Intraductal papillary neoplasm (IPN) is a rare condition characterized by noninvasive papillary neoplasms of the biliary tree for which treatment is still controversial. We present a case of orthotopic liver transplantation (OLT) for extensive IPN with carcinoma in situ (CIS) transformation.
In May 2010, a 42-year-old man was referred for acute cholangitis. His history was remarkable for recurrent cholangitis and a biliary cirrhosis of unknown etiology, for which he had been on a transplant waiting list for 2 years. During that time, follow-up magnetic resonance cholangiopancreatography (MRCP) showed progressive diffuse biliary dilation and stenosis.
On his arrival, MRCP showed known left intrahepatic biliary duct dilation with parenchymal atrophy and a new bilobular lesion of the main bile duct (Fig. 1). Endoscopic retrograde cholangiopancreatography and cholangioscopy showed excessive mucus discharge from the ampulla and a 26-mm polypoid lesion lying in the main bile duct, which biopsies revealed to be CIS. Because of the clinical presentation and the patient's history, the diagnosis of IPN was suspected. An extensive workup, including thoracic and abdominal computed tomography scans, a positron emission tomography scan, and biopsies of multiple enlarged hilar nodes showed no metastatic disease.
Considering the patient's end-stage liver disease with a Model for End-Stage Liver Disease score of 28, the suspicion of extensive IPN of intrahepatic and extrahepatic ducts, and CIS with a completely negative metastatic workup, we decided that liver transplantation remained the better treatment option.
On June 26, 2010, the patient successfully underwent OLT with Roux-en-Y hepaticojejunostomy. The final pathology results showed biliary cirrhosis and diffuse IPN of extrahepatic and intrahepatic ducts with multiple high-grade dysplasia and CIS foci. No infiltrative cholangiocarcinoma was found. Unfortunately, the patient died 19 months later because of relapsing disease in the intrapancreatic portion of his native main bile duct with subsequent cholangiocarcinoma transformation.
IPN is a rare disease with only approximately 160 cases reported in the literature. Treatment for this condition is still very controversial: palliative stenting and drainage, radiotherapy,1 cholangioscopic laser ablation,2 and hepatectomy have all been tried with mixed results. However, the prognosis remains poor because of the high recurrence of the disease elsewhere in the biliary tree3 and the frequency of malignant transformation. The mean survival time ranges only from 28 to 61 months with hepatectomy and from 11 to 37 months with palliative care.4, 5 In our case, the extent of the disease and the associated cirrhosis led us to consider liver transplantation as a viable alternative, as already suggested by some authors.6 However, the presence of CIS was an initial source of concern for us.
To our knowledge, only 9 other cases of liver transplantation for IPN have been reported in the literature.7-15 With our case, there are now 2 reported recurrences of the disease in the native biliary tree left in place during surgery.15 Both patients died from that relapse. On the other hand, all patients who underwent pancreaticoduodenectomy concomitantly with OLT remained alive after follow-up periods of 22, 18, and 24 months, respectively.8, 10, 14
As for neoplasia, 2 of the 3 cases with frank invasive carcinoma according to the final pathology results died within a few months of OLT.13, 15 On the other hand, 3 of the 4 cases reported to have moderate- to high-grade dysplasia or CIS according to the final pathology results were well and alive 15 months, 18 months, and 16 years, respectively, after OLT.7, 10, 12 As for our case, the patient died from recurrent disease in his native biliary duct, but he had not shown any signs of metastasis up until that relapse. Therefore, we believe that his death cannot be attributed to the presence of the many high-grade dysplasia and CIS foci found in the explanted liver during OLT.
In conclusion, OLT for extensive high-grade IPN without any evidence of basement membrane transgression or metastasis on a full extension workup is a safe and possible treatment. However, the complete removal of the native biliary tree with concomitant pancreaticoduodenectomy should be mandatory, no matter what the extent of the disease is. We do not recommend transplantation for patients presenting with local or distal malignant invasion.