Chapter Contents
Introduction 953
Incidence and survival 954
Neuroblastoma 954
Clinical features 954
Staging 954
Stage 4s disease 954
Diagnosis 958
Treatment 958
Prognosis 959
Screening 959
Teratoma and other germ cell tumours 959
Acute leukaemia 960
Transient myeloproliferative disorder and Down syndrome 960
Renal tumours 961
Brain tumours 961
Retinoblastoma 962
Sarcomas 963
Liver tumours 963
Histiocytosis 964
Other rare tumours 964
Introduction
Neonatal cancer is rare, a surprising fact in view of the rapid cell division and growth occurring throughout fetal life. Our understanding of the factors affecting cell growth and the genetic events responsible for the development or progression of malignant disease continues to increase at a rapid rate. Genes controlling cell growth are termed proto-oncogenes. Research efforts have led to the identification of two major classes of genes associated with malignancy. Oncogenes are mutated proto-oncogenes and give rise to excessive cell growth and proliferation, whilst tumour-suppressor genes act in normal cells to suppress proliferation, but, if inactivated, remove the normal constraint to growth, and target cells are allowed to proliferate in an uncontrolled way ( ).
Knudson’s ‘two-hit’ theory of carcinogenesis has been verified by this knowledge of the genetic factors that control cell growth ( ). The ‘hits’ could be a wide variety of agents – viral, chemical or radiation – and cause mutation of a proto-oncogene or inactivation or loss of a tumour-suppressor gene. This first ‘hit’ would allow all cells in the body, including the germ cells, to carry the defect, which could then be passed on to the next generation. The second ‘hit’ would be in the somatic cells of a target organ. The proto-oncogene would become an oncogene, or the loss of a homologous tumour-suppressor gene would allow uncontrolled cellular growth. The time during which the second ‘hit’ could occur is probably confined to the period when the cells of the target organ are undergoing mitotic activity, but ceases when they are fully mature. For example, retinoblasts differentiate to become photoreceptor cells by the age of 3 years, and this may explain why retinoblastoma is unusual in older children or adults.
Oncogenes exert their effect on cells through a variety of mechanisms. These include control of cellular growth factors or their receptors, or by modifying the signals sent from growth receptors to the nucleus of the cell. This may result in an effect on DNA repair, apoptosis or the cells’ ability to metabolise toxins.
Neonatal malignancy presents many therapeutic challenges. Chemotherapy is poorly tolerated in young infants, and myelosuppression and life-threatening complications of therapy are common ( ). This may be because of altered pharmacokinetics in the neonatal age group ( ). The long-term effects of chemotherapy, surgery and radiation in terms of growth, development and second tumours ( ) have been recognised for many years, and both short-term and long-term effects of treatment should be taken into account when planning therapy. Improvements in surgery, anaesthesia and supportive care, including avoidance of therapeutic complications such as tumour lysis syndrome with new agents like raspuricase, have all contributed to better survival ( ). Increasingly, cancer research is attempting to exploit the underlying genetic mutations for therapeutic purposes. This, in the future, may provide more specific tumour-targeted therapies, increasing cure rates with a reduction in toxicity.
The routine use of antenatal ultrasound, and the improved quality of the images, has led to an increase in the diagnosis of congenital tumours, particularly teratomas and neuroblastomas, and an increase in the understanding of their natural history ( ). It allows close monitoring of affected pregnancies and management planning with appropriate multidisciplinary team involvement ( ).
Incidence and survival
Neonatal malignancy is disproportionately represented within childhood, where the incidence of cancer is 11–15 per 100 000 population less than 15 years of age ( Table 36.1 ). Defining neonatal malignancy as malignant and central nervous system (CNS) tumours diagnosed in the first 6 weeks of life, the UK National Registry of Childhood Tumours (NRCT) incidence between 1981 and 2000, from 394 cancer registrations, was 2.74 per 100 000 live births, with 45.4% of these tumours presenting in the first week of life, 14.8% in the second and approximately 10% per week thereafter. This is similar to reports from other cancer registries ( Table 36.1B ). Suspected risk factors for the development of childhood cancer include certain congenital abnormalities ( ) ( Table 36.2 ), in utero exposure to certain drugs (e.g. diethylstilbestrol), vaginal adenocarcinoma and irradiation (all cancer types). There remains no convincing evidence that intramuscular vitamin K given at birth is associated with an increased risk of childhood leukaemia ( ). However, childhood leukaemia might be initiated in utero and more than one study has suggested that high birthweight is associated with this risk ( ).
| Table 36.1A | |||||||
|---|---|---|---|---|---|---|---|
| Single-centre experience | |||||||
| INSTITUTION | TORONTO, Canada ( ) | PHILADELPHIA, USA ( ) | LOS ANGELES, USA ( ) | TEXAS, USA ( ) | GLASGOW, UK ( ) | DURHAM, USA ( ) | MEMPHIS, USA ( ) |
| Years | 1922–1982 | 1952–1978 | 1958–1982 | 1941–1981 | 1955–1986 | 1930–1998 | 1962–1988 |
| Percentage of all paediatric cancers | 2% | 2.6% | 2% | 3.2% | |||
| Male : female ratio | 1.7 : 1 | 1 : 1.1 | 1 : 1.4 | 1 : 2.3 | 1 : 1 | ||
| Survival | 42% | 2-year 45% | 37% | 78% (solid tumours only) | Approx. 50% † (solid only) ‡ | Approx. 60% § | 68% |
| Tumour numbers | 102 | 22 | 49 (61*) | 45 | 16 (35) | 15 (8) | 34 |
| Neuroblastoma | 48 | 11 | 14 | 6 | 7 | 5 | 19 |
| Retinoblastoma | 17 | 2 | 3 | 3 | 4 | 3 | |
| Sarcoma | 12 | 3 | 8 (16) | 15 | 4 (4) | 1 | |
| Central nervous system | 9 | 5 | 5 | 4 | |||
| Leukaemia | 8 | 3 | 11 | 13 | 6 | ||
| Wilms’ tumour | 4 | 1 | 3 (3 mesoblastic nephroma) | 1 | (9 mesoblastic nephroma) | 2 | |
| Liver tumours | 1 hepatoblastoma | 1 hepatoblastoma (3 hamartoma) | (2 haemangioma, 1 hamartoma) | ||||
| MGCTs (teratoma) | 1 | 3 | 1 (39 other teratomas) | 1 (18 SCT, 1 orbital teratoma) | 1 retroperitoneal (6 other teratomas) | 1 SCT 1 oropharyngeal | |
| Others | 1 schwannoma, 1 YST testis | 1 parotid carcinoma | 2 carcinoma, 2 LCH | 2 melanoma | 1 squamous cell carcinoma | (1 glossal glial choristoma, 1 haemangioma with Kasabach–Merritt) | 2 melanoma |
| MGCT, malignant germ cell tumour; YST, yolk sac tumour; LCH, Langerhans’ cell histiocytosis; SCT, sacrococcygeal teratoma. ( ) Number and type of benign neoplasms also reported. * Haemangiomas (five hepatic haemangiomas reported) and lymphangiomas excluded. † One patient unaccounted for (malignant SCT). ‡ Central nervous system tumours and leukaemias excluded. § One patient unaccounted for (rhabdomyosarcoma) | |||||||
| Table 36.1B | ||||
|---|---|---|---|---|
| Cancer registry experience | ||||
| CANCER REGISTRY | DENMARK ( ) | WEST MIDLANDS, UK ( ) | THIRD NATIONAL CANCER SURVEY, USA ( ) | NATIONAL Registry of Childhood Tumours, UK* |
| Years | 1943–1985 | 1960–1989 | 1969–1971 | 1981–2000 |
| Incidence per 100 000 | ||||
| Live births | 2.38 (up to 28 days old) | 7.2 (up to 3 months old) | 3.65 (up to 28 days old) | 2.74 (up to 6 weeks old) |
| Male : female ratio | 1 : 1.4 | 1 : 1.1 | Not reported | 1 : 1 |
| Survival | 5-year 25% | 1-year 55% † | Not reported | 1-year 57% |
| 5-year 47% † | 5-year 51% | |||
| Tumour numbers | 76 | 98 (72) | 39 | 394 (213 ‡ ) |
| Neuroblastoma | 20 | 31 | 21 | 113 |
| Retinoblastoma | 2 | 14 | 37 | |
| Sarcoma | 14 | 6 (11) | 4 | 38 |
| Central nervous system | 8 | 14 | 1 | 61 |
| Leukaemia | 12 | 21 | 5 | 74 |
| Wilms’ tumour | 4 | 1 (7 mesoblastic nephroma) | 5 including mesoblastic nephromas | 7 |
| Liver tumours | 2 hepatoblastoma, 1 rhabdoid tumour (5 unspecified) | 9 hepatoblastoma | ||
| MGCTs (teratoma) | 4 (2 other teratomas), all retroperitoneal | (49 mature teratoma – 4 malignant recurrences) | 40 MGCT, of which 2 gonadal | |
| Others | 8 unspecified | 3 HLH, 3 LCH, 1 malignant thymoma, 1 malignant stromal cell tumour of testes | 1 carcinoma, 1 lymphoma, 1 unspecified | 5 extrarenal rhabdoid tumours, 4 peripheral PNET, 3 melanoma, 1 malignant histiocytosis, 1 pancreatoblastoma,1 unspecified |
| MGCT, malignant germ cell tumour; LCH, Langerhans’ cell histiocytosis; HLH, haemophagocytic lymphohistiocytosis; PNET, primitive neuroectodermal tumour. ( ) Number and type of benign neoplasms also reported. * With thanks to Mr C Stiller, Childhood Cancer Research Group, University of Oxford, for providing data from the National Registry of Childhood Tumours. † Includes benign tumours. ‡ Further 213 non-malignant tumours reported (not population-based): 2 myelodysplasia/myeloproliferative disease, 26 mesoblastic nephroma, 12 LCH, 8 HLH, 10 fibromatosis, 9 haemangiopericytoma, 14 other non-malignant soft-tissue sarcoma, 5 neurofibromatosis, 120 (benign) teratomas, 7 unspecified. | ||||
| INHERITED SYNDROME | CHILDHOOD CANCER |
|---|---|
| Hamartoses | |
| Tuberous sclerosis | Giant cell astrocytoma |
| Neurofibromatosis | Gliomas |
| Basal cell naevus (Gorlin) syndrome | Medulloblastoma, basal cell carcinoma |
| Turcot syndrome | Medulloblastoma |
| Multiple mucosal neuroma syndrome | Medullary thyroid carcinoma, phaeochromocytoma |
| Neurocutaneous melanosis sequence | Melanoma |
| Aicardia syndrome | Germ cell tumour, hepatoblastoma |
| Metabolic disorders | |
| Glycogenosis type I, hereditary tyrosinaemia and α 1 -antitrypsin deficiency | Hepatocellular carcinoma |
| Chromosome breakage and repair defects | |
| Bloom syndrome | Leukaemia, Wilms’ tumour and gastrointestinal tumours |
| Ataxia telangiectasia | Leukaemia, lymphoma |
| Fanconi’s anaemia | Leukaemia, hepatoma, hepatoblastoma |
| Xeroderma pigmentosum | Skin cancers, melanoma |
| Werner syndrome | Sarcomas, meningioma |
| Immune deficiency disorders | |
| Wiscott–Aldrich syndrome | Leukaemia, lymphoma (often in the central nervous system) |
| X-linked lymphoproliferative disease (Duncan disease) | B-cell lymphoma |
| Severe combined immunodeficiency | Leukaemia, lymphoma |
| Bruton’s agammaglobulinaemia | Leukaemia, lymphoma |
| Xeroderma pigmentosa | Non-melanomatous skin carcinomas |
| Chromosomal anomaly | |
| Down syndrome (trisomy 21) | Acute leukaemias |
| Turner syndrome (45XO) | Neurogenic tumours, germ cell tumours |
| 13q syndrome | Retinoblastoma |
| 11p syndrome | Wilms’ tumour (nephroblastoma) |
| Monosomy 7 | Preleukaemia and non-lymphoblastic leukaemia |
| XY gonadal dysgenesis, aniridia–Wilms’ tumour association | Gonadoblastoma |
| Edwards syndrome (trisomy 18) | Wilms’ tumour (nephroblastoma) |
| Klinefelter syndrome (XXY) | Leukaemia, teratoma, breast carcinoma |
| Congenital anomaly | |
| Hemihypertrophy and Beckwith–Wiedemann syndrome | Wilms’ tumour, adrenal cortical carcinoma and hepatoblastoma |
| Sporadic aniridia, Denys–Drash syndrome, Fraser syndrome and Perlman syndrome, Sotos syndrome | Wilms’ tumour (nephroblastoma) |
| Simpson–Golabi–Behmel syndrome | Germ cell tumour, Wilms’ tumour |
| Poland anomaly | Leukaemia |
| Hirschsprung disease | Neuroblastoma |
| Pyloric stenosis | Germ cell tumour |
| Other | |
| Monozygotic twins | Sacrococcygeal teratoma |
| Very low birthweight (<1 kg) | Hepatoblastoma |
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
