ª Springer Science+Business Media New York 2014

Abdominal Imaging

Abdom Imaging (2014) DOI: 10.1007/s00261-014-0203-0

The gallbladder: uncommon gallbladder conditions and unusual presentations of the common gallbladder pathological processes Margarita V. Revzin, Leslie Scoutt, Edward Smitaman, Gary M. Israel Department of Radiology, Yale School of Medicine, 20 York St, New Haven, CT 06510, USA

Abstract This article reviews a spectrum of gallbladder conditions that are either uncommon or represent unusual manifestations of common diseases. These conditions are divided into four major categories: (a) congenital anomalies and normal variants including duplication, ectopia, and lymphangioma; (b) inflammatory processes and stone-related diseases and complications including adenomyomatosis, emphysematous cholecystitis, xanthogranulomatous cholecystitis, gangrenous and hemorrhagic cholecystitis, perforation, gallstone ileus, and Bouveret and Mirizzi syndromes; (c) gallbladder neoplasms including adenocarcinoma with associated porcelain gallbladder, squamous cell carcinoma, lymphoma, melanoma, and neurofibroma. A thorough understanding of the imaging characteristics of each condition can help the radiologist to make a timely and accurate diagnosis, thus avoiding potentially harmful delays in patient management and decreasing morbidity and mortality rates. Key words: Gallbladder ectopia—Cholecystitis complications—Duplication—Gallbladder cancer— Adenomyomatosis

A wide spectrum of diseases affects the gallbladder. An estimated twenty million Americans have gallbladder disease, and high mortality rates are associated with some forms of gallbladder pathology. A better understanding of various presentations of benign and malignant diseases of the gallbladder and their possible complications is necessary to improve patient management and outcomes. In this article, we will discuss imaging strategies used to differentiate many uncommon gallbladder conditions and unusual presentations of common gallbladder pathologies.

Congenital anomalies and normal variants General overview The mean average length of the gallbladder in adults is 7–10 cm, width 2–3.5 cm, volume 30–50 cc, and wall thickness 2–3 mm. The gallbladder is located in a fossa on the lower surface of the liver in the plane between the left and right hepatic lobes. The gallbladder wall is composed of four layers: mucosa, lamina propria, muscularis propria, and serosa; the gallbladder has no muscularis mucosa or submucosa [1]. Congenital malformations of the gallbladder may be characterized by location, size, number, and shape. Variation in the gallbladder location is the most common congenital anomaly. Agenesis and duplication of the gallbladder are rare. Multiseptate gallbladder is very uncommon.

Septations of the gallbladder and gallbladder duplication There are several types of gallbladder septations, including longitudinal septations, transverse septa, and diverticula [2]. Gallbladder duplications are rare with an incidence of 1 in 3-4000 and a female to male ratio of 1:2 [2, 3]. The imaging differential diagnosis includes a folded gallbladder, choledochal cyst, Phrygian cap, gallbladder diverticulum, focal adenomyomatosis, and fibrous or vascular bands [4, 5]. On imaging, a duplicated GB is divided by a longitudinal septum with two separate lumens and either a common or two cystic ducts (Fig. 1). The duplicated gallbladder may become inflamed with either independent involvement of one of the two lumens or both lumens may be involved.

Gallbladder ectopia Correspondence to: Margarita V. Revzin; email: [email protected] yale.edu

While anomalous positions of the gallbladder are rare, the most common ectopic locations are (1) under the left

M. V. Revzin et al.: The common gallbladder pathological processes

abnormally long mesentery suspending the gallbladder from the liver bed has increased propensity for rotational instability [7]. The diagnosis is usually made intraoperatively and can be benign if recognized early. Delay in diagnosis may lead to gallbladder rupture and biliary peritonitis.

Lymphangioma of the gallbladder wall

Fig. 1. Duplicated gallbladder in a 53-year-old female presented with abdominal pain. Axial T2 fat-suppressed MRI reveals duplicated gallbladder lumen each of which contains gallstones (arrows). Cystic ducts were separate at surgery, not shown.

hepatic lobe, (2) intrahepatic (Fig. 2), (3) transverse, and (4) retroplaced (retrohepatic or retroperitoneal). If the gallbladder is variably positioned on different imaging studies, this likely represent a floating GB, a condition which is due to loose peritoneal reflections [6]. Torsion of the gallbladder, or gallbladder volvulus, is a rare disease that leads to occlusive obstruction of biliary drainage and blood flow. The etiology of this condition is uncertain and may be related to a congenital anomaly of the gallbladder, such as floating GB described above, or alternatively could be sequela of acquired liver atrophy. It has been postulated that an

A lymphangioma arising from the gallbladder is an extremely rare condition, representing only 0.8 %–1% of all intraabdominal lymphangiomas [8]. On ultrasound, a lymphangioma appears as a simple or multilocular anechoic fluid-filled septated mass in the gallbladder fossa. No significant blood flow is detected on color or power Doppler evaluation (Fig. 3A). CT findings are nonspecific, revealing a cystic or multiloculated lesion of water density. The internal structure of the lymphangioma is less defined on contrast-enhanced CT. The walls may demonstrate enhancement. Ultrasound and CT are limited in their ability to determine the origin of the mass and its relationship to the gallbladder wall, lumen, and biliary tree. Axial T1- and T2-weighted images and MRCP allow for clear identification of the mass and its relationship to the gallbladder wall (Fig. 3B). MRCP aids in demonstration of possible communication with or preservation of bile ducts and cystic ducts, an important consideration in surgical management. When accompanied by hemorrhage or infection, differentiation from other cystic tumors may be difficult. Management of lymphangiomas is usually surgical excision. If the lesion is completely resected, prognosis is excellent [8].

Uncommon inflammatory and stonerelated diseases of the gallbladder Porcelain gallbladder

Fig. 2. Intrahepatic gallbladder in a 25-year-old asymptomatic female. Coronal contrast-enhanced CT demonstrating anomalous location of the gallbladder within the parenchyma of the liver. The gallbladder is entirely surrounded by the liver parenchyma.

Porcelain gallbladder is caused by calcium carbonate deposition in the gallbladder wall, with a 5:1 female to male predilection [9]. It is associated with chronic gallbladder inflammation. The clinical significance of porcelain gallbladder is an increased risk of gallbladder carcinoma, and 10%–25% of patients with this condition have gallbladder carcinoma [9]. On US, three patterns of wall calcification are recognized: (1) a hyperechoic semilunar structure with dense posterior acoustic shadowing, (2) a biconvex curvilinear echogenic structure with acoustic shadowing, and (3) irregular clumps of echoes with posterior acoustic shadowing [10] (Fig. 4A). Porcelain gallbladder should be differentiated from a gallbladder entirely filled with stones and sludge, which on ultrasound has a characteristic appearance termed as the ‘‘wall-echo-shadow’’ sign. If the posterior wall of the gallbladder is seen on gray scale, then a gallbladder filled with stones can be excluded. Another major differential

M. V. Revzin et al.: The common gallbladder pathological processes

Fig. 3. Lymphangioma of the gallbladder in a 26-year-old male presented with chronic epigastric pain. A Sagittal color Doppler ultrasound image through the gallbladder demonstrates an avascular multiloculated cystic mass (arrowheads) with tubular anechoic areas and thick septations within the gallbladder fossa, between the liver and gallbladder. B Coronal fat-suppressed T2WI demonstrates cystic composition of the mass (asterisk) that partially surrounds the gallbladder, septations are vaguely visualized. No communication is seen with the biliary system.

Fig. 4. Porcelain gallbladder. A Sagittal ultrasound image of the gallbladder reveals curvilinear echogenicity (arrow) along the anterior wall of the gallbladder with posterior acoustic shadowing. B Contrast-enhanced axial CT image in a different patient shows irregular clumps of calcification within the wall of the gallbladder.

Adenomyomatosis diagnosis for porcelain gallbladder is emphysematous cholecystitis, which has characteristic ring-down artifacts produced by the wall or luminal gas. In some cases, it is not possible to differentiate these three entities sonographically, and in these instances abdominal radiographs and CT are helpful [10] (Fig. 4B). When wall calcification is detected, a careful search should be made for evidence of malignancy. Due to the association of porcelain gallbladder with gallbladder cancer, prophylactic cholecystectomy is sometimes recommended.

Adenomyomatosis is a benign hyperplastic cholecystosis. Epithelium-lined cystic spaces or outpouchings in the thickened muscular layer of the gallbladder wall are called intramural diverticula or Rokitansky-Aschoff sinuses, which develop with increasing age. It is a common condition, identified in at least 5% of cholecystectomy specimens [11–14]. Cholesterol crystals, sludge, and calculi collect in the Rokitansky-Aschoff sinuses. Distinct morphological subtypes include diffuse, segmental (annular form with ‘‘hourglass’’ configuration of the gallbladder

M. V. Revzin et al.: The common gallbladder pathological processes

Fig. 5. Adenomyomatosis. A Sagittal gray scale ultrasound images through the gallbladder reveal a focal area of gallbladder wall thickening (arrow heads) with associated several echogenic foci with ‘‘comet tail’’ artifacts emanating from the fundal portion of the gallbladder consistent with a typical presentation of focal adenomyomatosis (arrows). B Sagittal gray scale image through the gallbladder in a 71-year-old male with right upper quadrant pain shows marked diffuse gallbladder wall thickening (long arrows). Multiple echogenic foci emanating from the wall of the gallbladder with associated ‘‘comet tail’’ artifacts represent cholesterol crystals within the Rokitansky-Aschoff sinuses (short arrow). Twinkle artifact was present on color Doppler images signifying the

presence of stones/calculi/cholesterol crystals within the sinuses (not shown). A stone is present within the neck of the partially decompressed gallbladder (arrow head), small amount of pericholecystic fluid is noted (star). C Contrastenhanced CT in a different patient shows discrete hypoattenuating intramural lesions (long arrows) representing large (>5 mm) Rokitansky-Aschoff sinuses. Focal calcifications are present within the sinuses (short arrow). D Axial T2WI of the gallbladder demonstrates a ‘‘pearl necklace sign’’ representing multiple dilated Rokitansky-Aschoff sinuses (arrows). Areas of signal void correspond to stones within the sinuses (arrows). Stones are also present within the gallbladder lumen.

likely due to the presence of a transverse congenital septum in the body of gallbladder), and focal or fundal (adenomyoma) [15]. Due to variation in morphology, adenomyomatosis can appear as diffuse gallbladder wall thickening or a focal lesion, simulating gallbladder carcinoma. Ultrasound is the primary modality for the detection of adenomyomatosis, which can be diagnosed when echogenic intramural foci with a ‘‘V-shaped’’ or ‘‘comet tail’’ posterior reverberation artifact (which will appear as a twinkle artifact on color Doppler) are observed. Adeno-

myomatosis is most easily found along the anterior wall as the echogenic contents of the underlying duodenum may obscure visualization of the findings along the posterior wall (Fig. 5A). In rare instances, adenomyomatosis may be very extensive and on ultrasound may have a more atypical presentation, with a markedly thickened irregular wall and multiple ‘‘comet tail’’ artifacts. This can make it difficult to differentiate from gallbladder carcinoma (Fig. 5B). In this situation, surveillance with annual ultrasounds and MRI may be necessary. If large enough

M. V. Revzin et al.: The common gallbladder pathological processes

(>5 mm), Rokitansky-Aschoff sinuses can be detected on contrast-enhanced CT, as discrete hypoattenuating intramural lesions with enhancing epithelium within, representing a ‘‘rosary sign’’ (Fig. 5C). On MR imaging, Rokitansky-Aschoff sinuses appear hyperintense on T2WI, hypointense on T1WI, and do not enhance. The ‘‘pearl necklace sign,’’ most specific sign of adenomyomatosis on MRI, is attributable to the necklace-like arrangement of the multiple ovoid diverticula visualized on T2WI. Intraluminal calculi, depending on their mineral content, may appear as signal voids on both T2WI and T1WI [15] (Fig. 5D).

Xanthogranulomatous cholecystitis Xanthogranulomatous cholecystitis (XGC) is an uncommon variant of chronic cholecystitis, usually presenting in 7th–8th decade of life, with a predilection for women [16, 17]. XGC is believed to develop as a sequela of rupture of the Rokitansky-Aschoff sinuses with subsequent intramural extravasation of inspissated bile and mucin into the wall of the gallbladder. Extravasated bile causes an inflammatory reaction with formation of characteristic intramural xanthogranulomatous nodules. Complications are found in 32% of cases and include perforation, abscess formation, fistulous tracts to the duodenum or skin, and extension of the inflammatory process to the liver, colon, or surrounding soft tissues [1]. On imaging gallbladder, wall thickening (3–25 mm), may be diffuse or focal, with or without definition of the wall margin is a hallmark of XGC [18, 19]. On ultrasound, the key point is recognition of the intramural hypoechoic nodules which correspond to small intramural abscesses and foci of xanthogranulomatous inflammation. Other sonographic findings include disruption of the mucosal lining, pericholecystic fluid, intraluminal stones and sludge, and mass-like hypoechogenicity of the adjacent liver [20]. CT findings include the presence of 5–20 mm intramural hypoattenuating nodules with general heterogeneous or poor wall enhancement. The key points to accurately differentiate this condition from carcinoma of the gallbladder wall are to see a combination of at least three of five characteristic CT findings: (1) continuous linear enhancement of the mucosa (intact 2–3-mm-thick mucosal lining), (2) intramural hypo-attenuated nodules, (3) diffuse thickening of the gallbladder wall (seen in 91% of XGC), as carcinoma is more focal in its presentation if solitary, (4) the absence of macroscopic hepatic invasion (45%), and (5) the absence of intrahepatic biliary ductal dilatation (36%) [21]. Lymphadenopathy may be seen in 36% of patients with XGC. MR imaging demonstrates focal or diffuse gallbladder wall thickening with preservation of linear mucosal enhancement suggestive of XGC rather than carcinoma. Small intramural abscesses may be demonstrated as foci of high signal on T2WI and low signal on T1WI and reveal no enhancement [22] (Fig. 6).

Fig. 6. Xanthogranulomatous cholecystitis in a 65-year-old female with chronic abdominal pain. Axial T2WI MR reveals a distorted gallbladder (arrow) with multiple cystic collections within the gallbladder wall (arrowheads) consistent with necrosis and infiltration by foam cells.

Emphysematous cholecystitis Emphysematous cholecystitis is a rare form of acute cholecystitis. There is a sex predilection with males being affected in 71% of cases [23, 24]. Most patients are presented in the 6th and 7th decades. Predisposing risk factors are diabetes (up to 50%), debilitating disease, cystic duct obstruction, and peripheral atherosclerotic disease causing vascular compromise to the cystic artery [24–26]. Emphysematous cholecystitis radiographically is characterized by the presence of air within the lumen of gallbladder, gallbladder wall, or pericholecystic tissue in the absence of an abnormal communication between the biliary system and gastrointestinal tract [23]. Sonographically, emphysematous cholecystitis is manifested as very bright reflections from a nondependent portion of the gallbladder wall with associated dirty shadowing, and in many cases with a ring-down artifact that is a reliable sign of gas (Fig. 7A). The pitfall on ultrasound is that gas may mimic a gallbladder full of stones or porcelain gallbladder. However, gas may change in position with patient movement, thus helping to reach the correct diagnosis [27]. CT imaging has 100% sensitivity for detection of emphysematous cholecystitis (Fig. 7B). On MRI, a distinct rim of hypointense signal around the gallbladder signifies the presence of air (Fig. 7C). Management is emergent surgical intervention.

Gangrenous cholecystitis Gangrenous cholecystitis is a severe form of acute cholecystitis. The incidence of gangrenous cholecystitis ranges from 2% to 29.6% in patients admitted with acute cholecystitis. Usually, it affects males with cardiovascular disease, and is associated with leukocytosis [28, 29].

M. V. Revzin et al.: The common gallbladder pathological processes

Emphysematous cholecystitis in a 79-year-old diabetic male with low grade temperature and abdominal pain. A Sagittal gray scale image through the gallbladder fossa reveals echogenic arc lines (arrows) in the nondependent portion of the gallbladder with associated dirty shadowing and reverberation artifacts. This appearance could easily be mistaken for air in the duodenum. B Noncontrast CT shows extensive air within the wall of the gallbladder (arrow). C T2 HASTE MR image at a later time reveals gallbladder wall thickening and associated signal void in the gallbladder wall corresponding to the intramural air (arrow). A small amount of pericholecystic fluid is present. Note an air-fluid level in the gallbladder lumen.

b Fig. 7.

Asymmetric gallbladder wall thickening is attributable to intramural microabscesses, intramural hemorrhage, and complex pericholecystic fluid collections containing debris [30]. A Murphy’s sign is not detected in over 67% of patients due to ischemic denervation [31]. A striated appearance of the thickened gallbladder wall with alternating hypo and hyperechoic bands may be observed [32]. Air with associated dirty shadowing and reverberation artifacts is seen in complicated gangrenous cholecystitis. On contrast-enhanced CT, there are certain findings that should raise suspicion for gangrenous cholecystitis including gallbladder distension, irregular wall, wall striations, decreased wall enhancement, intraluminal membranes, pericholecystic inflammation, gallstones, pericholecystic fluid, pericholecystic liver enhancement, pericholecystic abscess, and gas in gallbladder wall [33–35]. Of these, decreased wall enhancement and pericholecystic stranding in the absence of gallstones are the most sensitive and specific findings. On unenhanced CT, the presence of a hyperdense wall is highly suggestive of acute gangrenous cholecystis and is attributable to intramural hemorrhage [36] (Fig. 8B). On MRI, a gangrenous cholecystitis may be diagnosed when the presence of the interrupted rim sign or patchy enhancement of the gallbladder mucosa is observed.

Hemorrhagic cholecystitis

On ultrasound, gangrenous cholecystitis can be suspected if one detects intraluminal membranes and marked asymmetry of the gallbladder wall sometimes with irregular mass-like protrusions into the gallbladder lumen or frank discontinuation of the mucosa (Fig. 8A).

Hemorrhage within the gallbladder is a rare complication of acute cholecystitis with a high mortality rate and an incidence of 8%–12% in patients with severe acute cholecystitis [37]. Hemorrhage is caused by infarction and erosion of the mucosa secondary to transmural inflammation of the gallbladder wall. Biliary colic, hematemesis, jaundice, and melena form a classic but uncommonly seen clinical syndrome in patients with hemorrhagic cholecystitis. Sonographic findings include a distended gallbladder with focal wall thickening and irregularity [38], intraluminal membranes, nonshadowing, and nonmobile avascular echogenic intraluminal material [39, 40] (Fig. 9A). The echogenicity of the blood products is very similar but typically slightly more heterogeneous than tumefactive sludge—a mimic of

M. V. Revzin et al.: The common gallbladder pathological processes

Fig. 8. Gangrenous cholecystitis in a 72-year-old female with right upper quadrant and shoulder pain. A Sagittal gray scale ultrasound image demonstrating a distended gallbladder with diffuse thickening and edema of the gallbladder wall. Intraluminal sludge is present. Mucosal lining is irregular with interruption of the mucosa in the mid portion of the gallbladder (arrow) consistent with perforation and associated moderate amount of pericholecystic fluid (asterisk). B Axial contrastenhanced CT showing distended gallbladder with irregularity of the gallbladder wall, the presence of intraluminal membranes (arrow), pericholecystic fluid, and inflammation.

intraluminal hemorrhage on US [38]. In some instances, layering of the echogenic material can be seen. An organized thrombus can simulate an intraluminal mass/ cancer but will not demonstrate blood flow on Doppler interrogation. CT findings include high attenuation material within gallbladder lumen sometimes with fluidfluid levels [38, 41] (Fig. 9B). Urgent cholecystectomy is necessary to prevent perforation. On MR imaging, hemorrhagic components are hyperintense on T1WI and may have variable signal intensity on T2WI based on the oxygenation state of the hemoglobin, i.e., time course.

Fig. 9. Hemorrhagic cholecystitis in a 43-year-old female with right upper quadrant pain and elevated LFTs. A Sagittal color Doppler image demonstrates distended gallbladder with large amount of intraluminal echogenic heterogeneous avascular layering material, compatible with blood products (arrows). Thickening of the gallbladder wall is less apparent due to silhouetting by the echogenic material. B Axial contrast-enhanced CT demonstrates hyperdense material within the distended gallbladder (curved arrow). Associated thickening of the gallbladder wall, intraluminal calculi (arrow), and pericholecystic inflammatory changes are also seen.

Perforated gallbladder Perforation of the gallbladder is an uncommon complication of acute cholecystitis, seen in 6%–12% of cases, and is associated with a high mortality rate [42–44].

M. V. Revzin et al.: The common gallbladder pathological processes

Fig. 10. Gallstone ileus in a 60-year-old female with epigastric pain and several dilated segments of small bowel. Coronal contrast-enhanced CT demonstrates Rigler’s triad manifested by dilated loops of small bowel secondary to bowel obstruction, pneumobilia (arrowhead), and ectopic gallstones (circle) in the right lower quadrant. Decompressed gallbladder with thickened wall (arrow).

Fig. 12. Mirizzi’s syndrome in a 30-year-old female with epigastric pain. A, B Sagittal gray scale and Color Doppler images of the gallbladder fossa reveal an impacted stone (arrow) at the gallbladder neck at the level of the porta hepatis with associated dilatation of the CBD (asterisk) more proximal to the stone.

abscess, Type III—chronic, manifested by formation of internal (bilio/ biliary or biliary-enteric) or external fistulae [45]. On US, CT, and MRI, the findings are similar and include the presence of pericholecystic complex fluid collections, the presence of focally disrupted gallbladder wall, gallbladder wall thickening, bulging, layering, and cholelithiasis [44, 46] (Fig. 8A). Fig. 11. Bouveret Syndrome in a 68-year-old male with acute onset of abdominal pain and vomiting. Axial unenhanced CT image demonstrates markedly distended stomach (asterisk) consistent with gastric outlet obstruction; and ectopic gallstones in the gastric pylorus (circled). Extensive pneumobilia was present (not shown).

Three types of gallbladder perforation are recognized: Type I—acute, present with generalized peritonitis, Type II—subacute, manifested by formation of pericholecystic

Type III perforation of the gallbladder with fistula formation Cholecystoduodenal/gastric/CHD fistulization is formed by erosion of a gallstone into an adjacent viscous.

Gallstone ileus Gallstone ileus is a mechanical intestinal obstruction caused by a gallstone that has eroded into the

M. V. Revzin et al.: The common gallbladder pathological processes

gastrointestinal tract (bowel lumen). High mortality (10%– 25%) is attributable to delayed diagnosis and the presence of comorbidities in the elderly [47–49]. There is predilection for female elderly patients, with reported mean age of 74–80 years [50, 51]. There is a female:male ratio of 6:1 [52–54]. Gallstone(s) usually erode into the bowel lumen at the level of the duodenum. The site of obstruction is commonly either at the ileocecal valve, the narrowest caliber of the bowel, or at the duodeno-jejunal junction [55–57]. Rarely, the obstruction occurs in the stomach or proximal duodenum (Bouveret’s syndrome) [58]. Sonographically, findings related to acute cholecystitis with intraluminal air and pneumobilia secondary to the fistula may be observed. Signs of bowel obstruction can also be detected with US in 44% of cases [59]. The characteristic CT findings, an equivalent of Rigler’s triad, include bowel obstruction, intraheptic and cholecystic pneumobilia (both gallbladder and bile ducts), and a radiopaque ectopic gallstone at the transition point of the bowel obstruction (seen in 82%) (Fig. 10). The full or complete Rigler’s triad is observed in 78% of patients on CT [59].

Bouveret syndrome Obstruction of the gastric outlet is a rare variant of gallstone-induced ileus. Bouveret syndrome is a gastric obstruction produced by a gallstone impacted in the distal stomach or proximal duodenum, accounting for only 2%–3% of all intestinal gallstone obstructions [58, 60] (Fig. 11). Endoscopic management and early diagnosis with CT or MR have improved mortality rates.

Mirizzi syndrome Mirizzi syndrome is a rare complication of cholelithiasis that is caused by extrinsic right-sided compression and subsequent obstruction of the common hepatic duct by large gallstone impacted in the cystic duct, the gallbladder neck, or in the cystic duct remnant. This usually is accompanied by chronic inflammatory reaction. Two types of this syndrome are recognized: Type I representing a simple obstruction of the common hepatic duct and Type II in which erosion of the wall of the common hepatic duct (CHD) results in formation of a fistula between the gallbladder and common hepatic duct. Predisposing anatomical conditions include parallel course of the cystic duct in relationship to the common hepatic duct, and low insertion of the cystic duct. Sonographic, CT, and MRCP findings include identification of an impacted gallstone in the gallbladder neck or at the junction of the CHD and cystic duct, and associated biliary obstruction above the level of the cystic duct, smooth-curved segmental stenosis of the CHD, and inflammation of the gallbladder with thickening of the gallbladder wall (Fig. 12A, B). If not recognized, surgery may be complicated by injury to the hepatic duct [30, 61].

Fig. 13. Porcelain gallbladder with associated invasive gallbladder cancer in a 54-year-old woman with increasing abdominal pain. A Transverse gray scale ultrasound image through the gallbladder demonstrates curvilinear calcification with the gallbladder wall (arrow) with associated sharp acoustic shadowing posterior to the gallbladder wall calcification (asterisk) indicative of porcelain gallbladder. In the adjacent liver parenchyma, there is a hypoechoic heterogeneous area compatible with invasion of the adjacent liver by cancer (arrow heads). B Axial fat-suppressed T2WI demonstrates hypointense line within the gallbladder wall compatible with the gallbladder wall calcifications (arrow head). A hyperintense heterogeneous area in the adjacent liver parenchyma corresponds to the necrotic mass invading the adjacent liver parenchyma (arrow). Note gallstones, sludge, small metastatic lesion in the segment 6 of the liver. Incidental note is made of a complex mass in the right kidney.

Neoplasms Primary gallbladder cancer: adenocarcinoma and adenosquamous/squamous cell carcinoma Primary carcinoma of the gallbladder is an uncommon but aggressive malignancy. In the United States it is the sixth most common GI malignancy, usually affecting the elderly population [62–65]. Adenocarcinomas account for 90% of gallbladder malignant neoplasms [65]. Adenosquamous/squamous cell carcinomas (ASC/SCC)

M. V. Revzin et al.: The common gallbladder pathological processes

Fig. 15. Gallbladder lymphoma in a 50-year-old male with abdominal pain. Axial fat-suppressed T2 WI MR demonstrate diffuse mural thickening of the gallbladder wall (arrow) and extensive retroperitoneal lymphadenopathy encasing the celiac axis (asterisk). Note the gallbladder is underdistended.

Fig. 14. Primary squamous cell carcinoma of the gallbladder in a 77-year-old female with jaundice and right upper quadrant pain. A Sagittal color Doppler ultrasound through the right upper quadrant demonstrates a large circumferential heterogeneous slightly hyperechoic mass infiltrating the wall of the gallbladder (short white arrows). Internal vascularity is demonstrated. Stones are seen in the dependent portion of the gallbladder. Associated biliary ductal dilatation is present (not shown). B Coronal T2 HASTE MR image reveals a large heterogeneous mass centered in the gallbladder, slightly hyperintense to the liver (arrows), that is invading the right hepatic lobe (asterisk). The mass was also extending into the porta hepatis and adjacent duodenum (not shown). Marked intrahepatic biliary ductal dilatation is evident (long white arrow).

account approximately for 1.7%–12% of all gallbladder cancers [64, 66]. Other gallbladder malignancies include sarcomas, lymphomas, carcinoid, metastases, and other unusual malignancies. All histologic subtypes of gallbladder malignancy demonstrate a gender predilection, with a female:male ratio of 3:1. Cholelithiasis is a major risk factor, with gallstones present in 74%–92% of cases [67, 68]. Porcelain gallbladder is also a known risk factor

and 10%–25% of patients with this condition have gallbladder carcinoma [9] (Fig. 13A, B). It is important to note that no significant correlation has been found between the presence of a porcelain gallbladder and the development of squamous cell GB carcinoma. The radiological features of adenocarcinoma have been well described, due to its substantially higher incidence when compared to the other histological subtypes of gallbladder malignancy. On cross-sectional imaging, they may present in the following three major patterns: (1) mass replacing the gallbladder (40%–65%), (2) focal or diffuse gallbladder wall thickening (20%–30%), and (3) intraluminal polypoid mass (15%–25%) [69–72]. Adenocarcinoma may completely replace the gallbladder and have irregular margins and heterogeneous echotexture on US, reflecting areas of tumor necrosis. Echogenic foci and acoustic shadowing within the tumor mass may be related to coexisting gallstones, gallbladder wall calcification (porcelain gallbladder), or tumoral calcification. Invasion of the adjacent liver and biliary tree, lymph node metastases, and biliary obstruction at the level of the porta hepatis are common associated findings in advanced adenocarcinomas and are best seen on CT and MRI (Fig. 13A, B). Cystic components may also be observed in rare mucin-producing form of adenocarcinomas. Adenosquamous/squamous cell carcinomas (ASC/ SCC) are second most common histopathologic subtypes of primary gallbladder cancer. The pure form of primary squamous cell carcinoma of the gallbladder is rare and constitutes only 0.5%–3% of all malignancies of this organ [73]. Because of the low incidence of ASC/SCC, their clinical presentation, pathophysiology, and radiological features have not been well characterized. In the

M. V. Revzin et al.: The common gallbladder pathological processes

Metastatic gallbladder melanoma in a 59-year-old female. A Sagittal gray scale image shows an immobile mass (arrow) that is isoechoic to liver parenchyma, adjacent to the anterior gallbladder wall. Note that the mass was much smaller on prior imaging 1 year earlier (not shown). B Power Doppler ultrasound reveals no significant flow within the mass. C Fat-suppressed post contrast axial MR image shows robust enhancement of the gallbladder mass. Also note a partially necrotic peripancreatic mass representing a retroperitoneal metastases (star).

b Fig. 16.

literature, these malignancies have only been described in case reports or in case series. The female to male ratio is similar to adenocarcinomas and is 3.8:1. The mean age of patients at presentation is 65-year old [74]. Patients are usually asymptomatic in the early stage of the disease and most commonly present at an advanced stage with persistent abdominal pain and discomfort in the right upper quadrant. Major risk factors are the presence of gallstones and parasitic infestation [75]. On imaging, a large mass arising from the gallbladder fossa is usually observed. Due to advanced stage at the time of diagnosis, invasion of adjacent organs such as liver, duodenum, stomach, colon, pancreas, and extrahepatic bile duct is commonly seen. In contrast to adenocarcinoma, which also has a tendency to invade the liver, these tumors are larger in size and demonstrate more dramatic invasion of the liver [76]. It is important to note that ASC tends to be more aggressive and invasive than SCC, which is a slower growing malignancy with more localized and well-defined invasion [77]. It is reported that SCC of the gallbladder spreads primarily by direct extension, with fewer metastases to lymph nodes or other organs, suggesting that the metastatic potential of this rare tumor may be lower than that of adenocarcinoma. However, the high frequency of local invasion associated with SCC and ASC tumors and the typically advanced stage at the time of initial diagnosis often precludes their resection, thus resulting in an overall poorer prognosis than adenocarcinoma. When ASC/SCC is resectable at presentation, it has a better prognosis than adenocarcinoma. On US, ASC/SCC often presents as a large heterogenous echogenicity immobile mass centered within the gallbladder fossa that either replaces the gallbladder or circumferentially infiltrates the gallbladder wall. Coexisting gallstones may be present, usually layering in the dependant portion of the gallbladder. Power and color Doppler imaging usually demonstrates blood flow with low resistance arterial waveforms, reflecting tumoral neovascularity (Fig. 14A). Contrast-enhanced CT may demonstrate a hypo or iso-attenuating mass in the gallbladder fossa with invasion of the liver and other neighboring organs. Biliary and bowel obstructions are frequently seen due to direct extension of the primary mass, best seen on CT and MRI (Fig. 14A, B).

M. V. Revzin et al.: The common gallbladder pathological processes

The diagnosis of gallbladder cancer can be challenging when only focal or diffuse gallbladder wall thickening is present, and differentiation of malignancy from benign conditions such as chronic or xanthogranulomatous cholecystitis is very difficult [78, 79]. Pronounced wall thickening (i.e., >1.0 cm) demonstrated by US or CT [78, 80] with associated mural irregularity or marked asymmetry should raise concern for malignancy or complicated cholecystitis [81]. The presence of regional lymphadenopathy, soft tissue extension into the liver, and hematogenous metastases favors the diagnosis of gallbladder carcinoma [65]. MR imaging clearly demonstrates invasion of the liver and adjacent structures (Figs. 13B, 14B). The presence of early ill-defined enhancement on dynamic gadolinium-enhanced MR imaging can help to differentiate mural thickening caused by gallbladder cancer from benign diseases such as adenomyomatosis [82] and chronic cholecystitis [83].

Lymphoma of the gallbladder Lymphoma of the gallbladder is extremely rare and accounts for only 0.1%–0.2% of all malignant gallbladder neoplasms [84–86]. It has been postulated that radiological features of lymphoma depend on the pathological classification. High grade lymphomas (diffuse large B cell) tend to form a solid and bulky mass within the gallbladder or marked irregular wall thickening, whereas most low grade lymphomas (MALT-omas or follicular lymphomas) manifest as slight thickening of the gallbladder wall. On MRI, lymphomas of the gallbladder demonstrate low SI on fat-suppressed T1WI and high SI on T2WI in comparison to signal intensity of the normal liver parenchyma [30, 87]. Intact mucosa with infiltration of the submucosal layer of the gallbladder is a characteristic finding [88]. Periportal lesions and para-aortic mass lesions are commonly associated findings [30] (Fig. 15).

Melanoma Metastatic melanoma of the gallbladder is rare, although it is the most common metastasis to the gallbladder, accounting for more than 50% of all cases of metastases found there [89–91]. Metastatic melanoma may manifest either as multiple flat nodules, infiltrative lesions, or as a single polypoid lesion [92]. Sonographic findings include either a single or multiple immobile intraluminal mural masses greater than 1 cm with associated focal wall thickening. Vascularity is detected on color/power Doppler. CT findings include focal wall thickening and one or more enhancing intraluminal polypoid masses (Fig. 16A, B). These are indistinguishable on ultrasound and CT imaging from the polyps of the gallbladder and should be considered if history of metastatic melanoma is

Fig. 17. Neurofibromatosis Type 1 in a 65-year-old male with multiple skin lesions, Ethanol-intoxicated pedestrian trauma. A Coronal color Doppler ultrasound demonstrating two ovoid hypoechoic masses with mild peripheral vascularity located immediately subjacent to the medial gallbladder wall. B Axial contrast-enhanced CT demonstrates peripherally enhancing hypodense neurofibromas medial to the gallbladder (arrow). Multiple other neurofibromas were present throughout the abdomen and pelvis (not shown). Note innumerable cutaneous neurofibromas (arrow head).

provided. Due to the presence of melanin, these lesions demonstrate T1 hyperintensity with variable T2 hypointensity based on the concentration of melanin and the presence of necrosis and/or hemorrhage. Melanoma metastases demonstrate robust enhancement on post contrast CT and MRI [93] (Fig. 16C). Metastatic diseases from other primary malignancies such as renal cell cancer or liposarcoma may have very similar appearance, presenting as a polypoid-enhancing mass or masses.

M. V. Revzin et al.: The common gallbladder pathological processes

Gallbladder neurofibroma Neurofibromas of the gallbladder are uncommon and usually are associated with type 1 neurofibromatosis [1, 94, 95]. Neurofibromas of the gallbladder can present as polypoid intraluminal masses or intramural nodules [96]. On US, the lesions are heterogeneously hypoechoic with variable through transmission (Fig. 17A). On contrast-enhanced CT, the lesion is hypodense with hyperdense center and rim. Intravenous contrast enhancement may be homogeneous or heterogeneous. Hyperdensity within the mass can be attributable to the presence of focal collagen (Fig. 17B). Most neurofibromas are smooth round masses [97].

Summary There are a variety of conditions that affect the gallbladder. A thorough understanding of the imaging characteristics of each condition can help the radiologist to make a timely and accurate diagnosis, thus avoiding potentially harmful delays in patient management and decreasing morbidity and mortality rates. Acknowledgments. We extend special thanks to Denise Hersey, Clinical Support Librarian, for her tremendous help with this project. Disclosures. Margarita Revzin, Leslie Scoutt, Gary Israel, Edward Smitaman have no any relevant financial interests, arrangements, or affiliations with a commercial interest.

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The gallbladder: uncommon gallbladder conditions and unusual presentations of the common gallbladder pathological processes.

This article reviews a spectrum of gallbladder conditions that are either uncommon or represent unusual manifestations of common diseases. These condi...
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