Diffuse Large B-Cell Lymphoma Flashcards
what is diffuse large B-cell lymphoma?
large B-cell lymphoma (DLBCL) is an aggressive form of lymphoma
it is the most common form of non-Hodgkin’s lymphoma (NHL), accounting for 35% of all NHL
DLBCL arises from B lymphocytes
what does the microscope view of DLBCL look like?
the normal architecture of the lymph nodes is lost and replaced by the random pattern of growth of malignant B cells - hence the name “diffuse”
also the B cells are at least twice the size of normal lymphocytes
what populations does DLBCL effect?
usually seen in adults, with an average age of 60-65 years at time of diagnosis
but also occurs in children
often develops in immunocompromised patients and it is the most common HIV-related lymphoma
What is the most common non-Hodgkin lymphoma?
Diffuse large B-cell lymphoma is the most common non-Hodgkin lymphoma. It is also the most common HIV-related lymphoma.
where are B cells found in the lymph node?
cortex
specifically, they populate an area called the germinal follicle and they remain there until they get exposed to antigens, a turning point that dramatically changes their lives
where are plasma cells found in the lymph node?
medulla
where are T-cells found in the lymph node?
paracortex
what is anergy?
migrant naïve (baby) B cells are confronted with limited options: fight back or enter an unresponsive state called anergy
the naïve B cells that rise to the challenge and fight back form the germinal center (GC)
what happens to B-cells in the GC?
GC= germinal center of the lymph node
B cells in the GC proliferate, undergo somatic hypermutation, and differentiate into plasma cells before they migrate to the medullary cord
what are the two parts of the GC?
dark zone
light zone
what are centroblasts?
the B-cells that inhabit the dark zone of the germinal center
whencentroblasts migrate to the light zone and express their membrane-bound
immunoglobulins, they become centrocytes
what are centrocytes?
when centroblasts migrate to the light zone and express their membrane-bound
immunoglobulins, they become centrocytes
what are immunoblasts/plasmablasts?
B-cells destined to plasma cell
differentiation
once fully differentiated and mature, plasma cells leave the
germinal center to the medullary cords
what are memory B cells?
they develop from centrocytes in the GC and then migrate to the bone marrow, their hometown
well-known for their longevity
What subpopulation of B cells is found in the light zone of the germinal center?
Centrocytes are found in the light zone of the GC
when centroblasts migrate from the dark zone to the light zone and express their membrane-bound immunoglobulins, they become centrocytes
what do centroblasts look like?
large centrofollicular cells with pale, round nuclei with coarse chromatin and two or more nucleoli
what do centrocytes look like?
small, cleaved follicular center cells with scant cytoplasm
what do immunoblasts look like?
the largest lymphoid cells in the lymph node
they have deeply basophilic cytoplasm and pale nuclei and one or two centrally located very large nucleoli
what are the types of B-cells?
- centroblasts
- centrocytes
- immunoblasts (plasma cell)
- memory B cell
DLBCL cells can resemble any of these different cell types!!!
what is the germinal center?
a specialized microstructure that forms in secondary lymphoid tissues, producing long-lived antibody secreting plasma cells and memory B cells, which can provide protection against reinfection
a microenvironment in which B-cell maturation and differentiation take place
at this stage, B cells are vulnerable to somatic mutations that might lead to lymphoma or leukemia
Why might B-cell lymphoid malignancie develop from the germinal center?
B cells undergo somatic hypermutation and class switching in the germinal center
that’s a threat to the genomic integrity of B cells that might lead to the development of lymphoma or leukemia
what’s the clinical presentation of DLBCL?
usually presents as a rapidly-growing mass
unlike other lymphomas, which almost exclusively present in lymph nodes, DLBCL frequently presents in extranodal places, such as the GI tract, skin, bone, brain, and CNS
can also have continuous low-grade fever, unintentional weight loss, and drenching night sweats
what are B symptoms of lymphoma?
continuous low-grade fever, unintentional weight loss, and drenching night sweats
What is the most common presentation of DLBCL?
Painless, fast-growing lymphadenopathy is the most common presentation of DLBCL
how do you confirm a DLBCL diagnosis?
biopsy
how are HL, NHL and DLBLC staged?
they are staged according to the Ann Arbor Staging System
every stage is assigned an A or B modifier based on the absence (A) or presence (B) of B symptoms
there are stages 1-4
what is stage 1 of the Ann Arbor Staging system?
this is how how are HL, NHL and DLBLC staged
Stage 1: Single group of lymph nodes is affected
what is stage 2 of the Ann Arbor Staging system?
this is how how are HL, NHL and DLBLC staged
Stage 2: two or more groups of lymph nodes are affected either above or below the diaphragm
what is stage 3 of the Ann Arbor Staging system?
this is how how are HL, NHL and DLBLC staged
Stage 3: Lymph nodes on both sides of the diaphragm are affected
what is stage 4 of the Ann Arbor Staging system?
this is how how are HL, NHL and DLBLC staged
Stage 4: Lymphoma is found outside the lymphatic system or in the bone marrow
how severe is DLBCL?
DLBCL is an aggressive lymphoma, and is rapidly fatal if not treated
with intensive chemotherapy, about 60-80% of patients achieve a complete remission, and 40-50% are cured
what test must be done to clarify a DLBCL diagnosis?
immunophenotyping
immunophenotype is a molecular identification code that is unique to the malignant cells being investigated
malignant cells express certain genes to form proteins or markers that give these cells their characteristic molecular identity, signature, or code
morphological classification of DLBCL is not very predictive of the clinical course and therapeutic response
what is immunophenotyping?
think of an immunophenotype as a code
i.e., a molecular identification code that is unique to the malignant cells being investigated, with each code consisting of a group of molecular markers represented by letters and numbers
you then decipher that code using flow cytometry or immunohistochemistry techniques
what are the pan-B-cell markers in immunophenotyping?
CD19
CD20
CD22
CD79a
PAX5
what can immunophenotyping tell you about DLBCL?
immunophenotyping tells us if DLBCL is derived from a certain stage of B-cell differentiation e.g., pre-GC, GC or post-GC cell of origin
unique molecular identity indicates if the cell of origin was naïve, GC, or an activated B cell
What are the two major immunophenotypes of DLBCL?
Germinal-center derived and non-germinal-center derived
1st phenotype: GC B-cell like, DLBCL originates from GC B cell = GC phenotype
2nd phenotype: DLBCL originates from a B cell in another stage of differentiation = non-germinal-center (NGC) phenotype
what are the most common variants of DLBCL cells?
centroblastic, immunoblastic,
and anaplastic variants
65-year-old man presented to the outpatient clinic for a lump in his armpit that he felt while showering. He also complained of low-grade fever, weight loss, and night sweats. The doctor scheduled a lymph node biopsy that came back positive for lymphoma. What is the most likely diagnosis?
diffuse large B-cell lymphoma
DLBCL is the most common non-Hodgkin lymphoma
it typically presents as painless, fast-growing lymphadenopathy that might be associated with B symptoms (continuous low-grade fever, weight loss, and drenching night sweats).
DLBCL is usually seen in adults with an average age of 60-65 years at time of diagnosis
all other choices are less common than DLBCL
In which part of the germinal center are centroblasts found?
dark zone
once centroblasts migrate to the light zone and express their membrane-bound immunoglobulins, they become centrocytes
Centroblasts migrate from the dark zone of the germinal center to the light zone and express their membrane-bound immunoglobulins. What is the name of the B cells at this stage of differentiation?
centrocytes
