Lec 16 Pathology of Lymphoma Flashcards
What is structure of normal lymph nodes? And which type of cells in each part?
cortical follicles = B lymphocytes
paracortex = T lymphocytes
subscapular and medullary sinuses = histiocytes
What does follicular hyperplasia of lymph node suggest?
suggests B cell proliferative response
How do you distinguish follicular hyperplasia from follicular lymphoma?
greater variation in size and shape of follicles
preserved lymph node architecture
greater cellular heterogeneity
only malignant lymphoma will demonstarte light chain restriction = either lambda or kappa but not both b/c its polyclonal
What are some specific disease associated with follicular hyperplasia?
- syphilis
- rheumatoid arthritis
- giant lymph node hyperplasia [castlemans disease]
- HIV
What does diffuse lymphoid hyperplasia suggest?
expansion of T cells; associated with large number of immunoblasts = fully transformed large lymphoid cells with prominent central nucleoli and abundant cytoplasm
What are some common causes of diffuse lymphoid hyperplasia?
- post vaccination and viral
- dilantin + drug sensitivity
- angioimmunoblastic lymphadenopathy
- dermatopathic lymphadenitis
What is angioimmunoblastic lymphadenopathy [AILD]?
have fever, anemia, polyclonal hyperglobulinemia
1/3 may progress to overt lymphoma
What are two specific causes of lymph node mixed hyperplasia?
- mononucleosis
- acute toxoplasmosis
What are clinical signs of infectious mononucleosis?
fever, pharyngitis, cervical lymphadenopathy
atypical lymphocytes on peripheral blood
What do you see on peripheral smear in EBV?
circulating atypical T cells reacting against EBV infected B cells
What are the two compartments of the spleen?
white pulp = periarteriolar lymphoid sheeth and follicles
red pulp = cords and sinusids = a macrophage filter for removing abnormal cellular elements from the blood
What is gauchers disease?
glucoserebroside accumulation in macrophages secondar to genetic deficiency of glucocerebrosidase
What is neiman pick?
sphingomyelin accumulation secondary to sphingomyelinase deficiency
What defines malignant lymphoma?
clonal proliferation of lymphocytes confined to lymph nodes or spleen
What is role of EBV in lymphoma?
associated with development of burkitt’s lymphoma, post-transplant lymphoproliferative disorders [PTLDs], and hodgkins lymphoma
What is PTLD?
post trasnplant lymphoproliferative disorder –> constitutive activation of nuclear transcription factor NF-kappaB
What is role of HTLV1 in lymphoma?
associated with adult T cell leukemia/lymphoma
Where is HTLV1 endemic?
Japan, west africa, carribean
What is role of HHV8 in lymphoma?
associated wtih kaposi sarcoma
also plays a role in primary effusion lymphomas in immunosuppressed pts
What is role of helicobacter pylori in lymphoma?
associated with MALT = mucosal associated lymphatic tissue lymphoma [aka extranodal marginal zone B cell lymphoma]
What oncogene and translocation in burkitt’s lymphoma?
c-myc oncogene
t(8;14) = translocation of c-myc [8] and heavy chain Ig [14]
What oncogene and translocation in follicular lymphoma?
bcl-2 oncogene
t(14;18) = translocation of heavy chain Ig [14] and bcl-2 [18]
What oncogene and translocation in mantle cell lymphoma?
bcl-1 [cyclin D1]
t(11;14) = translocation cyclin D1 [11] and heavy chain Ig [14]
What oncogene and translocation in diffuse large B cell lymphoma?
bcl-2 oncogene
t(14;18) = translocation of heavy chain Ig [14] and bcl-2 [18]
What are the common features of non-hodgkins lymphoma?
- effacement of node architecture
- capsular invasion
- monoclonality
- involvement of other sites
What is typical clinical presentation of non-hodgkins lymphoma?
painless lymphadenopathy
rubbery lymph nodes; non-tender and moveable
more advance –> fever, night sweats, weight loss
What are some signs of extranodal involvement in lymphoma?
- cytopenia due to BM involvement [myelophthisis]
- bone pain
- neuro findings
What are the 4 low grade lymphomas?
- follicular
- marginal zone
- MALT
- small lymphocytic
What are characteristics of low grade lymphomas?
- have severeal years
- almost always have systemic disease and BM invovlement
- relaspe common
- not curable
What is richters transformation?
low grade lymphomas transform to intermediate or high grade
What are the 5 intermediate/high grade lymphomas?
- diffuse large B cell
- mantle cell
- anaplastic large cell
- burkitts
- lymphoblastic
What are characteristics of intermediate/high grade lymphomas?
- more rapidly progress
- potentially curable with chemo
How do you diagnose lymphoma type?
excisional biopsy of lymph node [rather than fine needle aspirate]
What are characteristics of small lymphocytic lymphoma?
proliferation well differentiated small B lymphocytes = tissue phase of CLL
disease of the elderly
What are characteristics of follicular lymphoma?
proliferation of B lymphocytes arising from lymphoid follicle
What is morphology of follicular lymphoma?
have cells with nuclear clefts = small cleaved follicular center cells
What is typical presentations of follicular lymphoma?
painless waxing and waning lymphadenopathy
What is MALT lymphoma?
mucosa associated lymphoid tissue lymphoma
characteristically involved GI
What are characteristics of diffuse large cell lymphoma?
tumor of large transformed lymphocytes resembling blasts; have few cell markers
increased frequency in immunodeficient
Who gets diffuse large B cell lymphoma?
usually older adults; but 20% in kids
Is diffuse large b cell lymphoma curable?
yes with aggressive chemotherapy
What is characteristic of T lymphoblastic lymphoma?
seen in male adolescents
anterior mediastinal mass
can have CNS/BM involvement and leukemic conversion
What markers seen in T lymphoblastic lymphoma?
TdT and + E rosette
What is burkitts lymphoma?
small non-cleaved B lymphocytes
Who gets burkitts lymphoma?
adolescents or young adults
What are the 3 types of burkitts lymphoma?
- endemic = african; in kids + EBV; large jaw tumors
- non-endemic [western] = older children; less frequently EBV; abdomen/pelvis involvement
- HIV assocaited
What is characteristic appearance of Burkitts lymphoma?
starry sky = clear areas of macrophages ingesting dead cells
What is mycosis fungoides / sezary syndrome?
- T cell lymphomas that involve the skin = cutaneous T cell lymphoma
sezary has diffuse skin involvement and circulating lymphoma cells
What are characteristics of adult T cell lymphoma?
see lytic bone lesions, hypercalcemia, rash
circulating abnormal flower cells w/ T cell markers
What is difference in prognosis lymphomas that express characteristics of germinal center B cells vs activated B cells?
better prognosis when express germinal center B cell markers
WHat is use of bendamustine?
treat low grade lymphomas es in combination with rituximab
What is action/use of rituximab?
monoclonal antibody binds CD20; used to treat B cell lymphoma esp low grade
What is most common regimen for high grade lymphomas?
Cytoxan
Hydroxyldanorubicin [adriamycin]
Oncovin [vincristine]
Prednisone
CHOP
Who gets hodgkins lymphoma?
bimodal = young adults and > 55 yo; associated with EBV; more common in men except nodular sclerosing type
significantly associated with defects in cell-mediated immunity
What is pathogenesis of hodgkins lymphoma?
have localized single group of nodes wtih contiguous spread
Is prognosis better for hodgkins or non-hodgkins lymphoma?
better for hodgkins
How do you diagnose hodgkins lymphoma?
presence of reed-sternberg cells on excisional biopsy of affected node AND normal small lymphocytes, lots of inflammatory reactive cells
What is morphology of reed steinberg cells?
binucleated, large inclusion like esoinophilic nucleoli, express CD15 and CD30
lack expression of normal B cell markers like CD19 and CD20
What type of hodgkins lymphoma expresses CD2?
nodular lymphocyte predominant subtype
What are chracteristics of nodular sclerosing hodgkins lymphoma?
- affects men and women equally
- have birefringent collagen bands, lacunar cells = mononuclear RS cells that look like they are surrounded by halo
- lots of eosinophils
What types of cells make up majority in hodgkins lymphoma?
majority of cells are reactive
WHat is nodular lymphocyte predominant hodgkins?
have few RS cells
more indolent than classical
express B cell antigens CD19 and CD20 and have germinal center specific BCL6
rarely epxress CD15 and CD30; few RS cells
What are the 4 tpes of classical hodgkins lymphoma?
- nodular sclerosing = have lacunar cells
- lymphocyte rich = least aggressive
- mixed cellularity = lots of RS cells
- lymphocyte depleted = more aggressive
What is normal presentation of hodgkins lymphoma?
asymptomatic lymph node enlargement usually in neck
B symptoms [fever, night sweats, weight loss]
What do you see on lab in hodgkins lymphoma?
eosinophils + monocytes
lymhpocytopenia in more advanced disease
ESR elevated
Who are most favorable prognostically in hodgkins lymphoma?
- early stage
- less than 50 yo
- without large mediastinal adenopathy
- ESR less than 50
- no B symptoms
What is typical treatment of early stage hodgkins?
combo chemo —> 2-4 cycles of ABVD
What is typical treatment of advanced stage hodgkins?
6-8 cycles of ABVD
What is ABVD therapy?
- adriamycin
- bleomycin
- vinblastine
- dacarbazine
What is the name of the monoclonal antibody drug against CD30?
brentuximab vedotin = anti-tubulin agent linked to CD30 antibody
