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fibrolamellar hepatocellular carcinoma ( fl - hcc ) is a rare primary liver tumor , usually presenting in the younger population ( < 40 years ) [ 1 , 2 ] , which was first described by edmondson   in 1956 .
it is characterized histologically by well - differentiated malignant hepatic cells with abundant eosinophilic and granular cytoplasm due to the presence of numerous mitochondria , and by the presence of fibrous stroma arranged in thin parallel lamellae interspersed between tumor cells . while it is a variant of hcc ,
it does not present in patients with underlying liver disease [ 1 , 4 ] and is associated with a better prognosis than conventional hcc [ 2 , 4 ] .
presenting symptoms are nonspecific , and involve abdominal pain , weight loss , and malaise .
in contrast to conventional hcc , it generally does not produce -fetoprotein ( afp ) .
instead , it has been associated with elevations in neurotensin levels . even though surgery is the standard of care , it has a high rate of recurrence months to years after primary resection ( up to 80%percnt ; in 5 years ) . while sites of recurrence usually include the liver , regional lymph nodes , peritoneum , and lung , metastasis to the pancreas is extremely rare , with only 2 other cases reported in the literature to our knowledge [ 7 , 8 ] .
we present the case of a 46-year - old patient with metastatic fl - hcc to the pancreas 30 years after he had first been diagnosed and 26 years since his last resected liver recurrence .
this is a 46-year - old male with a previous history of fl - hcc diagnosed in 1985 when he was 16 years old . at that time he underwent a routine physical examination , where he was noted to have a positive skin test for tuberculosis .
while isoniazid was being considered for treatment , he was found to have elevated liver function tests , which led to further imaging where he was found to have a mass in the liver .
he underwent liver resection in 1985 and subsequently a liver transplant in 1989 after his fl - hcc had recurred . in 2000
he was found to have hepatitis c , genotype 1b , presumably from his blood transfusions at the time of his previous surgeries .
he had done well since his liver transplantation until august 2014 , when a left lung nodule 3 cm in size was noted on a pet ct , in addition to a 2-cm borderline hypermetabolic lesion in the tail of the pancreas .
he underwent a ct - guided biopsy of the left lung that showed metastatic fl - hcc .
subsequent mri showed a 2.6-cm hyperenhancing round mass in the tail of the pancreas ( fig .
the patient was then referred for evaluation and diagnosis of the pancreatic mass by endoscopic ultrasound - guided fine - needle aspiration ( eus - fna ) . on physical examination , he had no significant findings .
laboratory tests were normal , except for a creatinine level of 1.3 mg / dl , alt of 57
the afp level was 3.2 ng / ml . he was on cyclosporine and mycophenolate mofetil for liver transplant immunosuppression . on eus , a 3.5  3.0 cm isoechoic
heterogeneous well - defined round mass with small cystic spaces within was visualized in the tail of the pancreas ( fig .
2 ) . fna with a 19-gauge needle yielded a bloody sample without a core .
this prompted the use of a 25-gauge needle , obtaining adequate specimens , and pathology revealed metastatic fl - hcc ( fig .
the patient was then referred to surgery for resection of his lung nodule and pancreatic tail mass .
he had a simultaneous left - lung video - assisted thoracoscopic surgery wedge resection and distal pancreatectomy with splenectomy ( fig .
he has now initiated hepatitis c treatment with ledipasvir / sofosbuvir and ribavirin for 12 weeks .
fl - hcc is a rare tumor , accounting for < 1%percnt ; of hcc in the usa .
although recurrence and metastasis are common in this type of tumor ( 6070%percnt ; ) [ 4 , 9 ] , metastasis to the pancreas is extremely rare . in our patient
, it recurred 30 years after he had first been diagnosed and 26 years since his last liver recurrence , which was treated with a liver transplant .
in contrast to conventional hcc , afp levels in fl - hcc are usually normal , although elevated levels have been reported in up to 25%percnt ; of patients with fl - hcc [ 1 , 10 ] .
to date , this is the third case reported of metastatic fl - hcc to the pancreas .
although recurrence can develop months to years after resection , this is the longest  recurrence - free period reported in the literature to our knowledge .
lifelong surveillance should be considered in this type of tumor , due to its propensity to recur many years after first presentation . in our patient ,
histopathology from the eus - fna of the pancreatic mass showed morphologic features of tumor cells compatible with metastasis from the patient 's known fl - hcc with expression of hepatocyte - specific antigen , glutamine synthetase , glypican-3 , and positive cd34 in a canalicular pattern .
the surgical pathology from the resected specimens showed focal thin fibrous bands within the metastatic foci ; however , definitive diagnostic features of a fibrolamellar variant of hcc were not identified within the metastatic lesions .
fl - hcc has certain histologic features that distinguish it from several other tumors and conventional hcc .
these include the presence of sheets of large polygonal or spindle - shaped tumor cells with abundant granular eosinophilic cytoplasm , prominent nuclei , and paucicellular fibrous stroma arranged in thin parallel lamellae around tumor cells .
pale bodies devoid of nucleus and intracytoplasmic hyaline droplets as well as an increased number of mitochondria have also been reported [ 1 , 11 ] .
immunohistochemical studies have found that fl - hcc expresses markers associated with biliary ( ck7 and epithelial membrane antigen ) and hepatic ( hepar-1 and glypican-3 ) differentiation as well as markers associated with hepatic stem cells ( cd133 and cd44 ) that help differentiate it from conventional hcc [ 12 , 13 ] . in our patient
, mri showed , in addition to the nodule in the left lower lobe , a 2.2  2.6 cm well - defined round mass in the tail of the pancreas visualized in the arterial phase , with decreased enhancement in the portal venous phase suggesting vascularity .
although the enhancement appeared similar to the lesion in the lung , there was no fibrous central scar  which is one of the main characteristics of this lesion when presenting as a primary liver tumor .
other imaging features associated with fl - hcc are the presence of calcifications , which can be seen in 4068%percnt ; of cases .
due to its indolent clinical course , the diagnosis of fl - hcc usually occurs at an early stage , when primary resection or transplantation can be offered . to date , the treatment of choice is surgical resection , with 5-year survival rates reported as high as 7085%percnt ; after partial hepatectomy [ 4 , 16 , 17 ] . although median survival rates after transplantation have been reported to be only 2832 months , and there is a 5-year survival of about 35%percnt ; , these data come from the 1990s , when less strict criteria were used for liver transplantation , likely explaining the poorer outcomes [ 16 , 18 , 19 ] .
more recent studies report a 5-year survival between 5060%percnt ; after liver transplantation [ 17 , 20 , 21 ]
. the overall prognosis of fl - hcc compared to conventional hcc is 3034 vs. 716%percnt ; [ 2 , 20 ] , although this largely depends on staging at the time of diagnosis , the presence of cirrhosis , and whether surgery was performed . in fact , a recent meta - analysis found that there seemed to be no difference in survival between fl - hcc and conventional hcc in noncirrhotic patients or when transplantation was used as the therapeutic option .
although recurrences and metastasis are common , surgery is still the treatment of choice for resectable metastasis , given the lack of other effective treatment options such as chemotherapy [ 4 , 6 ] .
however , chemotherapy and radiation are still options for advanced cases where surgery is not an option [ 6 , 21 , 22 ] . in conclusion , this is the third reported case of metastatic fl - hcc to the pancreas .
interestingly , in this patient , metastasis occurred 30 years from first diagnosis and 26 years since his last resected liver recurrence .
attention to the radiologic findings on mri and eus may alert the clinician when a mass in the pancreas appears in the setting of a previous history of fl - hcc .
lifelong surveillance should be considered in this type of tumor , due to its propensity to recur years after its first presentation . because of its indolent clinical course , resection of metastatic lesions is the treatment of choice .
fibrolamellar hepatocellular carcinoma ( fl - hcc ) is a rare variant of hepatocellular carcinoma , usually presenting in the younger population ( < 40 years ) without underlying liver disease . 
 although it has a better prognosis than hepatocellular carcinoma , it has a high rate of recurrence months to years after primary resection . while sites of recurrence usually involve the liver , regional lymph nodes , peritoneum , and lung , metastasis to the pancreas is extremely rare , with only 2 other cases reported in the literature . 
 we present the case of a 46-year - old patient with metastatic fl - hcc to the pancreas 30 years after diagnosis and 26 years since his last resected liver recurrence .