HOW TO DIAGNOSE LYMPHOMA

Dr Mark Smith Derriford Hospital, Plymouth

Normal lymphocyte function

Normal lymph node structure

General principles of lymphoma diagnosis

Specific lymphomas

Lymphocytes produce antigen receptor to

recognise foreign antigen.

EXTERNAL foreign antigen – bacteria

INTERNAL foreign antigen - virus

B Lymphocytes - Immunoglobulin

B

Ag

Ag

Ab

T lymphocytes – T cell receptor

T

MHC class 1

T cell receptor

processed pepticle

memory

virgin

lymphocyte Centroblast Plasma cell

Foreign Ag

Ab

HEV

HEV - High Endothelial Venules

Lymph

Lymph

HEV

HEV

Foreign

antigen in

lymphatics

LYMPH NODE –

CONFLUENCE OF

TWO STREAMS

Lymphocytes

Lymph Node

Foreign antigen

Lymphocytes

Supporting cells

Macrophages – enhance antigen presentation

Architectural units - factories

SINUS

GC

PC

MC

MC

Lymph node compartments

GC – germinal centre

PC – paracortex

MC – medullary cord

Lymphoma

Hodgkin Lymphoma Non-Hodgkin Lymphoma

B T

Low-grade High-grade

Grade in B-cell NHL

Lymphocytes Blasts

All ‘cytes - low grade

Cytes/blasts – low grade

Blasts – high grade

• C Y T O L O G I C A L

• A R C H I T E C T U R A L

Malignant Tumour

Cytological

High nuclear / cytoplasmic ratio

Nuclear pleomorphism

Many mitoses / abnormal mitoses

Architectural

Invasion

Destruction of normal tissues

Abnormal location

Lymphoma Diagnosis

Cytologic abnormality

Architectural abnormality

Monotony

Reactive Lymph Nodes

Polymorphic

Lymphocytes

Blasts

Macrophages

Eosinophils

Monomorphic v Polymorphic

Sheets of same cell type

Monotony (monomorphic)

Lymphoma Diagnosis

Morphology

Immunohistochemistry

Molecular biology

Lymphocyte Antigens

B cell T cell

CD79a CD3

CD20 CD5

CD2

Aberrant Phenotype

B-cell NHL

CD20 POS

CD5 POS

(CLL and mantle cell lymphoma)

Aberrant Phenotype

T-cell NHL

CD2 POS

CD3 NEG

Aberrant Phenotype

CLONALITY

Immunoglobulin

LIGHT CHAINS

K L

Reactive

K L K

L K K

K L

B - NHL

L

L L L

L L

L

B - NHL

K

K

K

K K

K

K

Immunohistochemistry

B-cell NHL – aberrant pattern

B-cell NHL - light chain restriction

T-cell NHL - aberrant pattern

Lymphoma Diagnosis

• Morphology

• Immunohistochemistry

• Molecular biology

Follicular Hyperplasia

FOLLICULAR PATTERN with follicular dendritic cell (CD21 pos) scaffolding.

POLYMORPHIC

Centroblasts

Centrocytes

Tingible body macrophages

bcl-2 negative follicle centres

Follicular Lymphoma (B-cell NHL)

Follicular pattern with CD21 scaffolding

Monomorphic

bcl-2 positive follicle centres

Diffuse large B-cell NHL

T-CELL NHL