Diffuse Large B-Cell Lymphoma Flashcards by daniela kaissieh

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

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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

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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

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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.

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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

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where are plasma cells found in the lymph node?

medulla

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where are T-cells found in the lymph node?

paracortex

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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)

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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

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what are the two parts of the GC?

dark zone

light zone

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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

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what are centrocytes?

when centroblasts migrate to the light zone and express their membrane-bound
immunoglobulins, they become centrocytes

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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

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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

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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

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what do centroblasts look like?

large centrofollicular cells with pale, round nuclei with coarse chromatin and two or more nucleoli

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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