Correlative Imaging of Gallbladder Cancer: How to Differentiate from Acute Cholecystitis - HD

Introduction

Good morning.
My name is Han Bunim
and I'm a professor of radiology at Oakland University,
William Beaumont School of Medicine.
Today I'm going to talk about correlative imaging
of gall bladder cancer.
How to differentiate from acute cholecystitis.

Gallbladder Cancer Overview

Gall bladder cancer is an uncommon
but highly fatal malignancy
with fewer than 5,000 new cases diagnosed each year in the
United States, it is three
to four times more common in women than men
and typically seen in older patients 65 years
or older with longstanding cosis.
The overall poor prognosis of gall bladder cancer is related
to the often advanced stage at diagnosis
with a five year survival rate of two to 8%
and a median survival of less than six months.
Early diagnosis can improve the clinical outcome
and cure rate with the long-term survival rates
ranging from 85 to 100% for T one stage disease
where the cancer has not yet spread beyond the gallbladder.
Unfortunately, fewer than 10% of symptomatic patients
and only about one of five patients with
incidentally diagnosed gallbladder cancer have
early stage disease.
The early spread of gall bladder cancer is attributed
to the absence of a submucosal layer in the wall,
which promote early
and direct invasion of the cancer
to the adjacent hepatic parenchyma also to the biliary tree.
The cancer spreads to the liver mainly by direct invasion
and also along the portal tract to
involve the biliary tree along the hepato ligament
to involve the lymph nodes and vascular channel
and then peritoneal cavity
and then distant metastasis at histology.
90% of gall bladder cancer are adenocarcinoma.

Risk Factors

The main risk factors of gall bladder cancer is gallstones,
especially untreated chronic symptomatic gallstones.
Other risk factors include chronic cholecystitis,
porcelain gallbladder, gallbladder polyps,
congenital biliary cyst,
and anomalous pancreatic biliary junction.

Diagnosis

The diagnosis of gall bladder cancer is usually unsuspected.
It may be diagnosed incidentally on imaging
intraoperatively at cholecystectomy,
but the more common scenario is that found incidentally
by histopathology after cholecystectomy for gallstones
or cholecystitis with a reported rate of up to 3%
of patients undergoing cholecystectomy
on cross-sectional imaging, gallbladder cancer can present
as one of the three imaging patterns corresponding
to microscopic examination.
The most common pattern is that of a soft tissue mass
replacing the gallbladder
and invading the liver as seen in this cut section
of micro gross pathology here, gallbladder infiltrating,
replacing the cancer, replacing the gallbladder
with direct invasion into the adjacent liver parenchyma.
In this section there are also hepatic metastasis
and lymph node metastasis.
The second most common presentation is that of focal
or diffuse gallbladder wall thickening as well
as asymmetric wall thickening as seen on this
growth photograph.
Here gallstones are commonly seen
with the gall bladder cancer
and here shows focal
irregular thickening of the gallbladder wall
where the tumor has infiltrated.
The third pattern is that of an
intraluminal poly point mass.

Ultrasound Imaging Features of Gallbladder Cancer

First, the first pattern, gallbladder cancer presenting
as a soft tissue mass replacing the gallbladder
when the cancer has totally replaced the gallbladder.
On ultrasound, we see non visualization
of the gallbladder with the presence
of gallstones within the mast
and this is usually most diagnostic.
Otherwise we see a heterogeneous predominantly hypo coic
mass with irregular margin and with associated shadowing.
Echogenic foci related to coexisting gallstones
or gom blood wall calcification
or tumoral calcification evidence of hepatic,
biliary and nodal invasion seals.
The diagnosis c doppler sonography is helpful in
differentiating tumor effective slit from mass, but CT
and MR imaging are better at confirming a mass when
ultrasound is non conclusive
and they're better at detecting adjacent organ invasion,
noder metastasis and distant metastasis.

Case Examples: Soft Tissue Mass Pattern

Here's an 87-year-old female presenting with abdominal pain.
Previous ultrasound studies show a normal gum bladder
on the current exam within the normal,
within the gallbladder fossa, we don't see the gallbladder,
but we do see a heterogeneous predominantly hypo coic mass
with multiple focal areas
of shadowing echogenic foci likely related to
gallstones within the gallbladder.
This image alone should be highly suspicious for
advanced stage of gallbladder cancer looking closely,
there is no definition
or lack of definition between the gallbladder margin
and the hepatic parenchyma.
Again, highly suspicious
for direct liver invasion from gall bladder cancer.
Then one look for evidence of metastatic disease.
The liver contains focal hepatic lesions.
The combination of stenographic findings highly favor
advanced stage gallbladder cancer.
Here is the same patient with correlative CT imaging
that show heterogeneous enhancing gallbladder mass,
replacing the gallbladder presence of gallstones.
That's direct invasion
of the cancer into the liver parenchyma
and multiple liver metastasis CT
and MR are better at detecting nodal metastasis
as in this case here in this patient with
lymph node metastasis, another older female
representing with right upper quadrant pain.
Here's the gallbladder which is filled
with soft tissue mass gallstones.
The evaluation for direct liver invasion is limited On this
ultrasound study looking for evidence of metastatic disease,
we see multiple small hepatic lesions against the findings
are most worrisome for gall bladder cancer
with liver metastasis.
Here is the correlative CT imaging that show gall bladder,
mass gallstones, direct liver invasion,
and multiple liver metastasis
of this advanced stage gallbladder cancer.
How about this case? This patient present with pain,
again, older patient.
The gallbladder has multiple gallstones.
There is soft tissue within the gum bladder.
Is it sludge debris or is it mass color?
Doppler sonography is the key here that show the neovascular
of the lesion within the gallbladder lumen indicative
of gallbladder cancer.
Another patient presenting with pain.
The gallbladder show presence of a mass that is
significant per pancreatic
lymphadenopathy and color flow.
Doppler again show evidence
of vascularity within the soft tissue
lesion within the gallbladder, highly consistent
with gallbladder carcinoma.
Here's a correlative MR study that show bulky
per pancreatic lymphadenopathy compressing the Porto venous
confluence, a intermediate to high signal intensity
mass within the gallbladder lumen on this tissue.
Two weight images that shows significant
persistent enhancement on the post contrast images
with evidence of direct invasion into the liver parenchyma.
So again, C-T-A-M-R
and MR are better for the evaluation of adjacent
organ invasion, biliary invasion
and lymph nodes metastasis.

Second Pattern: Intraluminal Polypoid Mass

The second imaging pattern of gall bladder cancer is that
of an intraluminal poly point mass.
On ultrasound. We look
for a non-mobile inter luminal poly point mass
to differentiate from mobile tumor effective sludge,
but at time it can be difficult to distinguish
from non shadowing adherence stone
or sludge color flow doppler is helpful
but in case where the diagnosis is not clear, CT
and MR should be very helpful
in confirmation of a mass.
The differential diagnosis
for a intraluminal gall bladder mass include not only cancer
but adenomatous
and cholesterol polyps, the uncommon carcinoid tumor
or metastatic disease such as for melanoma.
So as I mentioned, cauli flow doppler is extremely helpful,
but there are features of a poly poly lesion
that will help us raise the index
of suspicions for malignancy.
And these are the features that are highly associated
with malignancy that we should be aware of.
When the poly poly lesion is greater than 10 millimeter,
there's high prevalence of malignancy,
which has been reported anywhere between 37 to 88%.
Key feature, the poly poly lesion is associated
with thickening or nodularity of the gallbladder wall.
The lesion if it's sesi or broad pay base
or it has cauliflower feature, is also highly suspicious.
And obviously if one sees evidence of hepatic invasion
and o lymph neuropathy,
that again also favors gallbladder malignancy.

Case Examples: Intraluminal Polypoid Mass

Here's a 77-year-old patient on an
outside renal stone.
Non-contrast enhanced CT
show a two centimeter gallbladder mass.
An ultrasound was performed
that beautifully demonstrate a polypoid lesion
color flow sono double sonography show the evidence
of vascularity.
Note, the wall
of the gallbladder gallbladder cancer will not
be associated with an intact wall.
The wall is usually violated
and that is focal thickening
of the gallbladder wall here associated
with this poly poly lesion, which turned out to be
an early gallbladder cancer cancer.
For this, patient who is very fortunate
to have an early stage gallbladder cancer,
here is another case, a patient who present with
weight loss and decreased appetite.
In contrast, enhanced CT scan show
a small eight millimeter poly population within the
gallbladder lumen.
An ultrasound was performed confirming this 10 millimeter
lesion within the lumen of the gallbladder.
Note, the irregularity nodularity focal thickening
of the gallbladder wall, which is
we should be suspicious.
That is not just a simple polyp,
but there is increased risk of malignancy.
The patient had a cholecystectomy
and indeed there was chronic cholecystitis
and an invasive adenocarcinoma of the gallbladder.
This is a beautiful case,
given by Dr.
AKA that show the small poly poly lesion on these T two
weighted images that has this very irregular feature
contrast enhanced CT look for the subtle irregularity
and focal and thickening
and nodularity that is associated
with this very small poly poly lesion.
These subtle features are very helpful for us
to raise our suspicion that this polyp may be a
malignant polyp, which indeed this turn out to be
In contrast to this benign polyp,
here we see a small polyp.
It doesn't have the CSI broad base appearance.
Note, the intact gallbladder wall, smooth intact.
Here's a growth specimen on the stock.
MR Imaging show smooth associate wall.
There's no focal noll area
or thickening of this benign gall bladder poly.
Here's a patient coming in with right upper quadrant pain.
It was reported there is a,
heterogeneous echogenic material within the
gallbladder lumen that has somewhat
of an irregular surface here.
Color flow showed no obvious vascularity, so
it was interpreted as
possible sludge even though it was not mobile,
that was no stenographic Murphy's signed.
The liver function test was normal
and the patient was recommended
to have a follow-up ultrasound.
The patient, came back to the ER one week later
with severe pain
and the surgeon took the patient to the OR
to do cholecystectomy
and that path there was a 3.7 centimeter
primary go bladder cancer.
Let's take a look at the image again.
Here is the gallbladder wall. It is fo thickened.
The gallbladder wall is not intact here
and when we see must like
structure within the gallbladder lumen, even though
color flow do blood did not show any vascularity,
we should be suspicious and take prudence
and recommend the appropriate further imaging
with contrast and hence Mr to exclude the presence
of a mass and that's what
should have been done in this case.
But fortunately, the patient did have surgery that,
diagnosed early gum bladder cancer.

Third Pattern: Focal or Diffuse Wall Thickening

The third imaging pattern of gum bladder cancer is that
of diffuse of focal wall thickening.
This is the most diagnostic challenging pattern of the three
because it mimics the appearance of the more common acute
and chronic inflammatory conditions of the gallbladder
and other non gum bladder benign conditions.
In these cases, we really need to look for the subtle
findings that may suggest malignancy in conjunction
with the clinical presentation
that will help us determine the cause of the process.
Here's the list of differential diagnosis
for diffuse gum blood one thickening including non-fasting
state acute
and chronic cholecystitis liver disease,
low albumin renal cardiac disease, ace
and gallbladder malignancy.
And here's the list for differential diagnosis
of focal blad wall thickening including cancer
polyps metastasis at adenomyosis.
So what are the characteristics that are suggestive
of malignancy in these cases?
Again, as we emphasize, look
for asymmetric irregular wall thickening.
Obviously other associated findings including invasion
of liver, hepatic metastasis, lymphadenopathy,
lymph biliary obstruction, all will favor the
suspicions of malignancy.

Case Examples: Wall Thickening Pattern

Let's take a look at a few cases here.
This is a 58-year-old patient
with right upper quadrant pain.
Note the gallbladder wall thickening in the fundus
irregular asymmetric gallbladder cancer occurs in
the fundal region in about 60% of cases,
30% in the body
and 10% occur in the neck.
So pay very special attention
to the gallbladder fundus color flow.
Doppler sonography show vascularity
of this irregular focal thickening looking for
evidence of metastasis show multiple hepatic lesion
biliary obstruction.
Again, the combination of findings should lead us
to the appropriate diagnosis of gall bladder cancer.
Here is the mr exam of that patient show
diffuse thickening
of the gallbladder wall which is enhancing,
but look at the irregular asymmetric thickening
of the gallbladder wall in addition to presence
of multiple liver meta enhances of this patient
with advanced stage of carcinoma.
Here's a case on CT again to emphasize
the irregular nodular, asymmetric thickening
of the gall bladder gallstones, biliary dilatation
and evidence of neuropathy.
Again, the combination of findings are highly suspicious for
metastatic gallbladder cancer.
Here's a patient with biliary invasion from
a gallbladder mass seen
as focal thickening in the region of fundus.
The tumor has spread along the hepato ligament
that cause compression
and invasion of the biliary tree
and bulky perp pancreatic lymphadenopathy.
So this is a case of again,
an advanced stage gall bladder cancer with no do
and biliary invasion.
Here is a courtesy of Dr.
Samka that shows beautiful evidence of persistent
thickened enhancement,
of the thickened gallbladder wall.
Look at the irregularity,
asymmetric on the diffuse thickening
with irregularity of the wall with evidence
of adjacent liver invasion.
Multiple liver metastasis in addition to vascular metastasis
as evidenced by occlusion of the portal vein in this patient
with gall bladder cancer with hepatic invasion
and vascular invasion.
Here's an interesting case, 80-year-old patient which
who presented with weakness and confusion.
Non-contrast CT show a gallbladder with
probable gallbladder while thickening
and may be tiny gallstone.
A ultrasound was obtained that showed this interesting
layered appearance
of the gallbladder wall, which is thickened.
There is no peric lytic fluid.
There's a tiny little gallstone
color doppler sonography show vascularity
of the gallbladder wall here,
although there was negative sonographic Murphy's sign,
the imaging findings are suggestive
of cholecystitis.
A he scan was suggested and it was negative.
And an MRI was performed on MR imaging,
T two weighted images showed the more typical
gallbladder wall thickening of cholecystitis
with a double layered patterned
and an inner hypo intense T two layer of mucosa
and the muscle layer and the outer hyperintense layer
of stromal edema, of
suggestive of acute cholecystitis.
On the contrast enhanced study that is smooth enhancement
of the mucosa with delay enhancement
of the gallbladder wall.
Again, the findings are more suggestive
or more consistent with cholecystitis.
The patient was taken to the OR for cholecystectomy
and the path show
diffuse large B-cell lymphoma of the gallbladder,
a primary gallbladder lymphoma, a very,
more uncommon gallbladder malignancy.

Differentiating from Acute Cholecystitis

Let's turn our attention to acute cholecystitis
and how we differentiate from gallbladder cancer.
In 90% of cases acute cholecystitis is caused
by in an impact stone in the gallbladder neck
or the cystic neck or the cystic duct.
So it is imperative that we looked
for this impacted stone in the gallbladder
neck or the cystic duct.
In the remaining cases the cholecystitis is due
to acute a calculus cholecystitis which is usually seen
in critically ill or injured patients.
The primary ultrasound findings of acute cholecystitis
was reported by raw ol,
which include the combination of gallstones
and a positive stenographic mu sign.
This combination of ultrasound finding has a 92% positive
predictive value for acute cholecystitis.
As I mentioned since it's most likely due
to a stone impacting the cystic duct
and the gallbladder neck, if we see
an impact on the diagnosis of acute cholecystitis is easy.
Gallbladder wall thickening is a secondary one
of the secondary ultrasound findings of acute cholecystitis.
The other associated secondary findings are also very useful
including peric cystic fluid, gallbladder distension
and hyper hyper vascularity of the wall
of the gallbladder even though it is a later sign.

Case Examples: Acute Cholecystitis

Here is a typical case of acute cholecystitis
patient with positive sonographic Murphy
signed in this case.
We have a non non-mobile stone impacting the neck
of the gallbladder
that is diffused gallbladder while thickening
but it is smooth.
There is also paralytic fluid in this clinical presentation.
This is acute cholecystitis.
This patient also present with right upper quadrant pain.
We see a stone impacting the gallbladder neck
positive sonographic morph sign even though without
gallbladder one thickening, this is consistent
with acute cholecystitis.
The patient has an MR the next day
and that is marked change.
Here we see the gallbladder is now more distended.
There is a stone impacting the neck of the gallbladder
that is double layered gallbladder wall hyperintense,
inner hyperintense outer
and the smooth enhancement of the gallbladder wall.
So these findings are consistent with acute cholecystitis.
There's no feature that is suggestive at least by imaging
of gallbladder cancer here.
How about this case, the patient with pain,
the gallbladder is abnormal.
We do have stones.
We do have a non-mobile stone in the region of the neck
suspicious for impaction of the neck of the gallbladder
that is thickening
but very irregular gallbladder wall.
There's soft tissue material within the gallbladder lumen.
Is that slur or is that a mass colored doppler?
Sonography did not show evidence of hypovascular
an MR was performed to define the disease further
here we see the typical double layered
gum bladder wall edema more consistent
with an inflammatory process.
Gallstones and contrast enhanced studies show
this intense hyperemic changes within the
hep adjacent hepatic parenchyma.
Very helpful sign of acute inflammation
and also these little septi within the lumen
of the gallbladder representing slough mucosa
of acute complicated gangrenous cholecystitis.
Looking at the gallbladder again, I would also be suspicious
for this linear membrane within the gallbladder lumen
raising the suspicions for acute gangs cholecystitis.
So in this case of complicated cholecystitis,
sometime it is difficult to differentiate from
gallbladder carcinoma,
but with appropriate further imaging
exam, we should be able to differentiate
between gallbladder cancer
and complicated cholecystitis.
How about this case? The patient with
me metastatic colon cancer
who is on chemotherapy is rather sick.
The patient has abdominal pain.
An ultrasound was obtained that show
gallbladder wall thickening echogenic material within the
gallbladder lumen that is not vascular, probably sludge
in the appropriate clinical setting.
We should be concerned about a calculus c sitis,
especially when early exams show normal
gallbladder wall.
Here we have progressive thickening of the gallbladder wall.
In the absence of ascites congestive heart failure,
one should raise a suspicions for a countless cholecystitis
HI scan was performed.
Hi scan can be helpful in a countless cholecystitis
because the bile can be very viscous
and the slush can also be very thick and viscous
and can obstruct the cystic duct.
So again,
a countless cholecystitis Be aware
of the progressive gallbladder wall thickening without
presence of other causative factors.
If the patient start out with gallbladder thickening
and we are suspicious
of a calculus cholecystitis MRI is also very helpful.
Again, this case is courtesy of duct alca.
We see in this patient gallbladder luminal distension.
This beautiful T two weighted double layered gallbladder
wall edema, smooth sludge
contrast enhanced study early show the adjacent
hyperemic vascularity
of the liver parenchyma adjacent to the gallbladder.
Very helpful sign for acute inflammation.
And here we see smooth mucosal wall enhancement
of this, gallbladder, which is consistent
with the a calculus cholecystitis.

Adenomyomatosis

Let's move on to adenomyosis.
We also need to be aware of the findings on this entity
because it can mimic gall bladder cancer.
It is a common non-inflammatory condition
with epithelial proliferation, muscular hypertrophy
and intramural diverticular or kansky ash of sinuses.
The disease process can be focal secondmental or diffused.
On ultrasound one, look for evidence of intramural cysts
with the echogenic foci with V-shaped
or cele artifacts that are hallmarks of eno
eno mytosis on ultrasound color flow dolus also helpful
that show the twinkle artifacts due to the irregularity
of the crystals within the
rusky op sinuses.
MRI is also very specific.
The intramural cysts are seen as a string of beat
of her necklace sign.

Case Examples: Adenomyomatosis

Here's the patient with the typical findings of an
mytosis on ultrasound.
This echogenic foci with V-shape
or cele artifacts that are very unique for
cho for eno mytosis due
to the cholesterol crystals within the lumina of the
roky edge of sinuses.
Here is a patient of focal thickening in the fundus
with some cystic changes
color flow double sonography showed this twinkle artifact
due to the cholesterol crystals within the sinuses against
a finding of adeno mytosis of the gallbladder.
He is MRI demonstrating the nice
string upbeat sign up her necklace sign due
to the intramural cysts within this focal while thickening
in the fundus of the gallbladder, the hallmark
of endo myosis on Mr with very high specificity.
92% specificity for the diagnosis
of adeno mytosis on CT eno mytosis
may be difficult in this case is seen as a focal thickening
and or mass in the region of the fundus.
MRI was appropriately performed that show
this typical her necklace
or string of beads signed on this heavily T two weighted
image that is the hallmark of adenoma mytosis.

Xanthogranulomatous Cholecystitis

And lastly, we should talk about
zyl granulomatous cholecystitis on
although it's uncommon, variant
of chronic cholecystitis characterized
by lipid latent inflammatory process comparable
to zen granuloma santyl granulomatous pyelonephritis
on imaging finding we see marked
gallbladder wall thickening with intramural
nodules that are consistent with intramural abscesses
or these foci of granulomatous inflammation
without the associated features suggestive
of gall bladder cancer such as liver invasion,
b duct invasion or nodal metastasis.
The distinction between these two
entities often are impossible preoperatively.

Case Example: Xanthogranulomatous Cholecystitis

He's the beautiful case of zen granuloma cystitis
as a courtesy again of doctor from Dr.
Ska that show significant marked
gallbladder wall thickening
with multiple intramural abscesses
or nodules of the zyl granuloma
that is consistent with
zen granuloma cholecystitis.
Again in this case the preoperative di differentiation
between this entity
and gallbladder cancer may be difficult,
without the associated, metastatic findings
of gallbladder cancer.

Conclusion

So in conclusion,
gall bladder cancer is a lethal cancer typically diagnosed
incidentally for routine cholecystectomy or by imaging.
It's often diagnosed at advanced stage
with very poor survival rates,
but early diagnosis
of gallbladder cancer can improve the clinical outcome
and cure rate and imaging may allow earlier diagnosis,
but there may be significant overlaps
between gallbladder cancer
and benign disease of the gallbladder.
So our challenging, our challenging tasks are one
to identify and to differentiate between the benign lesions
and early gallbladder cancer, which requires prudence
and appropriate imaging techniques
and familiarity with the subtle differentiating features so
that we can diagnose early gall bladder cancer, which,
can improve the outcome for the patients outcome.
Our task also includes to accurately assess extent
or stage the disease,
which is vital in the treatment planning
and prognostication.
And as we have seen, our task is
to emphasize the complementary roles of ultrasound,
CT and MRI imaging for better evaluation
of both benign and malignant gallbladders diseases.
Thank you very much for your attention.