Pediatric pancreatic tumors: The orphan looking for a home

I n the UK National Registry of Childhood Tumors, during the period 1971–2000, 41 cases of pancreatic tumors were reported. Of this total, 25 were malignant and 16 were nonmalignant. Based on these data the total annual incidence is 0.1 per million, but this is likely to be an underestimate as some nonmalignant tumors were probably not registered [1]. Comparable data are available from the US from the North American population-Based Surveillance, Epidemiology and End results (SEER) database [2]. Between the period 1972 and 2006, 69 patients were registered under 20 years of age with a diagnosis of tumor arising from the pancreas. A variety of different histiotypes were registered including 12 cases of pancreatoblastoma, 32 of carcinoma and 6 endocrine tumors. According to the SEER data, the estimated age-adjusted annual incidence of pancreatic tumors in 0–19 year olds is 0.191 per million population [2]. The slightly higher incidence for the SEER data reflects the upper age limit of the SEER database being 19 years versus 15 years for the UK Registry, explaining also the higher proportion of carcinomas. Pancreatic tumors are therefore rare in children, but what does ‘‘rare’’ mean as an ever-increasing blanket term in pediatric oncology. Cancer is rare in childhood compared to the older age groups, affecting approximately 1 in 500 children during the first 15 years of life. However, some tumors are so rare that even pediatric oncologists may only encounter them once in their lifetime practice. Any definition of ‘rare’ is bound to be arbitrary; perhaps a good working definition of rare childhood cancers are those categories in the International Classification of Childhood Cancer, 3rd edition (ICCC-3) that have an age standardise annual incidence (ASR) of <1 per million children in Great Britain, excluding tumors of unspecified morphology [3]. Pancreatoblastoma has an ASR of 0.04 compared to other ‘‘rare’’ tumors one encounters in pediatric oncology practice such as thyroid carcinoma with an ASR of 0.6 or for example adrenocortical carcinoma with an ASR of 0.24 [3]. In this issue of Pediatric Blood & Cancer Dall’Igna et al. report from the TREP project (Tumori Rari in Eta Pediatrica [Rare Tumours in Paediatric Age]) their initial data on 21 pancreatic tumors, in subjects <18 years old who were registered between January and July 2009. In the same time period, 488 patients under the age of 18 years with rare tumors were prospectively registered in the TREP database by 36 Italian pediatric oncology and pediatric surgery units. Over half the patients had a solid pseudo-papillary tumors (n1⁄4 12), the commonest malignant tumor was pancreatoblastoma (n1⁄4 4), other tumor types included two pancreatic carcinomas and three neoplasms of the endocrine pancreas. This study highlights several important points regarding pancreatic tumors and perhaps as a surrogate model for rare tumors highlights also issues for this whole group. First it demonstrates that despite the dedication and effort of the TREP Group, in nearly 9 years the numbers of individual tumor types remain too low to draw any definitive conclusions to what might be the best treatment for pancreatic tumors. Specifically, they demonstrate the importance of surgery for pancreatic tumors. However, this is influenced by over half their pancreatic tumors being solid pseudopapillary tumors (Frantz tumors). The outlook of this slow growing tumor is closely related to the extent of surgical resection with the majority of children who achieve complete resection being long term survivors [4]. The second point Dell’Igna et al. demonstrate is despite the international reputation of the TREP project and the effort and work in providing guidance for management of some of the more challenging rare tumors, pancreatoblastoma for example in this publication, none of the patients with pancreatoblastoma in this series particularly followed those guidelines with the PLADO regimen of chemotherapy. They suggest that while the Italian centers have been rather successful in registering patients, they had been less so in complying with treatment guidance. The numbers so far are too small to draw any definitive conclusions from this, but possibly suggest that a more strict and international protocol for certain rare tumors may be more closely adhered to and may lead to results from which to develop research questions and hypotheses. So far the TREP group have registered significant numbers of rare tumors and have started to publish some of their findings [5]. The next step is for national childhood cancer registries to combine their data to possibly strengthen the epidemiology of individual rare tumors and, where possible, assess outcome from similar treatment pathways. This has started to happen in Europe with the formation of an expert group with national representation from Italy, France, Poland, Germany and the UK. Our focus, however, should be on unique rare tumors of childhood, and in particular, those which have poor outcomes such as some types of pleuropulmonary blastoma or adrenocortical carcinoma, as well as those rare tumors which are not currently included on international protocols compared to rare tumors for which trials exist, such as hepatocellular carcinoma.