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Gastroenterol Hepatol (N Y). 2008 October; 4(10): 735–737.
PMCID: PMC3104186

Gallbladder Cancer

Adenoma-Carcinoma or Dysplasia-Carcinoma Sequence?
Vivek Trivedi, MD,1,3 Vivek V. Gumaste, MD,corresponding author1,3 Shaojun Liu, MD, PhD,2,3 and Joel Baum, MD1,3

Gallbladder carcinoma is the sixth most common carcinoma of the digestive tract, with an incidence of 2.5 cases per 100,000 in the United States.1 There is a strong association between cholelithiasis and gallbladder cancer, with gallstones found in nearly 80% of all cases. Other risk factors for gallbladder carcinoma include a calcified gallbladder (known as porcelain gallbladder), a long common channel, and a chronic typhoid carrier state. Adenomas figure less prominently or not at all in the list of precursors.2

Unlike the colon, in which the concept of a definite adenoma-carcinoma sequence is accepted, in the gallbladder the relationship between adenoma and carcinoma is nebulous. Here, we present the case of a Bangladeshi man who underwent surgery for a polypoid lesion in the gallbladder detected incidentally on computed tomography scan in whom a gallbladder carcinoma was found arising from an adenoma.

Case Report

A 45-year-old Bangladeshi man who had visited the emergency room 2 weeks earlier for an acute bout of left lower quadrant pain of 1 day's duration was seen in the primary care clinic as part of his follow-up care. At presentation, the patient was asymptomatic. He denied having any abdominal pain, nausea, vomiting, fever, jaundice, or weight loss, as well as any history of smoking or drinking alcohol. He also denied having any similar episodes in the past, any other illness, or any family history of cancer.

On examination, the patient's vital signs were stable and he was afebrile. His abdomen was soft and nontender, with normal bowel sounds, and the remainder of the examination was unremarkable. His blood count, electrolytes, blood urea nitrogen, creatinine, and liver function tests were all within normal limits. Ultrasound examination of the abdomen revealed multiple polyps in the gallbladder suggestive of cholesterolosis, with a polypoid mass measuring 2.5 cm × 1.8 cm in the fundus of the gallbladder. There were no gallstones, and a computed tomography scan confirmed the finding of a lobular polypoid lesion in the fundus of the gallbladder (Figure 1).

Figure 1
Computed tomography scan showing a polypoid lesion in the gallbladder.

The patient subsequently underwent laparoscopic cholecystectomy. Histologic examination revealed that the lesion in the gallbladder was a superficially invasive, well-differentiated adenocarcinoma arising from a tubular adenoma (Figure 2). There was no lymphatic, venous, or perineural invasion, and the patient remains well after surgery.

Figure 2
Microscopic image of a tubular adenoma of the gallbladder with superficial invasion. The image shows a tubular adenoma in the upper right corner, from mucosal surface to deep Rokitansky-Aschoff sinus, characterized by complex tubular structures of intestinal-type ...


Gallbladder polyps are found in approximately 5% of the worldwide population.3,4 In a study involving 194,767 asymptomatic patients undergoing ultrasound examination, 10,926 patients (5.6%) had polyps.4 Ninety-five percent of gallbladder polyps are nonneoplastic in origin and the result of cholesterolosis, adenomyomatosis, or inflammation. Adenomas are rare and account for approximately 5% of all gallbladder polyps.2 In one study of resected gallbladder specimens, adenomas were found in only 0.15% of cases.5

When the size of a gallbladder polyp is less than 10 mm, the likelihood of malignancy is extremely rare. No cases of cancer were detected in a study of 38 patients with gallbladder polyps less than 10 mm in size who were followed for 5 years.6 However, polyps larger than 10 mm in size may be associated with malignancy, particularly if they are solitary or found in patients older than 60 years of age.7 In our patient, the lesion measured 2.5 cm × 1.8 cm, a size that is consistent with this finding, though the patient was only 45 years old.

Unlike the colon, in which the adenoma-carcinoma sequence is the accepted mechanism of carcinogenesis, in gallbladder cancer, the dysplasia-carcinoma pathway appears to be the predominant mechanism accounting for the majority of cases.8,9 This theory conjectures that chronic inflammation leads to dysplasia, which eventually causes cancer.9

The role of gallbladder adenoma in the pathogenesis of gallbladder carcinoma is controversial. It is thought that adenoma may play a role in some cases of gallbladder cancer. The adenoma-carcinoma sequence was first suggested by Kozuka and associates, who conducted a study of 1,605 resected gallbladder specimens and found 7 adenomas with malignant change and evidence of adenomatous residue in 15 of 79 (19%) invasive carcinomas. All adenomas with malignant change were more than 12 mm in size.10 The concomitant presence of adenoma and carcinoma seen in our patient is not a common finding8,11 and lends credence to the adenoma-carcinoma theory.

Other researchers, however, do not subscribe to the adenoma-carcinoma sequence for gallbladder carci-noma.12,13 Wistuba and coworkers performed molecular studies on tissue from gallbladder adenomas and detected no mutations in the TP53 gene, a frequent finding in dysplasia, carcinoma in situ, and invasive cancer, which led the researchers to conclude that adenomas are not precursors of invasive gallbladder carcinoma.12 Similarly, Roa and associates found no evidence of adenoma residue in their study of completely mapped early carcinomas of the gallbladder.13

Countries with a high incidence of gallbladder cancer include Chile, Poland, India, and Japan. There is also a very high incidence of this cancer among women in Northern India (21.5/100,000) and female Native American Indians (14.5/100,000).14 Our patient was of Bangladeshi (ie, the Indian subcontinent) origin. A recent study of 137,655 patients indicated that Indian ethnicity was an independent risk factor for developing gallbladder carcinoma in patients with gallbladder polyps.15 In this study, 50% of gallbladder polyps that were cancerous were less than 5 mm in size. An Indian patient with a single gallbladder polyp had a 1-in-13 likelihood of developing cancer. The authors concluded that the mere presence of a gallbladder polyp, regardless of size, in a patient of Indian descent should warrant further investigation or cholecystectomy.

In summary, our case report is important for two reasons: it emphasizes the importance of ethnic background in the management of patients with gallbladder polyps, and it indicates that the adenoma-carcinoma pathway may be valid in the pathogenesis of at least some gallbladder carcinomas.


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