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 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?
Summarise the staging for lymphoma.
Given a number I-IV + a letter (A [none] , B [systemic symptoms] and E [extranodal] in HL)
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 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?
