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

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