory cytokine production

Question 2

what does generalized adenopathy usually indicate?

Answer 2

generalized adenopathy: in 3+ non-contiguous lymph node areas

think systemic diseases: infection, Lupus, lymphoma

Question 3

what is the significance of Waldeyer’s ring regarding lymphoma?

Answer 3

Waldeyer’s ring: lymphoid tissue in pharyngeal area that forms tonsils (nasopharyngeal, palatine, lingual)

common extra-nodal site for lymphoma

Question 4

upon physical examination of a patient’s lymph node, what are some findings that would provide concern for neoplastic disease?

Answer 4

if patient is >40

hard or firm
non-tender (no signs of inflammation)
size >2cm

Question 5

what are the general features of lymphoma? how is it diagnosed?

Answer 5

painless lymph node enlargement (>2cm)

“B symptoms” due to inflammatory cytokines

Dx: lymph node biopsy (any lymph node >1cm and present >4 weeks without infection)

Question 6

Hodgkin lymphoma is defined by the presence of what cell type

Answer 6

Reed-Sternberg cell

if not present, it is non-Hodgkin (most cases)

Question 7

most lymphomas (derived from mature lymphocytes) are [T/B] cell origin and [Hodgkin/non-Hodgkin]?

Answer 7

most lymphomas are non-Hodgkin with B cell origin

develop in primary or secondary lymphoid structures

Question 8

follicular lymphoma

Answer 8

most common indolent (slow growing) lymphoma (B cell), mean onset 55y

painless lymphadenopathy that waxes and wanes, may not have B symptoms

diagnose via lymph node biopsy

Question 9

what is the pathogenesis (cause) of follicular lymphoma?

Answer 9

indolent (slow growing) B cell lymphoma

t(14;18) chromosomal translocation in germinal center B cells —> overexpression of BCL2 (anti-apoptotic)

can detect overexpression via immunostaining

Question 10

how does follicular lymphoma impact lymph node architecture?

Answer 10

follicular lymphoma: indolent B cell lymphoma, t(14;18) causes overexpression of BCL2 (anti-apoptotic)

mature lymphocyte clonal population expands in lymph node - follicles seen throughout (not just cortex)

*note they’re not growing faster, they’re just not dying

Question 11

what is significant about the finding that in follicular lymphoma, BCL2 is expressed not only in the mantle zone of follicles but also in the center?

Answer 11

BCL2 (anti-apoptotic) should not be found in the middle of the germinal centers, where apoptosis is occurring for B cell selection

in follicular lymphoma it is found throughout (helps distinguish from reactive lymph node from infection, etc)

*remember follicular lymphoma is indolent B cell cancer

Question 12

how is follicular lymphoma treated?

Answer 12

no cure, treating patients with asymptotic disease does not improve survival (indolent)

rituximab (anti-CD20, kills B cells) for patients with symptoms (only palliative)

mean survival ~10 years

Question 13

what kind of cancer does this describe?
- BCL-2 overexpression
- waxing and waning lymphadenopathy
- rarely extranodal

Answer 13

follicular lymphoma: indolent B cell cancer

*t(14;18) —> BCL2 (anti apoptotic) overexpression

Question 14

what is a MALT-oma?

Answer 14

extranodal marginal zone B cell lymphoma in MALT (mucosa associated lymphoid tissue), indolent

associated with chronic inflammation (*Helicobacter pylori) —> most MALT lymphomas are in the stomach

—> peptic ulcer symptoms, abdominal symptoms

Question 15

how does Helicobacter pylori infection cause MALT lymphoma?

Answer 15

via chronic inflammation

*if patient has early MALT-oma due to H.pylori and you treat infection, cancer can regress and go away

[remember MALT-oma is indolent]

Question 16

MALT lymphoma, associated with chronic inflammation, can progress to _____ if not controlled/treated

Answer 16

diffuse large B cell lymphoma (aggressive, rapidly growing B cell lymphoma)

[recall that MALT-oma is indolent]

Question 17

what are the general characteristics of aggressive non-Hodgkin lymphomas? (3)

Answer 17

1. rapidly growing mass
2. systemic B symptoms
3. high levels of serum LDH and uric acid (breakdown product of nucleic acid synthesis)

Question 18

mantle cell lymphoma

Answer 18

aggressive lymphoma of mantle zone, which contains “pre-germinal center” B cells (surrounds germinal center)

t(11;14) translocation —> overexpression of Cyclin D1 (bypasses check points)

*sex hormone (testosterone) influence

Question 19

what mutation causes mantle cell lymphoma and what cell markers will be present?

Answer 19

t(11;14) translocation —> overexpression of Cyclin D1 (bypass cell cycle checkpoints)

MCL stains cyclin D1+
and tumor cells express CD19/20 and CD5 (T cell marker on a B cell)

[remember this is an aggressive B cell lymphoma]

Question 20

how does mantle cell lymphoma present?

Answer 20

usually advanced stage at diagnosis with poor prognosis (aggressive non-Hodgkin B cell cancer)

nodal disease + spleen, liver, and bone marrow enlargement

B symptoms

extranodal disease, commonly GI tract (lymphomatous polyposis)

ring [mantle] around the rosy, pocket full of posy [polyposis]

Question 21

what kind of cancer does this describe?
- t(11;14) Cyclin D1 overexpression
- aggressive behavior
- M>F presentation
- lymphomatosis polyposis
- immunostaining positive for CD19, CD20, CD5

Answer 21

mantle cell lymphoma: aggressive B cell cancer

lymphomatosis polyposis: involvement in GI tract

Question 22

diffuse large B cell lymphoma

Answer 22

most common lymphoma overall, mean age 70, sex hormone influenced

aggressive B cell lymphoma

de novo, transformation from low grade tumor, HIV!

BCL-6 and BCL-2 overexpression or mutation

Question 23

this lymphoma is the most common type and is associated with HIV/AIDS (AIDS-defining malignancy)

what is?

Answer 23

diffuse large B cell lymphoma: aggressive B cell lymphoma

400x increase risk of lymphoma in HIV+ patients, most DLBCL and highly aggressive

risk factors: low CD4, high HIV viral load

Question 24

what does diffuse large B cell lymphoma look like on histological slides?

Answer 24

diffuse effacement of lymph node by large cells with HIGH growth rate (aggressive cancer)

Ki-67 positive in cells that are rapidly proliferating

Question 25

what does positive Ki-67 staining indicate?

Answer 25

highly proliferating cells (absent from resting cells)

correlate with cells undergoing mitosis

level of staining can be graded to determine how rapidly a tumor is growing

Question 26

how does diffuse large B cell lymphoma present?

Answer 26

aggressive B cell lymphoma - quickly fatal if not treated

systemic “B symptoms” common

rapidly enlarging mass, usually lymph node and locally invasive

stomach/GI most common extranodal site

Question 27

what kind of cancer does this describe?
- BCL-6 and BCL-2 overexpression
- mostly affects adults
- extranodal disease in GI
- AIDS-defining malignancy

Answer 27

DLBCL: diffuse large B cell lymphoma (aggressive)

atypical large cells with prominent nucleoli, HIGH Ki-67 staining (indicates proliferation)

Question 28

for Burkitt Lymphoma, give:
origin
mutation
3 forms

Answer 28

origin: mature germinal center B cell (aggressive)

t(8;14) —> c-MYC overexpression (powerful transcriptional regulator)

3 forms:
1. endemic (African): vertical Epstein-Barr transmission
2. sporadic (American): typically pediatric
3. HIV-associated

Question 29

describe the histopathology of Burkitt lymphoma, an aggressive germinal center B cell cancer

Answer 29

starry sky pattern - dense area of lymphoma cells with spaces in between (apoptosis)

“tingible body” macrophages (contain cellular debris) in spaces

Question 30

contrast clinical presentation of endemic vs sporadic Burkitt Lymphoma

Answer 30

endemic (African): due to vertical transmission of Epstein Barr virus —> jaw or facial bone tumor

sporadic (American): typically pediatric, widespread disease in abdominal cavity

*both forms can involve testes, ovaries, CNS

Question 31

This type of lymphoma is extremely fast growing - it can double in 24h and has a high fraction of Ki-67+ cells (almost 100%)! However, it responds well to chemotherapy (yay!), if you catch it fast enough…
What is?

Answer 31

Burkitt lymphoma: aggressive germinal center B cell cancer

Question 32

what type of cancer does this describe?
- t(8;14) —> c-MYC overexpression
- EBV+ = endemic form
- typically affects children
- RAPID growth (24h doubling time) with HIGH Ki-67
- “starry sky” histopathology

Answer 32

Burkitt Lymphoma: aggressive germinal center B cell cancer

*c-MYC: powerful transcription regulator

“starry sky”: lots of lymphocytes with spaces in between which contain macrophages (“tingible bodies” of cellular debris) cleaning up apoptosis

Question 33

what are the 4 unique features of Hodgkin lymphoma?

Answer 33

1. Reed-Sternberg cell
2. origin is germinal center B cells that do NOT express B cell markers! (woah)
3. distinct pattern of spread - contiguous (spreads to its near neighbors)
4. most of tumor is NOT neoplastic

Question 34

what the heck are Reed-Sternberg cells ?!

Answer 34

special cells only seen in Hodgkin’s lymphoma (germinal center B cell cancer)

owl eye appearance - bilobed nucleus and 2 nucleoli

*note that these only make up small portion of tumor (tumor is mixed cell infiltrate) and most of tumor is NOT neoplastic

Question 35

Hodgkin lymphoma originates in germinal center B cells, but they [weirdly] do not express B cell markers… so what do they express?

Answer 35

CD15: adhesion molecule typical of myeloid cells
CD30: TNF receptor (100% will have this)

(markers on Reed-Sternberg cells)

Question 36

in Hodgkin’s lymphoma, most of the tumor is in fact NOT neoplastic, and only a small portion of the cells are Reed Sternberg cells

explain how this in fact benefits the tumor

Answer 36

Reed Sternberg cells make cytokines, chemoattractants, and growth factors for other cells (T cells, granulocytes, macrophages)

requirement of other cells “protects” Reed-Sternberg cells from host defenses (hiding within)

Question 37

how does Hodgkin lymphoma clinically present?

Answer 37

most commonly painless lymphadenopathy (neck + supraclavicular area, axilla)

mediastinal adenopathy (large lymph nodes in chest) common - can lead to persistent cough

B symptoms, pruritis

Question 38

describe the Nodular Sclerosis Type of Hodgkin lymphoma

Answer 38

most common in younger patients

“Lacunar” Reed-Sternberg cells, collagenous bands, mixed cellular background (most cells are not neoplastic)

presents with low stage, rarely associated with EBV (Epstein Barr virus)