Rick Allen

PATHOPHYSIOLOGY OF LYMPHOMAS

LYMPHOMA
Leukaemia involves widespread bone marrow involvement and a presence in peripheral blood. Lymphomas 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-B. 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
Arise:
Chronic

sites and MALTs

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

Adult T cell
Infected

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

Surrounds

and invades small vessels ischaemic necrosis. EBV involved

HODGKINS LYMPHOMA

Classical HL
Nodular

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

Lymphocyte pre-dominance (rare)

Difference? Immunophenotypes of ReedSternberg (RS) Cells.

HODGKINS LYMPHOMA

Aetiology:
B-cells

are from germinal/post-germinal

centre A mechanism (commonly EBV infection via LMP-1) NF-B inhibitor mutation act. Transcription factor NF-B 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-) and chemokines calling reactive cells (majority) release factors to promote

ROBBINS P621

HODGKINS LYMPHOMA

Pathophysiology:
spleen liver marrow/other tissues Suppressed Th1 immune response. Mediastinal involvement breathing issues. Generally slower progression
Node

HL VS. NHL

HL
more often localized to a single axial group of nodes (cervical, mediastinal, para-aortic) Orderly spread by contiguity Mesenteric nodes and Waldeyer ring rarely involved Extra-nodal presentation rare.

NHL
More frequent involvement of multiple peripheral nodes. Noncontiguous spread Waldeyer ring and mesenteric nodes commonly involved Extra-nodal presentation common