Week 2 - F - Lymphoma - Bacterial/viral/lymphoma/metastases lymphaendeopathy - NHL vs HL presentation, diagnosis, treatment

Question 1

What is lymphadenopathy defined as?

Answer 1

Lymphadenopathy is disease of the lymph nodes in which they are abnormal in size, shape or consistency

Question 2

What are some of the different causes of lymphadenopathy?

Answer 2

Lymphoma Infection - viral or bacterial Metastases Connective tissue disease

Question 3

When someone is awoken at night due to severe sweating, what can this be due to? What type of tumour is it where if someone takes a sip of alcohol or has alcohol there is pain?

Answer 3

Nights sweats - lymphoma, menopasuse, infection, thick duvet - not a specific sgn but linked with lymphoma anyway Hodgkin’s lymphoma is linked to night sweats and pain after drinking alcohol

Question 4

What are the main groups of palpable lymph nodes?

Answer 4

Have the cervical, axillary and inguinal nodes as the main palpable groups of lymph nodes in the body

Question 5

What are the 4 main categories for lymphoma then?

Answer 5

Bacterial infection Viral infection Lymphoma Metastatic cancer

Question 6

Basically, if there is lymphoma, is it malignancy (primary or metastatic) or is it reactive (bacterial or viral) Does viral or bacterial lymphadenopathy usually cause widespread or regional lymph node enlargement?

Answer 6

Generalised lymphadenopathy is more common in viral than bacterial infections Bacterial infections usually cause regional lymphadenopathy hence why the territory draining to a specific site should be examined

Question 7

Person has glandular fever What would show on the blood film?

Answer 7

There would be large atypical (reactive/activated) lymphocytes on blood film that scallop around red blood cells

Question 8

Breast cancer is a common cause of lymph node metastases as what percentage of breast lymph drains to the axilla? What is the sentinel node for breast cancer? The sentinel lymph node is the hypothetical first lymph node or group of nodes draining a cancer.

Answer 8

75% of lymphatics from the breast drain to the axillary lymph nodes The sentinel lymph node in breast cancer would be the anterior axillary lymph node

Question 9

What are the axillary lymph nodes and where do they drain from? Where are they located?

Answer 9

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Question 10

Approach to lymphadenopathy * Is it regional lymphadenopathy (inguinal node with lower limb cellulitis, axillary node with breast abscess)? * Is there generalised lymphadenopathy Lymphadenopathy can be classified under the reactive changes as bacterial, viral, or under malignant changes as lymphoma or metastases What are the 5 ways of describing the tumour for each of these categories?

Answer 10

Tender Consistency Surface Skin inflamed Tethered

Question 11

If the lymph node is tender what does this make you think? If the lymph node’s consistency is hard what does it back you think? What does a lymphoma’s consistency feel like?

Answer 11

If the lymph node is tender - makes you think bacterial or viral infection If the lymph nodes consistency is hard then this makes you think it could be viral, bacterial or metastatic Lymphomas normally present as nodes that are soft and rubbery

Question 12

Talked over tender and consistency What are the other three parts? Which disease change causes the surface of the node to feel irregular?

Answer 12

Surface Skin inflamed Tethered Metastatic disease would cause an irregular surface

Question 13

The skin is usually only inflamed in bacterial infection Which lumps are tethered and which are not?

Answer 13

Viral infections are not tethered, nor bacterial (normally) and lymphomas are not tethered, only metastatic disease is tethered

Question 14

State what the lymph nodes feel like due to Bacterial Lymphoma Virus and Metastatic change

Answer 14

Bacterial - tender, hard, smooth, can have inflamed skin, usually not tethered Lymphoma - not tender, soft/rubbery, smooth, no inflamed skin, not tethered Viral - tender, hard, smooth, no iflamed skin and not tethered Malignancy - not tender, hard, irregular surface, no skin inflamed, tethered

Question 15

If lymphoma or other malignancy is suspected, what is carried out?

Answer 15

If a lymphoma or other malignancy is suspected, would ask for a surgeon to carry out a lymph node biopsy

Question 16

What type of biopsy are you wanting to be performed for examination of the lymph node?

Answer 16

Want an excision biopsy as a big sample is needed to visualise the architecture of the specimen Core biopsy is often insufficiency and fine needle aspiration is virtually useless

Question 17

How is the diagnosis of Hodgkin’s lymphoma made?

Answer 17

Hodgkins lymphoma is a tissue diagnosis based on the appearance of Reed sternberg cells on microscopy

Question 18

Appreciation of architecture. Whole node excision sample preferred to CT guided biopsy as makes this easier. Some diagnoses are apparent just on histology. What is carried out to help confirm that the diagnosis is in fact a lymphoma and to further sub-classify the disease? How does the test work?

Answer 18

Immunohistochemistry is carred out - Choose an antibody against the cell you are interested in Give every protein a CD (cluster of differentiation) number to know which antibody you are targeting Antibody is bound to an enyme so that the enzyme changes colour to brown when binding occurs

Question 19

What is the difference between immunophenotyping and immunohistochemistry?

Answer 19

Immunophenotyping examines cells in a fluid state - uses fluorchrome light detection via laser to identify antibody binding Immunohistocehmistry examines cells in a solid tissue - use enzyme colour to change to identify antibody binding

Question 20

After cytogenetics to look for chromosome abnormalities, can carry out molecular analysis What are the different types of lymphoma?

Answer 20

Hodgkins lymphoma Non-hodgkins lymphoma Remember if suspecting lymphoma - Lymph node excision biopsy - look under microscope Immunohistochemistry - looks for cell surface antigens Cytogenetic analysis - chromosomal abnormalities Molecular analysis - any gene abnormalities

Question 21

Carrying out cytogenetics is also very useful for specific patterns of chromosomal abnormalities in certain lymphomas What is the technique used for cytogenetic analysis?

Answer 21

Usually FISH - looks for specific abnormalities in chromosomes by using a probe that emits a specific colour or the outdates Gbanding -aspirate node and grow cells to look at spread of chromosomes

Question 22

What are the different subgroups of non-hodgkins lymphoma?

Answer 22

This would be B cell NHL - 90% - can have high grade and low grade or T cell - NHL

Question 23

Lymphomas are caused by malignant proliferations of lymphocytes which accumulate in the lymph nodes causing lymphadenopathy. Lymphomas are histologically divided into Hodgkin’s and non-hodkgins lymphoma. What are the characteristic cells on histology that allows for this histological division?

Answer 23

These would be the cells with mirror image nuclei known as Reed-Sternberg cells

Question 24

How does a patient with Hodkins lymphoma typically present? Ie what age group, what are the symtpoms and what are the B symtpoms

Answer 24

There are two peaks of incidence in this disease - young patients ~20 and elderly Patient often presents with painless, non tender enlarged, smooth, rubbery lymph nodes Patients also often have constitutional ‘B’ type symtpoms - night seweats, weight loss >10% in the last 6 months, unexplained fever >38 degrees

Question 25

Hodgkins - young adults and elderly Painless, enlarged, smooth, rubbbery, non tethered lymph nodes Can have unexplained weight loos >10% in last 6 months, fever, night sweats What can happen in this condition when the person drinks alcohol?

Answer 25

There is usually some abdominal pain after drinking alcohol in hodgkins lymphoma

Question 26

Once a patient presents with the symptoms of hodgkins, then carry out the lymph node excision bipsy for tissue diagnosis The Hodgkin’s cell can be a characteristic Reed-Sternberg cell What may be seen on bloods in this lymphoma?

Answer 26

Might see a low platelet and low haemoglobin count Likely to see a lymphocytosis however

Question 27

After the lymph node biopsy, what is the tumour marker expressed on classical Hodgkins lymphoma seen when using immunohistochemistry? Immunohistochemical studies are invaluable in differentiating HL from other lymphomas as well as non-haematological processes.

Answer 27

Classical Hodgkins lymphoma is CD30+ve

Question 28

What is the system used to stage Hodgkins lymphoma? Describe each stage How is the staging carried out?

Answer 28

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Question 29

What is the treatment regime of Hodgkin’s lymphoma? Is the treatment curative or not?

Answer 29

ABVD is the treatment of Hodgkins lymphoma This is a combination of 4 different chemotherapy drugs Adriamycin, bleomycin, vinblastine and dacarzabine and radiotherapy can be used for the treatment of Hodgkins lymphoma The treatment is aimed for curative results yes

Question 30

What are different risk factors for NHL vs HL? Which has an association with EBV?

Answer 30

HL - previous EBV infection and a family history of the disease NHL - immunodificiency due to HIV, also an association with EBV for Burkitts lymphoma

Question 31

Non-Hodgkins lymphoma includes all lymphomas without Reed-Sternberg cells Is T or B cell lymphomas more common? How does non-hodgkins lymphoma present?

Answer 31

90% of NHL are B cell 10% are T cell Presents usually in adulthood and have multiple nodal involvement and extranodal involvement is common Can present with B type symptoms -weight loss, fever and night sweats

Question 32

What is measured in the bloods which gives An indirect indication of the proliferative rate of the lymphoma? It is important for prognosis and reflects a greatly increased red cell turnover

Answer 32

This would be measuring lactate dehydrogenase - increased reflects increased red cell turnover and poor prognosis

Question 33

Staging is done via the Ann arbor system also Talk through the stages What scans are generaly used to help with staging in NHL vs HL?

Answer 33

NHL - use CT/MRI to help with staging HL -use CT/PET to help with staging Ann Arbor Stage 1 - only one single node group affected Stage II - 2 or more affected on same side of diaphragm Stage III - involvement of nodes on both sides of the diaphragm Stage IV - extra-nodal involvement eg liver or bone marrow

Question 34

90% of non-Hodgins lymphomas are B cell – what we want to know is whether it is low grade or high grade What is the difference between treatment for low and high grade non-hodgkin lymphomas?

Answer 34

Chemotherapy targets cells undergoing cell division and therefor as Low grade lymphomas are slow dividing and a lot cells remain indolent - after chemo treatment many cells remain alive and therefore treatment is not curative whereas High grade lymphomas - these are rapidly dividing and therefore chemo can kill all the cancer cells makign it often curable although more aggressive

Question 35

High grade include lymphomas such as Large B cell lymphoma and a lymphoma which usually presents as childhood disease with characteristic jaw lymphadenopathy - what is this type of high grade lymphoma? What disease it associated with?

Answer 35

This would be Burkitts lymphoma - characterisitc jaw lymphadenopathy in children -associated with EBV

Question 36

What is the gene mutation that might occur potenitally predispoing to Burkitts lymphoma?

Answer 36

This would be a mutation in the c-myc gene Myc (c-Myc) is a regulator gene that codes for a transcription factor. The protein encoded by this gene is a multifunctional, nuclear phosphoprotein that plays a role in cell cycle progression, apoptosis and cellular transformation Myc is a proto oncogene and therefore when a mutation occurs - uncontrolled proliferation

Question 37

What is the mainstay of treatment for patients with high grade non-hodgkins lymphoma hoping for cure here? Low-grade tumours don’t necessarily require immediate medical treatment, but are harder to completely cure. High-grade lymphomas need to be treated straight away, but tend to respond much better to treatment and can often be cured.

Answer 37

R-CHOP Rivutuximab + 4 chemotherapy agents (Cyclophosphamide, hydroxydaunorubicin, vincristine (onconvin) and prednisolone)

Question 38

What is the aim of rituximab in the management of NHL?

Answer 38

It kills CD20+ve cells which almost all B cells by antibody directed cytoxicity and apoptosis induction. It also sensitses the cells to the CHOP (multi-agent chemotherapy treatment)

Question 39

What id different about the spread of non-hodgkins and hodgkins lymphoma? What is the difference in the history? (both have painless lymphadenopathies and can have B symptoms (more common in hodgkins) ) but what symptom may patients with hodgkins also have?

Answer 39

Non-hodkgins - non contigious spread - it can affect nodal groups anywehre in body without travelling contiguously Hodgkins -contigous spread - it affects one nodal group before moving to one close to it and so on Hodgkins lymphoma patients may also present with an itch - pruritus

Question 40

A 22-year old student is admitted for biopsy. He has a large cervical mass on the right side that has been present for a number of months. He has lost 2stone in weight. Of note he has recently experienced abdominal pain after consuming alcohol. On investigation Reed-Sternberg cells are found What is the diagnosis here? Describe what the treatment would be?

Answer 40

Single group of nodes affected Lost weight Alcohol induced pain Reed sternberg cells Patient has Hodgins lymphoma Treat with ABVD and radiotherapy

Question 41

61-year old male presents with growing lumps in his right groin & armpit that he has ignored for many months. He has attended the doctor as recently he has been getting night sweats & fevers. He has tried to lose weight in the past but says that recently it has been “falling off much more easily”. What is the diagnosis? State what the treatment would be?

Answer 41

Mutliple lymph node involvement B type symptoms also Non-hogkins lymphoma - doesnt mention reed sternberg cells Non-Hodgkin lymphoma can occur at any age, but your chances of developing the condition increase as you get older, with most cases diagnosed in people over 65.