PATHOPHYSIOLOGY OF LYMPHOMASRick Allen

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 G1-S 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 Reed-Sternberg (RS) Cells.

HODGKIN’S LYMPHOMA

Aetiology: B-cells are from germinal/post-germinal

centre A mechanism (commonly EBV infection via

LMP-1) 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 NHLmore 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