Haematology Flashcards
What is Myelodysplastic syndrome?
Myelodysplasia is a form of bone marrow failure where a line of myeloid blasts are produced rapidly, do not mature and then usually die, causing a deficiency in that line of cells. Around a third of cases will eventually transform to become acute myeloid leukaemia, where the bone marrow becomes > 20% filled with these myeloid blast cells.
What differentiates between Hodgkin’s and non-Hodgkin’s lymphoma?
Presence of Reed-steinberg cells in Hodgkins
Physiology of B cell maturation:
Lymphoid cells develop initially within the bone marrow primary lymphoid organ) into naïve B cells which travel in the blood to secondary lymphoid organs; the lymph node. They
undergo positive and negative selection, ensuring that they will not exert autoimmunity onto the
host cells. Once they become activated through pathogenic antigen stimulation ->
differentiate into centroblasts and form a germinal centre -> undergo class switching to
produce the relevant antibody.
They then mature into centrocytes, either of plasma or memory cell
type.
What is the most common type of Non-Hodgkin’s lymphoma
Diffuse large B-cell lymphoma
Diffuse large B-cell lymphoma:
Most common Non-Hodgkin and mean age of diagnosis is 70
- Palpable, non-tender mass in many lymph nodes: thrombocytopenia purpura
- B symptoms: fever, night sweats and severe weight loss
- Splenomegaly: abdominal discomfort
Mostly involve centeroblast formation in lymph nodes which are surrounded by small lymphocytes, histiocytes and eosinophils
CD20 innumophenotype marker in NHL
What are B symptoms and why are the significant?
Fever, night sweats, severe weight loss
Identify advanced, systemic disease rather than local
What Ix can be done for a lymphoma diagnosis?
tissue sampling, cytochemistry, bone marrow examination, cytology and
immunophenotyping, conventional cytogenetics, molecular studies and fluorescent in-situ
hybridisation.
PET scan is a very useful diagnostic procedure with the injection of 18-
fluorodeoxyglucose. This glucose analogue would accumulate in metabolically active areas, such as
the cancerous lymph nodes.
Describe the Ann Arbor staging:
- Stage I - single lymph node involvement
- Stage II is involvement of two or more lymph node regions on the same side of the diaphragm
- Stage III is involvement of lymph node regions bilaterally to the diaphragm
- Stage IV is disseminated involvement of one or more extra lymphatic organs.
A - no systemic symptoms
B - Systemic symptoms
E - extension to a single extra-lymphatic organ
S- splenic involvement
X - bulky disease (mass >10cm in diameter)
Treatment for DLBCL
Stage I-II - minoclonal antibodies (rituximab), cyclophosphamide, doxorubicin and prednisolone 3x following intense radiotherapy at involved sites
Stage III-IV - 6 rounds of chemotherapy
Follicular lymphoma:
2nd most common non-Hodgkin’s - Lymphoma of follicular centre B-cell which retains a follicular pattern.
Positive for B cell markers of CD10, CD20, CD19, CD22 BUT ALWAYS NEGATIVE FOR CD5.
Translocation between chromosome 14 and 18 -> overexpression of bcl-2-gene (gene responsible for regulating apoptosis)
Mixture of centerocytes and mutated centroblasts
Surrounded by non-malignant T cells
How can follicular lymphomas be classified based on WHO?
Grade I: <5 centroblasts per high-power field,
Grade II: 6-15 centroblasts per high-power field,
Grade III: >15 centroblasts per high-power field. This grade of disease is further sub-divided into 3A
indicating that centrocytes are still present, whereas class 3B is where the follicles consist almost
entirely of centroblasts. Grade 3B is also referred to as Diffuse Large B Cell Lymphoma.
What is R-CHOP?
R-CHOP is used to treat non-Hodgkin lymphoma (NHL).
R – rituximab C – cyclophosphamide H –doxorubicin (hydroxydaunomycin) O – vincristine (oncovin) P – prednisolone (a steroid)
What is Burkitt’s lymphoma?
Highly aggressive non-Hodgkins
Chromosomal translocation of the MYC gene from chromosome 8 to 14 -> overexpression
MYC gene controls cell death and division
What is Hodgkin’s lymphoma:
High predisposition with EBV exposure (50%)
5% cases are familial
- Painless mass in LN
- itchy skin (eosinophilia)
- fatigue
- B symptoms
- Hepatosplenomegaly
- Alcohol consumption eliciting LN pain
- Purpura and petechiae due to thrombocytopenia
What would a macroscopic and microsponic exam in hodgkin’s lymphoma show?
Macro: Enlarged lymph node which have retained their shape because capsule has not yet been infiltrates
A fibrin ring granuloma may be seen
Micro: Reed Sternberg cells which are bi-nucleated
Classical hodgkin’s Immunophenotype is CD30+, CD15+ but negative for CD20 and CD45.
What does a Reed Sternberg cell look like?
Large (giant) cells
Bi-nucleated
Abundant pale cytoplasm
What are the types of classical Hodgkin’s lymphoma:
- Nodular sclerosis: most common. scattered classical RSC with some sclerosis and fibrosis
- mixed cellularity: associated with EBV. classical RSC’s with no clerosis
- lymphocyte rich: many lymphocytes around few RSCs
- lymphocyte depleted: few lymphocytes around many RSCs
How would advanced stage myeloma present?
C - calcium elevated R - renal failure A - anaemia (infiltration into bone marrow) B - bone pain Infection
How is a myeloma diagnosed?
A myeloma diagnosis is given when one of the following criteria are present:
- Renal dysfunction: Hypercalcaemia, bone damage and anaemia,
- More than one bone lesion on a full-body scan (CT/MRI/PET),
- Free light chain ratio >100,
- > 60% plasma cells in the bone marrow (normally 5%).
Pathophys of multiple myelomas:
Translocation between chromosome 4 and oncogene on chromosome 14
- > cytokine release and dysregulation of oncogene -> proliferation of plasma and antibodies
- > antibodies aggregate and deposit in various organs causing kidney failure, polyneuropathy, bone problems and amyloidosis
Mutates plasma cells release paraprotein (non-functional antibody)
They produce more light chains which can be found in blood
or only produce light chains - Bence jones proteins
What are Bence - Jones proteins?
Mutated plasma cells which release paraproteins that only produce free light chain proteins.
5-10% of myelomas produce this
Treatment for myeloma:
Only for symptomatic myeloma:
High intensive chemo: thalidomide, dexamethasone
Bisphosphonates and analgesics
Stem cell transplant with melphalan
What is Acute myeloblastic leukemia?
Cells haven’t gone through complete differentiation so cant function normally.
Blast cells divide rapidly to replenish cell turnover therefore AML progresses rapidly
- pancytopenia
- >20% of blast cells being present in bone marrow
- Constitutes 80% of adult leukaemias with incidence increasing with age
Risk factors for AML?
Radiation
benzenes
Previous haematological malignancies and chemo
Bone marrow failure
Down’s syndrome
Preleukemic blood disorders: myelodysplastic and myeloproliferative disorders
Signs and symptoms of AML:
Pallor
Ecchysmoses or petechiae
Fatigue
Dizziness, palpitations, dyspnoea - anaemia
Infections or fever - neutropenia
Lymphadenopathy
Gum swelling and mucosal bleeding - infiltration of leukaemic cells in gum tissue
