Position paper: Challenges and specific strategies for constitutional mismatch repair deficiency syndrome in low-resource settings.

Germline biallelic mutations in one of the mismatch repair genes, mutS homolog 2, mutS homolog 6, mutL homolog 1, or postmeiotic segregation increased 2, result in one of the most aggressive cancer syndromes in humans termed as constitutional mismatch repair deficiency (CMMRD). Individuals with CMMRD are affected with multiple tumors arising from multiple organs during childhood, and these individuals rarely reach adulthood without specific interventions. The most common tumors observed are central nervous system, hematological, and gastrointestinal malignancies. The incidence of CMMRD is expected to be high in low-resource settings due to a high rate of consanguinity in these regions, and it is thought to be underrecognized and consequently underdiagnosed. This position paper is therefore important to provide a summary of the current situation, and to highlight the necessity of increasing awareness, diagnostic criteria, and surveillance to improve survival for patients and family members.

Successful treatment of multifocal unresectable hepatoblastoma with chemotherapy only.

We report the case of a girl with multi-focal hepatoblastoma in whom chemotherapy alone has resulted in long term event-free survival and possibly cure, without any surgical procedure apart from biopsy for initial diagnosis. At presentation she had a large tumour arising from the left lobe of liver and two other separate masses were noted in the right lobe, but the lungs were free of metastases. Histology showed a foetal type of hepatoblastoma. The serum alpha-feto protein (AFP) level was 44,000 iu/litre. Chemotherapy was started using the triple drug regime recommended for "high risk" (of relapse) patients in the SIOPEL 2 hepatoblastoma protocol of the International Society of Paedaitric Oncology (SIOP). Within a few weeks her abdominal girth decreased, the child became much more comfortable. Drug-induced cardiotoxicity, ototoxicity and nephrotoxicity were not observed. After a total of 4 courses of chemotherapy (completed at the end of August 1998) a CT scan showed that all 3 tumours were smaller but that there were residual multifocal defects in the liver neither hepatic resection nor liver transplantation were considered safe or appropriate. 6.5 years after completion of chemotherapy and now aged 8.5 years the child is in normal health and at school with normal liver size, serum AFP levels and chest imaging.