Haematology Flashcards
1
Q
What is multiple myeloma?
A
- Multiple myeloma (MM) is a haematological malignancy characterised by plasma cell proliferation.
- It arises due to genetic mutations which occur as B-lymphocytes differentiate into mature plasma cells. MM is the second most common haematological malignancy.
2
Q
What are some of the features of clinical presentation of myeloma?
A
- CRABBI
-
Calcium: Hypercalcaemia occurs as a result of increased osteoclast activity within the bones
- This leads to constipation, nausea, anorexia and confusion
-
Renal: Monoclonal production of immunoglobulins results in light chain deposition within the renal tubules -> renal damage -> dehydration and increasing thirst
- Other causes of renal impairment in myeloma include amyloidosis, nephrocalcinosis, nephrolithiasis
-
Anaemia: Bone marrow crowding suppresses erythropoiesis -> anaemia
- This causes fatigue and pallor
- Bleeding: bone marrow crowding also results in thrombocytopenia which puts patients at increased risk of bleeding and bruising
-
Bones: Bone marrow infiltration by plasma cells and cytokine-mediated osteoclast overactivity creates lytic bone lesions
- Presents as pain (especially in the back) and increases the risk of fragility fractures
- Infection: a reduction in the production of normal immunoglobulins results in increased susceptibility to infection
3
Q
How is myeloma ixd?
A
- Bloods: anaemia (FBC) and thrombocytopenia (FBC); raised U&E and raised calcium
- Peripheral blood film: rouleaux formation
- BLIP
- Bence Jones protein (raised concentrations of monoclonal IgA/IgG proteins in the urine)
- Serum free light chain
- Serum IgG
- Serum protein electrophoresis
- Bone marrow aspiration + trephine biopsy: confirms the diagnosis if the number of plasma cells is significantly raised
- Gold standard: Whole-body MRI (or CT if MRI is not suitable) is used to survey the skeleton for bone lesions
- Xray: ‘rain-drop’ skull. Dark spots seen on X-ray which due to bone lysis.
4
Q
How is symptomatic myeloma diagnosed?
A
- Monoclonal plasma cells in the bone marrow >10%
- Monoclonal protein within the serum/urine (as determined by electrophoresis)
- Evidence of end-organ damage e.g. hypercalcaemia, elevated creatinine, anaemia or lytic bone lesions/fractures
5
Q
How is asymptomatic myeloma + MGUS defined?
A
Assymptomatic myeloma
- Serum paraprotein >30 g/L
- +/- Clonal plasma cells >10% on bone marrow biopsy
- NO myeloma-related organ or tissue impairment
Mx: no treatment initially. Watch and wait approach was adopted
MGUS
- Serum paraprotein <30 g/L
- Clonal plasma cells <10% on bone marrow biopsy
- NO myeloma-related organ or tissue impairment
Mx: MGUS therefore usually requires no treatment.
6
Q
How is myeloma mxd?
A
- <65 - autologous stem cell transplant
- Induction therapy consists of Bortezomib + Dexamethasone
- > 65 - generally unsuitable for autologous stem cell transplantation*
- Induction therapy consists of Thalidomide + an Alkylating agent + Dexamethasone
7
Q
How are the sx of myeloma mxd?
A
- Pain: treat with analgesia
- Pathological fracture: Zoledronic acid
- Infection: patients receive annual influenza vaccinations
- Immunoglobulin replacement therapy.
- VTE prophylaxis
- Fatigue/ anaemia: treat all possible underlying causes. If symptoms persist consider an EPO analogue.
8
Q
What are the signs of waldenstroms macroglobulinaemia?
A
- monoclonal IgM paraproteinaemia
- systemic upset: weight loss, lethargy
- hyperviscosity syndrome e.g. visual disturbance
- the pentameric configuration of IgM increases serum viscosity
- hepatosplenomegaly
- lymphadenopathy
- cryoglobulinaemia e.g. Raynaud’s
9
Q
What is Waldenstrom’s macroglobulinaemia?
A
- Waldenstrom’s macroglobulinaemia is an uncommon condition seen in older men.
- It is a lymphoplasmacytoid malignancy characterised by the secretion of a monoclonal IgM paraprotein
10
Q
How is Waldenstrom’s macroglobulinaemia Ixd?
A
- Raised ESR, IgM (serum electrophoresis)
- +ve urine sulfosalicylic acid test
11
Q
What are the complications of Waldenstrom’s macroglobulinaemia?
A
- Free light chains accumulate and block renal tubules -> cause cast aggregates -> inflammation + obstruction
- Blood hyperviscosity
12
Q
What are some of the complications of radio/chemoteh
A
- Radiotherapy: SE: ↑ risk of second malignancies—solid tumours (especially lung and breast, also melanoma, sarcoma, stomach and thyroid cancers), ischaemic heart disease, hypothyroidism, and lung fibrosis due to the radiation field.
- Chemotherapy: SE: myelosuppression, nausea, alopecia, infection. non-Hodgkin’s lymphoma, and infertility may be due to both chemo- and radiotherapy
13
Q
How is Waldenstrom’s macroglobulinaemia mxd?
A
- No cure
- Tx: plasmapheresis, chemo (chlorambucil, fludarabine), immunotherapy
14
Q
From what cell does Hodgkin lymphoma (HL) arise?
A
B lymphocytes
15
Q
Name and describe two cell types present in Hodgkin lymphoma (HL).
A
- Large, multi-nucleated giant cells called ‘Reed-Sternberg’ cells
- Large, mono-nucleated cells called malignant ‘Hodgkin cells’.
16
Q
Name the 4 subtypes of Classical Hodgkin lymphoma (HL).
A
- Nodular Sclerosis - most common
- Mixed Cellularity
- Lymphocyte-rich
- Lymphocyte-depleted
17
Q
What are some RFs for HL?
A
An affected sibling; EBV, SLE; post-transplantation, smoking, FH, NHL, HIV
18
Q
What are some sx of HL?
A
- Lymphadenopathy: enlarged, non-tender, ‘rubbery’ superficial lymph nodes (60–70% cervical, also axillary or inguinal). Node size may fluctuate, and they can become matted.
- B type sx: Fever, weight loss, night sweats, pruritus, and lethargy.
- Possible alcohol-induced lymph node pain
- Mediastinal lymph node involvement: can cause mass effect, eg bronchial or SVCO or direct extension, eg causing pleural effusions.
19
Q
What are some of the signs of HL?
A
- Lymphadenopathy
- Cachexia
- Anaemia
- Spleno- or hepatomegaly.
- SVCO
- Paraneoplastic syndromes such as cerebellar degeneration, neuropathy or Guillain-Barré syndrome
20
Q
What Ix are used for HL?
A
- Bloods: FBC, film, ESR, LFR, LDH, urate, Ca2+. ↑ESR or ↓Hb indicate a worse prognosis. LDH↑ as it is released during cell turnover.
-
Tissue diagnosis: Lymph node excision biopsy
- Image-guided needle biopsy
- Laparotomy
- Mediastinoscopy may be needed.
- Imaging: CXR, Gold standard: CT/PET of thorax, abdo, and pelvis.
- Immunocytochemistry: CD15 and CD30 antigens are positively expressed on Reed-Sternberg cells
21
Q
What staging system is used for HL? (+NHL?
A
- ## Ann Arbor system: Done by imaging ± marrow biopsy if b symptoms, or stage iii–iv disease
- ## 1.Confined to single lymph node region.
- ## 2.Involvement of two or more nodal areas on the same side of the diaphragm.
- Involvement of nodes on both sides of the diaphragm.
- Spread beyond the lymph nodes, eg liver or bone marrow.
22
Q
How is NHL/HL mxd?
A
- Stages I-a and II-a: Radiotherapy + short courses of chemotherapy for (eg with ≤3 areas involved)
-
Stages II-a>: Longer courses of chemotherapy >3 areas involved through to iv-b.
- ‘ABVD: Adriamycin, (doxorubicin), Bleomycin, Vinblastine, Dacarbazine cures ~80% of patients.
- Relapsed disease: high-dose chemotherapy followed by autologous stem cell transplantation.
23
Q
What are the RF for NHL?
A
- Elderly
- Caucasians
- History of viral infection (specifically Epstein-Barr virus)
- Family history
- Certain chemical agents (pesticides, solvents)
- History of chemotherapy or radiotherapy
- Immunodeficiency (transplant, HIV, diabetes mellitus)
- Autoimmune disease (SLE, Sjogren’s, coeliac disease)
24
Q
What are the sx of NHL?
A
- Painless lymphadenopathy (non-tender, rubbery, asymmetrical)
- Constitutional/B symptoms (fever, weight loss, night sweats, lethargy)
- Extranodal Disease - gastric (dyspepsia, dysphagia, weight loss, abdominal pain), bone marrow (pancytopenia, bone pain), lungs, skin, central nervous system (nerve palsies)
25
How can you differentiate HL from NHL?
* **Lymphadenopathy** in Hodgkin's lymphoma can experience **alcohol-induced** pain in the node
* **'B' symptoms** typically occur earlier in Hodgkin's lymphoma and later in non-Hodgkin's lymphoma
* **Extra-nodal disease** is much more common in NHL than in HL
26
What ix are used for NHL?
* **Blood**: FBC, UE, LFT, ↑LDH: worse prognosis, reflecting ↑cell turnover.
* **Marrow and node biopsy** for classification (complex, based on the who system of high- or low-grade).
* **Staging**: Ann Arbor system (CT± PET of chest, abdomen, pelvis.
* Cytology of any effusion: LP for CSF cytology if CNS signs
27
How does mx differ for high grade vs low grade NHL?
* **Low-grade lymphomas:** indolent, often incurable and widely disseminated.
* Include: follicular lymphoma, marginal zone lymphoma/malt, lymphocytic lymphoma (closely related to CLL and treated similarly), lymphoplasmacytoid lymphoma (produces IgM = Waldenström’s macroglobulinaemia
* **High-grade lymphomas:** more aggressive, but often curable. There is often rapidly enlarging lymphadenopathy with systemic symptoms.
* **Include:** Burkitt’s lymphoma (childhood disease with characteristic jaw lymphadenopathy) lymphoblastic lymphomas (like all), diffuse large b-cell lymphoma
28
What is polycythaemia vera?
* Myeloproliferative disorder caused by clonal proliferation of a marrow stem cell leading to an increase in red cell volume, often accompanied by overproduction of neutrophils and platelets.
* Mutation in **JAK2** is present in approximately 95% of patients with polycythaemia vera
* Peaks in the sixth decade.
29
What are some of the signs and sx of polycythaemia vera?
* hyperviscosity
* pruritus, typically after a hot bath
* splenomegaly
* haemorrhage (secondary to abnormal platelet function)
* plethoric appearance
* hypertension in a third of patients
* low ESR
30
What ix are used for polycythaemia?
* FBC/film (raised haematocrit; neutrophils, basophils, platelets raised in half of patients)
* JAK2 mutation
* Serum ferritin
* UE, LFTs
* If JAK2 mutations is -ve:
* red cell mass
* arterial oxygen saturation
* abdominal ultrasound
* serum EPO level
* bone marrow aspirate + trephine
* cytogenetic analysis
* erythroid burst-forming unit (BFU-E) culture
31
How is polycythaemia mxd?
* **aspirin**: reduces the risk of thrombotic events
* **venesection**: to keep the haemoglobin in the normal range
* **chemotherapy**: hydroxyurea + phosphorus-32 therapy
