The Lymphatic System

Question 1

What are the two main components of the lymphatics system?

Answer 1

• a conducting system (lymph vessels) which transport lymph from the
interstitium to the circulation.
• lymphoid tissue (lymph nodes, MALT, spleen etc).

Question 2

What is lymph?

Answer 2

Lymph is the name given to interstitial fluid when it enters the lymphatic system.

Question 3

What is the role of lymph?

Answer 3

lymph transports antigen-presenting cells (APCs) to the lymph nodes and MALT (mucosa-associated lymphoid tissue). APCs present antigen to naïve lymphocytes in the lymph nodes and MALT thus stimulating an adaptive immune response.

Question 4

What is lymphadenopathy?

Answer 4

Enlarged lymph nodes

Question 5

What is the best way to investigate lymphadenopathy?

Answer 5

Fine needle aspiration (FNA) is a useful investigation as part of the work up of lymphadenopathy.

Question 6

What are the causes of lymphadenopathy?

Answer 6

Causes of lymphadenopathy can be divided into three main groups:

1. Reactive to infection
   • acute infection eg. influenza, infectious mononucleosis.
   • chronic infection eg. TB, HIV.
2. Malignant tumour
   • Primary ie. lymphoma.
   • Secondary (metastatic tumour such as carcinoma or melanoma which have spread from elsewhere to
   involve lymph nodes).
3. Multisystem disorders eg. sarcoidosis, SLE, Rheumatoid arthritis.

Question 7

What is the cause of lymphoma?

Answer 7

Lymphomas occur due to progressive accumulation of DNA alterations in a lymphocyte that has left the bone marrow and taken up residence in a lymph node.

Question 8

What type of lymphocytes are most lymphomas derived from?

T or B?

Answer 8

Over 90% of lymphomas are derived from B lymphocytes.

Question 9

Why are B lymphocytes more likely to cause lymphoma than T lymphocytes?

Answer 9

B lymphocytes undergo somatic hypermutation (in response to antigen stimulation they re-arrange their immunoglobulin genes to produce an infinite range of possible antibodies). where as T lymphocytes do not and are therefore at lower risk of malignant transformation.

Question 10

What are the 2 main classifications of lymphomas?

Answer 10

Non-Hodgkin lymphomas Hodgkin lymphomas

Question 11

Hodgkin lymphoma summary

Answer 11

33%
Reed sternberg cells
very good cure rate

Question 12

Non hodgkins lymphoma summary

Answer 12

66%

1. B cell NHL (>90% cases)
   - Indolent (low grade), generally not considered curable
   - Aggressive (high grade), complete cure is possible
2. T cell NHL (<10% cases)
   - Usually aggressive and responds poorly to therapy.

Question 13

Hodgkins lymphoma incidence

Answer 13

Hodgkin lymphoma represents a special group of lymphomas which account for about 1 in 3 lymphomas.

There is a bimodal distribution of incidence: a peak in young adulthood (15-35yo) and a second peak in the over 55yo age group.

Question 14

Aetiology of hodgkins lymphoma?

Answer 14

The aetiology of Hodgkin lymphoma is poorly understood.
There are established risk factors which include:
• history of Epstein Barr Virus (EBV) infection (the mechanism is not understood).
• immunosuppression eg. HIV infection.
• family history. Siblings of an affected individual have a 3- to 7x increased risk of developing the disease.

Question 15

Hodgkins lymphoma presentation?

Answer 15

Hodgkin lymphoma usually presents clinically with lymphadenopathy (typically supraclavicular or cervical). There may be ‘B symptoms’ (systemic symptoms) eg. fever, weight loss, night sweats.

Question 16

How is Hodgkins lymphoma diagnosed?

Answer 16

Diagnosis requires tissue for histological examination, ideally excision of an entire node (rather than a core biopsy).

Question 17

What is the defining pathological feature of Hodgkins lymphoma?

Answer 17

Reed-Sternberg cells seen on histology.

They are tumour cells derived from B lymphocytes.

They are large cells with two nuclei (binucleate) and predominant pink nucleoli, imparting an “owls eye” appearance

Question 18

What is the mainstay of treatment in hodgkins lymphoma?

Answer 18

The mainstay of treatment is chemotherapy +/- radiotherapy.

Hodgkin lymphoma generally has a favourable prognosis.

Question 19

What is the incidence of NHL?

Answer 19

Non-Hodgkin Lymphomas (NHL) account for about 2 in 3 lymphomas.
NHL is the sixth most common malignancy in the UK.
Most arise from B lymphocytes (about 90%); a minority arise from T lymphocytes. [A very small minority arise from natural killer (NK) cells but these won’t be considered further].

Question 20

What is the aetiology of NHL?

Answer 20

The aetiology of Non Hodgkins lymphoma is poorly understood. Causative factors include:
• infections including Epstein Barr Virus and H pylori are associated with certain NHLs.
• immunosuppression eg. HIV infection or recipients of an organ transplant.
There is a slightly elevated risk in family members but NHL is not generally considered hereditary

Question 21

Presenting features of NHL?

Answer 21

The presenting features of NHL are diverse. Patients generally present with lymphadenopathy or splenomegaly.

Question 22

Investigations of NHL?

Answer 22

Diagnosis requires tissue for histological examination, ideally excision of an entire node (rather than a core biopsy).

Question 23

What are the 2 groups of B cell NHL?

Answer 23

aggressive and indolent.

Question 24

What type of behaviour do T cell NHL usually show?

Answer 24

aggressive clinical behaviour.

Question 25

Aggressive (high grade) B cell non-Hodgkin lymphomas

Answer 25

Aggressive (high grade) B cell non-Hodgkin lymphomas (eg. diffuse large B cell lymphoma, Burkitt’s lymphoma)
• aggressive lymphomas usually follow a rapidly progressive course which, if untreated, is often rapidly fatal.
• typical treatment is chemotherapy combined with rituximab (a monoclonal antibody against the B cell- specific surface antigen CD20). Some patients may be offered localised radiotherapy.
• in general, patients with high grade lymphoma respond very well to treatment. About 60-70% of patients are cured and will never have a relapse of their lymphoma.

Question 26

Indolent (low grade) B cell non-Hodgkin lymphomas

Answer 26

Indolent (low grade) B cell non-Hodgkin lymphomas (eg. follicular lymphoma, marginal zone lymphoma)
• indolent lymphomas are generally not considered curable. An exception is the small number of patients with who have localised disease which may be cured by surgical excision or radiotherapy.
• most patients with indolent lymphoma present at high stage and their lymphoma is best managed as a life-long chronic disease. It typically follows a relapsing-remitting course.
• most patients with asymptomatic disease are managed with a “wait and watch” approach and may never need treatment.
• indications to start treatment include systemic symptoms, bulky lymphadenopathy, progressive nodal enlargement and threatened compromise of vital organ function.

Question 27

What is the most common type of B cell lymphoma?

Answer 27

Diffuse large B cell lymphoma

Question 28

Staging of Hodgkin/Non-Hodgkin lymphoma

Answer 28

Lymphoma is staged using the modified Ann-Arbor system:
Stage I - involvement of one lymph node region.
Stage II - involvement of two or more lymph node regions on the same side of the diaphragm.
Stage III - involvement of lymph node regions on both sides of the diaphragm.
Stage IV - involvement of extranodal sites eg. liver, bone marrow, lungs.

A - no B symptoms.
B - B symptoms present (night sweats, fever, weight loss).

Question 29

What staging system is used to stage lymphoma?

Answer 29

Ann Arbor

Question 30

What imaging modality is used for staging of lymphoma?

Answer 30

CT or PET-CT from neck to pelvis is used for staging.

Question 31

What is sarcoidosis?

Answer 31

Sarcoidosis is a multisystem disease of unknown aetiology characterised by the presence of non-caseating granulomas in tissues and organs.

Sarcoidosis may involve virtually any organ, but some are involved more often than others

Question 32

What is effected in sarcoidosis?

Answer 32

Lymph nodes. Virtually all cases of sarcoidosis involve lymph nodes. Any lymph node may be involved but the most common are the hilar and mediastinal nodes. Enlargement of these nodes is usually picked up on a chest radiograph.

Lungs. The lungs are frequently involved by sarcoidosis. Healing of the granulomas may lead to varying degrees of lung fibrosis. Severe sarcoidal lung disease may lead to cor pulmonale (right heart failure due to lung disease) and respiratory failure.

Skin. Skin involvement typically presents as lupus pernio - an asymptomatic maculopapular rash on the face and trunk. Erythema nodosum may be associated with sarcoidosis.

Eyes. Eye involvement typically causes uveitis (= inflammation of the uveal tract). Anterior uveitis, which causes a red, painful eye with photophobia, is often self-limiting. Posterior uveitis, which causes floaters due to inflammatory cells appearing in the vitreous with some blurring of vision, is the more chronic form of the disease.

Lacrimal and salivary gland involvement of the lacrimal and salivary glands may lead to dry eyes and dry mouth.

Nervous system. Sarcoidosis can affect the central and peripheral nervous systems. A CNVII palsy is common. Hypothalamic involvement is also common, resulting in diabetes insipidus due to destruction of the ADH- producing neurones.

Question 33

What is acute sarcoidosis?

Answer 33

Acute sarcoidosis (most patients)
• it is associated with manifestations that include bilateral hilar lymphadenopathy, anterior uveitis and a
CNVII palsy.
• it has a good prognosis; typically spontaneous resolution within 1-2yr of diagnosis and no long-lasting
consequences.

Question 34

What is chronic sarcoidosis?

Answer 34

Chronic sarcoidosis (about 5% of patients)
• it tends to persist and lead to permanent organ damage.
• it is associated with lupus pernio, pulmonary fibrosis and posterior uveitis.
• these patients are at higher risk of developing permanent organ damage. End-stage lung fibrosis is the most serious consequence for patients with severe chronic sarcoidosis, leading to respiratory failure and cor pulmonale (right heart failure).

Question 35

How do you investigate sarcoidosis?

Answer 35

Investigations
Simple haematological and biochemical blood tests can be helpful in supporting a suspected diagnosis of sarcoidosis, though they are not specific:
• ESR is often raised.
• Hypercalcaemia is present in about 10% of cases (due to conversion of vitamin D into active 1,25-
dihydroxycholecalciferol within the granulomas).
• serum levels of angiotensin-converting enzyme (ACE) are raised in most patients with active sarcoidosis.
[the granulomas produce ACE and so the serum ACE levels may be used to help establish the diagnosis and predict relapse or remission].

Question 36

When would you do a biopsy in sarcoidosis?

Answer 36

Biopsy
In typical cases of sarcoidosis, the clinical picture and other simple investigations can be sufficient to make an accurate diagnosis of sarcoidosis.
In less clear-cut cases, biopsy of an affected organ may be necessary to demonstrate the presence of non- caseating granulomas and exclude other differential diagnoses.

Question 37

What are the indications for steroids in sarcoidosis?

Answer 37

Parenchymal lung disease, uveitis, hypercalcaemia and neurological or cardiac involvement.