A Case of Tubular Adenoma of Gallbladder Diagnosed Using Contrast-Enhanced Ultrasonography.

Contrast-enhanced ultrasound (CEUS) has been used to diagnose gallbladder (GB) diseases for recent years because it is sensitive to visualize vascularity. Herein, we report a case who had a 1.7 cm × 1.2 cm polypoid lesion located in the gallbladder fundus with a feeding artery located in the stalk. On CEUS, the lesion showed early arterial phase enhancement (time to peak enhancement 18 s), persisting throughout the venous and delay phases. This enhancing pattern suggested that the lesion was a GB adenoma rather than a GB carcinoma. Cholecystectomy was performed, and pathology of the tissue revealed tubular adenoma of the GB.

INTRODUCTION

Gallbladder (GB) polyps are classified into neoplastic polyps (e.g. adenomas and adenocarcinomas) or nonneoplastic polyps (e.g., cholesterol polyps and adenomyomatosis.[1] In addition, motionless GB sludge can sometimes mimic polypoid lesion. Precisely, distinguishing benign polypoid GB lesions from malignant ones can help delineate better operative options and avoid unnecessary liver resection.[23] Contrast-enhanced ultrasound (CEUS) has been used to diagnose GB polypoid lesions for recent years because it can detect smaller (>40 um) blood vessels better than color Doppler (>100 um).[45] In this case report, we demonstrate how we used CEUS to distinguish GB adenoma from GB carcinoma in an older female patient.

CASE REPORT

A 75-year-old female was admitted to our hospital presenting fever with chills that had started 2 days prior. Physician examination found deep tenderness of the right upper quadrant of abdomen, for which abdominal sonography was arranged to rule out cholecystitis. While there was no evidence of acute cholecystitis on abdominal sonography, we found a polypoid lesion (1.7 cm × 1.2 cm) in the gallbladder fundus. The lesion had a cauliflower-like surface and was hyperechoic compared to the adjacent liver parenchyma. Color Doppler revealed a feeding artery in the stalk of the lesion, peak systolic velocity 15.2 cm/s, and resistive index 0.47 [Figure 1]. Our first impression was tumor growth. However, because grayscale and Doppler ultrasound cannot sufficiently differentiate benign lesions from malignant ones, we arranged for the patient to receive dynamic computed tomography (CT) study and CEUS. The dynamic CT study showed arterial enhancement and delayed phase washout of the GB lesion. This CT characteristic favors GB adenocarcinoma. On the contrary, on CEUS, the lesion showed early arterial phase enhancement (time to peak enhancement 18 s), with enhancement persisting throughout the venous and delay phases [Figure 2], which suggested that the lesion was more consistent with GB adenoma than adenocarcinoma. Cholecystectomy was performed, and the pathology of the tissue revealed tubular adenoma and chronic cholecystitis. The cause of the patient's fever was probably due to urinary tract infection. The urine analysis revealed pyuria, but urine culture only revealed yeast-like organism, and there was no growth of organism in both two sets of blood culture. The patient was discharged after complete empirical intravenous antibiotic treatment for 2 weeks and 6 days postsurgery.

Figure 1

(a and b) A 1.7 cm × 1.2 cm polypoid lesion in gallbladder fundus. The lesion has cauliflower-like surface and is hyperechoic compared with adjacent liver parenchyma. (c and d) Color Doppler revealed a feeding artery in the stalk of the lesion with peak systolic velocity 15.2 cm/s and resistive index 0.47

Figure 2

Contrast-enhanced ultrasound of the polypoid lesion: (a) 18 s, arterial phase; (b) 45 s, venous phase; and (c) 200 s, delay phase. (d) Enhancement intensity of gallbladder lesion and liver parenchyma over time. Notice the early arterial enhancement and persisting throughout the venous and delay phases. The time-to-peak enhancement was about 18 s

DISCUSSION

On grayscale ultrasound, GB adenomas, which are richly vascularized tumors, appear as sessile polypoid lesions and are isoechoic or hyperechoic compared with the liver.[56] On CEUS, GB adenomas appear with arterial enhancement and synchronous washout contrast enhancement pattern and homogeneity at peak-time enhancement.[7] It is challenging to differentiate GB adenomas from adenocarcinomas because early-stage adenocarcinoma may also present as a polypoid lesion with arterial enhancement.[6] Two studies have compared GB adenocarcinomas and with other benign GB lesions.[48] GB adenocarcinomas have been found more in older patients and males and larger in size and have a lower echogenicity on ultrasound (compared with liver), have wider stalks, longer time to peak enhancement (on CEUS), branch or liner intralesional vascularity (on CEUS), a heterogeneous enhancement pattern, and evidence of wall destruction.[48] Of these characteristics, destruction of GB wall integrity is the best diagnostic indicator of malignancy.[79] When using CEUS to study a polypoid GB lesion, if time to peak enhancement is >20 s, it is highly possible that it is GB adenocarcinoma (89% sensitivity and 84% specificity); however, if time to peak enhancement of the lesion is <20 s, it is more likely a GB adenoma or cholesterol polyp.[8] Malignant lesions have been found to have a shorter washout time than benign lesions.[10] According to one study,[11] lesions with washout time longer than 35 s are presumed benign and those with washout times <35 s malignant. One retrospective study found an irregular shape, branched intralesional vessels, and hypoenhancement in the late phase to indicate malignancy in lesions.[9] CEUS is generally a reliable, noninvasive, and nonradiative imaging modality with high sensitivity and specificity for detection of GB carcinomas,[12] which appear as “slowly” arterial enhancement and early washout. Knowledge of these characteristics is important because our ability to distinguish GB adenomas and adenocarcinomas allows to arrange for the most suitable surgical strategy and helps us avoid unnecessary resection of liver.

In the case presented here, on CEUS, the lesion showed early arterial enhancement with a time to peak enhancement of 18 s, which was <20 s, and enhancement persisting throughout the venous and delay phases. This enhancement pattern indicates that the patient's lesion was a GB adenoma, not GB cancer. CEUS can also help differentiate other polypoid-like GB lesions such as cholesterol polyps and motionless sludge or GB wall thickening such as that found in adenomyomatosis. Cholesterol polyps are usually found in multiples, between 2 and 5 mm in size, and in contact with the GB wall.[56] On CEUS, arterial enhancement is noted in up to 93% of the lesions, and in late phase, hypoenhancement or isoenhancement can be seen.[25613] Differentiating GB adenomas from cholesterol polyps could be difficult. While GB polyps are more heterogeneous at peak-time enhancement than adenomas,[17] some researchers have found no significant difference in enhancement pattern between the two; instead, cholesterol polyps tend to have lower enhancement intensity and narrower stalks.[3] Adenomyomatosis may present as focal, segmental, or diffuse.[14] On grayscale ultrasound, it presents as focal or diffuse GB wall thickening with small anechoic cystic spaces, intramural echogenic spots, or “comet tail” artifacts, depending on the content filling the Rokitansky–Aschoff sinuses (RAS).[561415] Without the typical presentations above, it would be difficult to distinguish a thickening wall associated with adenomyomatosis from GB carcinoma. On CEUS, adenomyomatosis is seen as a “moth-eaten” enhancement pattern in the arterial phase; a pattern results from nonenhancement of the RAS zone contrasted by normally enhanced healthy wall.[5681314] The use of CEUS can improve visualization of RAS and intact GB wall.[13] Dense motionless sludge balls can mimic neoplastic lesions. Color Doppler shows no blood flow on sludge. However, a Doppler signal might be detected in sludge due to motion artifact, and its signal might not be seen in neoplastic lesions due to slow perfusion.[5] CEUS has higher sensitivity than color Doppler for detecting blood flow, which makes it more useful for differentiating a nonenhancing sludge ball from enhancing neoplasm. On CEUS, no enhancement is observed at any time during visualization because there is no vascularization in sludge.[2] Therefore, CEUS has a sensitivity of almost 100% when differentiating motionless sludge from GB carcinomas.[6] The summary of polypoid GB lesions is shown in Table 1.

Table 1

Summary of polypoid gallbladder lesions

	Grayscale	Doppler	CEUS
Adenomas	Solitary, usually 5-20 mm	Intra-lesional vascularity	Arterial enhancement (shorter time-to-peak enhancement)
	Isoechoic or hyperechoic		Homogenous enhancement
	No GB wall destruction		Enhance persistent to venous and delay phases
Adenocarcinoma	Solitary, usually > 1cm	Intra-lesional vascularity	Arterial enhancement (longer time-to-peak enhancement)
	Hypoechoic		Heterogeneous enhancement
	GB wall destruction		Washout in venous and delay phases
	Wider stalks
Cholesterol polyp	Multiples, usually 2-5mm	Intra-lesional vascularity	Arterial enhancement
	Narrower stalks
			Variable echogenicity in later phases
Focal adenomyomatosis	Usually in fundus, usually 10-20mm	No significant vascularity	“Moth-eaten” pattern in arterial phase
	“Comet tail” artifacts	“Twinkling” artifacts
	± Small anechoic cystic spaces
	± Intra-mural echogenic spots
Motionless sludge balls	Variable echogenicity, ± punctate hyperechoic foci	No significant vascularity	No enhancement
		“Twinkling” artifacts
	No posterior acoustic shadowing

Limitations of current studies of the use of CEUS in detecting GB carcinoma are a small number of patients with GB cancer, and there is a shortage of enhancement intensity data. More studies with a larger population are needed for evaluating the rule of CEUS in differential GB polypoid lesions.

In recent guideline,[16] management of GB polyp is based on its size for GB polyp >1 cm having increased risk of malignancy and cholecystectomy should be considered. GB polyps can be categorized into cholesterol polyps, adenomas, and adenocarcinomas. Cholesterol polyps are usually <1 cm and only needs regular follow-up. For GB polyps >1 cm, CEUS can be used to differentiate GB adenomas from adenocarcinomas. While GB adenomas are recognized by early enhancement at arterial phase persisting throughout the venous and delay phases, adenocarcinomas are recognized by early enhancement in the arterial phase and early washout in the venous phase. Although CEUS has not been recommended by European Federation of Societies for Ultrasound in Medicine and Biology guidelines for the routine differentiation of benign from malignant GB polyps,[17] we believe that it can play an important role in precisely differentiating GB polypoid lesions. We have found that CEUS helps us diagnose polypoid GB lesions with more confidence, decide on suitable operative strategies for the patients.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.