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van Breda Vriesman et al. Diffuse Gallbladder Wall Thickening

H e p a t o b i l i a r y I m ag i n g • P i c t o r i a l E s s ay

Diffuse Gallbladder Wall Thickening: Differential Diagnosis Adriaan C. van Breda Vriesman1 Marc R. Engelbrecht2 Robin H. M. Smithuis1 Julien B. C. M. Puylaert3 van Breda Vriesman AC, Engelbrecht MR, Smithuis RHM, Puylaert JBCM

Keywords: abdominal imaging, acute abdomen, adenomyomatosis, cholecystitis, CT, gallbladder carcinoma, gallbladder disease, gallbladder thickening, sonography DOI:10.2214/AJR.05.1712 Received September 26, 2005; accepted after revision November 12, 2005. 1Department

of Radiology, Rijnland Hospital, Simon Smitweg 1, PO Box 4220, NL-2350 CC Leiderdorp, The Netherlands. Address correspondence to A. C. van Breda Vriesman ([email protected]).

2Department

of Radiology, UMC Radboud, Nijmegen, The Netherlands.

3Department

of Radiology, MCH Westeinde Hospital, The Hague, The Netherlands.

AJR 2007; 188:495–501 0361–803X/07/1882–495 © American Roentgen Ray Society

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OBJECTIVE. The objective of our study was to review and illustrate the various clinical entities that may cause diffuse thickening of the gallbladder wall on diagnostic imaging studies. CONCLUSION. Diffuse gallbladder wall thickening may be caused by a wide range of gallbladder diseases and extracholecystic pathologic conditions. In most cases its cause can be determined by correlation of the clinical presentation and associated imaging findings. hickening of the gallbladder wall is a relatively frequent finding on diagnostic imaging studies. Historically, a thick-walled gallbladder has been regarded as proof of primary gallbladder disease, and it is a well-known hallmark feature of acute cholecystitis. The finding itself, however, is nonspecific and can also be found in a variety of conditions unrelated to intrinsic gallbladder disease. Diffuse gallbladder wall thickening may produce a diagnostic problem because it occurs in symptomatic and asymptomatic patients and in patients with and those without an indication for cholecystectomy. Misinterpretation of the cause of this imaging finding can lead to an unnecessary cholecystectomy in patients without intrinsic gallbladder disease and, conversely, misdiagnosis in patients who do require a cholecystectomy may result in delayed treatment with increased morbidity. In this essay, we discuss and illustrate the various causes of a thickened gallbladder wall because knowledge of its differential diagnosis is essential for the correct interpretation of this finding.

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Normal and Thickened Gallbladder Sonography, CT, and MRI all allow direct visualization of the normal and thickened gallbladder wall. Traditionally, sonography is used as the initial imaging technique for evaluating patients with suspected gallbladder disease because of its high sensitivity in the detection of gallbladder stones, its real-time character, and its speed and portability [1]. However, CT has become popular for evaluating the acute abdomen and often is the first technique to show gallbladder wall thicken-

ing [2], or CT may be used as an adjunct to an inconclusive sonography examination or for staging of disease. The potential value of MRI in the evaluation of gallbladder disease has been shown [3], but it still plays little role. The normal gallbladder wall appears as a pencil-thin echogenic line on sonography (Fig. 1) and is usually visible on CT as a thin rim of soft-tissue density that enhances after contrast injection (Fig. 2). The thickness of the gallbladder wall depends on the degree of gallbladder distention, and pseudothickening can occur in the postprandial state (Fig. 1). A thickened gallbladder wall measures more than 3 mm, typically has a layered appearance at sonography [1], and frequently contains a hypodense layer of subserosal edema that mimics pericholecystic fluid at CT [2] (Fig. 3). Primary Gallbladder Disease Acute Cholecystitis Acute cholecystitis is the fourth most common cause of hospital admissions for patients presenting with an acute abdomen [4], and it is the prime diagnostic concern when a thick-walled gallbladder is found at imaging. This feature, however, is not pathognomonic, and additional imaging signs should be present to support the diagnosis of acute calculous cholecystitis, such as an obstructing gallstone (Fig. 4), hydropic dilatation of the gallbladder (Figs. 4 and 5), a positive sonographic “Murphy’s” sign (i.e., pain elicited by pressure over the sonographically located gallbladder), pericholecystic fat inflammation or fluid (Figs. 4 and 5), and hyperemia of the gallbladder wall at power Doppler imaging (Fig. 6).

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van Breda Vriesman et al. Acute acalculous cholecystitis mainly occurs in critically ill patients presumably because of increased bile viscosity from fasting and taking medication that causes cholestasis. The imaging features are those of acute cholecystitis except for the absence of stones and the presence, usually, of gallbladder sludge (Fig. 6). Because gallbladder abnormalities are frequently found secondary to systemic disease in critically ill patients, as we discuss later in this article, acalculous cholecystitis can be difficult to diagnose [5]. In these patients, a percutaneous cholecystostomy can be both diagnostic and therapeutic. Chronic Cholecystitis “Chronic cholecystitis” is a term used clinically to refer to symptomatic gallbladder stones that cause transient obstruction that leads to low-grade inflammation with fibrosis [1]. Correlation of the imaging finding of a stone-containing, slightly thick-walled gallbladder (Fig. 7) with clinical history is critical. Xanthogranulomatous cholecystitis is an unusual variant of chronic cholecystitis that is characterized by a lipid-laden inflammatory process comparable to xanthogranulomatous pyelonephritis. Imaging studies show marked gallbladder wall thickening, with the wall often containing nodules that are hypoechoic at sonography and hypoattenuating at CT (Fig. 8); these nodules are abscesses or foci of xanthogranulomatous inflammation. These features overlap with those of gallbladder carcinoma, often making preoperative distinction between these entities impossible [6]. A porcelain gallbladder is a rare disorder in which chronic cholecystitis produces mural calcification (Fig. 9). In these patients, a prophylactic cholecystectomy has been advocated because porcelain gallbladder has been associated with gallbladder carcinoma [4]; however, this association appears to be weak. Gallbladder Carcinoma Gallbladder carcinoma is the fifth most common malignancy of the gastrointestinal tract and is found incidentally in 1–3% of cholecystectomy specimens [4]. It is often detected at a late stage of the disease because of the lack of early or specific symptoms. Gallbladder carcinoma has various imaging appearances, ranging from a polypoid intraluminal lesion to an infiltrating mass replacing the gallbladder, and it may also present as diffuse mural thickening (Fig. 10). Associated findings such as invasion of adjacent structures, secondary bile duct dilatation, and liver or nodal metastases may help in

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differentiating it from acute or xanthogranulomatous cholecystitis [2, 4]. Adenomyomatosis Adenomyomatosis of the gallbladder is characterized by epithelial proliferation, muscular hypertrophia, and intramural diverticula (Rokitansky-Aschoff sinuses), which may segmentally or diffusely involve of the gallbladder. It is a benign condition that requires no specific treatment and occurs as an incidental finding in up to 9% of cholecystectomy specimens [6]. The sonographic finding of cholesterol crystals, shown as comet-tail reverberation artifacts (Fig. 11) within a thickened wall of the gallbladder strongly suggests this diagnosis. Air may produce a similar artifact; however, patients with emphysematous cholecystitis are usually ill in contrast to those with adenomyomatosis. MRI may be able to differentiate adenomyomatosis from gallbladder carcinoma by depicting RokitanskyAschoff sinuses [7]. Secondary Gallbladder Involvement Diffuse thickening of the gallbladder wall may occur in patients who do not have a primary gallbladder disease, but in whom the gallbladder is secondarily involved in an extrinsic pathologic condition. In these patients, a cholecystectomy is unwarranted, and gallbladder wall thickening will usually return to normal after correction of its extrinsic cause. Systemic Diseases Systemic diseases, such as liver dysfunction, heart failure, or kidney failure, may lead to diffuse gallbladder thickening [1, 2]. The exact pathophysiologic mechanism leading to edema of the gallbladder wall in these diverse conditions is uncertain, but it is likely due to elevated portal venous pressure, elevated systemic venous pressure, decreased intravascular osmotic pressure, or a combination of these factors. Liver cirrhosis (Fig. 12), hepatitis (Fig. 13), and congestive right heart failure (Fig. 14) are relatively frequent causes. Hypoproteinemia has also been reported as a cause of extrinsic gallbladder disease, but this finding has been disputed [8]. Extracholecystic Inflammation Extracholecystic inflammation may secondarily involve the gallbladder, thereby causing wall thickening due to the direct spread of the primary inflammation or, less frequently, due to an immunologic reaction [8]. Theoretically, gallbladder wall thicken-

ing may be caused by any inflammation that extends to the region of the gallbladder, but only a few entities are regularly encountered, including hepatitis, pancreatitis (Fig. 15), and pyelonephritis. Gallbladder wall thickening has also been reported in patients with infectious mononucleosis [9] and in patients with AIDS due to opportunistic infections or secondary neoplastic infiltration [2]. Conclusion Diffuse gallbladder wall thickening can result from a broad spectrum of pathologic conditions, including surgical and nonsurgical diseases. Although, at times, a definite imaging diagnosis may be impossible, the cause of gallbladder wall thickening can be determined in most cases by correlation of the clinical presentation and associated imaging findings.

References 1. Rumack CM, Wilson SR, Charboneau JW. Diagnostic ultrasound, 2nd ed. St. Louis, MO: Mosby, 1998:175–200 2. Zissin R, Osadchy A, Shapiro M, Gayer G. CT of a thickened-wall gallbladder. Br J Radiol 2003; 76:137–143 3. Jung SE, Lee JM, Lee K, et al. Gallbladder wall thickening: MR imaging and pathologic correlation with emphasis on layered pattern. Eur Radiol 2005; 15:694–701 4. Gore RM, Yaghmai V, Newmark GM, Berlin JW, Miller FH. Imaging of benign and malignant disease of the gallbladder. Radiol Clin North Am 2002; 40:1307–1323 5. Boland GWL, Slater G, Lu DSK, Eisenberg P, Lee MJ, Mueller PR. Prevalence and significance of gallbladder abnormalities seen on sonography in intensive care unit patients. AJR 2000; 174:973–977 6. Levy AD, Murakat LA, Abbott RM, Rohrmann CA. Benign tumors and tumorlike lesions of the gallbladder and extrahepatic bile ducts: radiologic–pathologic correlation. RadioGraphics 2002; 22:387–413 7. Yoshimitsu K, Honda H, Jimi M, et al. MR diagnosis of adenomyomatosis of the gallbladder and differentiation from gallbladder carcinoma: importance of showing Rokitansky-Aschoff sinuses. AJR 1999; 172:1535–1540 8. Kaftori JK, Pery M, Green J, Gaitini D. Thickness of the gallbladder wall in patients with hypoalbuminemia: a sonographic study of patients on peritoneal dialysis. AJR 1987; 148:1117–1118 9. Yamada K, Yamada H. Gallbladder wall thickening in mononucleosis syndromes. J Clin Ultrasound 2001; 29:322–325

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Diffuse Gallbladder Wall Thickening

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Fig. 1—35-year-old healthy male volunteer with normal gallbladder. A, Longitudinal sonogram of gallbladder, obtained after patient fasted for 12 hours, shows wall (arrow) as pencilthin echogenic line. B, Longitudinal sonogram in postprandial state shows pseudothickening of gallbladder wall (arrow) due to physiologic contraction.

Fig. 2—52-year-old man with normal gallbladder. Contrast-enhanced CT scan shows gallbladder wall as thin rim of enhancing soft-tissue density (arrowhead) surrounded by normal hypoattenuating fat.

Fig. 3—59-year-old woman with diffuse gallbladder wall thickening from acute cholecystitis. A, Longitudinal sonogram shows layered appearance of thickened gallbladder wall, with relatively hypoechoic region (arrowhead) between echogenic lines. B, Contrast-enhanced CT scan shows thick-walled gallbladder contains hypodense outer layer (arrow) that corresponds to subserosal edema, which may simulate pericholecystic fluid.

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Fig. 4—43-year-old woman with acute calculous cholecystitis. A and B, Contrast-enhanced CT scans show distended gallbladder (arrowheads, A) with slightly thickened wall and subtle regional fat stranding (asterisk, A). Impacted, obstructing stone (arrow, B) is seen in neck of gallbladder.

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B Fig. 5—62-year-old man with acute calculous cholecystitis. A, Transverse sonogram at spot of maximum tenderness shows noncompressible hydropically distended thick-walled gallbladder (arrowheads) and intraluminal stone and sludge or debris. B, Contrast-enhanced CT scan depicts extensive fat inflammation (arrowheads) surrounding gallbladder (arrow).

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Fig. 6—74-year-old man with acute acalculous cholecystitis. A, Longitudinal sonogram at spot of maximum tenderness shows mural thickening of gallbladder (arrow), which is completely filled with sludge (asterisk) without any stones. B, Power Doppler sonogram shows hypervascularity of gallbladder wall (arrowhead) as sign supporting diagnosis of inflammation. C, Contrast-enhanced CT scan depicts thick-walled gallbladder (arrow) filled with dense sludge (asterisk).

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Fig. 7—49-year-old woman with chronic cholecystitis. Longitudinal sonogram of gallbladder shows slight wall thickening (arrow) and intraluminal nonobstructing stone. This patient had fasted overnight, so wall thickening does not represent physiologic contraction. Correlation of these findings with her clinical history of recurrent coliclike right upper quadrant pain due to transient gallbladder obstruction is essential for diagnosis.

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Fig. 8—71-year-old man with xanthogranulomatous cholecystitis. A, Transverse sonogram of gallbladder shows marked wall thickening with intramural hypoechoic nodules (arrowheads) and intraluminal stone (arrow). B and C, Contrast-enhanced CT scans show deformed and thickened gallbladder wall (arrow, B) containing hypoattenuating nodules (arrowheads, C) that correspond to hypoechoic lesions, representing abscesses or foci of inflammation. Lumen contains several stones (arrow, C).

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Fig. 9—56-year-old man with porcelain gallbladder. A, Conventional abdominal radiograph depicts diffusely calcified gallbladder wall (arrowhead). B, Transverse sonogram of gallbladder shows calcification of anterior wall (arrowhead) with acoustic shadowing. C, Contrast-enhanced CT scan depicts circumferential calcification of gallbladder wall (arrow).

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van Breda Vriesman et al.

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Fig. 10—79-year-old man with gallbladder carcinoma. A, Longitudinal sonogram of gallbladder shows marked generalized wall thickening (arrowheads), replacing gallbladder lumen. Multiple gallbladder stones (arrow) indicate probable location of filled lumen. B, Contrast-enhanced CT scan depicts thick-walled gallbladder (arrowhead) with local infiltration of mass in adjacent liver (arrow). In absence of associated findings such as local invasion or metastases, it may not be possible to differentiate carcinoma from xanthogranulomatous cholecystitis. Note that gallstones are occult at CT.

C Fig. 11—39-year-old woman with adenomyomatosis of gallbladder. Longitudinal sonogram of gallbladder shows mural thickening with calcifications and stones, with characteristic comet-tail reverberation artifact (arrowhead) emanating from anterior wall. This is due to small cholesterol crystals within Rokitansky-Aschoff sinuses.

Fig. 12—56-year-old man with liver cirrhosis. A, Longitudinal sonogram of gallbladder depicts wall thickening (arrow) surrounded by ascites. Note irregular cirrhotic liver parenchyma. Secondary gallbladder wall thickening in patients with liver cirrhosis is presumably due to elevated portal venous pressure and decreased intravascular osmotic pressure. B, Contrast-enhanced CT scan shows wall of gallbladder (arrow) appears nearly normal because subserosal edema cannot be well differentiated from surrounding ascites at CT.

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Fig. 13—75-year-old man with drug-induced hepatitis. A, Longitudinal sonogram of nondistended gallbladder shows diffuse wall thickening (arrow) and incidental cholelithiasis, which may be confusing. B and C, MR images were obtained to evaluate bile ducts because of abnormal liver function tests. Axial SPIR (spectral presaturation by inversion recovery) T2-weighted image (B) shows small amount of ascites (arrowhead, B), which indicates that thickened gallbladder wall (arrow, B) probably has extrinsic systemic cause. Mural thickening of gallbladder (arrowhead, C) is also shown on oblique HASTE image (C) from MR cholangiography; this study excludes choledocholithiasis.

Fig. 14—74-year-old man with congestive right heart failure. A, Longitudinal sonogram of stone-free painless gallbladder depicts diffuse wall thickening (arrow). B, Transverse sonographic view through liver shows large-caliber hepatic veins (arrowheads) and inferior vena cava as supporting evidence of right heart failure.

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Fig. 15—56-year-old man with pancreatitis. Contrast-enhanced CT scan shows peripancreatic inflammatory changes (arrowheads) and thickening of wall of gallbladder (arrow), which is secondarily involved in pancreatic inflammation.

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