ONCOLOGY LECTURE 2016

Phase 3 UNSW Medical Students

CASES FOR DISCUSSION

Dr Susan Russell, MB BS, FRACP

 Topics to be discussed
• 1.Acute lymphoblastic leukaemia
• 2.T-cell lymphoma
• 3.Wilm’s tumour
• 4.Neuroblastoma
• 5.Brain tumour: medulloblastoma
CASE # 1.
 History

A four year old girl presented to casualty with

a 4 week history of bone pain and limp, and a
2 day history of petechiae
 Examination

She appeared to be well but miserable

afebrile
no significant lymphadenopathy
liver 3 cm below right costal margin
spleen 4 cm below left costal margin
generalised petechiae, purpura & occassional
scattered bruising.
Purpura
 Investigations

FBC: Hb 99 gm/L; WBC 211 x 109/L, 1%

neutrophils, 91% blasts; platelets 52 x 109/L
UEC, uric acid: normal; LFT: normal
CXR: normal
Bone marrow aspirate: morphology ALL
Immunophenotyping: CD 10 positive
Cytogenetics: 46 XX
Lumbar puncture: no blasts in the CSF
Bone Marrow Aspirate at Diagnosis
 Differential diagnoses

Acute Lymphoblastic Leukaemia:

T-cell or B-precursor
Acute Myeloid Leukaemia
Severe Aplastic Anaemia
no because she has hepatosplenomegaly & high WBC
Idiopathic Thrombocytopenic Purpura
in ITP rest of blood count should be normal
 Diagnosis

• Acute Lymphoblastic Leukaemia

• B-precursor
 Treatment
monitoring for tumour lysis syndrome
chemotherapy:
• induction of remission
• CNS intensification phase (intrathecal methotrexate +
may include cranial radiotherapy)
• maintenance therapy
Bone Marrow Aspirate in Remission
 Points for discussion

♦ 1. Clinical presentation of leukaemia

♦ 2. Diagnosis of leukaemia
♦ 3. Prognostic risk factors in ALL
♦ 4. Philadelphia chromosome t(9,22)
 Clinical Presentations of Leukaemia
♦ Petechiae, purpura, bruising & bleeding
♦ Pallor, anaemia; lethargy
♦ Infections: ENT; pneumonia; skin
♦ Bone pain; arthritis; pathological fracture
♦ Hepatosplenomegaly; lymphadenopathy
♦ Skin lumps; swollen gums
♦ Headache, nausea, vomiting
 Diagnosis of leukaemia
♦ Clinical picture
♦ Full Blood Count & film
♦ Bone marrow aspirate
– morphology
– Immunophenotyping: to distinguish
♦AML from ALL
♦T-cell vs B-precursor ALL
– cytogenetics
♦ Lumbar Puncture & Cerebrospinal fluid (CSF)
– cell count + cytospin
 Prognostic risk factors in ALL

white cell count

age
Cytogenetics/FISH
achieving remission
ploidy/DNA index
minimal residual disease
immunophenotyping
sex
 Prognosis in Childhood ALL

♦Overall: 85% cure rate (Complete remission

duration of 5 years)
♦Low risk: 90%
♦Medium risk: 80%
♦High risk: 65%
 Philadelphia chromosome t(9,22)
♦Occurs in CML & de novo ALL
♦results in fusion protein bcr-abl
– identified by cytogenetics, FISH. PCR studies
♦confers a poorer prognosis
♦Treatment:
– Imatinib (tki inhibitor) for CML
– Imatinib + chemotherapy for ALL
♦± BMT in first remission
CASE # 2
 History

A 16 year old boy presented with a 2 week

history of increasing breathlessness and dry
cough. He had lost 2 kg in weight in approx 1
month.
 Examination
afebrile, HR 120/min, RR 32/min
enlarged, non tender, bilateral cervical lymph
nodes, 1-4 cm in diameter.
distended veins over his neck and face and
eyelids were oedematous.
trachea was deviated to the right.
left hemithorax dull to percussion and air entry
was markedly reduced.
hepatosplenomegaly, 4 cm & 4 cm below the
costal margins respectively.
CXR at Diagnosis
SVC Obstruction
 Investigations
FBC: HB 140 gm/l, WBC 10 x 109 /L platelets 430 x
109 /L
Blood film: normal
CXR: large anterior mediastinal mass, left pleural
effusion causing deviation of the trachea.
 Further investigations
Tap of fluid from the pleural space
Cervical node biopsy: T-cell lymphoma
Bone marrow aspirate: negative
Lumbar puncture: negative
CT scan: enlarged liver and spleen
PET scan: positive
UEC, LFT, uric acid, LDH
 Differential diagnoses

T-cell non-Hodgkin’s lymphoma/leukaemia

Hodgkin’s lymphoma

Diffuse Large B-Bell Lymphoma of the mediastinum

Testing pleural fluid: T-cell lymphoblasts
 Diagnosis

♦T-cell lymphoma Stage III

 Treatment

At diagnosis:
hydration & monitoring for tumour lysis
monitoring of airway status & SVC obstruction
Chemotherapy to induce remission
includes prednisolone → rapid ↓ in mass size
Consolidation, intensification and maintenance
chemotherapy: total duration 2 years
CXR at end of remission-induction
 Prognosis
• Stage III T-cell lymphoma: 90%
• Stage IV T-cell lymphoma/leukaemia: 85%
 Points for discussion:
♦1. Reasons why this is an emergency
♦2. Tumour lysis syndrome:
♦risk factors
♦prevention
♦management
♦3. Superior vena cava syndrome
 1. Reasons why this is an emergency
♦Airway obstruction, respiratory compromise
♦SVC syndrome
♦May have bone marrow involvement ie
leukaemia
♦May develop tumour lysis syndrome
– spontaneous, or
– after starting chemotherapy
 2.Tumour lysis syndrome:
Patients at risk
♦High count acute leukaemias: ALL/AML
♦wbc > 50 x 109/L
♦Burkitt’s Non-Hodgkin’s Lymphoma/B-cell
leukaemia
♦T-cell Non-Hodgkins Lymphoma with large
mediastinal masses
 2.Tumour lysis syndrome: Features
♦Hyperuricaemia →
♦Acute renal failure (urate nephropathy)
♦Hyperkalaemia → arrhythmia/cardiac arrest
♦Hyperphosphataemia
♦Hypocalcaemia → tetany, seizures
♦Hypertension
♦Fluid overload, pulmonary oedema
 2.Tumour lysis syndrome: Prevention

Uricozyme prevents urate nephropathy

Allopurinol (xanthine oxidase inhibitor)
Hydration 3 L/m2/day
No K+ in IV
Monitoring
K+, urate, PO4=, Ca++, urea, creatinine
urine output, BP
 2.Tumour lysis syndrome: Treatment
♦Haemodialysis
♦Haemofiltration
♦Antihypertensives
♦Ca++ if tetany
 3.Superior Vena Cava Syndrome: Features

♦distended neck & upper thoracic veins

♦hoarse voice
♦dyspnoea, stridor, wheeze
♦dysphagia
♦oedema, plethora of the face
♦conjunctival oedema
♦headache
♦visual disturbance & altered consciousness
 3.Superior Vena Caval Syndrome:
Investigation

♦Examine for:
– lymph nodes
– tracheal deviation
– chest signs of collapse, effusion
– respiratory distress 20 tracheal compression
♦CXR: mediastinal mass
3.Superior Vena Caval Syndrome: Differential
Diagnosis

♦T-cell Non-Hodgkin’s lymphoma

♦Hodgkin’s lymphoma
♦SVC thrombosis:
♦spontaneous or catheter related
3.Superior Vena Caval Syndrome: Treatment

♦airway support
♦urgent treatment of underlying malignancy
♦if thrombosis:
– anticoagulation (heparin)
– removal of catheter
CASE # 3
 History
A five year old girl presented with an 8 week
history of tiredness, lethargy, weight loss and
abdominal pain. In the last 2 weeks she had
developed abdominal distension and
breathlessness. Two days before presentation she
developed a high fever.
 Examination
In casualty she was febrile 390 , HR 140/min, RR
40/min. She was cachectic and looked very
unwell. Chest examination showed course
crepitations in the right lung field. Abdominal
examination revealed a large , slighlty tender, hard
mass in the right hemi abdomen, measuring 15
cm in length.
 Investigations
FBC: Hb 70 gm/l, WBC 12 x 109 /L, platelets 480 x
109 /L, MCV 70 fl
UEC & LFT: normal
CXR & CT scan of chest: multiple cannon ball
metastases both lung fields; right upper lobe
collapse
AXR: large right sided abdominal mass, no
calcification
CT scan abdomen: right sided kidney tumour with
areas of necrosis & haemorrhage
CXR At Diagnosis

Cannon
ball
metastases
CT Scan Chest At Diagnosis
Cannon ball
metastases
CT Scan Abdomen At Diagnosis
CT Scan Abdomen At Diagnosis
 Diagnosis

♦Wilm’s Tumour, Stage IV

 Treatment
operation: removal of right kidney tumour
chemotherapy
abdominal radiotherapy to tumour bed
pulmonary radiotherapy
 Prognosis for Wilm’s Tumour

♦Stage 1 95%
♦Stage 2 90%
♦Stage 3 85%
♦Stage 4 80%

♦Favourable vs unfavourable histology

 Points for Discussion

♦ 1.Differential diagnosis of large abdominal

masses
♦ 2.Differential diagnosis of tumours that
metastasize to the lungs
♦ 3.Differential diagnosis of tumours that
calcify on plain abdominal X-ray
♦ 4.Effects of an abdominal mass
 Differential diagnosis of large abdominal
masses

• Malignant
Wilm’s
Neuroblastoma
Hepatoblastoma
Rhabdomyosarcoma
Non Hodgkin’s lymphoma
Germ cell tumours
 Differential diagnosis of large abdominal
masses

• Non-malignant
polycystic kidneys
hepatosplenomegaly
lymphadenopathy
benign teratoma

constipation
 Differential diagnosis of tumours that
metastasize to the lungs
Wilm’s
Hepatoblastoma
Rhabdomyosarcoma
Osteogenic sarcoma
Ewing’s sarcoma
Germ cell tumours
Differential diagnosis of tumours that calcify on
plain abdominal X-ray

Neuroblastoma
Hepatoblastoma
Germ cell tumours/Teratoma
Effects of an Abdominal Mass

♦ bowel obstruction
♦ urinary tract obstruction
♦ haemorrhage
♦ pain
♦ respiratory compromise
♦ hypertension
♦Wilm’s tumour
♦neuroblastoma
CASE HISTORY 4
 History & Examination
A 5 year old boy presented with a 3 week history
of pallor, irritability, periorbital bruising, bone pain
and limp.
He was pale and had bilateral periorbital bruising
and swelling. A mass was palpable around his jaw.
He walked with a limp in his right leg. BP 150/90.
A large right sided abdominal mass was palpated.
 Investigations
FBC Hb 6 gm/l; MCV 60 fl; WBC 10 x 109/L; plats
285 x 109/L
UEC & LFTs normal
ferritin, LDH: both raised
Urinary catecholamines: HVA, VMA & dopamine
markedly raised
Bone marrow aspirate/trephine: neuroblastoma
 Investigations
CXR normal
Plain abdo X-ray large mass with small areas of
calcification
Abdo U/S & CT scan: large right adrenal mass, no
intraspinal extension
MIBG scan increased uptake in skull, spine, right
hip & abdomen
Bone scan: increased uptake in skull, spine, right
hip
Biopsy of abdominal mass
CT Scan Orbits

Periorbital
masses
CT Scan Mandible

Jaw mass
 CT Scan Abdomen

Adrenal mass
MIBG scan
Bone Scan
 Diagnosis

♦Stage IV Neuroblastoma

♦ Presumably arises from neural crest derived cells

committed to sympathoadrenal development: spinal
sympathetic ganglia & adrenal chromaffin cells
 Treatment
antihypertensives
chemotherapy
resection of abdominal primary
tumour bed radiotherapy
autologous bone marrow transplantation
monoclonal antibody therapy
retinoic acid
 Points For Discussion
1. Prognostic risk factors in neuroblastoma
2. Causes of a limp
3. Differential diagnosis of periorbital bruising
4. Differential diagnosis of bone marrow
metastases
Prognostic risk factors in neuroblastoma

stage
age
N-myc amplification
 Prognosis in Neuroblastoma
♦Stage 1: 95%
♦Stage 2: 90%
♦Stage 3: 75%
♦Stage 4: 40%
 Causes of a limp 1
Trauma
transient synovitis
septic arthritis
osteomyelitis
Perthe’s disease
congenital dislocation of the hip
Haemophilia
 Causes of a limp 2

neuropathic causes eg polio

myopathic causes
bone secondaries/pathological fracture
leukaemia
neuroblastoma
spinal cord extension of tumour
neuroblastoma
Differential diagnosis of periorbital bruising

neuroblastoma
acute myeloid leukaemia
Langerhans Cell Histiocytosis
child abuse
trauma & underlying coagulopathy
 Differential diagnosis of bone marrow
metastases
neuroblastoma
Hodgkin’s/non-Hodgkin’s lymphoma
rhabdomyosarcoma
Ewing’s sarcoma/PNET
 Case #5

Medulloblastoma
 History
♦10 year old boy with 2 month history of
increasingly severe headaches
– associated with nausea
– worse in the mornings
♦double vision
♦clumsiness
♦deteriorating school performance
 On examination
♦Eye examination: blurred disc margins
(papilloedema)
♦Nystagmus on gaze to R > gaze to L
♦Left lateral gaze palsy = left 6th cranial nerve
palsy
♦Unable to heel-toe walk without falling over
 Fundi
Normal Papilloedema
 Investigations
♦CT scan
♦MRI brain scan
♦CSF cytology: negative
♦Bone scan: negative
Normal Sagittal MRI brain
Medulloblastoma

Dilated lateral
ventricle

Tumour
Medulloblastoma

Tunour

Cerebellum
 Coronal MRI Brain
Normal Dilated Ventricles

Normal
lateral Dilated lateral ventricle
ventrical
 Diagnosis

♦Medulloblastoma Standard Risk

 Treatment
♦Operation to remove tumour
♦Chemotherapy
♦Craniospinal Radiotherapy
MRI Post Surgery
 Prognosis
♦Standard risk: 90% at 2 years

♦High risk: 80% at 2 years