malignant tumors of the exocrine pancreas occur mainly in adults in their sixth or seventh decade of life .
they commonly present with late - stage disease , and have poor prognosis , even in cases with primary resectable disease .
less frequent histologies include intraductal papillary mucinous neoplasms with transition to an invasive carcinoma , serous cystadenocarcinomas or acinar cell carcinomas . in children ,
malignant pancreatic tumors are exceedingly rare , and only few reports are available [ 1 , 2 , 3 ] .
pediatric pancreatic tumors arise from embryonic precursor cells of ductal and acinar cells , and are termed pancreatoblastoma [ 3 , 4 ] . due to the stem cell origin of the tumor cells , pancreatoblastomas can subsequently differentiate to various histologic tumor cell types .
patients with pancreatic tumors often present with weight loss , jaundice , and varying abdominal symptoms due to the tumor mass effect .
the treatment algorithm chosen usually depends on the type and stage of the respective tumor .
an aggressive approach with complete tumor resection whenever possible seems to be the best primary option [ 2 , 6 , 7 ] .
primary systemic chemotherapy may be useful to reduce the tumor mass and allow subsequent secondary resection .
a 15-year - old boy presented in november 2009 with a 3.2-cm tumor of the head of the pancreas and multiple diffuse liver metastases ( fig .
liver and kidney function tests were within normal limits , serum alpha - fetoprotein ( afp ) was elevated ( 400 u / ml ) .
biopsy of the liver mass revealed a malignant tumor with acinar cell differentiation , bringing up the differential diagnosis of acinar cell carcinoma , or a mixed tumor with acinar cell differentiation including pancreatoblastoma .
chemotherapy was initiated with two cycles of cisplatin and doxorubicin ( plado regimen ) , resulting in a partial response of the primary tumor and the liver metastases .
based on the good response , a whipple duodenopancreatectomy and simultaneous wedge resection of the metastases of the left liver with ligation of the right portal vein were performed in march 2010 .
the metastases of the right liver lobe were resected by hemihepatectomy of the right liver , any other lesions in the remnant liver were removed by wedge resection .
in addition , focally infiltrated parts of the diaphragm were also resected . altogether , this accounted for a surgical tumor reduction of about 90% .
surgical pathology confirmed a mixed histology with differentiation of both , acinar cell carcinoma and ductal adenocarcinoma .
some morphologic features of the primary liver biopsy also resembled an embryonic tumor , but the pathognomonic squamoid differentiation of pancreatoblastoma was missing .
immunostaining was focally positive for afp in accordance with the initially elevated afp serum levels .
tumor regrowth in the liver was observed on positron emission tomography / computed tomography ( pet / ct ) scan already 1 month after the second surgery .
after subsequent second - line chemotherapy with two cycles of ifosphamide , carboplatin and etoposide ( ice regimen ) , a partial remission of the liver lesions was documented .
a living donor liver transplantation ( right hemiliver ) from his brother was performed in november 2010 . due to a severe bile leak with abscess formation and finally hepatic artery thrombosis ,
the former was subsequently tapered within 3 months , and tacrolimus was changed to everolimus . in april 2011 , multiple new lung metastases were detected while no tumor relapse was seen in the abdomen .
therefore , in may 2011 a new chemotherapy treatment with oxaliplatin , irinotecan , leucovorin and 5-fluorouracil ( folfirinox regimen ) was started .
the new treatment was tolerated well apart from neutropenia and thrombocytopenia up to grade 4 , resulting in dose reductions of the applied compounds .
after six biweekly cycles , pet / ct showed a complete metabolic and partial morphologic remission of all lung lesions ( fig .
, we decided to consolidate with tandem high - dose chemotherapy using carboplatin , etoposide and paclitaxel as conditioning regimen with subsequent autologous stem cell transplantation ( asct ) .
hematopoietic progenitor cells were successfully mobilized with filgrastim , and high - dose chemotherapy was performed in november 2011 and february 2012 . due to transiently elevated liver enzymes after the first high - dose treatment , etoposide was omitted in the second treatment to reduce the toxicity for the transplanted liver . in august 2012 ,
a progression of the pulmonary lesions was documented in a routine follow - up pet / ct .
treatment with folfirinox was once again initiated , resulting in a very good metabolic and morphologic remission after another six cycles until december 2012 .
chemotherapy was continued for 3 additional months . while all lesions except one remained responsive to the treatment , the latter lesion was treated with stereotactic irradiation using 3  12 = 36 gy . as of today
, the patient has a sustained metabolic remission of the known lung lesions and no new lesions developed with repeated use of folfirinox .
he is currently in excellent general condition and has no limitations of his quality of life .
no standard treatment for exocrine pancreatic tumors in pediatric patients has been defined due to the rarity of this disease .
accordingly , treatment decisions were based on guidelines and recommendations of the children 's cancer and leukaemia group ( cclg ) on the management of rare tumors like hepatoblastoma and pancreatoblastoma , as well as on treatment algorithms used in adult patients with pancreatic cancer .
surgical resection of large tumor masses seems to be the best first - line therapy in resectable tumors , even when microscopically incomplete .
recently , a successful treatment with high - dose chemotherapy and asct of a young patient with a pancreatoblastoma has been reported after incomplete primary resection .
the few reported cases of high - dose chemotherapy and asct in young patients suggesting a benefit from aggressive multimodality treatment prompted us to perform tandem transplantation in our patient after observing good tolerability and an excellent response to initial standard dose chemotherapy [ 11 , 12 , 13 ] .
predominantly , the primary tumor in the pancreas and most of the liver metastases showed a mixed acinar and ductal cell differentiation , while some liver lesions were predominantly of acinar cell type .
in addition , some morphologic features of the liver lesions resembled pancreatoblastoma , although a typical squamoid differentiation of the tumor cells was lacking .
one can speculate that this heterogeneous tumor may well have been a pancreatoblastoma with differentiation along various cell types , which could finally not be diagnosed due to the regressive changes of the tumor morphology after neoadjuvant chemotherapy .
recently , the phenotype of a pancreatic carcinoma showing combined acinar cell and ductal differentiation was described and discussed as a possible distinctive tumor entity with an aggressive clinical course .
irrespective of the diagnostic label , the tumor was regarded as malignant with mixed differentiation including acinar cell carcinoma , ductal adenocarcinoma , and blastomatous components , each associated with different biological behavior , respectively .
firstly , despite the fact that advanced and metastatic pancreatic tumors are generally considered to have a dismal prognosis , an aggressive multimodal treatment strategy in young and fit patients may result in improvement of quality of life and survival .
in addition , treatment with high - dose chemotherapy and subsequent asct was possible even after orthotopic liver transplantation .
our patient is now in excellent condition without showing any clinical symptoms related to the tumor almost 4 years after the initial diagnosis .
secondly , the repeated use of folfirinox may be highly active also in pancreatic tumors other than ductal adenocarcinoma . in our patient , the best response to systemic chemotherapy
was achieved with folfirinox , although only given as third - line chemotherapy and despite the pretreatment with various other compounds .
convincing data have been reported for the folfirinox treatment of adult patients with ductal adenocarcinoma of the pancreas in the first - line setting , but no data exist in pretreated patients with other rare tumor entities .
our patient showed an excellent response even after repeated use of this treatment combination . in conclusion ,
folfirinox has proven to be a highly active chemotherapy regimen in this heavily pretreated patient and may be a very good alternative to older and more toxic regimens for the treatment of pediatric patients presenting with rare pancreatic tumors .
 pancreatic tumors are rare in children and adolescents . here , we report the case of a 15-year - old boy who presented with a mixed acinar cell carcinoma / ductal adenocarcinoma with blastomatous components . 
 he received multimodal treatment including various chemotherapy regimens and multistep surgery including liver transplantation . 
 introduction of folfirinox after relapse repeatedly achieved a durable metabolic and clinical response with good quality of life . 
Introduction
Case Report
Discussion