Lymph node pathology

Question 1

What are the two main components of the lymphatic 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

Lymph is the name given to interstitial fluid when it enters the lymphatic system. What is the role of lymph within the immune system?

Answer 2

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

Question 3

What is lymphadenopathy?

Answer 3

enlarged lymph nodes

Question 4

What is a useful investigation for lymphadenopathy?

Answer 4

FNA

Question 5

What are the causes of lymphadenopathy?

Answer 5

• reactive to infection - acute (influenza, infectious mononucleosis) or chronic (TB, HIV)
• malignant tumour - primary (lymphoma) or secondary (metastatic tumour such as carcinoma or melanoma which have spread from elsewhere to involve lymph nodes)
• multisystem disorders - sarcoidosis, SLE, rheumatoid arthritis

Question 6

Lymphomas are a large group of haematological malignancies. Why do lymphomas occur and thus how do they present?

Answer 6

• lymphomas occur due to mutations in a lymphocyte that has left the bone marrow and taken up residence in a lymph node
• lymphomas therefore tend to present with solid mass lesions, particularly enlarged lymph nodes (rather than abnormal blood counts)

Question 7

Over 90% of lymphomas are derived from B lymphocytes. Why is this?

Answer 7

• B cells are able to produce specific antibodies to an almost infinite range of antigens
• B cells do this by a process of somatic hypermutation
• in response to antigen stimulation they re-arrange their immunoglobulin genes to produce an infinite range of possible antibodies
• during this re-arrangement phase they are at risk of acquiring mutations in growth-controlling genes which can give rise to malignant behaviour ie. development of lymphoma
• T lymphocytes do not undergo somatic hypermutation and so there is lower risk of malignant transformation in T lymphocytes

Question 8

Lymphomas are divided into two broad groups. What are they?

Answer 8

Question 9

Hodgkin lymphoma represents a special group of lymphomas which account for 1 in 3 lymphomas. What is the distribution of incidence?

Answer 9

• bimodal distribution of incidence
• peak in young adulthood (15-35yo)
• second peak in 55+ age group

Question 10

The aetiology of Hodgkin lymphoma is poorly understood. What are the established risk factors?

Answer 10

• history of Epstein Barr Virus (EBV) infection
• immunosuppression eg. HIV infection
• family history

Question 11

How does Hodgkin lymphoma present clinically?

Answer 11

• lymphadenopathy (typically supraclavicular or cervical)
• there may be ‘B symptoms’ (systemic) eg. fever, weight loss, night sweats

Question 12

Diagnosis of Hodgkin lymphoma requires exicison of a node for histological examination. What is the defining pathological feature of Hodgkin lymphoma?

Answer 12

• presence of Reed-Sternberg cells
• the tumour cells seen in Hodgkin lymphoma
• thought to be derived from B-lymphocytes
• typically large cells w/ 2 nuclei (binucleate)
• prominent pink nucleoli imparting an ‘owls eye’ appearance

Question 13

Non-Hodgkin lymphomas (NHL) account for about 2/3 lymphomas. Where do most arise?

Answer 13

• most arise from B lymphocytes (_~90%)
• minority arise from T lymphocytes

Question 14

The classification of NHLs is complex; you are not expected to know all the different types of NHL.

How can the two types of NHL be divided?

Answer 14

• B-cell NHLs can be divided into 2 groups depending on their clinical behaviour:
  
  • indolent
  • aggressive
• _T-_cell NHLs usually show aggressive clinical behaviour

Question 15

Describe characteristics of indolent non-Hodgkin lymphomas

Answer 15

• eg. marginal zone lymphoma
• tend to present w/ widely disseminated disease at diagnosis involving several nodal + extranodal sites
• typically follow a slowly progressive course
• can be controlled w/ treatment but cure rarely achievable
• survival is typically in region of 8-10 years

Question 16

Describe characteristics of aggressive non-Hodgkin lymphomas and what the most common type of Non-Hodgkin lymphoma is

Answer 16

• eg. diffuse large B cell lymphoma (most common NHL)
• tend to present w/ short Hx of rapidly growing mass at a localised nodal or extranodal site
• typically follow a rapidly progressive course
• usually rapidly fatal if untreated but therapy may lead to complete cure

Question 17

Describe the lymphoma staging system

Answer 17

Modified Ann-Arbor system:

• stage I - involvement of 1 lymph node region
• stage II - involvement of 2+ lymph node regions on same side of diaphragm
• stage III - involvement of lymph node regions on both sides of 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 18

What is sarcoidosis and what causes it?

Answer 18

• multisystem disease of unknown aetiology
• characterised by presence of non-caseating granulomas in tissues + organs
• an inflammatory response to some unidentified environmental agent in a susceptible host
• infective cause has long been sought, in particular a mycobaterium due to the granulomatous response
• however, no study has equivocally proven an infective aetiology
• inhaled antigens such as pine pollen + peanut dust have been incriminated
• existence of familial clusters suggests genetic factors may be involved

Question 19

Remember that a granuloma is an aggregate of activated macrophages. How do the granulomas in sarcoidosis differ from TB?

Answer 19

granulomas in sarcoidosis do not show caseous necrosis

Question 20

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

What is the involvement with lymph nodes?

Answer 20

• virtually all cases of sarcoidosis involve lymph nodes
• any lymph node may be involved
• most common are hilar and mediastinal nodes
• enlargement of these nodes usually picked up on CXR

Question 21

What is the involvement of sarcoidosis within the lungs?

Answer 21

• lungs frequently involved by sarcoidosis
• healing of granulomas may lead to varying degrees of lung fibrosis
• severe sarcoidal lung disease -> cor pulmonale (RHF due to lung disease) + resp failure

Question 22

What is the involvement of sarcoidosis with the skin?

Answer 22

• skin involvement typically presents as lupus pernio
• an asymptomatic maculopapular rash on face and trunk
• erythema nodosum may be associated w/ sarcoidosis

Question 23

What is the involvement of sarcoidosis and the eyes?

Answer 23

• typically causes uveitis (=inflammation of uveal tract)
• anterior uveitis -> red painful eye w/ photophobia, often self-limiting
• posterior uveitis -> floaters due to inflammatory cells appearing in vitreous w/ some blurring of vision, more chronic form of the disease

Question 24

What is the involvement of sarcoidosis and the lacrimal/salivary glands?

Answer 24

• dry eyes
• dry mouth

Question 25

What is the involvement of sarcoidosis with the nervous system?

Answer 25

* sarcoidosis can affect the central + peripheral nervous systems * a **CN VII (facial) palsy** is common * **hypothalamic** involvement also common -\> **diabetes inspidus** due to destruction of ADH-producing neurones

Question 26

Sarcoidosis may be divided into an acute and chronic form. Most patients get acute sarcoidosis - describe this?

Answer 26

* associated w/ manifestations that include **bilateral hilar lymphadenopathy, anterior uveitis + a CN VII palsy** * has a _good prognosis_ * typically spontaneous resolution within **1-2yr** of diagnosis * no long-lasting consequences

Question 27

About 5% of patients will develop acute sarcoidosis - describe this?

Answer 27

* tends to persist and lead to _permanent_ organ damage * associated w/ **lupus pernio, pulmonary fibrosis + posterior uveitis** * these pts at higher risk of developing permanent organ damage * _end-stage lung fibrosis_ is the most serious consequence for pts w/ severe chronic sarcoidosis * leading to resp failure + cor pulmonale

Question 28

Simple haematological blood tests can be helpful in supporting a suspected diagnosis of sarcoidosis, though they are not specific. What do they show?

Answer 28

* **_ESR_** often raised * **_hypercalcaemia_** is present in _~10% cases (due to conversion of vitamin D -\> active 1,25-dihydroxycalciferol within granulomas) * serum levels of **_ACE_** are raised in most pts w/ active sarcoidosis (granulomas produce ACE + so serum ACE levels may be used to help establish diagnosis + predict relapse or remission)

Question 29

In typical cases of sarcoidosis, the clinical picture + other simple investigations can be sufficient to make an accurate diagnosis of sarcoidosis. What can be done in less clear-cut cases?

Answer 29

**_Biopsy_** of an affected organ may be necessary to demonstrate the presence of **non-caseating granulomas** and exclude other differential diagnoses

Question 30

Review the haematopoeisis pathway and in particular where each cell type *_normally_* resides

Answer 30

Question 31

How does **_acute leukaemia_** result from the haematopoetic pathway?

Answer 31

Question 32

What happens if differentiation does occur in regards to haematopoeisis and haemotological malignancy?

Answer 32

Question 33

How are lymphomas different to leukaemias?

Answer 33

* mutations giving rise to malignant tumour occur in lymphocytes that have **_left**_ the bone marrow and taken up residence in _**lymph nodes_** or other organs * lymphomas therefore tend to present with **_solid mass lesions_**, particularly enlargement of lymph nodes, rather than an abnormal blood count

Question 34

What is the most common type of plasma cell malignancy?

Answer 34

* plasma cells are terminally differentiated B cells that have encountered antigens + fully matured into immunoglobulin-secreting cells * as part of their normal fxn, many plasma cells home _back to the bone marrow_ where they secrete their antibodies * most common type of plasma cell malignancy = **_multiple myeloma_** * myeloma is characterised by bony lesions due to destructive growth in the bone marrow * this reflects the fact that normal plasma cells home back to the bone marrow * in addition, patients w/ myeloma develop problems related to the large quantities of immunoglobulin the plasma cells produce