Three Part Question
In [a child with hemihyperplasia limited to the left leg] what [is the risk of cancer] and what [is the best follow up plan for early detection of these cancers]?
You have a 4 year old girl with hemihyperplasia limited to the left leg in your clinic come for review. This child was originally referred to your clinic a few weeks back after her mother noticed leg length discrepancy when she bought a new pair of trousers. You notice asymmetry between the two legs, with the left leg larger and longer than the right. An orthopaedic surgeon was consulted, who ruled out a hip problem and suggested the possibility of hemihyperplasia of the left leg. There is an increased risk of cancer, especially of Wilm's tumour in these children, and hence a paediatric surgeon was consulted. Ultrasound scan of abdomen ruled out an intra-abdominal tumour. Her parents were trained to feel their daughter's abdomen weekly. You are unsure about the actual incidence of the risk of tumour (cancer) development and the best scheme for surveillance. Hence you decide to look at the evidence base for these answers so that the family can be counselled appropriately.
Medline database (1996 to date and 1951 to date)
Medline: Hemi hypertrophy or hemi hyperplasia, tumours or neoplasm, follow up ultrasound scans
Pubmed: Four searches: hemi hypertrophy, hemi hyperplasia, tumours in hemihyperplasia, hemihypertrophy and review or follow up. Limits: birth to 18 years, human.
Medline:11 related articles, one was relevant which was a case series analysis of screening for Wilm's tumour in children with Beckwith-Wiedemann syndrome (BWS)/idiopathic hemihypertrophy (HH) (Choyke)
Pubmed: Two relevant studies identified. One was excluded as there were only 12 patients in the series. The other one was a prospective multicentre study of incidence of neoplasia and review in isolated hemihyperplasia (Hoyme)
|Author, date and country
||Study type (level of evidence)
|Hoyme et al|
|168 children||Prospective multicentre study of incidence of neoplasia and follow up over 10 year period||Tumour development on follow up abdominal ultrasound||Tumour incidence 5.9% (95% CI 2.3%–8.2%) compared to 0.17% in general population; follow up protocol varied among respondents; mostly abdominal palpation 6–12 monthly and USS abdomen 6 monthly||Prospective multicentre study, over 10 year period. Relatively large number of patients (with a rare condition). No control group Varied follow up protocols, varied duration of follow ups; tumour surveillance protocol suggested; abdominal USS 3 monthly till 6 years of age and 6 monthly afterwards until puberty|
|Choyke et al|
|74 children||Case series comparing late stage Wilm's tumour in patients with BWS/HH who are screened with ultrasound scans (4 monthly) against those who are not screened||Follow up sonograms; tumour development||None of the screened (n = 14) had late stage (stage III or IV) Wilm's tumour whereas 25 out of the 59 unscreened had late stage disease; benefit from sonograms at intervals of 4 months or less||Case series Both BWS and HH included in the study and hence difficult to correlate risk of tumour development and screening to isolated HH alone Small sample size, especially the screened group|
Hemihypertrophy is also known as hemihyperplasia. The terminology hemihyperplasia seems more accurate as the pathological process involves an abnormal proliferation rather than an increase in the size of these cells (Cohen). Asymmetric overgrowth of unknown aetiology may involve the whole of one side of the body or it may be limited in extent to one limb or a side of the face. There may be associated asymmetric hypertrophy of internal organs. The reported incidence of hemihyperplasia is 1 in 86 000 live births (Tomkooya). Hemihyperplasia may be an isolated finding or it may be associated with other syndromes such as Beckwith-Wiedmann, Klippel-Trenaunay-Weber, or McCune-Albright syndromes.
Predisposition to neoplasia (cancer) in isolated hemihyperplasia is well known, but the exact risk is not well documented. Green and colleagues in 1993 reported that only in one third of cases of children with Wilm's tumour and hemihyperplasia, was the hyperplasia diagnosed more than a month prior to the discovery of the tumour.
The case series by Choyke and colleagues concluded that children with BWS/HH may benefit from screening abdominal ultrasound scans at intervals of four months or less, but false positive screening results may lead on to unnecessary surgery and suggested a larger prospective study to determine if the benefits of screening outweigh the risk. It was difficult to draw a conclusion from this case series with regard to isolated HH alone as this case series involved a mixture of BWS and HH cases. Also the sample size, especially of the screened group, was too small.
The only multicentre prospective study looking at the risk of tumour development and follow up of children with hemihyperplasia was the one carried out by Hoyme and colleagues. In this study, of the total 168 children with isolated hemihyperplasia, 10 tumours developed in nine children (one child developed two tumours). Of these, six were Wilm's tumour, two were adrenal cell carcinoma, and there was one each of hepatoblastoma and leomyosarcoma of the small bowel. Follow up protocols varied in different centres. Two children, an infant and a 5 year old, developed Wilm's tumours at nine month and five months respectively after their previous abdominal ultrasound scan. This led the investigators to conclude that six months may be too long a screening interval, especially in early childhood.
Hence from the available evidence, the risk of tumour development in isolated hemihyperplasia is about 1 in 20 or approximately 5%. The best follow up plan on the basis of available evidence is that till the age of 6 years these children should have abdominal ultrasound scans at three monthly intervals. There is currently insufficient evidence to screen children above 6 years of age.
Clinical Bottom Line
Risk of tumour development in children with isolated hemihyperplasia is 5.9%. (95% CI 2.3%–8.2%); approximately 5% or 1 in 20. (grade A)
The best follow up plan for these children is to do abdominal ultrasound scans at three monthly intervals until the age of 6 years. (grade C)
Further clinical trials are needed to find the benefit of screening children older than 6 years of age as there is currently insufficient evidence to justify screening these children.
- Hoyme HE, Seaver LH, Jones KL. et al. Isolated hemihyperplasia (hemihypertrophy): report of prospective multicenter study of the incidence of neoplasia and review. Am J Med Genet 1998;79:274–8.
- Choyke PL, Seigel MJ, Craft AW. et al. Screening for Wilm's tumour in children with Beckwith-Wiedemann syndrome or idiopathic hemihypertrophy. Med Paedatr Oncol 1999;32:196–200.
- Tomkooya Y. Congenital hemihypertrophy and medullary sponge kidney. Br J Radiol 1988;61:851–3.
- Green DM, Breslow NE. Beckwith JB. et al. Screening of children with hemi hypertrophy, aniridia and Wiedemann-Beckwith syndrome in with Wilm's tumour. Med Paediatr Oncol 1993;21:188–92.
- Cohen MM Jr. A comprehensive and critical assessment of overgrowth and over growth syndromes. Adv Hum Genct 1989;18:181–303.