Malignancy Flashcards
Age at presentation
Leukaemia affects children at all ages
-Early childhood peak
Neuroblastoma and wilms tumour in first 6y
Hodgkin lymphoma and bone tumours in adolescence
Short term side effescts of chemotherapy
Bone marrow suppression Immunosupression Gut mucosal damage Nausea and vomiting Anorexia Alopecia Undernutrition Anaemia Thrombocytopenia and bleeding Neutropenia
Drug specific side effects
Doxorubicin: cardiotoxicity
Cisplatin: renal failure and deafness
Cyclophosphamide: haemorrhagic cystitis
Vincristing: neuropathy
Functions of chemotherapy
Primaru curative .e.g. ALL
Control primary or metastatic disease .e.g. sarcoma, neuroblastoma
Adjuvant treatment for residual disease .e.g. Wilms
High dose therapy with stem cell rescue
Transplantation of bone marrow stem cells to intensify treatment to potentially lethal doses of chemo
Stem cells may be allogeneic or autologous
Principally use in the management of high risk or relapse leukaemia (allogenic) and solid tumours (autologous)
Examples targeted therapies
Tryosine kinase inhibtors .e.g. Imatinib
-Taregtting BCR-ABL fusion gene (philadealphia chromosome ALL and CML)
Monoclonal antibodies .e.g. rituximab
-Anti CD20 for lymphoma
-Anti GD2 for high risk neuroblastoma
Presentation Acute Leukaemia
Peak age 2-5y
Develops over the course of several weeks
Malaise
Anorexia
Anaemia: pallor, lethargy
Neutropenia: infection
Thrombocytopenia: bruising, petechaie, nose bleeds
Bone marrow infiltation: bone pain
reticulo-endothelial: hepatosplenopmegalthy, lymphaneopathy
-superior mediastinal obstruction (uncommon)
CNS: headaches, vominting, nerve palsies
Testis: testicular enlargement
Ix Leukaemia
Abnormal FBC -low Hb -thrombocytopenia Circulating leukaemic blast cells Bone marrow examination for diagnosis Clotting screen (risk of DIC) LP for CSF involvement Chest Xray for mediastinal mass (T cell disease) Blood film
Mx ALL
Blood transfusion for anaemia Allopurinol to protect renal function Stages: -Remission induction: chemo + steroids -Intensification: consolidates remission -CNS: intrathecal chemo -Continuing therapy: ~3y w cotrimaxole prophylaxis -Relapse treatment: high dose chemo +/- irridation
Types of brain tumours
Astrocyoma ~ 40%
Medulloblastoma ~20% midline of posterior fossa
Ependymoma ~8% Posterior fossa
Brainstem glioma ~6% Poor prognosis
Craniophyngioma ~4% Squamous remnant of Ranthke pouch
Atypical teratoid/rhabdoid- rare, aggressive tumour
Poor prognostic factors in ALL
Age: <1y or >10y
Tumour load: >50 x 10^9
Genetics: MLL rearrangement, t4:11 haploidy
Chemo response: persistance of blasts in marrow
MRD: detectable MRD after induction
Presentation brain tumours
Persistent/recurrent vomiting Balance, co-ordination/walking problems Behavioural change Abnormal eye movements Seizures without fevers Abnormal head positioning Persistent or recurrent headache Blurred/double vision Lethargy Deteriorating school performance Delayed or arrested puberty Slow growth Developmental delay/regression Progressive increased in head circumference: separation of suture, bulging fontanelle
Brain tumour site and clinical features
Supratentorial: seziures, hemiplegia, focal neurology
Midline (craniopharyngioma): visual field loss, pituitary dailure (growth, DI, weight gain)
Cerebellar (medulloblastoma, astrocytoma, ependymoma): truncal ataxia, co-ordination difficulty, abnormal eye movements
Brainstem (glioma): cranial nerve defect, pyramidal tract signs, ataxia, no raised ICP
Ix Brain tumour
MRI scan
LP for suspected CSF metastasis (not in raised ICP)
Mx Brain tumour
Surgery first line -treat hydrocephalus -provide tissue diagnosis -maximum resection -Brain and optic pathway no op Radio/chemo variable
Long term effects brain tumours
Neurological disability
Growth and endocrine problems
Neuropsych and educational issues
Types of lymphoma
Hodgkin
Non-hodgkin
Burkitts
Features hodgkin lymphoma
Painless lymphadenopathy -usually in the neck Larger and firm lymph nodes Nodes may cause airway obstruction Long history Systemic features uncommon
Ix Hodgkin lymphoma
Lymph node biopsy
Radiological assessment of nodal sites
Bone marrow biopsy (staging)
Mx Hidgkin lymphoma
Combination chemotherapy
+/- rediotherapy
PET scanning to monitor treatement response
80% cure rate
Features non-hodgkin lymphoma
Mediastinal mass Bone marrow infltration SVC obstruction: dysponea, facial swelling, flushing, venous distention in neck, chest and arms Abdominal pain from obstruction -palpable mass -intussusception
Ix Non-hodgkin lymphoma
Biopsy
Radiological assessment of all nodal sites
Examination of bone marrow and CSF
Mx Non-hodgkin lymphoma
Multiagent chemotherapy
Survival 80%
Features Burkitt’s Lymphoma
Endemic variant occurs in regions with EBV
Characteristically involves the jaw and other facial bones
Usually associated with HIV and immunosupression post-transplantation
Features neuroblastoma
Arise from neural creast tissue in adrenal medulla and sympathetic nervous sytem
Most common before 5y
Abdominal mass
Large complex mass, crossing midline, enveloping blood vessels and lymph nodes
Paravertebral tumours: spinal cord compression
Children >2y typicaly mets: bone pain, bone marrow suppression
Ix Neuroblastoma
Raised urinary catecholamines metabolite (VMA/HVA)
Confirmatory biopsy
Bone marrow sampling and MIBG scan
Prognosis neuroblastoma
Age and stage at presentation main influencer
Most children >1y advanced disease and poor prognosis
Amplification of MYCN oncogene predicts aggressive behaviour
Risk of relapse high
Mx neuroblastoma
Localised primary- surgery alone
May resolve spontaneously in infants
Mets- chemo (high dose with autologous stem cell rescue), surgery, radio
Presentation neuroblastoma
Pallor Weight loss Abdo mass Hepatomegaly bone pain Limp Paraplegia Cervical lymphadenopathy Proptosis Periorbital bruising Skin nodules
Features Wilms tumour
Embryonal renal tissue
Most common renal tumour of childhood
Present <5y
Rare >10y
Presentation Wilms tumour
Abdominal mass Haematuria Abdominal pain Anorexia Anaemia Hypertension
Ix Wilms tumour
US/CT/MRI: intrinsic renal mass distorting normal structure
Staging to assess lung mets
Contralateral kidney function
Mx Wilms tumour
initial chemotherapy Delayed nephrectomy -histological staging radiotherapy in advanced disease Good prognosis except in relapse
Features soft tissue sarcoma
Cancers of connective tissue .e.g. muscle or bone
Most common: rhabdomyosarcoma
-orginates from primitive mesenchymal tissue
Clinical features sarcoma
Head and neck:
-Most common
-proptosis, nasal obstruction, bloodied nasal discharge
Genitourinary:
-dysuria, obstruction, scrotal mass, bloodied vaginal discharge
Mets:
-lung, liver, bone, bone marrow
-15% of patients at diagnosis (poor prognosis)
Ix sarcoma
Biopsy
Full radiological disease
Mets search
Mx Sarcoma
Multimodality: chemo, surgery, radio
Ill-define tumour margins makes excision unsuccessful
Cure rate ~65%
Features bone tumours
Uncommon before puberty
Limbs most common site
Localised persistent bone pain
Ix Bone tumour
Plain Xray -destruction -perosteal new bone formation -soft tissue mass in ewings sarcoma MRI and bone scan Chest CT: lung mets Bone marrow sampling
Mx Bone tumour
Combination chemotherapy
En bloc resection of tumour with endop[rosthetic resection
Radiotherapy in Ewings, pelvic or axial
Features retinoblastoma
White pupillary reflex
Squint
All bilateral tumours are hereditory (chromosome 13)
Present within 3y
Ix Retinoblastoma
MRI
Examination under anaestetic
Mx Retinoblastoma
Enucleation of the eye in advanced disease
Chemotherapy in bilateral disease to shrink tumours
local laser to retina
Radiotherapy mostly used in recurrence
Patients usually left visually impaired
Risk of 2’ malignancy esp. sarcoma
Features Kaposi sarcoma
Blood or lymph vessel triggered by HHV8 Rare in UK Relevant in immunodeficiency .e.g. HIV Generalised lymphadenopathy (Adults present with purple/brown skin rash) Chemo and antiretrovirals
Long term sequelae of childhood cancer
Nephrectomy
Toxicity from chemo affecting renal function, cardiac function
Growth hormone deficiency
Bone growth retardation
Gonadal irradiation/chemo agents causing infertility
Neuropsych problems from cranial irradiation and brain surgery
Secondary malignancy
Educational disadvantage
Manifestations of Langerhans cell histiocytosis
Bone lesions: pain, swelling, fracture
-Xray shows lytic lesion with well defined border, often skull
Diabetes insipidus
-proptosis and hypothalamic infiltration
Systemic LCH: most aggressive, seborrhoeic rash in infancy
-involvement of gums, ears, lungs, liver, spleen, lymph nodes, bone marrow
Pathology Langerhans cell histiocytosis
Rare disorder
Abnormal proliferation of histiocytes
Primary malignant liver tumours
Hepatoblastoma
Hepatocellular carcinoma
Presentation liver tumour
Abdominal distention
Mass
Pain and jaundice- rare
Ix liver tumours
Elevated serum alpha feroprotein
Good prognosis in hepatoblastoma
Germ cell tumrous pathology
Arise from primitive germ cells migrating from yolk sac endoderm to form gonads in sacrococcygeal region
Most found in the gonads
alphaFP and betaHCG serum markers
Mx germ cell tumours
Very responsive to chemotherapy
