Haematological Malignancies - Multiple Myeloma, Lymphoma, Leukiema Flashcards
Name all the types of haematological malignancies?
Lymphatic malignancies: Hodgkin’s and non Hodgkin’s lymphoma, and Multiple Myeloma
Leukaemia’s - AML, CML, ALL, CLL
Plasma cell malignancy - Polycythaemia vera
How are the different types of lymphomas classified?
On histology where there there is a presence of a
REED STERNBURG CELLS -
-Lymphocytes with an ‘owl eye’ nucleus (more than one nucleus)
Hodgkin’s: RS +
Non-Hodgkin’s: RS -
What is the epidemiology of lymphomas?
Non-Hodgkin’s is far more common accounting for nearly 80% of all Lymphomas,
Hodgkin’s lymphoma has bimodal distributions (early 20s and >70s) in teens and elderly. It is also highly associated with EBV
What are the different types of Non-hodgkin’s Lymphoma
Follicular - Low Grade
Diffuse B - High Grade
Burkitts (~EBV) - Very high grade
How may a patient present with lymphatic malignancy?
Skin Excoriations - Hodgkins, Skin rash - Non Hodgkins
Painless Rubbery Lymphadenopathy
(In Hodgkin’s, Alcohol can cause lymphatic pain)
+/- B symptoms
DX Lymphoma
FBC: Hodgkins- Neutrophilia, Non-Hodgkins - Neutropenia
Lymph Node Biopsy - Presence of Reed Sternberg cells
CT / MRI - Staging
What would Burkitt’s lymphoma present on a biopsy?
‘Starry sky biopsy’ -
This is due to the presence of macrophages with relatively clear cytoplasm as seen in the inset.
What is the classification system used for Lymphomas?
ANN ARBOUR STAGING +/- B Symptoms
What is ABVD indicated for?
ABVD describes multi-drug chemotherapy regimen for Hodgkin’s lymphoma:
Adriamycin (doxorubicin) ~ Infertility
Bleomycin ~ Lung Damage
Vinblastine ~ Nervous system
Dacarbazine ~ Cardiomyopathy
What is RCHOP indicated for?
Non-Hodgkin’s Lymphoma
Retuximab (mAb - CD20-Bcell)
Cyclophosphamide
Hydroxydaunorubicin
Oncovin (Vincristine)
Prednisolone
What are the complication of chemotherapy?
Febrile neutropenia
Tumour lysis syndrome
Increase risk of infection
Rash
What is multiple myeloma?
neoplastic monoclonal (50% - IgG / 20% IgA) proliferation of plasma cells
What is the epidemiology of multiple myeloma
Predominantly occurs in those over the age of 40
and more common in Black people
What condition is multiple myeloma associated with?
There is a close link to a condition called monoclonal gammopathy of undetermined significance (MGUS)
MGUS (monoclonal gammopathy of undetermined significance) is a condition in which there is a small amount of abnormal monoclonal immunoglobulin in the blood, but there are no other signs or symptoms of a plasma cell disorder. MGUS is considered a precursor condition to multiple myeloma
What are the cardinal factors of multiple myeloma?
OLD CRAB
>65 years old
Hypercalcemia
Renal Impairment
Anaemia
Bone lesions
What are the symptoms of CRAB?
Hypercalcaemia -> polydipsia, polyuria, constipation, abdo pain
Renal impairment
Anaemia -> fatigue, dizziness, pallor, headache, tachycardic
Bone lesions -> bone pain
+ signs of cancer - weight loss, TIAT
How can multiple myeloma cause multi organ damage?
Amyloidosis is a disorder in which abnormal proteins called amyloid fibrils accumulate in various tissue causing damage.
This may also occur in multiple myeloma due to excess ig production.
Excess Ig misfold and aggregate into amyloid fibrils.
Amyloid fibril stimulates grows of tumour cells. Also:
Amyloid fibrils deposited around the body leading to tissue damage and organ dysfunction:
- Renal - Nephrotoxic /
Shows presence of immunoglobulin light chains found in urine (BENCE JONES PROTEINS)
What’s the pathophysiology of Multiple myeloma’s Anemia?
Via a process called Myelodysplasia where haemopoitic tissue is replaced by dysplatic cells resulting in the suppression of normal blood cell production leading to anaemia, neutropenia, and thrombocytopenia.
What’s the pathophysiology of Multiple myeloma’s bone damage and how is this presented on an XRAY?
The neoplasm also disrupt bone homeostasis as it increases osteoclast activity and decreases osteoblast activity (release of cytokines among other things) = increased turnover of Bone = excess release of calcium into the body
This results in BONE LESIONS and HYPERCALCEMIA
-> Hypercalcemia presents as BSGM - bone/kidney stones/ abdo groans (n/v) /psychiatric moans memory loss, lethargy, depression
Hypercalcaemia -> polydipsia, polyuria, constipation, abdo pain
Renal impairment
-> Bone pain - ‘Punched Out holes’ + ‘Pepper pot skull’
Investigating multiple myeloma?
Diagnosis
FBC -> anaemia - Normocytic/normochromic
ESR -> raised
Blood film -> Rouleaux formation (RBC aggregates)
Serum - +/- Hypergammaglobinemia
Urine electrophoresis -> Bence Jones protein in urine
Bone marrow biopsy - Amyloid fibrils
Imaging (X-ray/CT) -> ‘Punched out’ / ‘Pepper Pot’ Bone lesion - Skulls
Managing Multiple Myeloma
Chemotherapy (VCD, VTD, MTP)
Stem cell transplant
Analgesia
Bisphosphonates (zoledronic acid)
Blood transfusions
What is polycythaemia?
Definition -> a high concentration of erythrocytes in the blood
What are the different types of polycythaemia
Types
Relative - No effect on RBC but reduction in plasma
~ Obesity, Dehydration, Alcohol
Absolute - Increase in number of erythrocytes, 2 types:
Primary - Polycythaemia vera - BM malignancy
associated with JAK 2 mutation
Secondary - Extrinsic disease causing overstimulation
of BM / EPO secretion
Disorders associated w/Hypoxia - EPO secreting tumour,
COPD, sleep apnea, renal cancer, renal artery stenosis
What is polycythaemia vera
A myeloproliferative neoplasm associated with JAK2 mutation. this leads to excessive number of wcc, rbc and plt
How may a patient with polycythaemia vera present?
Cardinal Feature: Itchy after BATH and HEPATOSPLEENOMEGALY
others:
Headache/ Dizziness
Blurred vision
Hypertension
Plethoric complexion (Swelled red skin face hand and feet)
DX VERA
FBC: Increase WCC, RBC, PLT, Haematocrit
Serum EPO - DOWN
Genetic Testing - JAK2 mutation
What other condition is associated with JAK2 mutation?
Essential Thrombocythemia - Elevated platelet count
50% ~ JAK2 mutation meaning TPO is constantly stimulating platelet production
Presentation: increased thrombus risk (PE, DVT, CSVT)
Workup:
FBC – thrombocytosis
Genetic testing for JAK mutation
Bone marrow biopsy - megakaryocytes
How to treat P.Vera
Venesection
Life long Aspirin
If thrombotic % - Hydroxycarbamide
?What is leukaemia
Bone marrow cancer caused by uncontrolled neoplastic proliferation of blast cells - myeloblast / lymphoblast
What are the cardinal sign of leukaemia?
All leukameias will show the following signs and symptoms
Bone marrow failure - Bone Pain
Tired all the time (TIAT)
Lymphadenopathy
Hepatosplenomegaly
+
Pancytopenia:
Low WCC- % of infection (except for CLL - leukocytosis)
Low platelet - Primary haemostasis bleeding disorder
Anaemia - pallor/fatigue/headache/exertional dyspnoea/tachycardia/palpitations
Chronic leukaemia - Wt loss, Night sweats, Fever / Chills
What causes pancytopenia in leukaemia?
myelodysplasia -Immature blast cells uncontrollably proliferate, taking up space within the bone marrow, and then infiltrating into other tissues
The lack of space within the bone marrow means fewer healthy cells can mature and be released into the blood
What are the epidemiology’s of all the different types of leukaemia
AML ~ Downs syndrome
CML ~ 65-74yrs old
ALL ~ MC in children (0-4yrs old) and / Downs syndrome
CLL ~ MC in adults - ~ 70 years old
What are the INDICTIVE presentations for each leukaemia
AML - GUM HYPERTROPHY
CML - MASSIVE HEPATOSPLENOMEGALY and GOUT
ALL - Swollen testes - CNS INFILTERATION - Headaches / CN Palsies
CLL - Often ASX but severe - hypogammaglobinaemia (immunecompromised)
Gym Hypertrophy is a characteristic sign of which leukaemia?
AML
MASSIVE HEPATOSPLENOMEGALY and GOUT is a characteristic sign of which leukaemia?
CML
Often ASX but severe - hypogammaglobinaemia (immunecompromised) is a characteristic sign of which leukaemia?
CLL
Swollen Testes and CNS INFILTERATION - Headaches / CN Palsies is a characteristic sign of which leukaemia?
ALL
What are the diagnostic procedure for Leukaemia?
FBC - Pancytopenia
Blood film
Bone Marrow Aspirate and Biopsy
What are the defining observation when investigating for each leukaemia?
Acute myelogenous leukaemia - Severe and rapid
AUER RODS + >20% Myeloblast
Chronic myeloid leukaemia -
Stages: Chronic <10% blast cells, Accelerated 10-19%, Blast >20%
Chronic - Pancytosis -> Pancytopenia
Cytogenic analysis: Chr9:22 Philadelphia chromosome
Acute lymphoblastic leukaemia-
>20% lymphoblast (75% B cell / 25% T cell)
Chronic lymphoblastic leukaemia -
Lymphocytosis
SMUDGE CELLS
What is a possible complication of chronic leuakemias?
they can become acute
In ALL - how does the pathogenesis of the diseases lead to muti-organ damage
Excessive proliferation of lymphoblast, leak and deposit into various tissue including: meninges, testes, brain:
resulting in: swollen testes and NX: CN palsy
Lymphocytosis
SMUDGE CELLS
CLL
AUER RODS + >20% Myeloblast
AML
Stages: Chronic <10% blast cells, Accelerated 10-19%, Blast >20%
Chronic - Pancytosis Blast crisis- Pancytopenia
Cytogenic analysis: Chr9:22 Philadelphia chromosome
CML
> 20% lymphoblast (75% B cell / 25% T cell)
ALL
What is a complication of CLL
RICHTER TRANSFORMATION - when neoplastic b cell from cml accumulates in the lymph, there is a high risk that it can transform into NON-Hodgkins lymphoma
Treatment for leukaemia
Chemotherapy:
AML - Anthracycline + Cytarabine
CML - Imatinib (TK Inhibitor)
ALL - Methotrexate
CLL - Rituximab- watch and wait / in early stages
ALLOPURINOL to prevent tumour lysis syndrome
2nd line Stem cell/ BM transplant
What is tumour lysis syndrome?
Chemotherapy complication caused by:
Collection of metabolic disturbances occurring with rapid destruction of neoplastic cells
Characteristically:
Hyperuricaemia, hyperkalaemia, hyperphosphatemia
Hypocalcaemia
AKI
SIgns: Arryhtmias/AKI/Bone pain/Nx/syncope/N/V
Treat with allopurinol
What is febrile neutropenia?
Neutropenia + Fever = massive risk of infections
Caused by: Infection - sepsis (TB), BM Disorders, Chemotherapy
Sx - Fever, Abdo pain, Mucositis
Tx with broad spec AB
