What is the cause of multiple 4‑mm gallbladder polyps in an asymptomatic 35‑year‑old woman?

Etiology of 4-mm Gallbladder Polyps

Multiple 4-mm gallbladder polyps in a 35-year-old asymptomatic woman are almost certainly benign cholesterol polyps, which represent the most common cause of small gallbladder polyps and carry negligible risk of malignancy. 1

Pathologic Classification

Gallbladder polyps are broadly categorized into two groups:

Nonneoplastic Polyps (Most Common)

• The vast majority of sonographically identified gallbladder polyps are nonneoplastic, most commonly benign cholesterol polyps or inflammatory-type polyps 1
• Nonneoplastic polyps are usually smaller than 10 mm in diameter with negligible, if any, risk of developing dysplasia or malignancy 1
• Cholesterol polyps result from cholesterol-laden macrophages accumulating in the gallbladder mucosa 2
• Other nonneoplastic causes include fibromyoglandular polyps, polypoid pyloric gland metaplasia, and inflammatory polyps 3

Neoplastic Polyps (Rare)

• Only 6% of all gallbladder polyps are neoplastic 1
• Approximately 0.4% of patients undergoing cholecystectomy are found to have neoplastic polyps 1
• Neoplastic polyps include pyloric gland adenomas and intracholecystic papillary neoplasms (ICPNs), which by WHO definition are ≥10 mm 1

Size-Based Risk Stratification

For 4-mm polyps specifically:

• Polyps smaller than 10 mm are overwhelmingly benign, with only 14% of polyps <10 mm proving neoplastic in pathologic series 3
• In a large pathologic study, the mean size of non-neoplastic polyps was 4.1 mm, occurring in younger patients (mean age 52 years) 3
• The positive predictive value of the ≥10 mm size cutoff for neoplasia is 94.3%, with a negative predictive value of 85% 3
• Incidentally noted pedunculated polyps smaller than 5 mm generally do not require follow-up 2

Clinical Context for This Patient

In this 35-year-old asymptomatic woman:

• The patient's young age (35 years) strongly favors benign etiology, as neoplastic polyps occur in older patients (mean age 61 years) 3
• The small size (4 mm) and multiple nature further support cholesterol polyps as the diagnosis 1, 4
• Polypoid lesions of the gallbladder affect approximately 5% of the adult population, with most individuals being asymptomatic 4

Important Caveats

While malignant transformation of small polyps is exceedingly rare, it has been documented:

• Case reports exist of 5-mm polyps transforming into carcinoma over 2 years, though this is exceptional 5
• Three asymptomatic polyps ≤10 mm (4%) had neoplastic changes in one surgical series, though the denominator included selected surgical cases 6
• The risk of malignancy in polyps <6 mm is essentially zero in most series, but cannot be stated as absolute zero 6

Risk Factors That Would Alter Assessment

The following factors increase concern for neoplasia, even in small polyps:

• Age over 50 years 4, 2
• Primary sclerosing cholangitis (PSC) 2, 6
• Coexistent gallstones 4, 2
• Solitary polyp (rather than multiple) 4
• Sessile morphology or focal wall thickening 1
• Documented growth on serial imaging 4, 6

None of these high-risk features appear to be present in this 35-year-old woman with multiple 4-mm polyps.