Biliary papillomatosis is a disease characterized by multiple papillary tumors of variable distribution and level in the intrahepatic and extrahepatic biliary tree or any one of them. The disease commonly affects adults older than 60 years and males are more prone to this disease than females. It's a rare pathological condition in human and very few cases are registered till date. As biliary papillomatosis is a rare biliary pathological entity, its clinical features and outcome are not much known to the researchers.
What is Biliary Papillomatosis?
Biliary papillomatosis is a papillary proliferation of the lining epithelium of the bile duct tree. The disease can be further classified into five classes according to the degree of cytological and structural abnormality in cells (biologically called atypia). These abnormalities occur in the parameters that include increased cytoplasmic ratio, loss of polarity, pleomorphism, prominent nucleoli, abnormal mitosis, cribriform pattern, hyperchromatism, and multilayering, and presence of invasion etc. The classes are as follows:
- Class 1. is defined as Biliary Papillomatosis with low-grade atypia,
- Class 2. is defined as Biliary Papillomatosis with high-grade atypia,
- Class 3. Biliary Papillomatosis with in-situ carcinoma (early stage of cancer),
- Class 4. Biliary Papillomatosis with microinvasive carcinoma
- Class 5. Biliary Papillomatosis with definite damage of the hepatic parenchyma or fibromuscular layer of the bile duct wall.
What are the Signs and Symptoms of Biliary Papillomatosis?
It's very tough to detect biliary papillomatosis by signs and symptoms. Most of the symptoms are in alignment with many other diseases, and hence only pathological tests can confirm BP. Here are some signs and symptoms commonly found in BP patients:
Colicky Abdominal Pain: It's a clinical symptom of sporadic abdominal pain occurs suddenly and also ceases suddenly.
Acute Cholangitis: It happens due to bacterial infection caused due to an obstruction in biliary tree. In biliary papillomatosis patients, it is accompanied by fever and jaundice.
Epidemiology and Prognosis of Biliary Papillomatosis
Biliary Papillomatosis is mostly observed in middle aged and elderly patients. Males are more affected by this disease and the male-female ratio is almost 2:1. Biliary Papillomatosis involves the only extrahepatic ducts in almost 58% of cases, intrahepatic ducts alone in 9%, and both extrahepatic and intrahepatic ducts in almost 33% cases. Biliary papillomatosis was previously considered to be a disease with low malignant potential. The current researches revealed a rate of malignant occurrence of approximately 41% of patients detected with Biliary Papillomatosis. It's also observed that in almost 83% of patients with Biliary Papillomatosis, a concomitant carcinoma was diagnosed after taking biopsies from adenomas (a benign tumor of epithelial tissue) cholangioscopically or examining the operated sample histologically.
After curative resection, the 5-years' survival rate for Biliary Papillomatosis is almost 80%; while for the Biliary Papillomatosis patients undergoing palliative drainage, the survival rate is almost 3-years.
What are the Common Causes for the Occurrence of Biliary Papillomatosis?
Biliary Papillomatosis is a very rare disease that is observed to be primarily caused by biliary obstruction. The other causes of Biliary Papillomatosis may be summarized as follows:
- Ulcerative Colitis
- Chronic empyematous cholangitis
- Chronic intrahepatic lithiasis
- Chronic salmonella infection
- Choledochal Cysts
- Caroli's Disease
- Liver Cirrhosis
- Biliodigestive Anastomosis
- Chronic Hepatitis B or C
- Biliary Parasites
Though none of the above mentioned causes can be said as a sure source of Biliary Papillomatosis, in certain habits and environmental condition like too much smoking, obesity, and inhaling certain pernicious chemicals frequently (due to working condition) may lead to Biliary Papillomatosis.
Diagnosis of Biliary Papillomatosis
There are two major imaging processes that are currently used to diagnose Biliary Papillomatosis, viz. diffuse involvement and intraductal mass. Let's have a look:
- Ultrasonography: USG shows a non-shadowing accumulation of solid mass of intermediate echogenicity within the duct. Lesions are generally prominent and demarcated clearly from the wall of the bile duct. Proximal ductal dilatation is usually present. USG shows simultaneous intrahepatic and extrahepatic duct calculi as the case may be.
- MRI - MRCP Scan:
- Features of signals in case of presence of lesions include the following:
- T1: Feeble signal
- T2: Slightly intensive signal
- T1 C+ (Gd): Do not significantly augment and stay hypointense when compared with the adjacent liver parenchyma.
- MRCP: It may allow direct visualization of the papillary lesions.
- CT Scan: Both intrahepatic and extrahepatic duct dilatation is visible. Hypoattenuation for intraductal soft-tissue masses take place in both before and after intravenous contrast.
- ERCP (Endoscopic Retrograde Cholangiopancreatography): It's a technique that takes help of endoscopy and fluoroscopy to diagnose irregularities in biliary or pancreatic ducts. In patients with Biliary Papillomatosis, characteristic ERCP findings comprise of multiple filling defects along with a dilated biliary tree having ragged abnormality in the bile duct wall. Due to obstruction and mucin discharge, the dilated bile ducts are not filled with contrast material. Therefore small papillomas may not be spotted.
In case of Biliary Papillomatosis, differential diagnosis is very essential since the disease closely resembles others diseases and is rather difficult to differentiate Biliary Papillomatosis from many other inflammatory and neoplastic diseases (a situation when abnormal tissues grow faster than normal ones). To make a precise distinction, all imaging modalities are needed. The differential diagnosis which needs to be ruled out are as depicted here:
- Inflammatory Polyps
Most bile duct lesions of above nature show intramural growth patterns and normally cause biliary strictures. Bile stones are the most common cause of bile duct obstruction. From MRCP imaging and USG, the movement pattern of stones and sludge in the bile ducts appear clearly which can help to distinguish these common entities from papillary masses.
It is indeed difficult to make a distinction of biliary papillomatosis from other forms of malignant lesions such as hepatocellular carcinoma and polypoid cholangiocarcinoma with intraductal growth on the basis of radiologic appearance alone. Hepatocellular carcinomas with intraductal growth may be detectable clinically. However, a perfect diagnosis is achievable only at surgery, because it is not possible to differentiate between malignant and benign disease on the basis of MRCP. However, signs of portal vein invasion, extrahepatic disease, and local lymphadenopathy at multidetector like CT scan, MRCP imaging, and USG may be indicative of malignancy.
Complications Associated with Biliary Papillomatosis
Apart from creating mechanical obstructions, the lesions present in the biliary duct may generate a mucus discharge or cellular rubbish that may originate septic cholangitis, chronic cholestasis, and ultimate liver failure.
Treatment of Biliary Papillomatosis
Resection is the only treatment when the disease is detected to be localized. If the patient is aged and not in a position to tolerate the surgery or not willing to undergo the surgery, then stenting, drainage palliative , or local ablation procedures are considered.
In case of diffuse papillomatosis, liver transplantation is the only ultimate curative option.
Till date not many Biliary Papillomatosis cases are found around the world. In developed nations like USA and UK, the system ensures registration of the case histories quite scientifically which is completely lacking in other nations. This is the primary cause behind unavailability of sufficient data on biliary papillomatosis. This rare and deadly disease needs more researches to let the medical fraternity know various aspects of the disease more precisely and only then proper treatment, causes of the disease and remedial measures will be known for the benefit of mankind.