CBL: Malignancies Flashcards
Li Fraumeni Syndrome - what is this? - what mutation does it involve?
Li-Fraumeni syndrome is a rare disorder that greatly increases the risk of developing several types of cancer, particularly in children and young adults
Mutation: TP53
Li Fraumeni Syndrome - when to consider (ages, FHx)
Consider if: - sarcoma <45 years old and 1st degree relative with any cancer <45 years old or sarcoma at any time
Li Fraumeni Syndrome 1. What cancers does it predispose to? 2. What management is there for a person with that syndrome?
- Rhabdomyosarcoma ( cancer of soft tissue, connective tissue or bone)
- ALL ( acute lymphoblastic leukemia )
- breast Ca, brain tumours, adenocorticoid tumours, colorectal cancer
. Genetic counselling and regular screening for cancers
Leukaemia presentation (symptoms)
- General malaise - Intermittent fevers Symptoms secondary to cytopenias: -Bleeding(mucosal), bruising, petechial rash - Anaemia, SOB, fainting, fatigue - Infection ; bacterial, fungal, viral -Pain (Bone, Joints, Abdomen, Chest, Head) - Lymphadenopathy & hepatosplenomegaly - Skin nodules
Leukaemia: What happens in the bone marrow and what does it do to the cells produced there?
Disruption in the regulation and proliferation of lymphoid precursor cells in the bone marrow leads to excessive production of immature blast cells and drop in the other three cell lines
What cancer is the most common among children?
Acute Lymphoblastic Leukaemia (ALL)
4 most common cancers in children are…
- Leukaemia (Acute Lymphoblastic Leukaemia)
- Brain and spinal tumours
(e. g. medulloblastoma, neuroblastoma, glioma) - Nephroblastoma (Wilm’s tumour)
- Lymphoma
Which are two sites difficult to treat in leukaemia?
Why?
Testicles -> due to blood-testicular barrier
CNS -> due to blood-brain barrier
- What’s tumour lysis syndrome? What happens?
- Tumour lysis syndrome - metabolic abnormalities resulting from a large number of tumour cells being killed off (lysed) -> cancer cells will release their content into blood stream
Happens in cancers that respond well to chemotherapy (e.g. leukaemia and lymphomas)
large amounts of: phosphorus, potassium and calcium leading to potential kidney damage
Complications of tumour lysis syndrome
nausea and vomiting, but more seriously acute uric acid nephropathy, acute kidney failure, seizures, cardiac arrhythmias, and death
Prevention of tumour lysis syndrome
- supportive
- drugs (two)
- prophylactic oral or IV allopurinol (a xanthine oxidase inhibitor à uric acid (following cell lysis) formation prevented
- IV hydration to maintain high urine output (> 2.5 L/day)
- Rasburicase is an alternative to allopurinol (reserved for people who are high-risk in developing TLS) àIt is a synthetic urate oxidase enzyme àacts by degrading uric acid
Leukaemia management:
Immediate/supportive, if:
- if WBCs are very high
- mass in mediastinum
- infection
Leukaemia management:
Immediate/supportive:
- Stabilise unwell child
- Hyperhydration -> if WBCs is very high -> in order to prevent hyperviscosity
- If a mass present in mediastinum and airways are at risk to be compromised -> steroids
- If infection/ sepsis -> antibiotics
FBC results in ALL
- Low haemoglobin
- Thrombocytopenia
- Evidence of leukemic blast cells
What is ALL
one marrow produces specialised cells called stem cells, which have the ability to develop into three important types of blood cells:
red blood cells – which carry oxygen around the body
white blood cells – which help fight infection
platelets – which help stop bleeding
Normally, bone marrow doesn’t release stem cells into the blood until they are fully developed blood cells.
But in acute lymphoblastic leukaemia, large numbers of white blood cells are released before they are ready. These are known as blast cells.
As the number of blast cells increases, the number of red blood cells and platelet cells decreases
Drugs used in chemotherapy for Leukaemia
Leukaemia management:
Drugs used in chemotherapy:
- 3 or 4 drug depending on risk group
(Dexamethasone, Vincristine, Asparaginase +/- Doxorubicin)
IX for suspected Leukaemia
- FBC - anaemia, leukocytosis, neutropenia, thrombocytopenia
- Peripheral blood smear - leukemic lymphoblasts
Bone marrow biopsy - Hypercellularlity and infiltrations by lymphoblasts
- U and E and LFTs - may be abnormal
- Coagulation profile - distorted
- Serum electrolytes - high calcium, K, uric and lactic acid
Leukaemia management:
- Simply outline what’s the main mode of Rx and supportive care
- is radiotherapy used?
- chemotherapy -> given IV, orally, and intra-thecally (into the CSF
- blood products(red cells, platelets)
- prophylactic anti-fungal therapy throughout treatment
*There is no role for radiotherapy in the management of ALL
2 types of T cell malignancies
- Acute lymphoblastic leukaemia
- Non hodgkin’s lymphoma
Signs and symptoms of bone marrow infiltration
- Anaemia - Pallor & Lethargy
- Neutropenia -Infection
- Thrombocytopenia - Bruising, petichae, nose bleeds
- Bone pain
Do we use cranial radiation (prophylactic) in the management of Leukaemia?
IT Methotrexate replaced prophylactic cranial RT
What medications are used in the ‘maintenance’ therapy for leukaemia?
MTX & Mercaptopurine +/- Steroids & Vincristine
How long is ‘maintenance’ therapy for Leukaemia?
girls -> 2 year
boys -> 3 years
Red flags for symtpoms (suspicion of leukaemia)
- Non-tender, firm or hard LN
- LN > 2cm
- Progressively enlarging
- Features of ill-health, fever or weight loss
- Pallor
- Unexplained bruising
- Hepatosplenomegaly
- Axillary nodes involved
–(in absence of local infection or dermatitis)
•Supraclavicular nodes involved
Risk factors for the development of Lymphoma
- being immunocompromised (transplant recipients)
- Epstein-Barr virus (EBV)
- past treatment for other cancers
Lymphoma
- what to look for in Hx
- what are ‘B symptoms’?
- non-specific symptoms
- a visible or palpable mass
- “B symptoms” such as:
- Weight loss
- Night sweats
- Fevers
- Non-specific symptoms of malignancy: such as lethargy and anorexia
Why there may be an airway compromise in Lymphoma?
- Mediastinal lymphadenopathy
- superior vena cava obstrution
Presentation: cough, wheeze, difficulty in breathing
Investigations for Lymphoma (and the reason behind them)
Bloods
- FBC -> to exclude infection
- U&Es -> to investigate for tumour lysis syndrome
- LDH -> lactate dehydrogenase -> usually elevated
Investigations for Lymphoma
(and reason behind them)
A. Imaging
B. Definitive diagnosis
A. Imaging:
- USS -> to identify other nodes and assist in biopsy
- X ray -> to check if there is a mediastinal node involvement
- full CT -> to check for extent of a disease (staging)
B. Definitive:
-Lymph node biopsy
4 steps of management of ALL
- Remission induction
- Blood transfusion to correct anaemia
- platelet transfusion - to correct risk of bleeding
- hydration and allopurinal - protect renal function against effects of rapid cell lysis
* 4 week combination chemotherapy* - Intensification
- intensive chemo to consolidate remission - CNS drugs - intrathetcal and special focus on cns because cytotoxic drugs don’t always penetrate
- Continuing therapy - modest intensity chemo continue for 3 years atleast
Staging of Lymphoma
Lymphoma is staged according to how many groups of lymph nodes or organs are involved:
- Stage 1: Disease is present in a single group of lymph nodes or a single organ
- Stage 2: Disease is present in 2 or more groups of lymph nodes or organs on the same side of the diaphragm
- Stage 3: Disease is present in lymph nodes or organs on both sides of the diaphragm
- Stage 4: There is diffuse involvement of lymph nodes and organs such as the liver and bones
What’s the role of ‘B symptoms’ in Lymphoma staging?
B symptoms (night sweats, fever, weight-loss) are associated with worse prognosis at each stage of the Ca
Immediate treatment of Lymphoma in cases of:
- airway compromise
- superior vena cava obstruction
- tumour lysis syndrome
- if airway compromise = emergency. -> high dose steroids and airway support
- Superior vena cava obstruction (SVCO) -> stenting of veins to keep them patent ( it will usually resolve with treatment of the underlying malignancy)
- tumour lysis syndrome, then hyperhydration is important -> Allopurinol or rasburicase are also used
Long-term treatment of Hodkin’s Lymphoma
Chemotherapy and radiotherapy
Dacarbazine -> chemotherapy agent
Presentation on non hodgkin’s lymphoma/ALL
- ‘Shortness of breath with a non productive cough’ - mediastinal mass can cause vena cava obstruction
- FBC - pancytopenia, low haem, thrombocytopenia
- Lymphadenopathy
Burkitt Leukaemia/ Lymphoma
- what mutations are present
- what do they result in
- Highly aggressive B cell (CD20 positive)
- C-myc amplification (FISH studies)
- Doubling time: 24-48hrs
Burkitt Lymphoma/ Leukaemia
- abdominal symptoms
- treatment
- prognosis
- Abdominal disease may present as intussusception
- Treatment with intensive chemotherapy
- 90% patients are cured overall
What is non Hodgkin’s lymphoma?
B-lymphocytes (a particular type of lymphocyte) start to multiply in an abnormal way and begin to collect in certain parts of the lymphatic system, such as the lymph nodes (glands).
What’s a peak incidence of Wilm’s tumour?
2-3 years old
*almost never occur in teenagers or adults
Among known factors of nephroblastoma pathology, what two factors may be implicated?
- genetic syndromes
A. Nephrogenic remnants (immature kidney) 1%
B. Mutation of Tumour suppressor gene
C. syndromes, such as WAGR (Wilm’s tumour, Aniridia, Genitourinary malformations, and Retardation), Denys-Drash and Beckwith-Wiedemann
Features in the Hx and examination that may suggest a diagnosis of nephroblastoma
- abdominal distention
- palpable mass of one or both kidney
- hypertension
- signs of compression on other abdominal organs (rarely, at very advanced stage)
Investigations for neuroblastoma and reason behind them
Bloods
- FBCs -> to investigate for a child’s general health
- U&Es -> to assess the condition of the kidneys
- urinalysis -> to check for haematuria
Investigations for neuroblastoma and reason behind them
Imaging
Definitive diagnosis
- USS -> to check for the mass
- CT /MRI-> to check how advanced a disease is
- biopsy -> definitive diagnosis
Staging in nephroblastoma
StageDefinition 1 The tumour is only confined to the kidney and can be completely removed with surgery 2 The tumour has begun to spread beyond the kidney, but can still be completely removed with surgery 3 The tumour cannot be completely surgically resected because it has spread to neighbouring lymph nodes or ruptured before/during surgery 4 There are distant metastases, most commonly to the lungs. 5 There are bilateral tumours (each can be allocated an individual stage)
Management of nephroblastoma
- Stage 1 and 2 -> solely with surgery (no additional benefit to giving chemotherapy which has additional risks later in life)
- Chemotherapy -> to reduce the volume of malignant tissue before surgery, or to treat any areas of malignant disease not removed by surgery
Surgery in nephroblastoma
- name
- aim
Surgery usually consists of nephrectomy, although in bilateral disease there is usually an attempt to preserve as much functioning renal tissue as possible (to avoid the requirement for renal replacement therapy).
- Prognosis in nephroblastoma
- follow up and why
- Prognosis for even metastatic disease is good, with over 85% of patients expected to be cured
- single functioning kidney -> to protect the remaining kidney (maintain a healthy blood pressure, as well as avoidance of contact sports - abdominal trauma)
- if chemotherapy and/or radiotherapy received -> follow up long term to monitor for potential late effects, such as cardiotoxicity
Neuroblastoma
tumors arising from neural crest tissue in the adrenal medulla and sympathetic nervous system
most common before the age of 5
- what tissues are involved in the development of neuroblastoma?
- what location is the most common for its origin?
- neural tissue
- adrenal glands -> the most common origin location for neuroblastoma development
*may also develop in neck, chest, abdomen and spine)
Symptoms of neuroblastoma
- bone pain
- lump in the abdomen, neck, or chest
- a painless bluish lump under the skin
Symptoms of neuroblastoma in relation to its location :
abdomen, chest, spinal cord, bone lesions, eyes/orbit, bone marrow
- abdomen -> distention, constipation
- chest -> difficulties in breathing
- spinal cord -> weakness, inability to crawl, stand or walk
- bone lesions -> pain, limping
- tumour around eyes, orbit -> bruising and swelling
- bone marrow infiltration -> pallor and anaemia
Treatment options for neuroblastoma (according to ‘risk’)
- low-risk disease can frequently be observed without any treatment at all or cured with surgery alone
- Intermediate-risk disease is treated with surgery and chemotherapy
- High-risk ->intensive chemotherapy, surgery, radiation therapy, bone marrow / hematopoietic stem cell transplantation,<a>[</a>biological-based therapy with 13-cis-retinoic acid (isotretinoin or Accutane) and antibody therapy
What are the risk groups in neuroblastoma?
low, intermediate and high -> they will determine treatment options and prognosis
Characteristics took into account: patient’s age, extent of disease, tumour microscopic appearance, possible genetic mutations
Diagnosis of neuroblastoma
Tissue biopsy
Treatment options for gliomas
Surgery (if possible), radiotherapy and chemotherapy (may be also used)
What’s prognosis and treatment options for Diffuse Intrinsic Pontine Glioma?
•Diffuse Intrinsic Pontine Glioma (DIPG)
–Cannot resect
–Radiotherapy may slow progression
–Fatal in >95% (9 months)
Treatment options and prognosis for medulloblastoma
•Multi-modal therapy
–Surgical resection
–Radiotherapy (age dependent)
–Chemotherapy
•Affected by Blood Brain Barrier
•Prognosis
–Varies significantly depending on age, mets, histology/ genetic subgroup
Symptoms of Hodgkin’s lymphoma
- Lymphadenopathy - cervical, abdominal,
- Abdominal lymphadenopathy - present as mass, intestinal obstruction, abdominal pain
- Biosy of mass is needed for diagnosis to confirm hodgkin’s
Some of the side effects of cancer treatment
- Hair loss (Usually temporary)
- Nausea & vomiting
- Anorexia/ poor nutrition
- Weakness/ tiredness/ lethargy
- Blood product requirement (transfusions)
- Immunosuppression (risk of life-threatening infection)
- Mucositis (sore gut)
- Bleeding & clots
- Headaches, seizures & encephalopathy
- Constipation/ileus
- Skin rashes
- psychological (isolation, fear, depression)
Type of B cell malignancy
Non hodgkin’s lymphoma
Side effects of chemotherapy with Anthracyclines
(treatment of many cancers)
Anthracyclines
–Cardiac impairment
Side effects of treatment with Cisplatin (long term)
Cisplatin:
–Hearing impairment
–Renal impairment
–Hypomagnesaemia
- Infertility
Side effects of treatment with Vincristine
Vinca-Alkaloids: (eg Vincristine)
–Peripheral neuropathy
Side effects of treatment with Etoposide
Topoisoemerase inhibitors: (eg Etoposide)
–second Leukaemia
Side effect of treatment with Ifosfamide
Ifosfamide:
–Encephalopathy
–Haemorrhagic cystitis
Side effects of a long-term use of steroids in Ca treatment
•Steroids
–Avascular necrosis
