Case 20- Haematological Malignancy Flashcards
Leukaemia
Cancer of stem cells in the bone marrow
Pathophysiology
Excessive production of one cell line leads to suppression of other cell lines causing underproduction of other cell types- results in pancytopenia (combination of anaemia, leukopenia, thrombocytopenia)
ALL CELLMATES HAVE COMMON AMBITIONS
Under 5 and over 45- ALL
Over 55- CLL
Over 65- CML
Over 75- AML
Presentation of leukaemia
Fatigue, fever (night sweats), failure to thrive children), pallor (anaemia), petechiae and abnormal bruising, abnormal bleeding, lymphadenopathy, hepatosplenomegaly, bone pain, frequent infections
Petechiae
Bleeding under the skin caused by thrombocytopenia. Differentials;
Leukaemia
Meningococcal septicaemia
Vasculitis
HSP
ITP
Non accidental injury
Investigations for leukaemia
1) FBC, blood film, LDH (raised)
2) Bone marrow biopsy- main investigation
3) CXR- mediastinal lymphadenopathy
4) Lymph node biopsy- assess lymph node involvement
5) CT MRI PET- staging and assessing other tumours
Bone marrow biopsy
Aspiration- take a few cells in a liquid sample (examines straight away)
Trephine- solid core sample of the bone marrow. Superior assessment (few days of preparation before examination)
Acute lymphoblastic leukaemia
Usually B lymphocytes- acute proliferation
Most common childhood malignancy (2-5 yrs)
Associated with Down’s syndrome
Blast cells on blood film
Chronic lymphocytic leukaemia
Chronic proliferation of the B lymphocytes
Warm autoimmune haemolytic anaemia
Can form high grade lymphoma- Richter’s transformation
Smear/ smudge cells on a film
Most common leukaemia in adults overall
High risk of infections
Chronic myeloid leukaemia
Philadelphia chromosome (t(9:22))
3 phases- chronic (5 year asymptomatic phase),accelerated, blast phase (often the fatal phase)
Increased granulocytes (at different stages of maturation ie. bands) and or thrombocytosis
Acute myeloid leukaemia
Can transform from a myeloproliferative disorder like PCRV or myelofibrosis
High proportion of blast cells- have rods inside them called Auer rods
Management of leukaemia
1) Discuss in MDT- refer to haematology and oncology
2) Chemotherapy, steroids, radiotherapy
3) Bone marrow transplant
Lymphoma
Affects the lymphocytes inside the lymphatic system (cancerous cells proliferate within the lymph nodes and cause lymphadenopathy)
Risk factors for Hodgkin’s lymphoma
HIV/ EBV
Rheumatoid arthritis and sarcoidosis
Family history
Presentation of Hodgkin’s lymphoma
Lymphadenopathy- neck, groin, axilla (non tender and rubbery, unilateral and spreading)
Pain on drinking alcohol (for Hodgkin’s)
B symptoms- fever, weight loss, night sweats
LDH raised
Others;
Fatigue, itching, cough, SOB, abdominal pain, recurrent infections
Investigations s for Hodgkin’s lymphoma
FBC, UE, LFT, coagulation profile, Ca (metastasis), LDH (raised) ESR, HIV test (risk for NHL), blood film
Excisional Lymph node biopsy- reed stern berg cells/mirror image nuclei (large B cells with multiple nuclei and nucleoli)
CT MRI PET scans- stage lymphoma
NB- reed sternberg (large cells with a bilobed nucleus and prominent eosinophilic inclusion-like nucleoli)
Management of Hodgkin’s lymphoma
Chemotherapy and radiotherapy- can be cured
Flu pneumococcal vaccines
Non Hodgkin’s lymphoma
Many different types (Burkitts, MALT lymphoma (H pylori), diffuse large B cell lymphoma).
Risk factors- HIV/ EBV/ H pylori/ Hep B or C/ trichloroethylene (several industrial processes)/ FH
Similar presentation to Hodgkin’s so can on,y be differentiated on biopsy
Chemo, radio, stem cell transplantation, monoclonal antibodies
Myeloma
Cancer of the plasma cells (B lymphocytes that produce antibodies). Found in the bone marrow
They produce immunoglobulins (antibodies)- heavy chains and light chains. IgG often produced in abundance in myeloma. The antibody produced by all the cancerous cells is identical so is referred to as a monoclonal paraprotein
Bence Jones protein found in the urine of myeloma patients- light chain of the immunoglobulin
Multiple myeloma
Myeloma that affects multiple areas of the body
MGUS (Monoclonal gammopathy of undetermined significance)
Excess of a single type of antibody or component, without features of myeloma or cancer
Very rarely progresses to myeloma
Anaemia
Cancerous plasma cells invade the bone marrow and suppress other cell lines- get anaemia, neutropenia and thrombocytopenia
Myeloma bone disease
Increased osteoclast activity and suppressed osteoblasts activity
Patchy imbalance between the 2 cell types leads to osteolytic lesions throughout the body (can get pathological fractures)
Get hypercalacemia due to the increased bone turnover
Myeloma renal disease
High levels of immunoglobulins attack the tubules
Hypercalacemia impairs renal function
Dehydration
Medications like bisphisphanates can be harmful to the kidneys
Hyperviscosity
More proteins in the blood- therefore it is more viscous
Causes many issues- easy bruising, easy bleeding, loss of sight (vascular disease of the eye), purple discolouration of the extremities, heart failure, stroke
Way to remember features of myeloma
CRABBI
Calcium
Renal failure (light chains deposited in tubules, also get nephrolothiasis and amyloidosis)
Anaemia (normocytic, normochromic)
Bone lesions/ pain (osteoporosis)
Bleeding (thrombocytopenia)
Infection
Myeloma investigations
Bloods- FBC (anaemia and thrombocytopenia), bone profile (Ca (raised)), ESR (raised), plasma viscosity (raised), LFT (metastasis), UE (urea and creatinine raised), serum protein electrophoresis (free light chains)
Urinalysis and electrophoresis- renal disease and bence Jones protein (urine electrophoresis)
Bone marrow aspiration and trephine biopsy
Imaging- asses bone lesions (MRI CT DEXA scan)
NB- MRI now first line scan
BLIP- bence Jones, serum free light chains, immunoglobulins and proteins
Management of myeloma
1) MDT- oncology and haematology
2) Chemotherapy
3) Stem cell transplantation
4) Bone complications- bisphisphanates, radiotherapy, orthopaedic surgery to stabilise bones
NB- non curable. Takes a relapsing and remitting course
TTP- thrombotic thrombocytopenic purpura
A type of thrombotic microangiography- platelets occlude the microvasculature
Risks for TTP
Pregnancy, cancer, HIV, SLE, clopidogrel, quinine, oestrogen Xs
Sx of TTP
Fever, neurological abnormalities, thrombocytopenia (petechiae/ purpura), microangiopathic haemolytic anaemia (fatigue/ jaundice), impaired renal function (haematuria/ proteinuria/ oliguria/ anuria)
Investigations for TTP
Bloods- FBC, peripheral smear (schistocytes), UE (creatinine increased, AKI)
HUS- Haemolytic Uraemic Syndrome
A thrombotic microangiography in which microthrombi (platelets) form and occlude the microvasculature
NB- often affects children and is caused by the shiga toxin of E. coli
Sx of HUS
Usually a diarrhoeal illness (bloody) precedes the onset of HUS Sx in many children;
Thrombocytopenia- petechiae
Micronagiographic haemolytic anaemia- fatigue, jaundice
Impaired renal function- hameaturia, proteinuria, oliguria, anuria
Treatment of TTP
Plasma exchange therapy
Steroids
ITP- Immune Thrombocytopenic Purpura
Diagnosis of exclusion in isolated thrombocytopenia
A) primary- viral infection causes an autoimmune reaction
B) secondary- lymphoma, leukaemia, SLE, HIV
Sx of ITP
Commonly asymptomatic
Features can include easy bruising, petechiae, haematuria, bleeding, malaena
NB- adults are usually treated with steroids
Most common childhood malignancy
ALL
Specific management of CML
Imatinib (inhibitor of tyrosine kinase)
CLL features in investigation
Lymphocytosis
Anaemia
Smudge cells
Immunophenotyping
Uncontrolled proliferation of small, mature lymphocytes in the bone marrow, lymph nodes (resulting in lymphadenopathy) and spleen (resulting in splenomegaly).
Implications of CLL
Anaemia
Hypogammaglobulinaemia (recurrent infections)
Warm autoimmune haemolytic anaemia)
Richters transformation (transformation to a high grade lymphoma)
Richters transformation features
Patient deteriorates very quickly and becomes unwell
Other features;
Lymph node swelling
Fever without infection
Weight loss
Night sweats
Nausea
Abdominal pain
Burrkitts lymphoma
High grade B cell neoplasm
Endemic form- maxilla or mandible (EBV)
Sporadic form- abdominal tumours
t(8:14)
Starry sky appearance on microscopy
Management of burkitts lymphoma
Chemotherapy, but can cause tumour lysis syndrome
Treat with rasburicase first
Complications of tumour lysis syndrome
Hyperkalaemia
Hyperphosphataemia
Hypocalcaemia
Hyperuricaemia
Acute renal failure
What malignancy can H pylori predispose somebody to?
Gastric lymphoma (MALT)
Nodular sclerosing Hodgkin’s lymphoma
Most common
Good prognosis
Common in women
Lacunar cells
Mixed cellularity Hodgkin’s lymphoma
20%
Good prognosis
Large number of reed stern berg cells
Lymphocyte predominant Hodgkin’s lymphoma
Best prognosis
Lymphocyte depleted Hodgkin’s lymphoma
Worst prognosis
Poor prognosis in Hodgkin’s lymphoma
B symptoms
-weight loss (>10% in 6 months)
-fever (>38)
-night sweats
Ann Arbor staging of lymphoma (NHL and HL)
I- single lymph node
II- 2 or more lymph nodes/regions on the same side of the diaphragm
III- nodes on both sides of the diaphragm
IV- spreads beyond’s the lymph nodes
A- no systemic symptoms other than pruritus
B- B symptoms present
MGUS
A cause of paraproteinaemia that is often mistaken for multiple myeloma
Features of MGUS
Asymptomatic
No bone pain or increased infections
10-30% have a demyelinating neuropathy
Differentiating MGUS and myeloma
Normal immune function
Lower levels of paraproteins
Stable levels of paraproteins
No clinical features of myeloma eg, lyric lesions or renal disease
Normal beta 2 micorglobulin levels
Myelodysplastic syndrome
Pre-leukaemia, may progress to AML
Presents with bone marrow failure (anaemia, neutropenia, thrombocytopenia)
Myelofibrosis
Myeloproliferative disorder
Hyperplasia of megakaryocytes
Haematopoiesis occurs in the liver and spleen
Features of Myelofibrosis
Anaemia eg. Elderly person with fatigue
Massive Splenomegaly
B symptoms- weight loss, night sweats, fever etc.
Laboratory findings of Myelofibrosis
Anameia
Tear drop poikilocytes on blood film
Unobtainable bone marrow biopsy (dry tap)- trephine biopsy needed
High urate and LDH
Rain drop. Vs pepper pot skull
Multiple myeloma- rain drop
Pepper pot skull- hyperparathyroidism
Differentiating HL and NHL
Alcohol induced pain in HL
B symptoms occur earlier in HL
Extra nodal disease is more common in NHL eg. Gastric (dyspepsia, dysphagia, abdominal pain), bone marrow (pain, pancytopenia), lung, skin, CNS (nerve palsies)
Prophylaxis of TLS
IV allopurinol or IV rasburicase
Complication of TLS
AKI
Arrhythmia
Diagnosis of clinical tumour lysis syndrome
Laboratory TLS + increased creatinine, or cardiac arrhythmia (even sudden death), or seizure
Waldenstroms macroglobulinaemia (lymphoplasmocytic leukaemia)
Paraproteinaemia
Weight loss, lethargy
Hyper-viscosity
Hepatosplenomegaly
Lymphadenopathy
Cryoglobulinaemia (raynauds)
What medication can be used to treat chronic neutropenia
filgrastim (or perfilgrastim)
What medication can be used to treat chronic neutropenia
filgrastim (or perfilgrastim)
Management of ITP (adult)
1) first-line treatment is oral prednisolone
2) pooled normal human immunoglobulin (IVIG) may also be used
it raises the platelet count quicker than steroids, therefore may be used if active bleeding or an urgent invasive procedure is required
splenectomy is now less commonly used
Investigations for HUS
FBC UE blood film
stool sample- shiga toxin
Management of HUS
treatment is supportive e.g. Fluids, blood transfusion and dialysis if required
there is no role for antibiotics, despite the preceding diarrhoeal illness in many patients
