Pathophysiology of Lymphomas - Ipswich-Year2-Med-PBL-Gp-2

January 30, 2018 | Author: Anonymous | Category: Science, Health Science, Immunology
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Rick Allen

PATHOPHYSIOLOGY OF LYMPHOMAS

LYMPHOMA Leukaemia involves widespread bone marrow involvement and a presence in peripheral blood.  Lymphoma’s arise in discrete tissue masses (commonly lymph nodes), with potentially only minor peripheral blood presence. 

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 Hodgkins Lymphoma (NHL)

ROBBINS P 599

NHL – PREM B AND T 

ALL



That is all

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 and trisomy 12q  Pathophysiolology: Growth confined to proliferation centres. Microenvironment stimulates NF-κB. Immune function buggered by unknown mechanism

NHL – PERIPHERAL B CELL NEOPLASM 

Follicular Lymphoma  Most

common form of indolent NHL  Immunophenotype: CD19/20/10, Ig, BCL 2 and 6  Aetiology: Germinal centre B cells, t(14:18) [BCL2]  Pathophysiolology: BCL2 antagonises apoptosis and promotes survival. Calls in reactive cells. Marrow, spleen and liver involvement common. Goes where B cells go (white pulp)

NHL – PERIPHERAL B CELL NEOPLASM 

Diffuse Large B-cell Lymphoma  Most

common NHL. Diffuse growth, massive cells  Immunophenotype: CD19/20, Ig, BCL 6  Aetiology: BCL6 overexpression mutation: represses germinal B cell differentiation and growth arrest, silences p53  Pathophysiolology: rapidly enlarging mass. Waldeyer ring is common. Destructive mass in liver or spleen (1 or 2). Aggressive, commonly fatal

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 a promoter  ↑ expression. p53 point mutation. EBV involvement  Pathophysiolology: extranodal sights in kids and young adults. Jaw and abdo viscera.

NHL – PERIPHERAL B CELL NEOPLASM 

Mantle cell Lymphoma  Resemble

mantle B cells (surround germinal centre). Nodular or diffuse  Immunophenotype: ↑ cyclin D1, CD19/20/5, Ig.  Aetiology: t(11;14) cyclin D1 upregulation  G1S phase progression  Pathophysiolology: Painless lymphadenopathy. Spleen and gut involvement  symptoms.

NHL – PERIPHERAL B CELL NEOPLASM 

Marginal zone Lymphoma  Extranodal

sites and MALT’s

 Arise:  Chronic

inflammation due to autoimmunity or infection (thyroid – Hashimoto, stomach – Heliobacter)  Localised for a fair period  May regress if ‘stimulant’ is removed.

PERIPHERAL T CELL LYMPHOMA Immunophenotype: CD2/3/5  Types 

Anaplastic Large-cell Lymphoma (rare)  Mycosis Fungoides/Sezary syndrome 

 CD4

Th cells go to the skin, invading the upper dermis and epidermis. 3 distinct phases. Uses adhesion molecule.



Adult T cell  Infected

with Human T cell leukaemia retrovirus type 1 (HTLV-1),  NF-κB. Bad prognosis.

Large Granular Lymphoblastic Lymphoma (rare)  Extranodal NK/T cell Lymphoma 

 Surrounds

and invades small vessels  ischaemic necrosis. EBV involved

HODGKIN’S LYMPHOMA 

Classical HL  Nodular

sclerosis  Mixed cellularity  Lymphocyte rich (rare)  Lymphocyte depletion (rare) 

Lymphocyte pre-dominance (rare)



Difference? Immunophenotypes of ReedSternberg (RS) Cells.

HODGKIN’S LYMPHOMA 

Aetiology:  B-cells

are from germinal/post-germinal centre  A mechanism (commonly EBV infection via LMP1)  NF-κB inhibitor mutation  act. Transcription factor NF-κB  act. Lymphocyte proliferation and survival genes  Theory: saves defective B cell from apoptosis, mutates to RS cell  RS secretes cytokines (IL-5,10,13, TNF-β) and chemokines calling reactive cells (majority)  release factors to promote tumour growth and survival.

ROBBINS P621

HODGKIN’S LYMPHOMA 

Pathophysiology:  Node

 spleen  liver  marrow/other tissues  Suppressed Th1 immune response.  Mediastinal involvement  breathing issues.  Generally slower progression

HL VS. NHL

HL

NHL

more often localized to a single axial group of nodes (cervical, mediastinal, para-aortic) Orderly spread by contiguity

More frequent involvement of multiple peripheral nodes.

Mesenteric nodes and Waldeyer ring rarely involved

Waldeyer ring and mesenteric nodes commonly involved

Extra-nodal presentation rare.

Extra-nodal presentation common

Noncontiguous spread

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