Non-Hodgkin's Lymphoma (NHL)

Question 1

What is Non-Hodgkin’s lymphoma?

Answer 1

A heterogeneous group of malignancies of the lymphoid system.
NHL is a disease of the immune system.

Question 2

Which autoimmune disorders is NHL linked to?

Answer 2

Sjogren’s syndrome
Rheumatoid arthritis
SLE
Coeliac disease

Question 3

Pathophysiology of NHL

Answer 3

Multi-step accumulation of genetic aberrations that confer a growth advantage and expansion of a monoclonal population of malignant lymphocytes.

Question 4

Classification of NHL

Answer 4

Aggressive B-cell lymphomas
Aggressive T-cell lymphomas
Indolent B-cell lymphomas
Indolent T-cell lymphomas

Question 5

Sub-types of aggressive B-cell lymphomas

Answer 5

DLBCL 
Mediastinal large B cell 
Primary CNS (95% are DLBCL) 
Primary effusion lymphoma/early cavity lymphoma 
Burkitt's and Burkitt-like 
Mantle cell

Question 6

Sub-types of aggressive T-cell lymphomas

Answer 6

Enteropathy-type T-cell lymphoma/interstitial T-cell lymphoma
Peripheral T-cell lymphoma
Subcutaneous panniculitis-like 
Systemic anaplastic 
Angioimmunoblastic

Question 7

Sub-types of indolent B-cell lymphomas

Answer 7

Follicular lymphoma

Marginal zone, gastric MALT-type

Question 8

Sub-types of indolent T-cell lymphomas

Answer 8

Mycosis fungoides/ Sezary syndrome

Primary cutaneous anaplastic large cell lymphoma

Question 9

Signs and symptoms of NHL

Answer 9

Clinical Hx depends on the type of lymphoma and the stage of presentation. 
- Aggressive lymphoma present with systemic symptoms like: 
Fever 
Weight loss (hypermetabolic state) 
SOB (pleural or lung) 
Drenching night sweats 
Malaise
Abdominal discomfort (hepatomegaly, splenomegaly, lymphadenopathy)
Dizziness
Ataxia (CNS involvement) 
Fatigue (anaemia) 
Cough (mediastinal mass/lymphadenopathy) 
Bone and back pain
-Signs may include: 
Lymphadenopathy
Pallor (anaemia) 
Jaundice (liver failure)
Skin nodules 
Hepatomegaly 
Splenomegaly 
Purpura (thrombocytopenia) 
Abnormal neurological exam

Question 10

Risk factors for NHL

Answer 10

Age > 50 years 
Male sex 
Immunocomprised host 
EBV 
Human T-lymphocytotrophic virus-1 (HTLV-1)
H.pylori 
Coeliac disease 
HIV 
HCV 
Sjögren’s syndrome 
Ataxia-telenglektasia 
Wiskott-Aldrich syndrome

Question 11

Investigations of NHL

Answer 11

FBC with differential (thrombocytopenia) 
Blood smear (nucleated RBCs) 
Lymph node biopsy (positive) 
Skin biopsy (positive) 
Bone marrow biopsy (positive) 
LFTs (elevated)
LDH (elevated)

Question 12

Differentials of NHL

Answer 12

Hodgkin's lymphoma 
Acute lymphocytic leukaemia 
Infectious mononucleosis 
HCV 
Sarcoidosis 
Rheumatoid arthritis 
CMV 
TB 
HIV 
Syphillis 
SLE

Question 13

Which staging system is used to stage NHL?

Answer 13

Modified Ann Arbor Staging System for NHL
I: Single lymph node group
II: Multiple lymph node groups on the same side of the diaphragm
III: Multiple lymph node groups on both sides of the diaphragm
IV: Multiple extranodal sites or lymph nodes and extranodal disease (an X denotes extranodal disease bulk >10 cm)
E: Extranodal extension or single isolated site of extranodal disease
B symptoms: weight loss >10%, fever, and drenching night sweats.

Question 14

Management of NHL

Answer 14

Huge range of options, depending on disease subtype

Question 15

Treatment of low-grade NHL

Answer 15

If symptomless, none may be needed
Radiotherapy may be curative in localised disease
Chlorambucil is used in diffuse disease
Remission may be maintained by using interferon alfa or rituximab.

Question 16

Treatment of high-grade NHL

Answer 16

R-CHOP regimen 
Rituximab 
Cyclophosphamide 
Hydroxylaunrubicin
Vincristine (oncovin) 
Prednisolone
-Granulocyte colony-stimulating factors (G-CSFs) help neutropenia e.g. filgrastim or lenograstim

Question 17

What is a major complication of IV chemotherapy?

Answer 17

Neutropenic sepsis

-This presents with fever 10-day post-treatment

Question 18

Prognosis of NHL

Answer 18

Histology is important. 
Prognosis is worse if, at presentation: 
Age > 60 years 
Systemic symptoms 
Bulky disease (abdominal mass >10cm) 
Increased LDH 
Disseminated disease

Question 19

Pathophysiology of B-cell lymphoma

Answer 19

• May arise during different stages of B-cell maturation.
• Immature B cells, mature antigen-naive B cells and mature antigen-activated B cells may transform to various types of NHL such as Burkitt’s lymphoma, diffuse large B cell lymphoma (DLBCL) and mantle cell lymphoma.
• In DLBCL, LDH is important in this pathology - 50% are cured and relapses are rare after 5 years.

Question 20

Pathophysiology of T-cell lymphoma

Answer 20

• Usually manifest in the skin
• It can manifest in different ways
• It can be aggressive

Question 21

What are the signs of hilar lymphadenopathy?

Answer 21

Chest pain, peri-hilar shadows on CXR

Question 22

What are the features of a malignant node?

Answer 22

Hard, painless and adherent to the surrounding tissues and hence they do not move freely

Question 23

What causes Tuberculous Lymphadenopathy?

Answer 23

Result of infection of the lymph nodes by the TB bacillus. Most commonly observed in immunocompromised.

Question 24

Why is grading lymphomas important?

Answer 24

Histological sub-type determines the behaviour, treatment and prognosis of lymphomas.
NHL are graded into low-grade (indolent) and high-grade

Question 25

What are indolent lymphomas?

Answer 25

These tumours grow slowly and may not require treatment for long periods.
When they do need treatment, they are likely to respond well to chemotherapy but they are rarely cured.

Question 26

Which grade is follicular lymphoma classified into?

Answer 26

Indolent

Question 27

What are high-grade lymphomas?

Answer 27

Tumours grow quickly and are frequently symptomatic.

More likely to be completely cured than low-grade lymphomas with chemotherapy.

Question 28

Which grade is DLBCL classified into?

Answer 28

High grade

Question 29

Which grade is Burkitt’s lymphoma classified into?

Answer 29

High grade