PAEDIATRIC SOLID TUMOURS Alan Davidson Haematology - Oncology Red Cross Children’s Hospital

CANCER IN CHILDHOOD US figures show total of 146 cancers per million children aged 0-14 per year ALL BRAIN TUMOURS NEUROBLASTOMA NHL WILMS TUMOUR AML HODGKIN’S DISEASE RHABDOMYOSARCOMA RETINOBLASTOMA OSTEOSARCOMA EWING’S TUMOUR OTHERS

CHILDHOOD CANCER AT RCCH Approximately 130 new cases per year Many present with advanced disease Many have presented to the health service several times over the preceding weeks or months ! These delays make treatment more difficult … and adversely effects prognosis.

SPECTRUM AT RCCH Numbers represent actual number of tumours for 2003 / 2004 / 2005 ALL BRAIN TUMOURS NHL AML WILMS TUMOUR NEUROBLASTOMA RHABDOMYOSARCOMA GERM CELL TUMOUR HODGKIN’S DISEASE HEPATOBLASTOMA BONE TUMOURS RETINOBLASTOMA OTHER

ONCOLOGY FOR THE PAEDIATRICAN: What’s the central message ? EARLY DIAGNOSIS MEANS … Improved prognosis Less treatment related morbidity NEEDS … Working knowledge of common tumours High index of suspicion

IMPROVED PROGNOSIS “WHAT A DIFFERENCE A DAY (OR TWO) MAKES” FAVOURABLE HISTOLOGY WILMS’ TUMOUR

BURKITT’S LYMPHOMA

EWING’S SARCOMA

LESS TOXICITY “SMALLER OMELETTE … LESS EGGS” WILMS’ TUMOUR TREATMENT… Surgery (primary or delayed) for all Chemotherapy Stage I or II: Vincristine + Dactinomycin Stage III or IV: Add DOXORUBICIN RENAL BED RADIOTHERAPY for local Stage III PULMONARY RADIOTHERAPY for lung metastases

CLASSIFYING CHILDHOOD MALIGNANCY LEUKAEMIAS ALL / AML / CML EMBRYONAL TUMOURS Neuroblastoma Nephroblastoma Rhabdomyosarcoma Hepatoblastoma Retinoblastoma PNET Germ Cell Tumour BRAIN TUMOURS Seperate textbook ! BONE TUMOURS Osteogenic Sarcoma Ewing’s Sarcoma RARE TUMOURS Thyroid Ca / Melanoma

NEPHROBLASTOMA Named for MAX WILMS Derived from the metanephros = hence the classic triphasic nature = epithelial / blastemal / stromal Associations Overgrowth = BWS / Hemihypertrophy Non-overgrowth = Aniridia / WAGR / Denys-Drash Age 0-5yrs (median 3yrs) Presents with Mass / Pain / Haematuria / Paraneoplasias Renal mass … L>R (not across midline) 10% bilateral Metastasis … lungs / liver / brain / (bone)

STAGING WILMS’ TUMOUR Stage I ... confined to kidney Stage II ... through capsule Stage III ... residual tumour Local spread Nodes IVC Thrombus Stage IV ... metastatic disease Stage V ... bilateral disease

DIAGNOSIS AND MANAGEMENT DIAGNOSIS and STAGING FBC / Urea & Creatinine / LDH Urine Ultrasound and CT Abdomen CXR and CT Chest Biopsy if deemed inoperable or protocol calls for pre-op chemo MANAGEMENT Two schools (NWTS and SIOP) Surgery + Chemo +/- XRT Same results ! In fact …

So good that we’re deintensifying treatment !! FAVOURABLE HISTOLOGY WILMS’ TUMOUR

NEUROBLASTOMA Derived from primitive neural crest cells of the sympathetic nervous system Hence they are found along the sympathetic chain 1/3 adrenal 1/3 abdominopelvic 1/3 thoracic or cervical Age 0-3yrs [median of 17m] [40% are infants] Prognosis inversely related to age … Younger kids usually have lower grade tumours (some of which regress spontaneously) in more favourable sites (cervicothoracic) and are much less likely to metastasize Staging: I: confined to organ II: extends outside organ (+/- nodes) NOT across midline III: across midline … involving contralateral nodes IV: Metastasis to Liver / Bone and BM / Skin IVS: I/II with remote disease in liver, skin, bone marrow (<10%)

CLINICAL PRESENTATION Abdominal mass > 50% … usually smooth and hard (crosses midline) Pelvic Mass Mediastinal or cervical mass Mass effect … proptosis / superior mediastinal syndrome / UAO / spinal cord compression Bone marrow … anaemia / thrombocytopaenia / bone pain with limp Metabolic (catecholamines and vasoactive intestinal peptides) … sweating / diarrhoea & vomiting / hypertension Bluish skin marks (typically blanch) Opsoclonus-myoclonus / Cerebellar ataxia

DIAGNOSIS AND MANAGEMENT DIAGNOSIS and STAGING FBC / Urea & Creatinine / LDH Urinary catecholamines (HVAs and VMAs) Calcified mass on plain AXR Imaging of abdomen, chest and possibly spine Bone Marrow / MIBG / Bone Scan Biopsy can be avoided if BM involved ! MANAGEMENT Surgery +/- Chemotherapy

RHABDOMYOSARCOMA Commonest soft tissue sarcoma of childhood Derived from primitive muscle Age 2-15yrs Prognosis varies with Histology: Embryonal > Alveolar Site: Orbit > Paratesticular > Vaginal > Bladder / Prostate > Retroperitoneal > Extremity > Parameningeal Stage Staging: I to IV based on complex system using TNM and Site IRS Grouping now generally followed … Group I completely excised Group II microscopic residua Group III macroscopic residua Group IV metastases

DIAGNOSIS AND MANAGEMENT DIAGNOSIS and STAGING FBC / Urea & Creatinine / LDH Local imaging … CT for abdomen / MRI for parameningeal tumours CXR and CT chest Bone Marrow MANAGEMENT Chemotherapy with Surgery +/- XRT

HEPATOBLASTOMA DIAGNOSIS MANAGEMENT Commonest paediatric liver tumour Age usually under 18 months Presents as hepatomegaly with elevated FP Metastasizes locally and to lungs DIAGNOSIS FBC / Renal and liver functions / FP CT abdmen and chest MANAGEMENT Chemotherapy Surgery

CLINICAL SCENARIOS IN SOLID PAEDIATRIC TUMOURS AN APPROACH FOR THE GENERAL PAEDIATRICIAN

1. PANCYTOPAENIA LEUKAEMIA LYMPHOMA or NEUROBLASTOMA ASK ABOUT … bone pain WATCH OUT FOR … swollen gums lymph nodes abdominal masses proptosis

1. PANCYTOPAENIA MUST exclude HIV infection … LEUKAEMIA (or LYMPHOMA) FBC: Hb Plt  WCC / … look for blasts Chemistry: LDH  (with a normal ALT) and Urate  CXR: mediastinal mass in T-cell lymphoma NEUROBLASTOMA Look for an Abdominal Mass ! FBC: typically anaemic with preserved platelets Chemistry: LDH  (with a normal ALT) and urinary HVAs Xrays: lytic bone lesions or calcified abdominal mass

1. PANCYTOPAENIA WHO SHOULD DO THE BONE MARROW ? Generally the receiving hospital but this matter should always be discussed! LEUKAEMIA (or ANY SUSPECTED MALIGNANCY) Aspirates and trephines  Flow cytometry  Cytogenetics  Ig gene rearrangements by PCR  FISH for translocations Complicated set of investigations: leave for referral centre ! OTHER INDICATIONS Disseminated TB / ITP / Storage disorders. Probably fine to do.

2. BONE PAIN NOT localised Wakes the child Limp or Reluctance to bear weight A toddler who stops walking Backache!!

2. BONE PAIN LEUKAEMIA or LYMPHOMA Again, malignancies involving the bone marrow… LEUKAEMIA or LYMPHOMA NEUROBLASTOMA Remember … if local pain and swelling (especially around the knee joint)… BONE TUMOURS eg. OSTEOGENIC SARCOMA

3. ABDOMINAL MASS from 6m to 6y … ABDOMINAL MASS is a tumour until proven otherwise ALWAYS CONSIDER SEDATING THE PATIENT IF YOU CAN”T PALPATE THE ABDOMEN !

3. ABDOMINAL MASS REFER WILMS TUMOUR HEPATOBLASTOMA NEUROBLASTOMA flank mass / typical imaging /  LDH HEPATOBLASTOMA hepatomegaly / typical imaging /  Feto-protein NEUROBLASTOMA adrenal mass / typical imaging /  LDH and HVAs ? signs of metastatic involvement BURKITT LYMPHOMA central abdominal mass / nodes on imaging /  LDH No need for BIOPSY !! REFER

(3. PELVIC MASS) REFER GERM CELL TUMOUR BURKITT LYMPHOMA  Feto-protein BURKITT LYMPHOMA  LDH and urate RHABDOMYOSARCOMA  LDH NEUROBLASTOMA No need for BIOPSY !! REFER

4. AN UNEXPLAINED MASS SITES Head and Neck Limbs Testis

5. UNEXPLAINED NEUROLOGY Headache > 2 weeks Early morning vomiting Ataxia / unsteady gait Cranial Nerve Palsy BRAIN TUMOURS (watch out for neurocutaneous syndromes) Posterior fossa … ataxia and cranial nerve palsies Supratentorial … headache and vomiting  hemiplegia RHABDOMYOSARCOMA (often occult in the sinuses) Lower cranial nerve palsies eg. VI, VII, IX, XII NEUROBLASTOMA (secondary to skull infiltration) Commonly VI nerve palsy

7. EYE CHANGES RETINOBLASTOMA White Reflex Recent Onset Squint Loss of Vision RETINOBLASTOMA Proptosis LEUKAEMIA especially Acute Myeloid Leukaemia NEUROBLASTOMA RHABDOMYOSARCOMA

7. EYE CHANGES Leukocoria REFER to an Ophthalmologist urgently for slit lamp examination

7. EYE CHANGES Proptosis CONSIDER Leukaemia / Neuroblastoma / Rhabdomyosarcoma … abnormal FBC means diagnosis might be made on BM examination … REFER OTHERWISE REFER to an Ophthalmologist for urgent biopsy

IN SUMMARY … REMEMBER THE WARNING SIGNS Pallor plus Bleeding Persistent Fever / Apathy / Weight Loss Bone Pain Adenopathy Unexplained Neurological Signs Unexplained Mass Eye Changes

THE BOTTOM LINE Be aware of the clinical spectrum of childhood cancer Don’t waste time with special investigations … Seek expert advice Refer cases early … and URGENTLY !