What is cholesterolosis in the pathology of the gallbladder?

Cholesterolosis of the Gallbladder: Pathology and Clinical Significance

Cholesterolosis is a benign condition characterized by the accumulation of cholesterol esters and triglycerides in macrophages within the gallbladder wall, which can appear in either diffuse or polypoid forms. 1

Pathological Features

• Cholesterolosis involves the deposition of cholesterol esters and triglycerides specifically in macrophages at the gallbladder wall level 1
• It can present in two distinct forms:
  • Diffuse cholesterolosis - affecting the entire gallbladder mucosa
  • Polypoid cholesterolosis - forming localized protrusions into the gallbladder lumen 1
• Microscopically, cholesterolosis is characterized by subepithelial foam-cell nests containing accumulated cholesterol esters 2
• The condition progresses through four stages over the course of decades 2

Epidemiology and Risk Factors

• The prevalence of cholesterolosis is reported to be approximately 4-8% of the population 1
• It appears to be more common in males 1
• Studies show conflicting results regarding associations with:
  • Serum cholesterol levels (though 85.1% of patients in one study had elevated cholesterol levels) 3
  • Body mass index
  • Lifestyle factors such as alcohol intake and smoking 1
• The relationship between cholesterolosis and gallstones remains controversial, with only some surgical series showing an association 1

Pathophysiology

• An increased activity of cholesterol ester enzyme has been observed in the gallbladder mucosa of patients with cholesterolosis 1
• This enzymatic change may contribute to increased cholesterol ester deposition in the gallbladder wall 1
• The condition is not associated with:
  • Cholesterol gallstones
  • Supersaturation of bile with cholesterol
  • Hyperlipidemia
  • Obesity
  • Atherosclerosis 4
• Studies have shown that sterol 27-hydroxylase deficiency is not a pathogenetic factor in cholesterolosis 5
• The amount of ACAT-1 protein (acyl-CoA:cholesterol acyltransferase) appears similar in patients with and without cholesterolosis 5

Imaging Characteristics

• Ultrasound is a sensitive tool for diagnosing cholesterolosis 1
• On ultrasound, cholesterol polyps typically appear as small, non-mobile, non-shadowing lesions attached to the gallbladder wall 6
• Cholesterol polyps may show stalk-like central enhancement on contrast-enhanced ultrasound (CEUS) 6
• Echoendoscopy (endoscopic ultrasound) is increasingly important in differentiating between benign cholesterol polyps and potentially malignant lesions 1
• MRI may show high T1-weighted signal in cholesterol polyps 6

Clinical Significance and Management

• The natural history of cholesterolosis is generally benign 1
• Most patients with cholesterolosis have non-specific symptoms, with the frequency of dyspeptic symptoms comparable to that in the general population 1
• For polyps between 6-10mm in size, yearly follow-up with ultrasonography is advisable 1
• Prophylactic cholecystectomy for gallbladder polyps is justified only if they are more than 10mm in diameter 2
• Laparoscopic cholecystectomy has been shown to be an effective, safe, and feasible treatment for symptomatic cholesterolosis 3

Differential Diagnosis

• Cholesterol polyps must be differentiated from other gallbladder lesions:
  • Adenomatous polyps (neoplastic)
  • Inflammatory polyps
  • Gallbladder cancer
  • Adenomyomatosis 4
• Key distinguishing features of cholesterol polyps:
  • They are typically small (<10mm)
  • They do not shadow on ultrasound (unlike gallstones)
  • They are non-mobile (unlike gallstones) 6
  • They may show stalk-like central enhancement on CEUS 6

Pitfalls in Diagnosis

• Cholesterol polyps may be mistaken for gallstones, but they are non-mobile and do not produce acoustic shadowing 6
• Approximately 95% of gallbladder polyps are cholesterol polyps that gradually empty over time 2
• The condition should not be confused with adenomyomatosis, which involves hyperplasia of gallbladder wall tissues with outpouches of the mucosa similar to diverticula 4