ICL 11.1: Lymphoma I Flashcards
what is lymphoma?
malignancy of lymphocytes that typically begins in the lymph nodes
where do lymphomas originate?
~2/3 Actually arise in lymph nodes
~1/3 of cases arise in extra nodal sites
like the GI tract, CNS, skin, eyes
what are the two major categories of lymphomas?
- Non-Hodgkin lymphoma
B cell (most common), T cell, and NK cell lymphomas
- Hodgkin Lymphoma
5 subtypes, WHO classification
classic and non-classic
what’s the difference between lymphoma and leukemia?
both are malignancies of the hematopoietic and lymphoid tissues…
but lymphomas are a malignancy of lymphoid cells that typically begins in the lymph nodes
and leukemias are a malignancy in either lymphoid or myeloid cells that begin in bone marrow
are lymphomas mono or polyclonal?
all lymphomas are derived from a single transformed cell and thus are monoclonal
B and T cell tumors are composed of cells derived from specific stages of their normal differentiation pathways
which lymphomas are derived from germinal center B cells?
follicular lymphoma
burkitt lymphoma
diffuse large B cell lymphoma
hodgkin lymphoma
which lymphomas are derived from precursor B cells?
B lymphoblastic leukemia/lymphoma
which lymphomas are derived from pre-GC B cells?
mantle cell lymphoma
which lymphomas are derived from post-GC B cells?
marginal zone lymphoma (MALT)
lymphoplasmacytic lymphoma
CLL/SLL
DLBCL
plasmacytoma
which lymphomas are derived from precursor T cells?
T lymphoblastic lymphoma/leukemia
where are B cells normally located in the lymph node?
cortex
where are T cells normally located in the lymph node?
paracortex
where are plasma cells normally located in the lymph node?
medulla
what happens to B cells once they’ve matured in the BM?
Naïve B-cell lymphocyte, move from bone marrow to lymph node cortex
they congregate in germinal follicle until they’re expose to antigens
naïve B cells in the germinal center proliferate, undergo somatic hypermutation, and differentiate into plasma cells
what are the different parts of the lymph node?
slide 11
explain the progression of the B cell through the lymph node dark and light zone
- naive B cell enters dark zone
- undergoes clonal expansion
- undergoes somatic hypermutation
- B cell enters light zone
the cells that underwent disadvantageous mutations get turned into apoptotic cells in the light zone and are destroyed
the B cells that had advantageous mutations get turned into plasma cells or memory B cells
what’s the clinical presentation of lymphoma?
Fever, night sweats, weight loss (any malignant disease)
Painless lymphadenopathy
Splenomegaly, hepatomegaly or mass
what’s the Ann Arbor staging system for lymphomas?
Stage 1: localized disease, single lymph node region or single organ
Stage 2: two or more lymph node regions on the same side of the diaphragm
Stage 3: two or more lymph node regions above and below the diaphragm
Stage IV: widespread disease, multiple organs, with or without lymph node involvement
what’s the Lugano classification system of lymphomas?
bulk ln Hodgkin lymphoma is defined as a mass greater than one-third of the thoracic diameter on CT of the chest or a mass >10 cm
for NHL, the recommended definitions of bulk vary by lymphoma histology
stages 1-4
how can you diagnose a lymphoma?
Fine-needle aspirate is inadequate for initial diagnosis. Excisional biopsy is recommended. Core-needle biopsy may suffice when excision not feasible
flow cytometry would help you with immunophenotyping
FISH would help you see translocations
PET and CT scans
***morphology is required to establish diagnosis
what is the philadelphia translocation?
t(9;22) seen in CML
contains afusion genecalledBCR-ABL1
this causes a tyrosine kinasesignalingprotein that is “always on”, causing the cell todivideuncontrollably by interrupting the stability of the genome and impairing various signaling pathways governing the cell cycle
presence of this translocation is a highlysensitivetest for CML, since all cases of CML are positive forBCR-ABL1
However, the presence of the Philadelphia chromosome is not sufficientlyspecificto diagnose CML, since it is also found inacute lymphoblastic leukemia and occasionally inacute myelogenous leukemia as well as mixed-phenotype acute leukemia (MPAL).
what is the Deauville 5-point scoring system?
an internationally accepted and utilized five-point scoring system for the Fluorodeoxyglucose (FDG) avidity of a Hodgkin’s lymphoma or Non-Hodgkin’s lymphoma tumor mass as seen on FDG
1: no 18-FGD uptake
2: uptake < mediastinal blood pool
3: uptake > mediastinum and < liver
4: uptake moderately > liver at any site
5: uptake markedly > liver at any site and/or new sites of disease
X: new areas of uptake unlikely to be related to lymphoma
what are the main characteristics of NHL?
B-cell or T-cell
Mostly malignant cells
Widespread disease at Dx
Waldeyers ring common site
Noncontiguous spread
Low grade types incurable
what are the main characteristics of HL?
Unique Reed-Sternberg cell (CD15 and CD30 +)
Many reactive cells, few malignant cells
Localized disease
Waldeyers ring rarely involved
Predictable contiguous spread
Generally curable
what cells are involved in HL?
NOT B- or T-cell by immunostains or flow cytometry
yet, thbimodal age distribution
ought to be germinal or post-germinal B cell origin
what population is HL most common in?
most patients are diagnosed peak between 15-30 age followed by another peak after 55 years of age
is there a good or bad prognosis for HL?
good prognosis
often curable with combined modality therapy (chemotherapy and radiation)
long term survival is dependent on stage
what diseases are HL patients at risk for?
At risk for AML, MDS, secondary solitary cancers including lung, thyroid and breast cancer, as well as cardiotoxicity
what is the immunophenotype for classical HL?
CD20-
CD15+, CD30+, PAX5+
what are the types of classical HL?
- nodular scelorisis
- mixed cellularity
- lymphocyte rich
- lymphocyte depleted
what is the immunophenotype for non-classical HL?
CD20+
CD15-, CD30-
what’s the immunophenotype for popcorn cells?
CD20+
CD15-
CD30-
they’re found in non-classical HL
slide 29
what cell type is involved in NHL?
85-90% are B cells
what are the different types of patterns seen in NHL?
- follicular pattern = always B cell
- diffuse pattern = B or T cell
- starry sky pattern = high grade lymphoma, especially Burkitt’s
what population is NHL most common in?
usually older than 60
EXCEPT for lymphoblastic lymphoma = teens/20s and Burkitt lymphoma which is in kids
what is the A and B distinction in the Ann Arbor staging system of lymphomas?
A = no systemic symptoms present
B = unexplained fevers, night sweats, weight loss
***Lugano modification of the Ann Arbor staging doesn’t use the A and B distinction
is diffuse large b-cell lymphoma HL or NHL?
NHL
it’s the most common form of non-Hodgkins lymphoma
what is DLBCL?
diffuse large B-cell lymphoma
agressive - painless, rapid growing mass
arises from B lymphocytes
extra nodal involvement is not unusual = liver, spleen GI tract, Waldeyers ring
immunocompromised, most common HIV related lymphoma
what population is DLBCL most common in?
60-65 years
what pattern is DLBCL?
diffuse pattern
normal architecture of lymph node replace by random pattern of malignant B cells
what’s the immunophenotype for DLBCL?
CD19 +
CD20+
CD10 +/-
which disease is DLBCL associated with?
HIV
DLBCL is immunodeficiency-associated
it’s seen in HIV or organ transplant patients due to severe T-cell decrease
malignant B-cells are usually infected with EBV
what is follicular lymphoma?
indolent course but incurable
enlarging adenopathy in neck, axilla or groin
spreads to other lymph nodes, then extranodal sites and eventually BM
can transform to more aggressive, DLBCL
what mutation is associated with follicular lymphoma?
t(14;18)
BCL-2 over activated with translocation, which blocks apoptosis
slide 44
what is the immunophenotype of follicular lymphoma?
CD10
CD19
CD20
what population is follicular lymphoma most common in?
60 years and up
what are the different grades of follicular lymphoma?
grade 1 = small cells
grade 2 = mixed small and large cells
grade 3 = mostly large cells
small cleaved cells = centrocytes
large non-cleaved cells = centroblasts
what are signs of a poor prognosis for follicular lymphoma?
B symptoms
metastasis
higher grade (large cells)
