A rare entity: Intraductal papillary neoplasm of the bile ducts

A 72 years-old man was referred to the ER from the primary care physician for dissociated asymptomatic cholestasis (AST 73u/L; ALT 109u/L, ALP425 u/L, GGT884 u/L, TBil1,14 mg/dL. Tumor markers were within normal limits, and no jaundice or other signs were remarkable. He had history of chronic renal failure.

A severe intra and extrahepatic dilation (up to 3 cm) was found by ultrasonography.

A non-contrast MRI (due to CRF)(fig.1) demonstrated a well-defined mass (24 x 16 mm) in the prepapillary common bile duct (CBD) which seemed to compress the bile duct wall and cause proximal CBD dilatation.  The main pancreatic duct was normal.
Contrast-enhanced CT observed an enhanced mass (fig.2), but CEUS an hypoenhanced one (fig.3).
As result of its well-defined shape, the differential diagnosis was between cholangiocarcinoma and a focal inflammatory lesion.

The gastroenterologist performed an endosonography and an ERCP, identifying CBD dilatation and a filling defect, both misinterpreted respectively as a lithiasis and a non-specific luminal stenosis.

Despite endoscopic results, due to the findings of contrast-enhanced CT, MRI with high probability of cholangiocarcinoma, and the bilirubin increasing (up to 6mg/dL in one month) the patient underwent Whipple's procedure, with no postsurgical complications, and cholestasis recovery.

The WHO’s reclassification of tumours introduced intraductal papillary neoplasm of the bile ducts (IPNB) as a rare premalignant tumour which is characterised by intraluminal papillary growth of neoplastic biliary epithelium, that can cause bile duct obstruction and dilatation.[1]

IPNB is considered a precursor lesion of cholangiocarcinoma, as this disease can progress from a premalignant phase with low-grade dysplasia to invasive carcinoma.[2,4]. Southeast Asian regions have reported the highest incidence, although worldwide the incidence is not clear.[3] IPNB has a male prevalence with a median age at presentation of 60 years[4]. Various studies have shown that IPNB share histopathological similarity to intraductal papillary mucinous neoplasm of the pancreas (IPMN-P) as have also reported a possible coexistence between these two lesions.[5,6]

Unlike their pancreatic counterparts, IPNB produces mucin only in one third of cases. Mucin is usually difficult to identify because can be anechoic as bile at US [7] and it‘s not visible on CT and MRI. However, it can be recognized on MRCP as hypointense linear areas in dilated ducts.
Symptoms include jaundice, intermittent and recurrent abdominal pain and fever.[8]

Park et al.[9] identified four subtypes of IPNB according to location, tumour morphology and degree of mucin secretion. These were: masses with proximal ductal dilatation (this subtype does not produce mucin), disproportionate dilatation without masses, mass with proximal and distal ductal dilatation and cystic lesion. The latest is the most common subtype of IPNB and, unlike others cystic hepatic lesions, communication with the ductal system can be observed.

The preoperative diagnosis is difficult, requiring the combination of several imaging tests. Ultrasonography usually shows dilated biliary ducts and intraluminal nodules with variable echogenicity and irregular wall thickness.

Contrast-enhanced CT or MRI allow better evaluation of the bile ducts. Large intraductal masses display hyper-enhancement in the arterial phase but rarely do so in delayed phase. The absence of enhancement during delayed phase is an important feature to differentiate it from cholangiocarcinoma. DWI, ADC and dynamic MRI with hepatocyte-specific contrast agent are useful to better define tumour invasion. Moreover, Fast Spin-Echo T2-weighted MRI is optimal for identifying papillary pattern of the tumour due to the high contrast resolution. For detecting IPNB, MRI shows the highest sensitivity, although small or flat tumours can be missed on cross-sectional imaging.[5, 8,9]

Given to the recurrence of this tumour, wide resection with negative margins is the treatment of choice to which all patients with IPNB should undergo.[9]

IPNB has a better prognosis and outcome than classic cholangiocarcinoma.