Lymphoma Flashcards
How do B cells mature?
BM stem cell > Mature in BM > Mature B lymphocytes > blood > Lymph nodes spleen > recirculates back into blood
How do T cells mature?
BM stem cell > Mature in thymus > Mature T lymphocytes > blood lymp > mucosal and cutaneous lymphoid tissues> recirculation into blood lymph
Classification for lymphomas:
Hodgkin & Non-Hodgkin Lymphomas
High grade and Low grade Lymphomas
B, T, NK cell Lymphomas
Timeline for lymphoma?
Clinical assessment
Histology
Staging ( scans, endoscopy, cytology, biopsy )
Prognostics
Treatment
Follow up
What happens in clinical assessment?
Age
race,
performance status,
co-morbidities,
medication
allergy
medical history,
B symptoms
lymphadenopathy
organomegaly
lumps/bumps
Laboratory assessments:
What laboratory assessments can be done?
FBC, organ functions,viral screen, G6PD,uric acid,LDH,B2microglobulin,ESR
Histology assessments:
Liquid phase cytology/ FCM ,Core biopsy, BM biopsy, LN excision, splenectomy
What is used for Staging:
CT,MRI, PET-CT, endoscopies ,biopsies
Ann-Arbor staging
Tumour bulk
Prognostics of lymphoma:
Patient characteristics ( performance status, age, co-morbidities )
Disease characteristics ( stage, LDH, extranodal involvement, response to treatment/PET-CT)
Genetics
Treatment for lymphomas:
Immunochemotherapy
Radiotherapy
Autograft
Allograft
Check Point Inhibitors
BITE
CAR-T/NK
What are lymphomas?
group of cancers that affect the lymphocytes inside the lymphatic system
cancerous cells proliferate within the lymph nodes and cause the lymph nodes to become abnormally large (lymphadenopathy).
Main lymph nodes?
Cervical, axillary, inguinal
What is Hodgkins lymphoma?
Hodgkin’s lymphoma is a specific disease
Overall 1 in 5 lymphomas are Hodgkin’s lymphoma.
It is caused by proliferation of lymphocytes. There is a bimodal age distribution with peaks around aged 20 and 75 years.
What is non-Hodgkins lymphoma?
non-Hodgkins lymphoma encompasses all the other lymphomas.
What are the risk factors for Hodgkins lymphoma?
HIV
Epstein-Barr Virus
Autoimmune conditions such as rheumatoid arthritis and sarcoidosis
Family history
What is the difference between leukaemia and lymphomas?
neoplastic cells predominantly involve the lymph nodes and extranodal sites, unlike leukaemia which predominantly involves the bone marrow and blood.
What is the presentation for Hodgkins lymphoma?
Lymphadenopathy is the key presenting symptom.
enlarged lymph node or nodes might be in the neck, axilla (armpit) or inguinal (groin) region.
haracteristically non-tender and feel “rubbery”.
Some patients will experience pain in the lymph nodes when they drink with alcohol.
Epidemiology of hodgkins lymphoma
- HL is a rare malignancy.
- In the UK, there were 2107 new cases of HL between 2015 and 2017, accounting for < 1% of total cancer cases.
- Bimodal age distribution: 15-35 years and > 60 years
- M>F
What happens in classical Hodgkin lymphoma?
B-cell in the germinal centre has an abnormal antibody gene rearrangement > doesnt undergo apoptosis > starts dividing uncontrollably becoming a neoplastic cell
These dont produce antibodies
What are the neoplastic cells like in Hodgkins lymphoma?
- large mononuclear cells called Hodgkin cells or multi-nucleated cells called Reed-Sternberg cells.
- In classical HL these cells don’t express CD45 or CD20, which are typically seen on B-cells.
What are neoplastic cells surrounded by?
non-neoplastic inflammatory cells - mostly T cells - which are attracted by chemokines
neoplastic cells also activate fibroblasts which make collagen, as well as eosinophils.
What can Hodgkins lymphoma be divided into?
Hodgkin Lymphoma can be split into classical HL (expressing CD15 and CD30), and lymphocyte predominant (non classical, expressing CD45 and CD20) HL.
Classical HL is further subdivided into 4 categories.
Classical HL 4 subcategories
Nodular sclerosing - Good prognosis
Mixed cellularity - GP
lYMPHOCYTE rich - GP - Best prognosis
Lymphocyte depleted - BP
B syptoms (systemic symptoms) of lymphoma:
Fever
Weight loss
Night sweats
Other symptoms:
Fatigue
Itching
Cough
Shortness of breath
Abdominal pain
Recurrent infections
Key diagnostic test for hodgkins?
Lymph node biopsy
Lactate dehydrogenase
blood test that is often raised in Hodgkin’s lymphoma but is not specific and can be raised in other cancers and many non-cancerous diseases.
Red-Sternberg
abnormally large B cells that have multiple nuclei that have nucleoli inside them.
This can give them the appearance of the face of an owl with large eyes. The Reed-Sternberg cell is a popular feature in medical exams.
Only in Hodgkins not in Non- Hodgkins
key finding from lymph node biopsy in patients with Hodgkin’s lymphoma.
What scans can be used for diagnosing and staging lymphomas?
CT, MRI and PET
Ann Arbor staging
used for both Hodgkins and non-Hodgkins lymphoma. The system puts importance on whether the affected nodes are above or below the diaphragm
Stage 1: Confined to one region of lymph nodes.
Stage 2: In more than one region but on the same side of the diaphragm (either above or below).
Stage 3: Affects lymph nodes both above and below the diaphragm.
Stage 4: Widespread involvement including non-lymphatic organs such as the lungs or liver.
Key treatments for hodgkins lymphoma
Chemotherapy and Radiotherapy
Chemo - increased risk of leukaemia and infertility
Radiotherapy - cancer, damage to tissues and hypothyroidism.
Rituximab - monoclonal antibdody targetting CD20 on lymphocytes
Complications secondary to chemotherapy
- Myelosuppression and neutropenic sepsis
- Tumour lysis syndrome - treatment with chemotherapy causes rapid cell destruction leading to hyperkalaemia, hyperphosphatemia, hyperuricemia, and hypocalcaemia. This can cause seizures, arrhythmias, and renal failure
Non-hodgkins lymphoma:
group of lymphomas. There are almost endless types of lymphoma.
Epidemiology of NHL
- NHL is far more common than HL
- Diffuse large B-cell lymphoma is the most common haematological malignancy overall
- B-cell lymphomas are more common than T-cell lymphomas
Notable non hodgkins lymphoma
Burkitt lymphoma is associated with Epstein-Barr virus, malaria and HIV.
MALT lymphoma affects the mucosa-associated lymphoid tissue, usually around the stomach. It is associated with H. pylori infection.
Diffuse large B cell lymphoma often presents as a rapidly growing painless mass in patients over 65 years.
Risk factor for non-hoodgkins lymphoma:
HIV
Epstein-Barr Virus
H. pylori (MALT lymphoma)
Hepatitis B or C infection
Age 50
Male
Immunodeficiency
Family history
What happens in non-Hodgkin lymphoma
genetic mutation in a lymphocyte - either a B- or a T-cell. Instead of undergoing apoptosis, they divide uncontrollably becoming a neoplastic cell
Usually, lymphomas develop in lymph nodes - nodal lymphomas.
What happens when lymphomas happens in other parts of the body?
- GI tract - bowel obstruction
- BM - Pancytopenia
- Spinal chord - Spinal chord compression
What are NHLs divided by
NHLs can be divided by cell type (proliferation of B cells, T cells, or NK cells), and grade (high or low).
B cell NHLs
Low grade - Follicular lymphoma, Marginal zone lymphoma, Hairy cell leukaemia
High grade - Diffuse large b-cell lymphoma, mantle cell lymphoma , Burkitt lymphoma
T cell NHL- (rare and typically involve the skin)
Low grade - Mycosis fungoides
High grade - Adult T cell leukaemia/ lymphoma
Management for non-hodgkins lymphoma:
Watchful waiting
Chemotherapy
Monoclonal antibodies such as rituximab
Radiotherapy
Stem cell transplantation
