Malignancy in a child Flashcards
What is the most common malignancy affecting children?
ALL (acute lymphoblastic leukaemia) also accounts for 80% of childhood leukaemia
Leukaemia accounts for 31% of all childhood cancers - is the most common childhood cancer
When is the peak incidence of ALL? Which sex is more affected?
2-5 years
Boys slightly more affected
What are the signs showing bone marrow failure in ALL?
- anaemia: lethargy and pallor
- neutropaenia: frequent or severe infections
- thrombocytopenia: easy bruising, petechiae
Which of these will be high in ALL?
- Hb
- Neutrophils
- Platelets
- Potassium
- Phosphate
- Uric acid
- Calcium
- LDS
Potassium, phosphate, uric acid and LDH will be high - these are due to high number of cells undergoing lysis.
Bone marrow fails to produce normal cells such as Hb, neutrophils or platelets so these are low.
What are the non-bone marrow failure features of ALL?
Other features
- bone pain (secondary to bone marrow infiltration)
- splenomegaly
- hepatomegaly
- fever is present in up to 50% of new cases (representing infection or constitutional symptom)
- testicular swelling
What are the three types of ALL?
- common ALL (75%), CD10 present, pre-B phenotype
- T-cell ALL (20%)
- B-cell ALL (5%)
What features of ALL are poor prognostic factors?
Poor prognostic factors
- age < 2 years or > 10 years
- WBC > 20 * 109/l at diagnosis
- T or B cell surface markers
- non-Caucasian
- male sex
What is a complication of ALL with high WCC that should be avoided? How do you treat infection in these patients?
Tumour lysis sundrome and subsequent renal failure - this can occur due to high cell breakdwon. Manage with hyperhydration and allopurinol.
Risk of gram negative sepsis, since there is neutropenia - so use broad spectrum antibiotics like piptazobactam/gentamycin.
A 3-year-old girl is brought in by her mother. Her mother reports that she has been eating less and refusing food for the past few weeks. Despite this her mother has noticed that her abdomen is distended and she has developed a ‘beer belly’. For the past year she has opened her bowels around once every other day, passing a stool of ‘normal’ consistency. There are no urinary symptoms. On examination she is on the 50th centile for height and weight. Her abdomen is soft but slightly distended and a non-tender ballotable mass can be felt on the left side.
What is the diagnosis?
Wilm’s nephroblastoma
What age group is most affected by Wilm’s nephroblastoma?
It typically presents in children <5 years , with a median age of 3 years old.
What are the genetic associations with Wilm’s nephroblastoma?
Most occur in healthy children but 10% occur in children with malformations e.g.
- Overgrowth syndromes (excess somatic growth causing macroglossia, nephromegaly and hemihypertrophy) e.g. Beckwith-Wiedemann syndrome or isolated hemihypertrophy
- No ‘overgrowth’ - e.g. trisomy 18 (Edwards syndrome), WAGR syndrome (Wilm’s with Aniridia, Genitourinary malformations, mental Retardation)
1-2% - Familial Wilms’ tumour - autosominal dominant transmission, associated with mutation in the WT1 gene (WAGR) or WT2 gene (BW) on chr11, or WT3 on chr16
What are the presenting features of Wilm’s nephroblastoma?
- abdominal mass (most common presenting feature) - unilateral in 95%
- painless haematuria
- UTI
- flank pain
- other features: anorexia, fever, respiratory symptoms if metastasised
How often is Wilm’s nephroblastoma unilateral? How common are metastases?
- unilateral in 95% of cases
- metastases are found in 20% of patients (most commonly lung)
What investigations are useful in diagnosing Wilms’ tumour?
Bloods: FBC, U&E, creatinine
Imaging: US/renal angiography - may show distorsion of renal pelvis/hydronephrosis
Staging: CT/MRI including chest for metastases
How quickly should children with suspected Wilm’s tumour be seen?
Refer to a paediatrician to be seen within 48 hours.
What is the prognosis with Wilm’s tumour?
Prognosis - good, 80% cure rate
Management - nephrectomy, chemotherapy, radiotherapy if advanced disease
What is the aetiology of childhood leukaemia?
- De novo mutations (most common)
- Genetic syndromes may predispose
- Chromosomal and genetic abnormalities:
- Translocation to TCR loci in ALL
- TF mutations regulating B cell development and maturation in ALL
- Aberrational disruption of genes coding for TFs and coactivators in AML
- BCR-ABL1 fusion and activation of multiple kinases in CML
What age is ALL/AML/CML most common?
- ALL - 2-3 years
- AML - <2 years
- CML - <1 year and young adolescents
What are the risk factors for leukaemia?
- Boys>girls
- Caucasian
- Cytogenetic abnormalities
- Down’s syndrome (x10-20 fold risk), Faconi’s anaemia, ataxia telangiectasia and Bloom’s syndrome
- Exposure to ionising radiation/maternal XR exposure during pregnancy
What are the presenting features of leukaemia?
- Anaemia, thrombocytopenia, hepatosplenomegaly, lymphadenopathy
- Malaise, fatigue, lethargy
- Prolonged fever
- Growth restriction/failure to thrive
- SOB/dizziness/palpitations
- Bone/joint pain
- Constipation
- Headache
- Nausea and vomiting (CNS infiltration)
- Repeated/severe common childhood infections
Signs:
- Pallor
- Petechiae/purpura/bruising
- Expiratory wheeze
- CN lesions
- Testicular enlargement
What investigations would you do for lymphoma?
- FBC with differential and blood film - pancytopenia due to bone marrow infiltration; WCC elevated due to blasts despite neutropenia
- BM aspiration and biopsy
- Imaging
- Immunophenotyping and cytogenic analysis (e.g. FISH) for risk stratification
- Lumbar puncture (if suspected CNS infiltration)
Summarise the management of ALL/AML/CML.
ALL - high intensity chemotherapy through Hickman lines or myeloablation with allogeneic BM transplantation in disease refractory to chemotherapy
AML - intensive chemotherapy to destroy leukaemic population ASAP
CML - imatinic anti-tyrosine kinase therapy being investigated; myeloablative HSCT mainstay therapy for now
Colony stimulating factors given to promote haematopoiesis following chemotherapy.
Which two electrolyte abnormalities are common in leukaemia?
hyperkalaemia and hyperphosphataemia (due to blast crisis)
What is the prognosis of childhood leukaemia?
- Five year survival is 79% and cure rates are 68%
- ALL cure rate is 80% and best in those ages 1-10 years
- Average time to cure in ALL is 19 years (due to relapse, secondary malignancy and toxicity)
- AML 5 year survival is 66%
What is lymphoma? What are the types?
Malignancy of the lymphatic system which includes lymph nodes, the spleen, the thymus and the bone marrow.
Two main types: Hodgkin’s and non-Hodgkin’s lymphoma
What is the difference between lymphoblastic lymphomas and lymphoblastic leukaemias?
Degree of bone marrow infiltration
lymphoma = <25% bone marrow involvement
leukaemia = >25% bone marrow involvement
How common is lymphoma?
Accounts for 10% of cancer cases in children
3rd most common cancer in children
- NHL - affects about 80 children per year in UK*
- HL - affect about 60 children per year in UK*
Which type of lymphoma is more common in boys?
Non-Hodgkin’s lymphoma
HL is equal in males:females
What is the aetiology of lymphoma?
- Abnormal proliferation of lymphocytes
- The malignant cells are MATURE lymphocytes which arise OUTSIDE of the bone marrow e.g. lymph nodes (unlike in leukaemia where blasts come from bone marrow)
- Usually unknown underlying cause or chromosomal abnormalities
Exceptions: rarely lymphoblastic lymphomas come from immature precursor lymphoblasts.
What are the risk factors for lymphoma?
-
Immunodeficiency:
- post-solid organ transplant (post-transplant lymphoproliferative disorders),
- ataxia telangiectasia,
- Nijmegan-Breakage syndrome,
- HIV,
- and immunosuppressant drugs
- EBV infection
What are the types of Hodgkin’s lymphoma?
NB: no difference in the prognosis or management of the different subtypes of classical Hodgkin’s lymphoma
What is the characteristic finding in Hodgkin’s lymphoma?
Reed-Sternberg cells (giant multinucleated cells) with associated smaller mononuclear cells, which arise from B lymphocytes
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What are the types of non-Hodgkin’s lymphomas?
What is the pathophysiology of most non-Hodgkin’s lymphomas? Name the most common type of NHL.
Most are high-grade lymphomas of B-cell origin
Burkitt’s (most common) then large B cell, lymphoblastic, anaplastic
How does B cell vs T cell NHL usually present?
B-cell NHL mostly affects lymph nodes in abdomen/GI tract but also in head and neck - usually localised lymph node disease
T cell NHL usually affects lymph nodes in the chest –> mediastinal mass with varying degree of BM infiltration
What complications may arise from T cell NHL?
T cell NHL –> mediastinal mass –> SVC obstruction may cause dyspnoea, facial swelling, flushing and venous distension in neck as well as chest and arms
What complications may arise from B cell NHL?
B cell NHL –> abdominal/head/neck localised lymph node disease –> in abdomen can present with pain from intestinal obstruction, palpable mass or intussusception in some cases with involvement of ileum
What are common presenting features of lymphoma?
- Painless progressive lymphadenopathy (weeks to months)
- Mediastinal involvement:
- Cough
- Dyspnoea
- Facial oedema
- Pruritus
- B symptoms:
- Fatigue
- Weight loss (>10% in 6 months)
- Drenching night sweats
- Fever
- Loss of appetite
Extranodal involvement is more common in NHL:
- BM: anaemia, infections, bruising
- Abdominal: bloating satiety, pain, constipation, vomiting
- Retroperitoneal lymphadenopathy: urinary retention
- Skin: new lesions like mycosis fungoides, jaundice
- Testicular swelling
- CNS: behavioural change, headache, confusion, N&V, seizures, weakness, sensory change, raised ICP
What investigations are used to diagnose paediatric lymphoma?
Bedside: swabs for infection, urine dip
Bloods:
- FBC - ancytopenia or differentiates leukaemia (anaemia, thombocytopenia and raised WCC)
- U&E - important for baseline treatent, in TLS electrolytes raised
- LDH - raised if high cell turnover
- LFTs - important basline for treatment, low albumin means poor prognosis
- Hep B/HIV/G6PD - complications of treatment may occur in these groups
Imaging: CXR, CT/MRI/PET for staging, US liver and spleen.
Invasive: biopsy for staging of lymph node +/- bone marrow
Which staging classifications are used for lymphoma?
Ann Arbor - HL
St Jude - NHL as more extranodal involvement
Summarise the staging for lymphoma.
Given a number I-IV + a letter (A [none] , B [systemic symptoms] and E [extranodal] in HL)
List the B symptoms.
- weight loss
- fever
- night sweats
NOT lymphadenopathy or fatigue
What is the general management of HL?
Chemotherapy is mainly used
Other:
- Radiotherapy if chemotherapy is not effective
- Lymphocyte-predominant HL usually has surgery or low-dose chemotherapy alone as it is slower growing
What is the general management of NHL?
Chemotherapy is mainly used - regimen depends on the type but generally:
- B-cell NHL has 4-6 courses of intensive therapy
- T-cell NHL has less intensive therapy but lasting 2-3 years.
Other:
- Biologics - e.g. rituximab is anti-CD20, used for high-risk B cell NHL
- BM tranplant - if relapsed
- Lymphoblastic lymphoma is treated like ALL
- Radiotherapy rarely used
What are the condition-related (long and short-term) complications of lymphomas?
Short term:
- SVC obtruction
- Bowel obstruction/perforation
- Pain from invasion
- Pericardial/pleural effusion
- Cytopenias
- Tumour lysis syndrome
Long term:
- Few
What are the treatment-related (long and short-term) complications of lymphomas?
Short-term:
- Alopecia
- Mucositis, diarrhoea
- Neutropenic sepsis
- TLS
- N&V
- Anorexia and weight loss
Long-term:
- Secondary cancers
- Growth impairment
- Infertility
- Cardiotoxicity/pulmonary toxicity/renal impairment
What is the prognosis of paediatric lymphomas?
90% of those with HL and >90% of those with NHL achieve remission.
But long term effects of treatment can be significant and require long-term follow up.
Summarise TLS.
- AKI
- Arrhythmias
- N&V
- Seizures
…may occur as a result of TLS which is most common in highly proliferative tumours and causes electrolyte disturbance:
- hyper-phosphataemia
- hyper-uricaemia
- hyper-kalaemia
- hypo-calcaemia
Tx: allopurinol (prevents uric acid production) and hyperhydration [+/- rasbiricase if WCC >50 to break down uric acid]
A 14-year-old girl complained of a cough for 2 weeks which was non-productive and worse at night. She had seen her general practitioner and her chest was clear. She returned 2 weeks later, as she had noticed a swelling in her neck. On examination, she had a large anterior cervical lymph node which was non-tender. On referral to hospital, she had a chest X-ray, which showed a large mediastinal mass (Fig. 22.10).
What is the differential diagnosis?
- T cell NHL/acute leukaemia
- HL
FBC was normal but biopsy confirmed Hodgkin lymphoma.
What are the types of Burkitt’s lymphoma? What is its pathophysiology and usual presentation?
Burkitt = B cell NHL and there are 3 types:
- Endemic - in malaria endemic regios where coinfection with EBV is common, invovles jaw or facial bones
- Sporadic - EBV-assciated
- Immunodeficiency related - linked to HIV or post-transplant
What are are benign vs malignat … bone tumours called?
- Bone
- Cartilage
- Fibrous tissue
- Bone marrow
- Vasculature
Benign (1) and malignant (2)
- Bone - osteoid osteoma vs osteosarcoma
- Cartilage - chondroma/osteochrondroma vs chondrosarcoma
- Fibrous tissue - fibroma vs fibrosarcoma
- Bone marrow - eosinophilic granuloma vs Ewing’s sarcoma/myeloma
- Vasculature - heamangioma vs angiosarcoma
What is the epidemiology of osteosarcoma?
- Most common primary bone malignancy in childhood
- More common in males (1.4 : 1)
- Mostly occurs after puberty at ages 10-25 (and >60 as a complication of Paget’s)
Which part of the bone does osteosarcoma usually affect?
Sites of rapid bone growth i.e. metaphysis or diaphysis of the distal femur, proximal tibia and proximal humerus.
75% of cases are around the knee
What are the presenting features of osteosarcoma?
Progressive pain but often presents painless
Pain at night
Soft tissue or bony swelling
What investigations are done to diagnose osteosarcoma?
Bedside:
Bloods: FBC, U&E, coagulation and CRP to exclude multiple myeloma, osteomyelitis; LDH (exclude secondary tumours), raised ESR, bone profile (ALP raised in osteoblast activity in osteocsarcoma), Ca (high in multiple myeloma and metastatic disease).
Imaging: plain radiograph (but cannot exclude), MRI for soft tissue extension (GOLD STANDARD), radionucleotide bone scan (shows malignant/metastases due to high metabolic activity) + CT (CAP for metastases),
Invasive: biopsy (must refer to bone sarcoma MDT first - only 5 centres in UK).
What is seen on XR in osteosarcoma?
‘Sunburst’ appearance in soft tissue as it calcifies
Combination of bone destruction and formation
How do you distinguish between malignant and benign bone lesion on plain radiograph?
What is the management of osteosarcoma?
Refer to a sarcoma multidisciplinary team (MDT)
Principles of treatment:
- Limb sparing surgeries: local excision and wide excision.
- Radical surgeries: resection with prosthetic replacement and amputation with prosthetic replacement.
- Adjuvant chemotherapy (pre and post operative) and radiotherapy
What are the complications of osteosarcoma (untreated and treated)?
Untreated:
- Pain, peripheral nerve and vessel compression
- Pathological fractures
- Metastasis
- Hypercalcaemia
Treatment-related (surgical):
- Pain, loss of function, neurovascular damage
- Blood clots, bleeding, infection
- Scarring, swelling, stiffness
- Failure of prosthesis
Where does osteosarcoma metastasise to?
Lung (rapidly)
What is the prognosis with osteosarcoma?
Localised - 70% 5-year survival
Metastatic/recurrent - <20% survival
What are poor prognostic factors in osteosarcoma?
- Primary metastases
- Axial/proximal involvement
- Large tumour volume
- Elevated serum ALP
- LDH raised
- Older age
What is Ewing’s sarcoma?
Primary neuroectodermal tumour arising from mesenchymal stem cells which mostly occurs in adolescents and has a male predominance. Occurs in bone extramities, pelvis, ribs and vertebrae and presents with mass/swelling. Diagnosed similarly to osteosarcoma but chemotherapy is usually first line treatment (VIDE) +/- radiotherapy +/- surgery. Survival rates similar to osteosarcoma.
