Pa Tho Physiology of Lymphomas

8/2/2019 Pa Tho Physiology of Lymphomas

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PATHOPHYSIOLOGY OF LYMPHOMAS

Rick Allen


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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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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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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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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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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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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

Pa Tho Physiology of Lymphomas

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