Lymphoma

Question 1

In which sites may lymphoma be found

Answer 1

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 2

What are the types of lymphoid malignancies

Answer 2

Hodgkin’s
- Classical
- Nodular lymphocyte predominant

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

Question 3

What are the types of classical Hodgkins lymphoma

Answer 3

Nodular sclerosing
Mixed cellular
Lymphocyte depletion
Lymphocyte rich

Question 4

What are the types of B cell non-Hodgkin lymphoma

Answer 4

Low grade
MALToma
Small lymphocytic lymphoma (CLL)
Follicular

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

Aggressive
Burkitt’s

Question 5

What are the types of T cell non-Hodgkin lymphoma

Answer 5

Anaplastic large cell lymphoma
Adult T cell leukaemia lymphoma (ATLL)
Enteropathy-associated T-cell lymphoma (EATL)
Cutaneous (mycoises fungoides)

Question 6

Describe the histology of a lymph node

Answer 6

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 7

What investigations should be done for lymphoma

Answer 7

Bloods:
- LDH: raised
- Albumin
- U&Es
- HIV, hep B serology ± HTLV-1 (ensure hep B will not reactivate)

Anatomical stage
- bone marrow biopsy
- CT/PET
- Lumbar puncture if risk of CNS involvement

Cytology (cells aspirated from lump)
Histology (tissue sections)

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

Question 8

What are the lymphoma CD markers for NHL

Answer 8

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

Question 9

Which Ig are associated with B cell lymphomas

Answer 9

Follicular NHL: IgH-BCL2
Mantle Cell lymphoma: IgH-Cyclin D1
Burkitt Lymphoma: IgH-MYC

Question 10

What are the symptoms of lymphoma

Answer 10

Painless progressive lymphadenopathy (neck, axilla groin)
Compression symptoms
- Renal failure
- Obstructive jaundice
- Large blood vessels
- Bowel obstruction
- Trachea
- Oesophageal
Infiltration
- Brain: stroke, lOC, memory problems
- Skin rash: plaques, ulceration, nodules
- Ocular: blindess
- Liver: liver failure
Recurrent infections
B symptoms: fever, night sweats, weight loss

Question 11

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

Answer 11

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

Question 12

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

Answer 12

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 13

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

Answer 13

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

Question 14

Give examples of MALT and their causes

Answer 14

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

Question 15

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

Answer 15

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

Question 16

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

Answer 16

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 17

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

Answer 17

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 18

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

Answer 18

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

Question 19

Describe enteropathy associated T-cell lymphoma (cause and association, histology, presentation, response to treatment, prevention)

Answer 19

Caused by chronic antigen stimulation to gluten/gliadin → associated with coeliac disease
Histology: Mature T cells TdT, CD19
Presentation:
- Abdo pain, obstruction, perforation, GI bleeding
- Malabsorption
- Systemic symptoms

Responds poorly to chemotherapy, generally fatal
Can be prevented by strict adherence to a gluten-free diet

Question 20

What are the associations with Adult T cell leukaemia lymphoma (ATLL)

Answer 20

HTLV-1 infection
Japanese and Caribbean ethnicity
Histo: flower cells

Question 21

What is cutaneous T cell NHL associated with

Answer 21

Mycosis fungoides

Question 22

What is the epidemiology of Hodgkin’s lymphoma

Answer 22

1% of all cancer
Less common than non-Hodgkin’s
M > F
Bimodal age - 20-29yo (most common), >60yo (smaller peak)

Question 23

What are the symptoms of Hodgkin’s lymphoma

Answer 23

Asymmetric painless lymphadenopathy
Pain in nodules after alcohol ingestion

Question 24

What are the diagnostic features of hodgkin’s lymphoma on investigation

Answer 24

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

Question 25

Describe the features of nodular sclerosing HL sub-type (epidemiology, symptoms)

Answer 25

Young women (20-29) Neck nodes and a mediastinal mass → SVC or trachea compression Spreads contiguously

Question 26

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

Answer 26

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

Question 27

Describe the staging of lymphoma

Answer 27

Ann Arbor Staging A = B symptoms absent B = B symptoms present E = involvement of single, contiguous, or proximal extranodal site I: One node region involved on 1 side of the diaphragm II: 2+ ipsilateral regions involved on 1 side of the diaphragm III: Bilateral node involvement on both sides of the diaphragm IV: HL: Involvement of extranodal sites beyond those designated by ‘E’ (below) NHL: Disseminated/multifocal involvement of ≥1 extralymphatic site OR isolated extralymphatic organ involvement with distant node involvement

Question 28

Describe the treatment of Hodgkin's lymphoma

Answer 28

Chemotherapy: ABVD (2-6 cycles, 4-weekly intervals) - adriamycin, bleomycin, vinblastine, DTIC (Dacarbazine) ± radiotherapy Second line: salvage chemotherapy (high dose chemo + HSCT) Third line: anti-CD30 (Brentuximab Vedotin)+ anti-PD1(nivolumab)

Question 29

What is the management for NHL

Answer 29

Chemotherapy: R-CHOP (6-8 cycles) - rituximab, cylophosphamide, adriamycin, vincristine, prednisolone Second line: autologous HSCT

Question 30

What is the prognosis for NHL

Answer 30

Burkitt's lymphoma – fastest growing human cancer Follicular lymphoma (an indolent disease) – possible 25 year survival HOWEVER, chance of being cured increases with more aggressive neoplasms

Question 31

What are the prognostic markers for NHL

Answer 31

LDH (marker of cell turnover) Performance status HIV serology Hep B serology (treatment for lymphoma may cause a dormant hep B to reactivated → fulminant liver failure)

Question 32

What is the prognosis for Hodgkin's lymphoma

Answer 32

Elderly patients do worse than the worst-prognosis HL (lymphocyte-depleted type) It is a highly curable disease, but the prognosis depends on stage Over 80% in stage I or II disease are cured 50% of stage IV are cured 10% die from relapse within 10 years and 10% die from complications after 10 years More likely to die of secondary malignancy of CV complications after 5 years

Question 33

What phenotype is indicative of CLL

Answer 33

Normal T cells are CD5 positive, and CD 19 and 20 negative. While normal B cells are the other way around. CLL B cells have an unusual phenotype (Monoclonal lymphocytosis with abnormal expression of CD5 = highly suggestive of CLL)

Question 34

What is the phenotype of T cells

Answer 34

CD3 positive CD4 or CD8 positive (Th-cell, CTL cell) CD19 NEGATIVE CD5 POSITIVE