Haematological Diseases Flashcards
What is Diffuse Large B cell Lymphoma
Most common type of non-Hodgkin lymphoma, and its a fast growing cancer that arises from B lymphocytes.
Diffuse = the cancerous B cells are spread out and not forming specific structures in the lymph node
Large B cells = the abnormal B cells are noticeable larger than normal lymphocytes
What is the pathophysiology of Diffuse Large B cell Lymphoma
Malignant B cells accumulate in Lymph nodes and extranodal sites like GI tract and skin
What are the genetic mutations that are present in Diffuse Large B cell Lymphoma
- BCL2
- BCL6
- MYC
These affect cell survival and proliferation
What is the histology of Diffuse Large B cell Lymphoma (DLBCL)
- There are diffuse sheets of large lymphoid cells with prominent nucleoli, open chromatin and high mitotic activity
- There is loss of normal lymph node structure
What is the immunophenotype of DLBCL
- CD20 positive (a B cell marker)
- High Ki-67 proliferation index
What is the etiology of DLBCL
Hereditary: people with Ataxia Telangiectasia have a higher risk of developing DLBCL
It can be acquired from viral-EBV
Autoimmune diseases like Rheumatoid Arthritis can also predispose to DLBCL
Progression form low grade lymphomas as well as immunosuppressants after chemo increase the
What are the clinical features of DLBCL
Depending on the site: LN, GI tract or CNS
- Obstruction, compression, pain and pancytopenia
Rapidly enlarging lymph node mass
Systemic B symptoms: drenching night sweats, and weight loss; hypercalcaemia, motor neuropathy, polymyositis, skin rash
How is DLBCL diagnosed
- Clinical examination: lymphadenopathy, hepatosplenomegaly
- Radiology: lymphadenopathy, depending on site of involvement
- Laboratory: high LDH, Cytopenia, Hypercalcaemia
- Biopsy: Histological examination with FISH or PCR
What is FISH
Fluorescence In-situ Hybridisation - a technique looking at certain abnormal chromosomal translocations/amplifications which are important in tumorigenesis such as c-myc, bcl2, bcl6
This is important in diagnosis, prognosis and treatment options
What is PCR
Polymerase Chain Reaction
A technique which looks at the DNA of cells and identifies clonality (clone is a group of cells deriving from the same cells, therefore neoplastic)
How it detects clonality:
- B cells: looks for identical rearrangements in the IgH gene
- T cells: checks for identical TCR (receptor) rearrangements
If PCR finds a monoclonal population, it supports a diagnosis of lymphoma
What are the treatments for DLBCL
Combination therapy - Cyclophosphamide
Rituximab - against CD20 monoclonal antibody
What is Multiple Myeloma
This is a type of blood cancer that arises from plasma cells (WBCs)
This is a malignant tumour involving proliferation of plasma cells in the bone marrow, pushing out normal blood cells
and causing anaemia and low immunity.
This also produces monoclonal immunoglobulin (paraprotein) and/or light chains (Bence Jones protein)
What are the effects of multiple myeloma
C - Calcium elevation: bone destruction releases calcium into the blood
R - Renal failure: Excess Bence Jones proteins damages kidneys
A - Anemia: Crowding out of red cell production in bone marrow
B - Bone Lesions: Plasma cells activate osteoclasts causing bone pain and fractures
How is multiple myeloma diagnosed
1) Blood and urine tests:
- High M protein levels
- Bence Jones proteins in urine
- High calcium, low haemoglobin
- Hyperviscosity: the blood becomes abnormally thick
2) Bone marrow biopsy
- Shows more than 10% clonal plasma cells
3) Imaging:
- X-rays, MRI or PET scans to detect bone lesions
What are clinical features of multiple myeloma
- Bone pain
- Pathological rib fracture
- Weakness
- Infections
- Spinal cord compression
- Bleeding
- Renal failure
- Peripheral neuropathy
What is the treatment for multiple myeloma
- Chemotherapy + targeted therapy
- Stem cell transplant
What is the pathology of multiple myeloma
The plasma cells would have eccentric nuclei, and a perinuclear clearing
There may be rouleaux formation (stacked RBCs) in blood smear due to sticky proteins
What is Hodgkin’s lymphoma
It is a cancer of the lymphatic system, which includes lymph nodes, spleen, thymus, and bone marrow.
It is characterised by the presence of a specific type of abnormal cell called the Reed-Sternberg cell that arise from germinal B cells
What is the pathology of CHL
A single clone of B cells becomes abnormal and starts multiplying in lymph nodes
These cells lose many normal B-cell features, and instead of making antibodies , they start releasing signals that attract other immune cells.
This causes the lymph nodes to swell and the immune system to act abnormally
What are the clinical features of CHL
- Fever
- Night sweats
- Weight loss
- Lymphadenopathy
- Pruritus
- Pain at sites of nodal disease, precipitated by drinking alcohol
How is CHL diagnosed
Lymph node biopsy
Immunohistochemistry: RS cells in CHL are usually CD15+ and CD30+
PET/CT scan to assess staging - Ann Arbor staging
What is the histology of Reed-Sternberg cells
- Large, bi-nucleated
- Owl-eye appearance due to prominent nucleoli
- Surrounded by background of reactive cells (like T cells, eosinophils, and plasma cells)
What is the treatment of CHL
- It is very treatable in the early stages
- Main treatments include ABVD chemotherapy and radiotherapy
- It develops very slowly with frequent relapses
- The prognosis is generally good, especially in young patients
What is Acute Myeloid Leukaemia
The clonal proliferation of malignant blood cells derived from primitive hematopoietic stem cells in bone marrow
Uncontrolled, functionless cells in blood, bone marrow and other organs leads to suppression of normal hematopoiesis and immunity
