Lymphoma Flashcards
the “B symptoms” of lymphoma (fever, malaise, night sweats, weight loss) are due to what?
increased inflammatory cytokine production
what does generalized adenopathy usually indicate?
generalized adenopathy: in 3+ non-contiguous lymph node areas
think systemic diseases: infection, Lupus, lymphoma
what is the significance of Waldeyer’s ring regarding lymphoma?
Waldeyer’s ring: lymphoid tissue in pharyngeal area that forms tonsils (nasopharyngeal, palatine, lingual)
common extra-nodal site for lymphoma
upon physical examination of a patient’s lymph node, what are some findings that would provide concern for neoplastic disease?
if patient is >40
hard or firm
non-tender (no signs of inflammation)
size >2cm
what are the general features of lymphoma? how is it diagnosed?
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)
Hodgkin lymphoma is defined by the presence of what cell type
Reed-Sternberg cell
if not present, it is non-Hodgkin (most cases)
most lymphomas (derived from mature lymphocytes) are [T/B] cell origin and [Hodgkin/non-Hodgkin]?
most lymphomas are non-Hodgkin with B cell origin
develop in primary or secondary lymphoid structures
follicular lymphoma
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
what is the pathogenesis (cause) of follicular lymphoma?
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
how does follicular lymphoma impact lymph node architecture?
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
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?
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
how is follicular lymphoma treated?
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
what kind of cancer does this describe?
- BCL-2 overexpression
- waxing and waning lymphadenopathy
- rarely extranodal
follicular lymphoma: indolent B cell cancer
*t(14;18) —> BCL2 (anti apoptotic) overexpression
what is a MALT-oma?
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
how does Helicobacter pylori infection cause MALT lymphoma?
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]
MALT lymphoma, associated with chronic inflammation, can progress to _____ if not controlled/treated
diffuse large B cell lymphoma (aggressive, rapidly growing B cell lymphoma)
[recall that MALT-oma is indolent]
what are the general characteristics of aggressive non-Hodgkin lymphomas? (3)
- rapidly growing mass
- systemic B symptoms
- high levels of serum LDH and uric acid (breakdown product of nucleic acid synthesis)
mantle cell lymphoma
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
what mutation causes mantle cell lymphoma and what cell markers will be present?
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]
how does mantle cell lymphoma present?
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]
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
mantle cell lymphoma: aggressive B cell cancer
lymphomatosis polyposis: involvement in GI tract
diffuse large B cell lymphoma
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
this lymphoma is the most common type and is associated with HIV/AIDS (AIDS-defining malignancy)
what is?
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
what does diffuse large B cell lymphoma look like on histological slides?
diffuse effacement of lymph node by large cells with HIGH growth rate (aggressive cancer)
Ki-67 positive in cells that are rapidly proliferating
what does positive Ki-67 staining indicate?
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
how does diffuse large B cell lymphoma present?
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
what kind of cancer does this describe?
- BCL-6 and BCL-2 overexpression
- mostly affects adults
- extranodal disease in GI
- AIDS-defining malignancy
DLBCL: diffuse large B cell lymphoma (aggressive)
atypical large cells with prominent nucleoli, HIGH Ki-67 staining (indicates proliferation)
for Burkitt Lymphoma, give:
origin
mutation
3 forms
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
describe the histopathology of Burkitt lymphoma, an aggressive germinal center B cell cancer
starry sky pattern - dense area of lymphoma cells with spaces in between (apoptosis)
“tingible body” macrophages (contain cellular debris) in spaces
contrast clinical presentation of endemic vs sporadic Burkitt Lymphoma
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
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?
Burkitt lymphoma: aggressive germinal center B cell cancer
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
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
what are the 4 unique features of Hodgkin lymphoma?
- Reed-Sternberg cell
- origin is germinal center B cells that do NOT express B cell markers! (woah)
- distinct pattern of spread - contiguous (spreads to its near neighbors)
- most of tumor is NOT neoplastic
what the heck are Reed-Sternberg cells ?!
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
Hodgkin lymphoma originates in germinal center B cells, but they [weirdly] do not express B cell markers… so what do they express?
CD15: adhesion molecule typical of myeloid cells
CD30: TNF receptor (100% will have this)
(markers on Reed-Sternberg cells)
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
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)
how does Hodgkin lymphoma clinically present?
most commonly painless lymphadenopathy (neck + supraclavicular area, axilla)
mediastinal adenopathy (large lymph nodes in chest) common - can lead to persistent cough
B symptoms, pruritis
describe the Nodular Sclerosis Type of Hodgkin lymphoma
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)
