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8/2/2019 Pa Tho Physiology of Lymphomas
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PATHOPHYSIOLOGY OF LYMPHOMAS
Rick Allen
8/2/2019 Pa Tho Physiology of Lymphomas
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LYMPHOMA
Leukaemia involves widespread bonemarrow involvement and a presence inperipheral blood.
Lymphomas arise in discrete tissue masses
(commonly lymph nodes), with potentiallyonly minor peripheral blood presence.
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CLASSIFICATION BASED ON CELL ORIGIN
Precursor B cell neoplasms(premature B)
Peripheral B cell neoplasms(mature B)
Precursor T cell neoplasm(premature T)
Peripheral T cell and NK cell
neoplasm (mature T and NK) Hodgkin (Reed-Sternberg cells
and variants)
Non
HodgkinsLymphoma(NHL)
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ROBBINS P 599
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NHL PREM B AND T
ALL
That is all
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NHL PERIPHERAL B CELL NEOPLASM
CLL/Small Lymphocytic Lymphoma
Tissue manifestation of CLL. Psuedofollicular.
Immunophenotype:CD 19/20/23/5
Aetiology:deletion of 13q (TSG), 14q, 17p andtrisomy 12q
Pathophysiolology:Growth confined to
proliferation centres. Microenvironmentstimulates NF-B. Immune function buggered byunknown mechanism
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NHL PERIPHERAL B CELL NEOPLASM
Follicular Lymphoma
Most common form of indolentNHL
Immunophenotype:CD19/20/10, Ig, BCL 2 and
6
Aetiology:Germinal centre B cells, t(14:18)[BCL2]
Pathophysiolology:BCL2 antagonisesapoptosis and promotes survival. Calls inreactive cells. Marrow, spleen and liverinvolvement common. Goes where B cells go
(white pulp)
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NHL PERIPHERAL B CELL NEOPLASM
Diffuse Large B-cell Lymphoma
Most common NHL. Diffuse growth, massivecells
Immunophenotype:CD19/20, Ig, BCL 6
Aetiology:BCL6 overexpression mutation:represses germinal B cell differentiation and
growth arrest, silences p53Pathophysiolology:rapidly enlarging mass.
Waldeyer ring is common. Destructive mass inliver or spleen (1 or 2). Aggressive, commonly
fatal
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NHL PERIPHERAL B CELL NEOPLASM
Burkitt Lymphoma
Mature B cells. Starry sky pattern. Diffuse.
Immunophenotype:CD19/20/10, IgM, BCL6
Aetiology:t(8,2/14/22), c-MYC gene with apromoter expression. p53 point mutation.EBV involvement
Pathophysiolology:extranodal sights in kidsand young adults. Jaw and abdo viscera.
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NHL PERIPHERAL B CELL NEOPLASM
Mantle cell Lymphoma
Resemble mantle B cells (surround germinalcentre). Nodular or diffuse
Immunophenotype: cyclin D1, CD19/20/5, Ig.
Aetiology:t(11;14) cyclin D1 upregulation G1-S phase progression
Pathophysiolology:Painless lymphadenopathy.Spleen and gut involvement symptoms.
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NHL PERIPHERAL B CELL NEOPLASM
Marginal zone Lymphoma
Extranodal sites and MALTs
Arise:
Chronic inflammation due to autoimmunity or infection(thyroid Hashimoto, stomach Heliobacter)
Localised for a fair period
May regress if stimulant is removed.
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PERIPHERAL T CELL LYMPHOMA
Immunophenotype:CD2/3/5
Types Anaplastic Large-cell Lymphoma (rare)
Mycosis Fungoides/Sezary syndromeCD4 Th cells go to the skin, invading the upper dermisand epidermis. 3 distinct phases. Uses adhesionmolecule.
Adult T cell
Infected with Human T cell leukaemia retrovirus type 1(HTLV-1), NF-B. Bad prognosis.
Large Granular Lymphoblastic Lymphoma (rare) Extranodal NK/T cell Lymphoma
Surrounds and invades small vessels ischaemic
necrosis. EBV involved
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HODGKINS LYMPHOMA
Classical HLNodular sclerosis
Mixed cellularity
Lymphocyte rich (rare) Lymphocyte depletion (rare)
Lymphocyte pre-dominance (rare)
Difference? Immunophenotypes of Reed-Sternberg (RS) Cells.
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HODGKINS LYMPHOMA
Aetiology:B-cells are from germinal/post-germinal
centre
A mechanism (commonly EBV infection viaLMP-1) NF-B inhibitor mutation act.Transcription factor NF-B act. Lymphocyteproliferation and survival genes
Theory: saves defective B cell from apoptosis,mutates to RS cell
RS secretes cytokines (IL-5,10,13, TNF-)and chemokines calling reactive cells
(majority) release factors to promote
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ROBBINS P621
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HODGKINS LYMPHOMA
Pathophysiology:
Node spleen liver marrow/other tissues
Suppressed Th1 immune response.
Mediastinal involvement breathing issues.
Generally slower progression
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HL VS. NHL
HL NHL
more often localized to a single
axial group of nodes (cervical,mediastinal, para-aortic)
More frequent involvement of
multiple peripheral nodes.
Orderly spread by contiguity Noncontiguous spread
Mesenteric nodes and Waldeyer
ring rarely involved
Waldeyer ring and mesenteric
nodes commonly involved
Extra-nodal presentation rare. Extra-nodal presentation
common