Haem - Lymphoma

Question 1

Define lymphoma

Answer 1

Neoplastic (malignant) proliferation/tumour of lymphoid cells to form discrete tissue masses

Question 2

In which sites may lymphoma be found

Answer 2

Lymph nodes, bone marrow and/or blood (the lymphatic system)
Lymphoid organs; spleen or the gut-associated lymphoid tissue
Skin (often T cell disease; e.g. Mycoses Fungoides)
Rarely “anywhere” (Sanctuary sites: CNS, ocular, testes, breast, etc.)

Question 3

What are the types of lymphoid malignancies

Answer 3

Hodgkin’s
- Classical
- Nodular lymphocyte predominant

Non-Hodgkin’s
- B cell (most common - 80%)
- T cell

Question 4

What are the types of classical Hodgkins lymphoma

Answer 4

Nodular sclerosing
Mixed cellular
Lymphocyte depletion
Lymphocyte rich

Question 5

What are the types of B cell non-Hodgkin lymphoma

Answer 5

Low grade
MALToma
Small lymphocytic lymphoma (CLL)
Follicular

High grade
Diffuse large B cell lymphoma (DLBCL)
Mantle cell

Aggressive
Burkitt’s

Question 6

What are the types of T cell non-Hodgkin lymphoma

Answer 6

Anaplastic large cell lymphoma
Adult T cell leukaemia lymphoma (ATLL) - HTLV-1 infection
Enteropathy-associated T-cell lymphoma (EATL) - coeliac disease
Cutaneous (mycoises fungoides)

Question 7

What are the positives and negatives of DNA instability in the immune system

Answer 7

Positive
Allows for recombination → diversity
Rapid proliferation for rapid response to infection
Apoptosis dependency for specificity, elimination of self-reactive clones

Negative
Recombination → unwanted point mutations
Rapid proliferation → replication errors
Apoptosis dependency: apoptosis may be switched off

Question 8

What are the stages of immunoglobulin and TCR gene recombination

Answer 8

1. VDJ recombination in the bone marrow involving RAG1 and RAG2
2. Class switch recombination: somatic hypermutation in the germinal centre - heavy chain of Ig changed and the oncogenes are brought closer to the promoter

Question 9

What are the divisions of the lymphoreticular system

Answer 9

1. Generative lymphoreticular (LR) tissue - generation/maturation of lymphoid cells in bone marrow and thymus
2. Reactive LR - immune reaction in lymph nodes and spleen
3. Acquired LR tissue - local immune reaction in extra-nodal tissue (skin, stomach, lungs)

Question 10

Describe the histology of a lymph node

Answer 10

Germinal centre of B cells and antigen presenting cells
Surrounded by the mantle zone - naive, unstimulated B cells
Surrounded by a paracortical T cell zone
Lymph node sinuses between follicles

Question 11

What investigations should be done for lymphoma

Answer 11

Cytology (cells aspirated from lump)
Histology (tissue sections):
- Architecture: nodular, diffuse
- Histology: small round, small cleaved, large cells
Immunophenotyping:
- Cell types (CD markers)
- Cell distribution
- loss of surface proteins
- Abnormal expression of proteins
- Clonality of B cells

Cytogenetics
FISH - chromosomal translocations
PCR - chromosomal translocations, gene rearrangement

Question 12

What are the lymphoma CD markers

Answer 12

CD19, CD20 = B-cells
CD3, CD5 = T-cells

Question 13

What are the features of follicular lymphoma (epidemiology, time course, molecular, histopathology)

Answer 13

Middle-aged or elderly
Indolent, relatively incurable
t(14;18) involving bcl-2 gene
Histo: neoplastic follicles, positive CD10 and bcl-6 staining

Question 14

What are the features of small lymphocytic lymphoma (association, epidemiology, histopathology)

Answer 14

CLL
Associated with Richter transformation (presents with NEW B symptoms)
Middle aged or elderly
Histo: small lymphocytes, arises from naive B cells, CD5 and CD23 positive

Question 15

What are the features of marginal zone lymphoma/MALToma (cause, timeline, management)

Answer 15

Response to chronic antigenic stimulation
Post germinal centre memory B cell
Indolent but could transform
Management: remove the antigenic stimulation

Question 16

Give examples of MALT and their causes

Answer 16

H. pylori → gastric
Sjogren’s → parotid gland
Hashimotos → thyroid MZL
Psittaci infection → lacrimal gland

Question 17

What are the features of mantle cell lymphoma (epidemiology, histopathology, molecular associations, prognosis)

Answer 17

Middle aged males
Histo: seen in the mantle zone, arising from pre-germinal centre cells, expression of CD5 and cyclin D1, clefted nuclei
Molecular: t(11;14), cyclin D1 overexpression
Prognosis: 2-5 years

Question 18

What are the features of Burkitt’s lymphoma (presentation, association, histopathology, molecular associations)

Answer 18

Jaw/abdo mass when young
Associated with EBV
Histo: starry-sky appearance, arises from germinal centre cells
Molecular: C-myC translocation (8;14) OR (2;8) OR (8;22)

Question 19

What are the features of diffuse large B cell lymphoma (epidemiology, histopathology, prognosis)

Answer 19

Middle aged and elderly
Histo: from germinal centre/post-germinal centre, sheets of large lymphoid cells
p53+: Poor prognosis

Question 20

What are the features of anaplastic large cell lymphoma (epidemiology, histopathology, molecular associations, prognostic factors)

Answer 20

Younger patients
Histo: large epithelioid lymphocyte, anaplastic
Molecular: t(2;5)
Alk-1 protein expression = better prognosis

Question 21

What are the features of classical non-hodgkin’s lymphoma

Answer 21

From germinal centre OR post-germinal centre
Associated with EBV
Histo: sclerosis, Reed-Sternberg cells, lymphoma cells
Eosinophils
Markers: CD30+, CD15+, CD20 -ve

Question 22

What are the features of nodular sclerosing lymphoma (epidemiology, signs)

Answer 22

Young females
Neck nodes
Mediastinal mass → compression of trachea and SVC

Question 23

What are the features of nodular lymphocyte predominant lymphoma (presentation, association, histopathology, diagnostic markers)

Answer 23

Isolated lymphadenopathy
May transform to a high grade B cell NHL
Histo: b cell rich nodules, NO eos/macro

NEGATIVE for CD30 + CD15 (which is seen in classical Hodgkin)
POSITIVE for CD20