Malignancy Flashcards
Myeloma definition
Malignant proliferation of plasma cells in the bone marrow characterised by
- a monoclonal paraprotein in the serum/urine
- bone changes leading to pain and pathological fractures
- excess plasma cells in the bone marrow
features of myeloma
- median age 60-65 years
- CRAB
- renal failure
- hypercalcaemia
- anaemia
- infections
- spinal cord compression (plasmacytomas), general bone pain
- amyloidosis (–> macroglossia, hepatosplenomegaly, cardiac failure, carpal tunnel syndrome and autonomic neuropathy
bone destruction in myeloma
- lytic lesions on xray
- osteoporosis AND lytic lesions
- vertebral collapse –> loss of height, back pain, kyphosis
- “pathological” fracture
Laboratory features of myeloma
- Anaemia (often with neutropenia, thrombocytopenia and ESR >100)
- Rouleaux on blood film with bluish background from increased protein
- Bone marrow >10% plasma cells often w/ multinucleate
- Paraprotein in serum and/or Bence Jones proteins in urine with suppression of normal serum Igs (can be IgG, IgA, IgM uncommon)
- Raised serum ß2 microglobulin often
Treatment of myeloma
Observation for symptomless patients (no CRAB)
If symptomatic
>70 years –> chemotherapy e.g. thalidomide, lenalidomide, bortezomib
<70 years –> chemotherapy e.g. melphalan + high dose therapy with autologous stem cell transplant
Mechanism of myeloma bone symptoms
Myeloma cells produce factors that result in:
- Activation of osteoclasts e.g. RANKL
- Inhibition of osteoblasts e.g. DKKI
These lead to bone resorption
Pain management in myeloma
- analgesics (caution in renal impairment)
- chemotherapy
- bisphosphonates
- radiotherapy (localised, severe pain)
- orthopaedic surgery –> fixation
- general measures - mobility, physio
Other causes of paraproteinaemia?
Other B cell or plasma cell neoplasms
- MGUS
- plasmacytomas
- Primary amyloidosis
What is MGUS?
Monclonal Gammopathy of Undetermined Significance
- Incidence increases from 5th decade onwards
- 1% per year evolve to myeloma, then watch and wait
- paraprotein present but less than myeloma levels
- bone marrow plasma cells <10%
- NO lytic lesions
- no myeloma-related symptoms
When to suspect myeloma?
Paraprotein +
- *C**alcium elevated
- *R**enal impairment
- *A**naemia
- *B**one pain/lytic lesions
What is a plasmacytoma?
Clonal proliferation of plasma cells identical to those in myeloma, but manifest as localised mass in bone or soft tissue:
- solitary plasmacytoma of bone
- solitary extramedullary plasmacytoma
Treatment: radiotherapy if truly localised, ie no underlying myeloma
What is primary amyloidosis (aka systemic AL)
- Protein confirmation disoreder associated with a clonal plasma cell problem, like a form of light chain MGUS
- multiple organ disease occurs from extracellular deposition of insoluble light chain fragments
How does Primary Amyloidosis affect different organs?
- Heart - congestive cardiomyopathy
- Kidneys - nephrotic syndrome +- renal insufficiency
- Nerves - peripheral neuropathy
- Liver - hepatomegaly
- Gut - macroglossia, malabsorption
- Skin..
How do you diagnose primary amyloidosis?
Tissue biopsy of affected organ + SC fat aspirate
Also assess plasma cells abnormality: serum/urine electrophoresis BM biopsy + skeletal survey
Treatment of primary amyloidosis?
- Organ specific - supportive treatments
- chemotherapy similar to myeloma (treats plasma clone not amyloid)
Difference between leukaemia and lymphoma
The distinction may be blurred
Leukaemia
- Widespread involvement of bone marrow
- tumour cells in peripheral blood
Lymphoma
- Discrete tumour masses
What is lymphoma
Malignant proliferation of lymphocytes. Derived from a single transformed cell
- monoclonal
- same antigen receptor gene rearrangement
- Reside where normal counterparts found
Types of lymphoma
- Hodgkin’s Lymphoma
- may be localised or widespread
- Non Hodgkin’s
- Usually disseminated at diagnosis
- B cell
- T cell and NK cell
- Histiocytic and dendritic cell
- Usually disseminated at diagnosis
What is Hodgkin’s Lymphoma
- Malignant disorders of lymphoid tissue
- Reed-Sternberg and mononuclear Hodgkin’s cells form a minority of the tumour
- Rest from lymphoblasts, granulocytes, fibroblasts and plasma cells
- EBV may play a role
AML causes what blood results?
- Anaemia
- Neutropenia
- Thrombocytopenia
therefore symptoms of anaemia, infection and haemorrhage
AML diagnostic tests
- Blood count and film - elevated WCC, can be normal/low, often blast cells, auer rods
- Bone marrow aspirate and trephine - blast infiltration
- Cytochemistry - positivity with Sudan black and myeloperoxidase
- Immunophenotyping - myeloid antigens e.g. CD13 and CD33
- Cytogenetics - BM sample sent
- Molecular Biology - PCR, FISH
AML treatment
- Red cell transfusion
- Platelet concentrates
- Broad spectrum Abx
- Chemotherapy -
- aiming for <5% blast cells in BM (complete remission)
- induction then consolidation
- daunorubicin and arabinoside
- Autologous stem cell transplantation
AML characteristic blood film features?
Auer rod in blast cells
AML definition
Presence of >20% blast cells in the BM at clinical presentation
AML presentation
- More common in the elderly
- Linked to Down’s syndrome and myelodysplasia
- Gum hypertrophy and infiltration
- CNS and skin involvement
- Bleeding
- common genetic mutation ASXL1
ALL pathophysiology
Malignancy of lymphoid cells can affect B and T cell lineages (more commonly B)
arrest maturation and promote proliferation of immature blasts
ALL presentation
- 2 peaks at 3-7 years and over 40yo
- Anaemia, bleeding, infection (BM failure)
- Hepatosplenomegaly
- Testicular infiltration
- Lymphadenopathy (parotid)
- CNS involvement
- B symptoms
- Associated with Down’s and radiation during pregnancy
- FAB classification (L1, L2, L3)
ALL treatment
- Chemotherapy
- vincristine, prednisolone, asparaginase, maybe MTX, cyclophosphamide and cytosine arabinoside
- Allogenic SCT in young patients
- Neutropenic regimen
- Prophylactic Abx
** can get tumour lysis syndrome - give allopurinol
ALL investigations
- >20% blasts in BM
- Pancytopenia
- Lumbar puncture
What is CML?
- Clonal myeloproliferative disorder which results from an acquired change in a pluripotent stem cell
- –> gross overproduction of neutrophils and their precursors
- Three phases
- chronic phase (benign)
- accelerated phase
- blast crisis (fatal)
Genetics of CML?
- Philadelphia Chromosome!
- Translocation of 9 and 22
- Causes BCR-ABL gene which encodes a protein with high tyrosine kinase activity
CML presentation
- Usually present in chronic phase
- anaemia, anorexia, weight loss, bruising
- Splenomegaly - pain, bloating, satiety
- Occasionally gout or hyperviscosity
- 40 - 60 years, M>F
- blast crisis - typical acute leukaemia symptoms
CML diagnostic Ix
- WCC above 100x10^9
- increase in myeloid cells, but highest numbers of myelocytes and neutrophils
- often absolute basophilia
- thrombocytosis and nucleated red cells may be present
- Increased urate
- FISH
CML treatment
- TKI - imatinib, dasotinib
- chemo
- allogenic SCT
hydroxycarbamide can be used to rapidly reduce WCC
What is CLL
- Clonal proliferation of B-lymphocytes
- Commonest leukaemia in western world
- Disease of the elderly, M>F
CLL presentation
- Lymphadenopathy
- splenomegaly
- immunosuppression/recurrent infections
- anaemia
- B symptoms
- can be asymptomatic
risk of herpes zoster, other infections, autoimmune haemolysis
CLL diagnostic Ix
- High lymphocyte count confirmed by blood film
- Cells resemble normal mature lymphocytes but often slightly larger with tendancy to burst - smear cells
- In situ or flow cytometry techniques to identify characteristics and single Ig lightchain
- BM aspirate shows increased numbers of small lymphocytes
- blood film may suggest autoimmune haemolysis or autoimmune thrombocytopenia
- *B DISEASE**
- B lymphocytes (95%)
- Bone marrow failure
- Bleeding
- Broken cells (smear cells)
CLL staging
Rai and Binet:
- Stage A: No anaemia or thrombocytopenia; less than 3 lymphoid areas enlarged
- Stage B: No anaemia or thrombocytopenia, Three or more lymphoid areas enlarged
- Stage C: Anaemia (Hb >100g/L) and/or plateless <100x10^9/L
0 - 12 year survival??
CLL Treatment
- Watch and wait until symptomatic - when disease is progressing rapidly
-
RFC: rituximab, fludarabine and cyclophosphamide
*
Hodgkin’s presentation?
- asymmetrical, painless lymphadenopathy, rubbery
- splenomegaly/hepatosplenomegaly occur
- B symptoms, pruritus
- LN pain after alcohol
Emergency: SVC obstruction - raised JVP, facial oedema, SOB, blackouts
Diagnosis of Hodgkin’s
- Biopsy of lymph node, BM aspiration and trephine biopsy in advanced cases
- whole body CT scan for staging, sypplemented by MRI and PET
- (may have been anaemia and increased LDH)
Hodgkin’s treatment
- radiotherapy
- chemotherapy ABVD
- adriamycin
- bleomycin
- vinblastine
- dacarbazine
What is Non Hodgkin’s Lymphoma?
Solid tumours of lymphoid tissue which are not Hodgkin’s
Most common haem malignancy
Presents at any age but median age is 50
Non Hodgkin’s Lymphoma classification
- High grade
- large poorly differentiated lymphoid cells
- aggressive course but often curable
- Low grade
- smaller, better differentiated cells
- more indolent clincally but more likely to repeatedly relapse
Non Hodgkin’s Lymphoma presentation
- More irregular spread and extranodal involvement that HL
- Painless lymphadenopathy
- Extranodal involvement e.g. intestinal may cause abdo pain
- may affect CNS, may arise in skin
- B symptoms
Non Hodgkin’s Lymphoma diagnosis
- Tissue biopsy - usually LN
- Histology
- Immunophenotyping - degree of maturation, B or T cell
- Staged with CT, MRI or PET
Treatment for Non Hodgkin’s Lymphoma
- Low grade
- often incurable
- Radiotherapy
- Interferon alpha or rituximab
- High grade
- RCHOP
- rituximab
- cyclophosphamide
- Hydroxydaunorubicin
- Vincristine
- Prednisolone
- RCHOP
What is aplastic anaemia?
Pancytopenia due to reduction in the number of pluripotent stem cells. May be exacerbated by marrow abnormality and autoimmunity
Presentation of aplastic anaemia
- Marrow failure - anaemia
- severe infections caused by neutropenia
- haemorrhagic tendancy - thrombocytopenia
- may be gradual onset
What is smouldering myeloma?
The transition point from MGUS to myeloma. Dx criteria include:
- monoclonal protein in serum >= 30g/L
- Monoclonal plasma cells >= 10% in BM or tissue biopsy
- No evidence of end-organ damage
- normal serum calcium, Hb, serum creatinine, no bone lesions
Should not be treated but watched closely
