Gallbladder polyps

Gallbladder polyps are elevated lesions on the mucosal surface of the gallbladder ¹. On ultrasound a gallbladder polyp is seen as an elevation of the gallbladder wall that protrudes into the lumen ². It should not be mobile or demonstrate posterior acoustic shadowing, which would suggest it is more likely a calculus ². It may be sessile or pedunculated. A clearly infiltrating or large mass should be treated as a gallbladder cancer rather than a polyp ². If there is clear reverberation or “comet tail” artefact present posterior to the lesion this should be identified as a pseudopolyp (focal adenomyomatosis or a cholesterol polyp) ³. The follow-up guidelines, therefore, do not need to be followed for these patients. Of note, not all pseudopolyps will demonstrate these findings. The vast majority of gallbladder polyps are benign (non-cancerous), but malignant forms are seen ⁴. On imaging, although gallbladder polyps may be detected by CT or MRI, they are usually best characterized on ultrasound as a non-shadowing and immobile polypoid ingrowth into gallbladder lumen.

Gallbladder polyp is classified according to the classification proposed by Christensen and Ishak in 1970 ⁵. Gallbladder polyps are classified into benign tumors such as adenoma, benign pseudotumors such as adenomatous hyperplasia, adenomyoma, inflammatory polyp, cholesterol polyp, and malignant polyps such as adenocarcinoma. The reported prevalence of malignant polyps among gallbladder polyps varies from 0% to 27% ⁶. It is well known that gallbladder cancer at an advanced stage reveals poor prognosis even with radical resection, thus early detection and early surgical intervention is particularly important.

Gallbladder polyps are relatively frequent, seen in up to 9% of the population ⁷. Over 90% are benign, and the majority are cholesterol polyps. Cholesterol polyps are most frequently identified in patients between 40-50 years of age and are more common in women (female:male, 2.9:1) ⁸.

Gallbladder polyps may be asymptomatic, or they may be related to symptoms of cholecystitis (right upper abdominal discomfort, nausea and food intolerances) ¹. Often gallbladder polyps are found inadvertently on ultrasound or CT scanning or can be incidentally found on pathologic examination of the gallbladder. Gallbladder polyps can be true neoplastic growths or pseudopolyps of cholesterol balls clinging to the wall of the gallbladder.

A wide variety of entities appear as gallbladder polyps and histology is variable:

• Benign gallbladder polyps: 95% of all polyps
  • cholesterol polyps: >50% of all polyps ⁷
  • adenoma: ~30%, possibly premalignant ⁹
  • inflammatory polyps: ~10% ⁷
  • other rare entities (see benign tumors and tumor-like lesions of the gallbladder)
• Malignant gallbladder polyps: 5% of all polyps
  • adenocarcinoma: ~90% of malignant polyps
  • other rare entities including:
    • metastases to gallbladder
    • squamous cell carcinoma
    • angiosarcoma

The most common type of gallbladder polyps are pseudo or cholesterol polyps. These account for 60% to 90% of all gallbladder polyps ¹. They are not true neoplastic growths, but rather they are cholesterol deposits that form as projections on the inner lumen of the gallbladder wall. They are formed from precipitation of cholesterol or bile salts. Presence of cholesterol polyps may be indicative of pathologic gallbladder disease such as chronic cholecystitis. Inflammatory polyps account for 5% to 10% of all gallbladder polyps. They are associated with inflammation of the gallbladder mucosa and wall. Usually, this type is associated with repeated bouts of cholecystitis and acute biliary colic. Both pseudopolyps and inflammatory polyps carry close to a zero risk of developing a gallbladder cancer. These polyps rarely exceed 1 cm in diameter and are often multiple. True adenomatous gallbladder polyps are considered neoplastic. They are rare and are often associated with gallstones. They can range in size from 5 mm to 20 mm. Once the polyp reaches a size of greater than 1 cm, consideration needs to be made for cholecystectomy, because of the potential malignant increases above 1 cm. Adenomyomatosis is a more common true poly. It has classically been considered a benign lesion of the fundus of the gallbladder. However, recent findings suggest these lesions do have premalignant potential. Malignant polyps tend to be singular and more than 2 cm in diameter ¹⁰.

Two percent to 12% of routine gallbladder pathology specimens may contain gallbladder polyps, but true adenomatous polyps are present in less than 0.5% of all gallbladder specimens. Cholesterol polyps show an increased cholesterol content and are associated with gallbladder cholesterolosis and sludge. Inflammatory polyps exhibit inflammation of the gallbladder wall with Rotatinski- Aschoff bodies, and findings of acute or chronic cholecystitis. True adenomatous polyps have a glandular histology. Malignant polyps can demonstrate cancerous changes characteristic of adenocarcinoma, squamous cell carcinoma, and adenoacanthoma. The degree of malignant differentiation usually correlates to polyp size ¹¹.

Despite many available imaging modalities such as ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), endoscopic retrograde cholangiography, and endoscopic ultrasonography, it is still difficult to differentiate benign polyp and malignant polyp in gallbladder polyps ⁴. Therefore treatment plan of gallbladder polyp should be established with consideration of many clinicopathologic characteristics altogether with information acquired from imaging studies.

The vast majority of gallbladder polyps are asymptomatic and carry a low risk of malignant degeneration. However, a small number of true gallbladder polyps will progress to malignancy. Patients with symptomatic gallbladder polyps or with enlarging polyps should be treated with cholecystectomy. The risks of performing a laparoscopic cholecystectomy are far less than missing a potential adenomatous polyp. It is recommended that if there is any indication of a gallbladder polyp being anything other than a pseudopolyp or cholesterol polyp, that cholecystectomy should be performed ¹².

Figure 1. Gallbladder polyps

Footnote: Male with previous diagnosis of ulcerative colitis. Presents with elevated liver enzymes. There are multiple polypoid lesions of the gallbadder measuring over 10mm.

[Source ¹³ ]

Gallbladder polyps causes

There a few risk factors associated with true gallbladder polyp formation. Some studies suggest conditions such as familial polyposis, Peutz-Jeghers, Gardner syndrome, and hepatitis B may be factors associated with polyp formation. Pseudo or cholesterol polyps can develop when the cholesterol or bile salt content in the bile is high. This leads to condensation of cholesterol clumps which can adhere to the wall of the gallbladder. This condition may be a precursor to gallstone formation and can also at times be seen in conjunction with gallstones. Other factors typically associated with gallbladder diseases such as obesity, sex, weight loss, and diabetes have not been shown to increase the formation of gallbladder polyps ¹⁴.

Factors associated with an increased prevalence of gallbladder polyps is unclear. Studies have shown that 4% to 7% of the population may develop gallbladder polyps. The average age of diagnosis of gallbladder polyps is around 49 years old. However, other studies have found the presence of polyps to be more prevalent in older patients ¹⁵.

Risk factors for malignant gallbladder polyp

The reported risk factors for malignant gallbladder polyp are age of the patient, total number of polyp, morphology, size, associated gallstone, and symptomatic polyp ¹⁶. Yeh et al. ¹⁷ identified age over 50 year and polyp size over 10 mm as the independent risk factors of malignant polyps. Yang et al. ¹⁸ reported that size over 10 mm, single gallbladder polyp, the presence of gallstone, age over 50 year, and clinical symptoms were associated with malignancy. Kubota et al. ¹⁹ proposed sessile polyp, isoechogenicity with the liver parenchyma, and rapid growth were also important factors predicting malignancy. Terzi et al. ²⁰ noted age over 60 year, size over 10 mm, and associated gallstone as the risk factors for malignancy. He et al. ²¹ proclaimed that cholecystectomies should be indicated in polyps with size over 10 mm and age over 50 year. Jang et al. ¹⁶ identified age, polyp size, polyp morphology as the risk factors.

Gallbladder polyp symptoms

Typically gallbladder polyps are incidentally found on upper abdominal imaging, usually during imaging for upper abdominal discomfort. Most gallbladder polyps are asymptomatic, unless large ⁴.

The presenting symptoms of gallbladder polyps are non specific and vague, and in many cases asymptomatic ⁴. For such reason, gallbladder polyps are often detected incidentally.

Patients with cholesterol stones related to hypokinetic gallbladder function, cholesterolosis, or stasis may exhibit symptoms of chronic cholecystitis. Right upper abdominal pain, food intolerance, bloating, and nausea may be present. Elicitation of a positive Murphy’s sign, pain with deep palpation to the right upper abdomen, is often present. Patients with larger adenomatous lesions may have more severe and persistent right upper abdominal pain. Cases of progressive polyps that have deteriorated into a malignancy may present with jaundice, due to growth and impingement of the common or hepatic bile duct. There may also be a palpable mass in the right upper abdomen ²².

Along with easier accessibility to routine medical check-ups, recent advancements in imaging modalities such as ultrasonography and endoscopic ultrasonography, the detection of gallbladder polyps is becoming more frequent. Although there are some differences according to reports, the prevalence of gallbladder polyps in healthy subjects is 3% to 7%, and gallbladder polyps are found in 2-12% of cholecystectomy specimens ²³.

Gallbladder polyp diagnosis

Gallbladder polyps are often found coincidentally with imaging such as an abdominal CT or an abdominal ultrasound. In cases of patients being worked up for gallbladder disease, the polyps are usually seen on abdominal ultrasound. They may present as a single lesion, or they may be multiple in nature. Gallbladder polyps can occur in conjunction with gallstones but are often seen in the absence of stones. Differentiation must be made between gallstones and gallbladder polyps. Gallstones are usually mobile, and polyps are fixed to the wall of the gallbladder lumen. Most polyps are hypodense and smaller than 1 cm in diameter. They can appear polypoid or sessile. Singular polyps that have a tissue density and are larger than 1 cm in diameter carry a higher malignant potential ²⁴.

Gallbladder polyp treatment

Gallbladder polyps that have the appearance of pseudo or cholesterol polyps, in asymptomatic patients, can be followed with yearly gallbladder ultrasounds. These patients have a very low malignant risk. If serial ultrasounds reveal that the polyp is enlarging or if the patient becomes symptomatic, then cholecystectomy should be recommended. Patients with symptoms of chronic cholecystitis are usually best treated with laparoscopic or open cholecystectomy. Gallbladder polyps that are 1 cm or greater in size should undergo cholecystectomy due to the increased risk of developing gallbladder cancer. Early intervention is preferred because an early gallbladder neoplasm has a much higher rate of cure than a more advanced lesion. In fact, stage 0 gallbladder cancer has about an 80% 5-year survival rate, and stage 1 has less than a 50% survival rate. Less than 10% of all gallbladder cancers are diagnosed at stage 1 or lower. More advanced gallbladder cancers require an open cholecystectomy with resection of the gallbladder fossa of the liver along with regional lymph node removal ²⁵.

Figure 2. Gallbladder polyps management guidelines

[Source ² ]

Gallbladder polyps treatment guidelines

In 2017 joint guidelines between the European Society of Gastrointestinal and Abdominal Radiology, European Association for Endoscopic Surgery and other Interventional Techniques, International Society of Digestive Surgery – European Federation and European Society of Gastrointestinal Endoscopy were published and provide the most up to date and comprehensive guidance ²:

• Gallbladder polyp >10 mm: increased risk of malignancy, cholecystectomy recommended
• Gallbladder polyp <10 mm
  • symptoms attributed to the gallbladder: cholecystectomy suggested if no other cause for the symptoms determined (polyp may be indicative of underlying occult calculus or inflammation)
  • if the patient has risk factors for gallbladder malignancy (risk factors: >50 years, primary sclerosing cholangitis, Indian ethnicity, sessile polyp including focal wall thickening >4 mm):
    • gallbladder polyp <6 mm
      • follow-up ultrasound at 6 months, then yearly for 5 years
      • an increase in size ≥2 mm: consider cholecystectomy
    • gallbladder polyp >6 mm: consider cholecystectomy
• • no risk factors for gallbladder malignancy:
    • gallbladder polyp <6 mm: follow-up ultrasound at 1, 3 and 5 years
    • gallbladder polyp >6 mm:
      • follow up ultrasound at 6 months, then yearly for 5 years
      • an increase in size ≥2 mm: consider cholecystectomy

Statistically, gallbladder polyps are common and gallbladder cancer is rare, so very few polyps progress to gallbladder cancer. There is also controversy regarding the development of gallbladder cancer and some suggest that polyps may not actually progress to cancer ²⁶.

A previously commonly accepted strategy is:

• ≤6 mm: no further follow up necessary ²⁶
• 6-9 mm: follow up to ensure no interval growth; follow-up interval varies from 3 to 6 months ²⁷
• ≥10 mm: surgical consultation
  • usually warrants cholecystectomy
  • if no cholecystectomy, annual follow up is justified ²⁸

Lower thresholds for follow up or intervention may be warranted if the patient population is known to have a higher risk of gallbladder carcinoma (e.g. higher incidences in Pakistan, Ecuador, and females in India).

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