Polypoid Lesions of the Gall- bladder: Disease Spectrum with

Note: This copy is for your personal non-commercial use only. To order presentation-ready
copies for distribution to your colleagues or clients, contact us at www.rsna.org/rsnarights.
Polypoid Lesions of the Gallbladder: Disease Spectrum with
Pathologic Correlation1
Vincent M. Mellnick, MD
Christine O. Menias, MD
Kumar Sandrasegaran, MD
Amy K. Hara, MD
Ania Z. Kielar, MD
Elizabeth M. Brunt, MD
Maria B. Majella Doyle, MD
Nirvikar Dahiya, MD
Khaled M. Elsayes, MD
Abbreviations: FDG = fluorine-18 fluorodeoxyglucose, H-E = hematoxylin-eosin, PSC =
primary sclerosing cholangitis
RadioGraphics 2015; 35:387–399
Published online 10.1148/rg.352140095
Content Codes:
From the Mallinckrodt Institute of Radiology (V.M.M.), Department of Pathology (E.M.B.), and Department of Surgery
(M.B.M.D.),Washington University School
of Medicine, 510 S Kingshighway Blvd, Box
8131, St Louis, MO 63110; Department
of Radiology, Mayo Clinic, Scottsdale, Ariz
(C.O.M., A.K.H., N.D.); Department of Radiology, Indiana University School of Medicine,
Indianapolis, Ind (K.S.); Department of Radiology, University of Ottawa Faculty of Medicine, Ottawa, Ontario, Canada (A.Z.K.); and
Department of Radiology, University of Texas
MD Anderson Cancer Center, Houston, Tex
(K.M.E.). Presented as an education exhibit
at the 2013 RSNA Annual Meeting. Received
March 20, 2014; revision requested June 27
and received July 1; accepted July 3. For this
journal-based SA-CME activity, the authors,
editor, and reviewers have disclosed no relevant relationships. Address correspondence
to V.M.M. (e-mail: mellnickv@mir.wustl.edu).
1
SA-CME LEARNING OBJECTIVES
After completing this journal-based SA-CME
activity, participants will be able to:
■■Describe the spectrum of polypoid lesions of the gallbladder.
■■List
the salient features that may help
guide differential diagnosis of these lesions.
■■Discuss
the management of polypoid
lesions of the gallbladder.
See www.rsna.org/education/search/RG.
Gallbladder polyps are seen on as many as 7% of gallbladder ultrasonographic images. The differential diagnosis for a polypoid gallbladder mass is wide and includes pseudotumors, as well as benign
and malignant tumors. Tumefactive sludge may be mistaken for a
gallbladder polyp. Pseudotumors include cholesterol polyps, adenomyomatosis, and inflammatory polyps, and they occur in that order
of frequency. The most common benign and malignant tumors are
adenomas and primary adenocarcinoma, respectively. Polyp size,
shape, and other ancillary imaging findings, such as a wide base,
wall thickening, and coexistent gallstones, are pertinent items to
report when gallbladder polyps are discovered. These findings, as
well as patient age and risk factors for gallbladder cancer, guide
clinical decision making. Symptomatic polyps without other cause
for symptoms, an age over 50 years, and the presence of gallstones
are generally considered indications for cholecystectomy. Incidentally noted pedunculated polyps smaller than 5 mm generally do
not require follow-up. Polyps that are 6–10 mm require follow-up,
although neither the frequency nor the length of follow-up has been
established. Polyps that are larger than 10 mm are typically excised,
although lower size thresholds for cholecystectomy may be considered for patients with increased risk for gallbladder carcinoma, such
as patients with primary sclerosing cholangitis.
©
RSNA, 2015 • radiographics.rsna.org
Introduction
Gallbladder polyps are defined as sessile projections of the gallbladder wall into the lumen. They are typically incidentally found at
ultrasonography (US). Unlike gallstones, gallbladder polyps are not
significantly associated with female sex, obesity, or multiparity (1).
Management of gallbladder polyps relies on imaging findings and
various clinical factors. Potential courses of action range from no
further action to open cholecystectomy and lymph node sampling.
There is some overlap in the appearance of benign and malignant
gallbladder polyps. In this article, we describe common and uncommon types of gallbladder polyps with pathologic and radiologic examples and discuss appropriate management of these lesions.
GASTROINTESTINAL IMAGING
387
388 March-April 2015
TEACHING POINTS
■■
At US, cholesterol polyps appear as small, round, smoothly
contoured, intraluminal lesions that are attached to the wall.
The stalk is rarely seen, an appearance that gives rise to the
“ball on the wall” sign.
■■
At MR imaging, the Rokitansky-Aschoff sinuses cause a “pearl
necklace” sign of multiple round spaces that are hyperintense
on T2-weighted images, a finding that has been reported to
have 92% specificity for adenomyomatosis.
■■
At US, inflammatory gallbladder polyps have a nonspecific
appearance. A diagnosis of inflammatory polyps may not be
made with certainty at imaging.
■■
In patients with PSC, a substantial number (60%) of gallbladder polyps are malignant.
■■
US clues to a polypoid gallbladder carcinoma include a solitary polyp larger than 10 mm, a wide polyp base, focal wall
thickening of more than 3 mm, and coexisting gallstones.
Clinical Considerations
Gallbladder polyps are relatively common, with
a reported prevalence of 3%–7% at abdominal
US and 2%–12% in cholecystectomy specimens (1–5). A wide array of pseudotumors,
as well as benign and malignant tumors, may
manifest as gallbladder polyps. By far, most
gallbladder polyps are benign. Nevertheless, it
is important to recognize gallbladder cancer at
an early stage, when it may be resectable for
cure. Radiologic findings can be used to stratify
gallbladder polyps into three groups: those that
need no further follow-up, those that require
follow-up, and those that should be excised (ie,
cholecystectomy). In addition to the likelihood
of malignancy on the basis of imaging findings,
a surgeon’s judgment on whether to perform
cholecystectomy relies on clinical factors, such
as patient age, medical comorbidities, and the
presence of symptoms that are attributable to
gallbladder disease.
Imaging Protocols
Gallbladder polyps are mostly identified at US
but are increasingly seen at computed tomography (CT), magnetic resonance (MR) imaging,
and positron emission tomography (PET). Patients should fast for several hours before undergoing US to allow distention of the gallbladder.
Typically, a phased-array sector or curvilineararray probe with a relatively low frequency (2–5
MHz) is used. US protocols should include
multiplanar gray-scale images, as well as color
and spectral Doppler images of detected lesions
(6). Lesions should be imaged in more than one
position (eg, supine and left decubitus) to avoid
mistaking mobile sludge balls for polypoid lesions (Fig 1). It is important to note the size and
shape (eg, pedunculated or sessile) of a polypoid
radiographics.rsna.org
lesion and the presence of gallstones, which increase the likelihood that the polyp is a neoplastic lesion (7,8). Other findings to note include
gallbladder wall thickening adjacent to the polypoid lesion, multiple polyps, biliary strictures,
and hepatic masses. The presence of twinkling
artifact may help diagnose adenomyomatosis
(9). Size comparison with prior imaging studies,
including CT and MR imaging, is helpful. When
contrast material–enhanced US is available, lesion enhancement may be a useful discriminator
between benign and malignant polyps (10).
CT, PET/CT and MR imaging may also depict larger polypoid lesions within the gallbladder
(11,12). These modalities are usually used for
staging of known or suspected gallbladder cancer
(13). MR imaging has good sensitivity for depiction of vascular and bile duct invasion, and the
protocol should include thin- and thick-section
MR cholangiopancreatography, as well as diffusion-weighted and multiphase contrast-enhanced
imaging (14).
Mimics of Gallbladder Polyps
Adherent gallstones and gallbladder sludge may be
immobile and mimic true gallbladder polyps. The
characteristic acoustic shadowing of gallstones
may be difficult to visualize in obese patients or
when calculi are deep in the gallbladder neck.
Gallbladder sludge is usually easy to diagnose and
is seen as mobile small intraluminal, hyperechoic,
nonshadowing, nonvascular balls. However, adherent, tumefactive sludge may appear as a mass lesion (Fig 2). In cases in which tumefactive sludge
is suspected but cannot be confirmed, a shortterm follow-up examination may be of use, particularly if the original study was performed after a
prolonged period of fasting (15).
Classification
of Gallbladder Polyps
Gallbladder polyps may be classified as pseudotumors, benign tumors, or malignant tumors.
The imaging and clinical aspects of each of these
groups are discussed herein.
Pseudotumors
Cholesterol polyps, adenomyomatosis, and inflammatory polyps, in that order of frequency, constitute the major polypoid pseudotumors. Cholesterol polyps and adenomyomatosis are hyperplastic noninflammatory conditions with different histologic features. The gallbladder wall is composed
of four layers: mucosa, lamina propria, muscularis
propria, and serosa. It does not have a muscularis
mucosae or a submucosa layer. The wall thickening that occurs in adenomyomatosis involves
hyperplasia of both the mucosa and muscularis
RG • Volume 35 Number 2
Mellnick et al 389
Figure 1. Mobile sludge ball in a 37-year-old woman with abdominal pain. US images obtained with the patient lying down
(a) and standing (b) show a polypoid intraluminal gallbladder mass (arrowhead) that moves to a different location in the gallbladder when the patient stands, a classic feature of a sludge ball. The presence of acoustic shadowing (arrow in a) indicates
that small stones are likely present within the sludge ball.
Figure 2. Tumefactive sludge in a 62-year-old man with right upper quadrant abdominal discomfort. US images show
a nonmobile polypoid mass (arrowhead) in the gallbladder that does not move when the patient changes position.
Results of pathologic analysis confirmed the presence of sludge and underlying chronic cholecystitis.
propria. In adenomyomatosis, cholesterol accumulation is intraluminal, and crystals precipitate in
bile trapped in intramural diverticula (RokitanskyAschoff sinuses) lined by the epithelial layer of the
mucosa. Gallbladder wall thickening and intramural diverticula containing cholesterol crystals, or
calculi, are pathognomonic of adenomyomatosis
(16). In contrast, in cholesterol polyps, there is
deposition of triglycerides and cholesterol esters
within macrophages in the lamina propria, and the
polyp is covered by normal epithelium.
Cholesterol Polyps.—The cholesterol polyp is
by far the most common polypoid lesion found
in the gallbladder, accounting for 60%–70% of
lesions in some studies (2,17). It predominantly
occurs in middle-aged women. Cholesterol pol-
yps are typically multiple and need not be associated with gallstones (18). At gross examination,
the diffuse form of cholesterolosis manifests as a
bright red mucosa with interposed areas of yellow
lipid, an appearance referred to as a “strawberry
gallbladder” (19). Cholesterol polyps have no
malignant potential (12).
At US, cholesterol polyps appear as small,
round, smoothly contoured, intraluminal lesions
that are attached to the wall. The stalk is rarely
seen, an appearance that gives rise to the “ball on
the wall” sign (Fig 3) (20). Cholesterol polyps are
usually echogenic with no acoustic shadowing;
however, particularly when multiple cholesterol
polyps are confluent and/or larger than 1 cm,
they cannot be definitively differentiated from
other benign or malignant lesions at imaging.
390 March-April 2015
radiographics.rsna.org
Figure 3. Cholesterol polyps in a 58-year-old woman with abdominal pain. (a) US image shows multiple small
round intraluminal lesions (arrowheads) attached to the gallbladder wall. (b) Sagittal T2-weighted MR image
shows the gallbladder polyps (arrowheads). (c) Photomicrograph (original magnification, ×40; hematoxylineosin [H-E] stain) of a specimen obtained after cholecystectomy shows lipid-laden macrophages (arrowhead)
within the papillary fronds (arrows) of the cholesterol polyp.
Adenomyomatosis.—Adenomyomatosis may be
seen in as many as 9% of cholecystectomy specimens and accounts for about 25% of all polypoid
lesions in the gallbladder (17,21). The focal form
of adenomyomatosis may be seen as a fundal
polypoid lesion at imaging. The segmental form
typically affects the body, demonstrates concentric circumferential wall thickening, and may give
rise to an hourglass configuration of the gallbladder. Although some studies have reported an association between segmental adenomyomatosis
and gallbladder cancer, others have not (21–24).
Current thinking is that adenomyomatosis is not
premalignant but may be seen in chronically inflamed gallbladders, which have a higher risk for
developing cancer.
Imaging findings of adenomyomatosis parallel
its histologic features: intramural diverticula that
may be filled with inspissated bile and appear
as multiple small cystic spaces that are anechoic
at US. When the intramural diverticula contain
sludge, stones, or papillary projections, they appear echogenic with multiple acoustic interfaces
at US, creating twinkling or comet-tail artifacts
(25). The cystic spaces may be visible at CT,
which can help differentiate between fundal adenomyomatosis and gallbladder carcinoma (26).
At MR imaging, the Rokitansky-Aschoff sinuses
cause a “pearl necklace” sign of multiple round
spaces that are hyperintense on T2-weighted images, a finding that has been reported to have
92% specificity for adenomyomatosis (Fig 4)
(27). There have been reports of increased uptake
of fluorine-18 fluorodeoxyglucose (FDG) within
areas of adenomyomatosis at PET, a potential
source of false-positive results when characterizing gallbladder lesions (28).
Inflammatory Polyps.—Inflammatory polyps
represent 10% of all gallbladder polyps in surgi-
RG • Volume 35 Number 2
Mellnick et al 391
Figure 4. Gallbladder adenomyomatosis in two patients. (a) US image obtained in a 62-year-old man with
pain shows a polyp (arrowhead) with foci of echogenicity in the gallbladder fundus. An echogenic focus with
a comet-tail artifact (arrow) is also seen, a finding indicative of adenomyomatosis. (b) Coronal T2-weighted
MR image obtained in a 71-year-old woman with suspected pancreatic cysts shows the pearl necklace sign
(arrowhead), which consists of round foci of hyperintensity arranged in a partial ring in the gallbladder fundus. (c) Photomicrograph (original magnification, ×10; H-E stain) obtained in the same patient as in b shows
markedly dilated Rokitansky-Aschoff sinuses (arrowheads) lined by benign biliary epithelium (arrows) and
smooth muscle.
cal series and are usually multiple and small,
measuring less than 10 mm in diameter (17).
They typically occur secondary to gallstones and
chronic inflammation. It is thought that they develop from chronic deposition of cholesterol in
the gallbladder wall and subsequent mucosal irritation, which leads to formation of granulation
and fibrous tissue. As is the case with chronic
cholecystitis, inflammatory polyps may lead
to mucosal epithelial dysplasia (29). However,
there is no definitive evidence that inflammatory
gallbladder polyps have an increased risk for
adenocarcinoma.
Little is known about the imaging features of
inflammatory polyps. Case reports have described
a relatively wide range of US appearances, including iso- and hypoechogenicity, as well as hyperechogencitiy, both focally within and surrounding
the lesion (30–32). At US, inflammatory polyps
have a nonspecific appearance. A diagnosis of
inflammatory polyps may not be made with certainty at imaging (Fig 5).
Tumorous Polyps
The most important considerations are epithelial
lesions, adenoma, and adenocarcinoma. Benign
mesenchymal tumors, such as leiomyomas, lipomas, neurofibromas, and neuroendocrine tumors, account for 1% of gallbladder polyps (17).
Rarely, metastases and lymphoma may manifest
as polypoid gallbladder lesions.
Adenomas.—Gallbladder adenomas are rare,
occurring in 0.15% of all cholecystectomy specimens and accounting for 4%–7% of all gallbladder polyps (17,33). In contrast to colonic polyps,
for which an adenoma-to-carcinoma sequence is
well established, the role of gallbladder adenomas
in the pathogenesis of gallbladder carcinoma is
controversial (34). Studies, including genetic
analyses, have shown that a dysplasia-to-carcinoma sequence is more likely to occur than malignant transformation of adenomas (35,36).
Adenomas may cause symptoms but are typically incidentally found. They are most frequently
392 March-April 2015
radiographics.rsna.org
Figure 5. Inflammatory polyp in a 48-year-old woman with right upper quadrant abdominal pain. (a, b) Gray-scale (a) and
color Doppler (b) US images show a polypoid intraluminal gallbladder mass (arrowhead) with internal vascularity. (c) Pho­­to­­
micrograph (original magnification, ×10; H-E stain) of a surgical specimen shows pseudopapillary fronds (arrowheads) with
reactive mucosal changes, inflammation, and increased vascularity, findings in keeping with an inflammatory polyp.
seen in patients with primary sclerosing cholangitis (PSC) and gastrointestinal polyposis syndromes, such as Peutz-Jegher and Gardner syndromes. Cytologically, gallbladder adenomas may
be classified as having a pyloric (most common),
intestinal, foveolar, or biliary subtype (34).
At US, gallbladder adenomas may vary in size
(up to 20 mm), have a sessile or pedunculated
appearance, demonstrate internal vascularity at
color Doppler interrogation, and are typically
solitary. At CT and MR imaging, gallbladder adenomas typically demonstrate enhancement similar to that of adenocarcinoma (Fig 6). Adenomas
cannot be reliably differentiated from polypoid
gallbladder adenocarcinoma at imaging.
Adenocarcinoma.—The most common malig-
nant gallbladder polyp is primary adenocarcinoma of the gallbladder. It is the fifth most common gastrointestinal malignancy worldwide,
with higher incidences in Chile and Japan (37).
It is more commonly seen in women and the
elderly.
Gallbladder carcinoma carries a very poor prognosis because it is often detected at an advanced
stage. It has a strong association with gallstones; in
one large autopsy series, over 95% of cases of gallbladder cancer had concomitant cholelithiasis (7).
Chronic gallbladder inflammation may also lead to
wall calcification—the so-called porcelain gallbladder—which is associated with gallbladder cancer.
Other risk factors for gallbladder cancer include
PSC, anomalous pancreaticobiliary ductal union,
and most types of choledochal cysts (5,38–40). In
patients with PSC, a substantial number (60%) of
gallbladder polyps are malignant (Fig 7) (41).
Gallbladder adenocarcinoma is divided into
multiple subtypes, the most common of which
is the papillary form, although signet ring and
mucinous adenocarcinomas, among others, also
occur. Pathologically, papillary adenocarcinomas
appear as densely cellular papillary fronds protruding into the gallbladder lumen, with dysplasia
and increased mitoses (19). Although adenocarcinoma represents the overwhelming majority
of primary gallbladder tumors, adenosquamous
RG • Volume 35 Number 2
Mellnick et al 393
Figure 6. Adenomatous gallbladder polyps in three patients. (a) US image obtained in an 81-year-old man
with biliary colic shows an intraluminal polyp (arrowhead) with papillary fronds and internal vascularity that
was proved to be an adenoma at surgery. (b) Axial CT image obtained in a 74-year-old man to assess a hernia
shows a large (4-cm) enhancing mass (arrowhead) that was worrisome for cancer. Pathologic analysis of a
surgical specimen indicated adenoma. (c) Axial unenhanced MR image obtained in a 61-year-old woman with
chronic liver disease shows an incidental 2-cm mass (arrowhead) that is hypointense relative to muscle. (d) Axial
contrast-enhanced MR image shows the mass (arrowhead), which demonstrates mild enhancement. (e) Photomicrograph (original magnification, ×20; H-E stain) shows benign glandular structures and squamous morules
(arrowhead). There was no cancer in this specimen.
carcinoma, small cell carcinoma, and sarcomas
have also been described; however, it is uncommon for these rare tumors to manifest as a polyp.
Even less common are primary neuroendocrine
carcinoma and melanoma of the gallbladder.
Gallbladder adenocarcinoma most commonly manifests as a mass in the gallbladder
fossa, with engulfed gallstones or irregular eccentric gallbladder wall thickening at imaging.
In 15%–25% of cases, it may manifest as an
intraluminal polyp (13,42,43). US clues to a
polypoid gallbladder carcinoma include a solitary polyp larger than 10 mm, a wide polyp
base, focal wall thickening of more than 3 mm,
and coexisting gallstones (Fig 8) (44). At color
and spectral Doppler US, linear color signal at
the polyp base and an increased resistive index
394 March-April 2015
radiographics.rsna.org
Figure 7. Gallbladder adenocarcinoma in a 34-year-old
man with long-standing PSC. Endoscopic retrograde cholangiopancreatogram shows classic irregular biliary duct
strictures (arrowheads) and polypoid filling defects (arrows) along the gallbladder wall. Endoscopic US–guided
biopsy demonstrated adenocarcinoma arising from PSC.
Figure 8. Synchronous gallbladder cancer in a 74-year-old man with
esophageal cancer. (a) US image shows a 3-cm wide-based mass (arrowhead) with adjacent focal wall thickening (arrows). (b) Axial contrast-enhanced MR image shows the frondlike mass (arrowhead), which
demonstrates enhancement. (c) Axial PET/CT image obtained to stage
esophageal carcinoma shows the mass (arrowhead), which demonstrates marked FDG uptake. (d) Photomicrograph (original magnification, ×20; H-E stain) of a surgical specimen shows the dense cellularity and atypical architecture (arrowhead) of the fronds, an indicator of
cancer. The cellular characteristics of malignancy were seen at higherpower evaluation.
may indicate a cancerous polyp (6). Diffuse or
branched enhancement and an abruptly rising,
persistent time-intensity enhancement curve at
contrast-enhanced US have been associated with
malignant gallbladder lesions (45).
Endoscopic US has been suggested as a
superior modality to transabdominal US for
imaging gallbladder lesions because of its use
of high-frequency probes, which provide better
resolution of small lesions (46). Endoscopic US
may be useful for identifying benign features
of a polyp—such as cystic spaces or comet-tail
artifact, which is associated with adenomyomatosis—that may not be visible with a transabdominal approach (46). An endoscopic US
scoring system to predict malignancy in a gall-
bladder polyp on the basis of its size, its internal
echo pattern, and the presence of hyperechoic
spotting has been suggested, with sensitivity and
specificity of 78% and 83%, respectively (47).
FDG PET has also been shown to be useful
in the setting of gallbladder cancer. Although
it is chiefly used for staging in the setting of a
known carcinoma, FDG uptake within a gallbladder polyp greater than that in the background liver is an indication of malignancy (Fig
8) (48). Delayed FDG uptake and retention of
RG • Volume 35 Number 2
Mellnick et al 395
Figure 9. Use of DWI in a 67-year-old woman with biliary colic. (a, b) Unenhanced (a) and
contrast-enhanced (b) T1-weighted MR images show a 3.5-cm polypoid enhancing gallbladder mass (arrowhead). (c) Diffusion-weighted image (b = 800 sec/mm2) shows the mass (arrowhead), which is hyperintense. (d) Apparent diffusion coefficient (ADC) map shows that
the mass is hypointense (arrowhead), a finding that indicates restricted diffusion, favors malignancy, and was concordant with subsequent pathologic findings.
radiotracer within a gallbladder lesion is a useful
characteristic for diagnosing gallbladder malignancy (49). However, false-positive results may
occur in the presence of acute cholecystitis, a
limitation of FDG PET.
In the case of larger gallbladder polyps, CT
and MR imaging can provide some of the same
diagnostic information as US, namely, the shape,
size, number, and location of lesions. At CT, lesions that are larger than 10 mm and visible on
unenhanced images may be more likely to be
malignant (50). Enhancement characteristics of
gallbladder polyps at MR imaging, such as early
prolonged enhancement without washout, which
is more common in malignant lesions than in benign lesions, may be useful (51). Several studies
have indicated that, at diffusion-weighted imaging (DWI), malignant gallbladder lesions tend
to have a lower apparent diffusion coefficient
(ADC) than do benign lesions (Fig 9) (52–54). It
is best to incorporate DWI with the protocol for
assessing hepatobiliary disease; the presence of
hyperintensity on high–b value diffusion-weighted
images may raise concern for malignancy in lesions that are indeterminate on MR images obtained with conventional sequences (55,56).
Metastatic Disease and Lymphoma.—Me-
tastases to the gallbladder can occur with any
primary malignancy and typically do so in the
setting of widespread metastatic disease. In the
western medical literature, the most common
primary tumor to metastasize to the gallbladder
is melanoma, which represents 60% of all gallbladder metastases (Fig 10) (57). In the Asian
medical literature, the most common source of
gallbladder metastases is gastric cancer (58).
Cancers of the kidney and lung may hematogenously spread to the gallbladder, whereas hepatocellular carcinoma and cholangiocarcinoma
396 March-April 2015
radiographics.rsna.org
Figure 10. Polypoid melanoma metastasis in a 43-year-old man. (a) Axial T2-weighted MR image
shows a polypoid lesion (arrowhead) in the gallbladder lumen. (b) Unenhanced T1-weighted MR
image shows the lesion (arrowhead), which is mildly hyperintense, a finding that may be related to
the presence of internal melanin. (c) Contrast-enhanced MR image shows enhancement of the mass
(arrowhead). (d) Photograph of the gross pathologic specimen shows an eccentric, hemorrhagic mass
(arrowhead) that was proved to be a melanoma metastasis.
may directly invade the gallbladder (Fig 11).
Patients with gallbladder metastases are usually
asymptomatic, but they may develop acute cholecystitis if the cystic duct becomes obstructed.
Lymphoma of the gallbladder is rare and occurs either as a primary tumor or, more commonly, as a result of secondary involvement of
the gallbladder by adjacent lymphadenopathy.
Because lymphoid tissue is not normally found
in the gallbladder wall, it has been suggested
that primary gallbladder lymphoma arises in the
setting of chronic inflammation (59). The most
common subtypes of lymphoma involving the
gallbladder are diffuse large B-cell and mucosaassociated lymphoid tissue (MALT) lymphoma.
As at other sites, lymphoma of the gallbladder
may have varied appearances (59).
Management Algorithm
Although imaging features of gallbladder polyps
may, at times, indicate a specific diagnosis, there
is a large degree of overlap in the appearances
of benign and potentially malignant gallbladder
lesions. According to the management algorithm, which was determined by a review of the
literature, management of gallbladder polyps
primarily relies on the size of the lesion (Fig 12)
(1,3,17,44,60,62–71). Two large series confirmed
that a size larger than 10 mm is the best indicator of malignancy and warrants cholecystectomy
(60,61). There is controversy regarding the risk
for malignancy in polyps that measure 6–10 mm.
Some studies have reported that this risk is close
to zero at long-term follow-up US (62–65). In
a study of cholecystectomy specimens that were
6–10 mm at preoperative US, 7% were malignant
(61). In general, incidental polyps of this size may
be followed with serial imaging rather than being
surgically removed. The frequency and duration
of follow-up examinations has not been established. It is our practice to image polyps of this
size after 6 and 12 months and, if they are stable,
RG • Volume 35 Number 2
Mellnick et al 397
Figure 11. Gallbladder polyp caused by invasive hepatocellular carcinoma in a 49-year-old
man with cirrhosis. US (a) and axial contrast-enhanced T1-weighted MR (b) images show a
large mass in the right hepatic lobe (arrowheads) that invades through the gallbladder wall
and protrudes as an intraluminal polypoid mass (arrow).
Figure 12. Flowchart shows
the best practice algorithm for
management of gallbladder (GB)
polyps.
to perform annual follow-up US. An increase
in size to more than 10 mm or the onset of biliary symptoms may indicate a need for surgery.
Management of polyps that measure 5 mm or
less is also not clearly established. A study found
that, among patients with sub–5-mm polyps at
preoperative US, no focal lesion was seen in cholecystectomy specimens from more than 80% of
patients (66). Another study reported that 24%
of sub–5-mm polyps were not seen at follow-up
US (63). It is probable that a substantial number of polypoid lesions of this size are adherent
stones or sludge. A recent large study suggested
that polyps of this size have no malignant potential and may be ignored (67). In our practice,
we do not follow up patients with pedunculated
polyps smaller than 5 mm. It is important to note
that the size of a gallbladder polyp should not
be viewed in a vacuum. Other factors, such as
the presence of gallstones, a patient age over 50
years, a wide polyp base, and focal gallbladder
wall thickening of more than 3 mm, should favor
surgical management. In addition, patients with
PSC should be considered for cholecystectomy
if a gallbladder polyp of any size is identified (5).
The role of contrast-enhanced and endoscopic
US in determining management of smaller polyps requires further research.
Conclusions
Imaging plays a pivotal role in evaluation of gallbladder polyps, not only in determining lesion size
but also in depicting other important findings.
The radiologist must integrate imaging findings
with clinical features to determine the risk for gallbladder malignancy and recommend management.
References
1. Myers RP, Shaffer EA, Beck PL. Gallbladder polyps: epidemiology, natural history and management. Can J Gastroenterol
2002;16(3):187–194.
2.Lee KF, Wong J, Li JC, Lai PB. Polypoid lesions of the
gallbladder. Am J Surg 2004;188(2):186–190.
398 March-April 2015
3. Terzi C, Sökmen S, Seçkin S, Albayrak L, Uğurlu M. Polypoid
lesions of the gallbladder: report of 100 cases with special reference to operative indications. Surgery 2000;127(6):622–627.
4. Jørgensen T, Jensen KH. Polyps in the gallbladder: a prevalence study. Scand J Gastroenterol 1990;25(3):281–286.
5. Andrén-Sandberg A. Diagnosis and management of gallbladder polyps. N Am J Med Sci 2012;4(5):203–211.
6.Hirooka Y, Naitoh Y, Goto H, Furukawa T, Ito A, Ha­
yakawa T. Differential diagnosis of gall-bladder masses using
colour Doppler ultrasonography. J Gastroenterol Hepatol
1996;11(9):840–846.
7. Misra S, Chaturvedi A, Misra NC, Sharma ID. Carcinoma
of the gallbladder. Lancet Oncol 2003;4(3):167–176.
8.Randi G, Franceschi S, La Vecchia C. Gallbladder cancer
worldwide: geographical distribution and risk factors. Int J
Cancer 2006;118(7):1591–1602.
9. Ghersin E, Soudack M, Gaitini D. Twinkling artifact in gallbladder adenomyomatosis. J Ultrasound Med 2003;22(2):229–231.
10.Numata K, Oka H, Morimoto M, et al. Differential diagnosis of gallbladder diseases with contrast-enhanced
harmonic gray scale ultrasonography. J Ultrasound Med
2007;26(6):763–774.
11. Kim SJ, Lee JM, Lee JY, et al. Analysis of enhancement pattern
of flat gallbladder wall thickening on MDCT to differentiate
gallbladder cancer from cholecystitis. AJR Am J Roentgenol
2008;191(3):765–771.
12.Furukawa H, Kosuge T, Shimada K, et al. Small polypoid
lesions of the gallbladder: differential diagnosis and surgical
indications by helical computed tomography. Arch Surg
1998;133(7):735–739.
13.Furlan A, Ferris JV, Hosseinzadeh K, Borhani AA. Gallbladder carcinoma update: multimodality imaging evaluation, staging, and treatment options. AJR Am J Roentgenol
2008;191(5):1440–1447.
14.Kim JH, Kim TK, Eun HW, et al. Preoperative evaluation
of gallbladder carcinoma: efficacy of combined use of MR
imaging, MR cholangiography, and contrast-enhanced dualphase three-dimensional MR angiography. J Magn Reson
Imaging 2002;16(6):676–684.
15. Fakhry J. Sonography of tumefactive biliary sludge. AJR Am
J Roentgenol 1982;139(4):717–719.
16.Levy AD, Murakata LA, Abbott RM, Rohrmann CA Jr;
Armed Forces Institute of Pathology. From the archives of
the AFIP: benign tumors and tumorlike lesions of the gallbladder and extrahepatic bile ducts—radiologic-pathologic
correlation. RadioGraphics 2002;22(2):387–413.
17.Gallahan WC, Conway JD. Diagnosis and management
of gallbladder polyps. Gastroenterol Clin North Am
2010;39(2):359–367, x.
18.Sternberg SS. Diagnostic surgical pathology. New York:
Raven, 1989.
19. Goldblum JRORD. Surgical pathology of the GI tract, liver,
biliary tract, and pancreas. Philadelphia, Pa: Elsevier, Saunders, 2009. [expert consult online + print].
20.Kurtz AB, Middleton WD. Ultrasound. St Louis, Mo:
Mosby, 1996.
21. Ootani T, Shirai Y, Tsukada K, Muto T. Relationship between
gallbladder carcinoma and the segmental type of adenomyomatosis of the gallbladder. Cancer 1992;69(11):2647–2652.
22. Nabatame N, Shirai Y, Nishimura A, Yokoyama N, Wakai T,
Hatakeyama K. High risk of gallbladder carcinoma in elderly
patients with segmental adenomyomatosis of the gallbladder.
J Exp Clin Cancer Res 2004;23(4):593–598.
23. Nishimura A, Shirai Y, Hatakeyama K. Segmental adenomyomatosis of the gallbladder predisposes to cholecystolithiasis.
J Hepatobiliary Pancreat Surg 2004;11(5):342–347.
24.Kim JH, Jeong IH, Han JH, et al. Clinical/pathological
analysis of gallbladder adenomyomatosis, type and path­
ogenesis. Hepatogastroenterology 2010;57(99-100):
420–425.
25. Raghavendra BN, Subramanyam BR, Balthazar EJ, Horii SC,
Megibow AJ, Hilton S. Sonography of adenomyomatosis of
the gallbladder: radiologic-pathologic correlation. Radiology
1983;146(3):747–752.
26.Ching BH, Yeh BM, Westphalen AC, Joe BN, Qayyum A,
Coakley FV. CT differentiation of adenomyomatosis and
gallbladder cancer. AJR Am J Roentgenol 2007;189(1):­62–66.
radiographics.rsna.org
27. Haradome H, Ichikawa T, Sou H, et al. The pearl necklace
sign: an imaging sign of adenomyomatosis of the gallbladder
at MR cholangiopancreatography. Radiology 2003;227(1):
80–88.
28. Maldjian PD, Ghesani N, Ahmed S, Liu Y. Adenomyomatosis of the gallbladder: another cause for a “hot” gallbladder
on 18F-FDG PET. AJR Am J Roentgenol 2007;189(1):
W36–W38.
29. Seretis C, Lagoudianakis E, Gemenetzis G, Seretis F, Pappas
A, Gourgiotis S. Metaplastic changes in chronic cholecystitis:
implications for early diagnosis and surgical intervention
to prevent the gallbladder metaplasia-dysplasia-carcinoma
sequence. J Clin Med Res 2014;6(1):26–29.
30.Susumu S, Matsuo S, Tsutsumi R, Azuma T, Obata S,
Hayashi T. Inflammatory polyp of the gallbladder mimicking
early polypoid carcinoma. Case Rep Gastroenterol 2009;3
(2):255–259.
31.Maeyama R, Yamaguchi K, Noshiro H, Takashima M,
Chijiiwa K, Tanaka M. A large inflammatory polyp of the
gallbladder masquerading as gallbladder carcinoma. J Gastroenterol 1998;33(5):770–774.
32.Hallgrimsson P, Skaane P. Hypoechoic solitary inflammatory polyp of the gallbladder. J Clin Ultrasound 1988;16(8):
603–604.
33. Yang HL, Sun YG, Wang Z. Polypoid lesions of the gallbladder: diagnosis and indications for surgery. Br J Surg 1992;
79(3):227–229.
34.Albores-Saavedra J, Chablé-Montero F, González-Romo
MA, Ramírez Jaramillo M, Henson DE. Adenomas of the
gallbladder: morphologic features, expression of gastric and
intestinal mucins, and incidence of high-grade dysplasia/
carcinoma in situ and invasive carcinoma. Hum Pathol 2012;
43(9):1506–1513.
35.Trivedi V, Gumaste VV, Liu S, Baum J. Gallbladder cancer: adenoma-carcinoma or dysplasia-carcinoma sequence?
Gastroenterol Hepatol (N Y) 2008;4(10):735–737.
36.Wistuba II, Miquel JF, Gazdar AF, Albores-Saavedra J.
Gallbladder adenomas have molecular abnormalities different
from those present in gallbladder carcinomas. Hum Pathol
1999;30(1):21–25.
37.Shaffer EA. Gallbladder cancer: the basics. Gastroenterol
Hepatol (N Y) 2008;4(10):737–741.
38.Lee SE, Jang JY, Lee YJ, et al; Korean Pancreas Surgery
Club. Choledochal cyst and associated malignant tumors
in adults: a multicenter survey in South Korea. Arch Surg
2011;146(10):1178–1184.
39.Rustagi T, Dasanu CA. Risk factors for gallbladder cancer
and cholangiocarcinoma: similarities, differences and updates.
J Gastrointest Cancer 2012;43(2):137–147.
40.Funabiki T, Matsubara T, Miyakawa S, Ishihara S. Pancreaticobiliary maljunction and carcinogenesis to biliary
and pancreatic malignancy. Langenbecks Arch Surg 2009;
394(1):159–169.
41. Buckles DC, Lindor KD, Larusso NF, Petrovic LM, Gores
GJ. In primary sclerosing cholangitis, gallbladder polyps
are frequently malignant. Am J Gastroenterol 2002;97(5):
1138–1142.
42. Reid KM, Ramos-De la Medina A, Donohue JH. Diagnosis
and surgical management of gallbladder cancer: a review. J
Gastrointest Surg 2007;11(5):671–681.
43. Rodríguez-Fernández A, Gómez-Río M, Medina-Benítez A,
et al. Application of modern imaging methods in diagnosis
of gallbladder cancer. J Surg Oncol 2006;93(8):650–664.
44.Park JK, Yoon YB, Kim YT, et al. Management strategies
for gallbladder polyps: is it possible to predict malignant
gallbladder polyps? Gut Liver 2008;2(2):88–94.
45. Xie XH, Xu HX, Xie XY, et al. Differential diagnosis between
benign and malignant gallbladder diseases with real-time contrast-enhanced ultrasound. Eur Radiol 2010;20(1):239–248.
46. Sugiyama M, Xie XY, Atomi Y, Saito M. Differential diagnosis of small polypoid lesions of the gallbladder: the value
of endoscopic ultrasonography. Ann Surg 1999;229(4):
498–504.
47.Sadamoto Y, Oda S, Tanaka M, et al. A useful approach
to the differential diagnosis of small polypoid lesions of the
gallbladder, utilizing an endoscopic ultrasound scoring system.
Endoscopy 2002;34(12):959–965.
RG • Volume 35 Number 2
48. Lee J, Yun M, Kim KS, Lee JD, Kim CK. Risk stratification
of gallbladder polyps (1–2 cm) for surgical intervention with
18F-FDG PET/CT. J Nucl Med 2012;53(3):353–358.
49.Nishiyama Y, Yamamoto Y, Fukunaga K, et al. Dualtime-point 18F-FDG PET for the evaluation of gallbladder
carcinoma. J Nucl Med 2006;47(4):633–638.
50.Park KW, Kim SH, Choi SH, Lee WJ. Differentiation of
nonneoplastic and neoplastic gallbladder polyps 1 cm or
bigger with multi-detector row computed tomography. J
Comput Assist Tomogr 2010;34(1):135–139.
51.Yoshimitsu K, Honda H, Kaneko K, et al. Dynamic MRI
of the gallbladder lesions: differentiation of benign from
malignant. J Magn Reson Imaging 1997;7(4):696–701.
52.Kim SJ, Lee JM, Kim H, Yoon JH, Han JK, Choi BI. Role
of diffusion-weighted magnetic resonance imaging in the
diagnosis of gallbladder cancer. J Magn Reson Imaging 2013;
38(1):127–137.
53.Lee NK, Kim S, Kim TU, Kim DU, Seo HI, Jeon TY.
Diffusion-weighted MRI for differentiation of benign from
malignant lesions in the gallbladder. Clin Radiol 2014; 69
(2):e78–e85.
54.Yoshioka M, Watanabe G, Uchinami H, et al. Diffusionweighted MRI for differential diagnosis in gallbladder lesions
with special reference to ADC cut-off values. Hepatogastroenterology 2013;60(124):692–698.
55. Irie H, Kamochi N, Nojiri J, Egashira Y, Sasaguri K, Kudo
S. High b-value diffusion-weighted MRI in differentiation
between benign and malignant polypoid gallbladder lesions.
Acta Radiol 2011;52(3):236–240.
56.Sugita R, Yamazaki T, Furuta A, Itoh K, Fujita N, Takahashi S. High b-value diffusion-weighted MRI for detecting
gallbladder carcinoma: preliminary study and results. Eur
Radiol 2009;19(7):1794–1798.
57.Nelms JK, Patel JA, Atkinson DP, Raves JJ. Metastatic
malignant melanoma of the gallbladder presenting as
biliary colic: a case report and review of literature. Am Surg
2007;73(8):833–835.
58. Yoon WJ, Yoon YB, Kim YJ, Ryu JK, Kim YT. Metastasis
to the gallbladder: a single-center experience of 20 cases
in South Korea. World J Gastroenterol 2009;15(38):
4806–4809.
Mellnick et al 399
59.Ono A, Tanoue S, Yamada Y, et al. Primary malignant
lymphoma of the gallbladder: a case report and literature
review. Br J Radiol 2009;82(973):e15–e19.
60. Park JY, Hong SP, Kim YJ, et al. Long-term follow up of gallbladder polyps. J Gastroenterol Hepatol 2009;24(2):219–222.
61.Zielinski MD, Atwell TD, Davis PW, Kendrick ML, Que
FG. Comparison of surgically resected polypoid lesions of the
gallbladder to their pre-operative ultrasound characteristics.
J Gastrointest Surg 2009;13(1):19–25.
62. Colecchia A, Larocca A, Scaioli E, et al. Natural history of
small gallbladder polyps is benign: evidence from a clinical
and pathogenetic study. Am J Gastroenterol 2009;104(3):
624–629.
63. Csendes A, Burgos AM, Csendes P, Smok G, Rojas J. Late
follow-up of polypoid lesions of the gallbladder smaller than
10 mm. Ann Surg 2001;234(5):657–660.
64.Donald G, Sunjaya D, Donahue T, Hines OJ. Polyp on
ultrasound: now what? The association between gallbladder
polyps and cancer. Am Surg 2013;79(10):1005–1008.
65.Ito H, Hann LE, D’Angelica M, et al. Polypoid lesions of
the gallbladder: diagnosis and followup. J Am Coll Surg
2009;208(4):570–575.
66. Konstantinidis IT, Bajpai S, Kambadakone AR, et al. Gallbladder lesions identified on ultrasound: lessons from the
last 10 years. J Gastrointest Surg 2012;16(3):549–553.
67. Corwin MT, Siewert B, Sheiman RG, Kane RA. Incidentally
detected gallbladder polyps: is follow-up necessary? Long-term
clinical and US analysis of 346 patients. Radiology 2011;
258(1):277–282.
68. Cha BH, Hwang JH, Lee SH, et al. Pre-operative factors that
can predict neoplastic polypoid lesions of the gallbladder.
World J Gastroenterol 2011;17(17):2216–2222.
69. Kratzer W, Haenle MM, Voegtle A, et al. Ultrasonographically detected gallbladder polyps: a reason for concern? A
seven-year follow-up study. BMC Gastroenterol 2008;8:41.
70.Sarkut P, Kilicturgay S, Ozer A, Ozturk E, Yilmazlar T.
Gallbladder polyps: factors affecting surgical decision. World
J Gastroenterol 2013;19(28):4526–4530.
71. Wiles R, Varadpande M, Muly S, Webb J. Growth rate and
malignant potential of small gallbladder polyps: systematic
review of evidence. Surgeon 2014;12(4):221–226.
TM
This journal-based SA-CME activity has been approved for AMA PRA Category 1 Credit . See www.rsna.org/education/search/RG.