Carcinoma in the porcelain gallbladder:

A relationship revisited
Antonia E. Stephen, MD, and David L. Berger, MD, Boston, Mass

Background. Gallbladder cancer is the most common biliary tract malignancy. Calcification of the gall-
bladder wall is reported to be associated with gallbladder cancer. In the literature, the incidence is quoted
to be between 12% and 61%. This study aims to clarify the risk of cancer in a calcified gallbladder.
Methods. The charts and pathology reports at the Massachusetts General Hospital were reviewed, and
patients with either gallbladder cancer or a calcified gallbladder were included in the study. The Fisher
exact test was used to test for the association between cancer and gallbladder wall calcifications.
Results. From 1962 to 1999, there were approximately 25,900 gallbladder specimens analyzed at the
Massachusetts General Hospital. There were 150 patients with gallbladder cancer and 44 patients with
calcified gallbladders. Two types of calcified gallbladders were noted: those with complete intramural cal-
cification (n = 17) and those with selective mucosal calcification (n = 27). The incidence of cancer aris-
ing in a gallbladder with selective mucosal wall calcification was approximately 7%. There was a sig-
nificant association between gallbladder cancer and selective mucosal calcification with an odds ratio of
13.89 (P = .01). There were no patients with diffuse intramural calcification and cancer.
Conclusions. A calcified gallbladder is associated with an increased risk of gallbladder cancer, but at a
much lower rate than previously estimated. The incidence of cancer depends on the pattern of calcifica-
tion; selective mucosal calcification poses a significant risk of cancer whereas diffuse intramural calcifi-
cation does not. (Surgery 2001;129:699-703.)

From the Department of Surgery, Massachusetts General Hospital, Boston, Mass

GALLBLADDER CANCER is the fifth most common
cancer of the gastrointestinal tract and the most
common cancer of the biliary system. The progno-
sis for patients with gallbladder cancer is extreme-
ly poor. The overall 5-year survival is 5% and the 1-
year mortality is 88%.1 Gallbladder cancer has a
variable and nonspecific presentation. Patients are
often diagnosed late in the course of their disease.
In 1966, an association between gallbladder cancer
and a calcified gallbladder wall was identified.2
Currently, the incidence of gallbladder cancer aris-
ing in a calcified gallbladder is said to be anywhere
from 12% to 61%.3 The term porcelain gallbladder is
often used to describe calcification of the gallblad-
der wall. The term originated from the description
of a gallbladder wall extensively infiltrated with
and replaced by calcium. This process resulted in
a gallbladder with a fragile, brittle consistency and
Accepted for publication December 31, 2000.
Reprint requests: David L. Berger, MD, Department of Surgery,
ACC 465, Massachusetts General Hospital, 15 Parkman St,
Boston, MA 02114.
Copyright © 2001 by Mosby, Inc.
0039-6060/2001/$35.00 + 0 11/56/113888
doi:10.1067/msy.2001.113888
a blue discoloration, hence the phrase porcelain
gallbladder.
In this study, a more accurate estimate of the
incidence of gallbladder cancer in a calcified gall-
bladder is proposed. Two types of gallbladder wall
calcification are described: selective mucosal calci-
fication and diffuse intramural calcification, the
latter type being consistent with the traditional
description of a porcelain gallbladder. We aim to
clarify the relationship between gallbladder cancer
and the different types of calcified gallbladders.
METHODS
The charts and pathology reports from
Massachusetts General Hospital from 1962 to
1999 were reviewed and selected for patients who
had the diagnosis of either gallbladder cancer or
a calcified gallbladder wall. Included in the study
were patients who underwent a complete chole-
cystectomy with pathologic examination of the
specimen. Patients with a diagnosis of gallblad-
der cancer determined solely on radiographic
studies or surgical exploration and biopsy speci-
men examination were excluded from the final
analysis. The Fisher exact test was used to test for
the association between finding cancer in the

SURGERY 699
700 Stephen and Berger
Fig 1. Abdominal ultrasonography of a patient with gall-
bladder cancer and flecks of calcium in the gallbladder
wall mucosa on pathologic examination. This parasaggital
view through the gallbladder fossa shows irregular thick-
ening along the anterior wall (white arrow) suspicious for a
gallbladder mass. There are several nonshadowing gall-
stones layering along the posterior wall (black arrowheads).
No gallbladder wall calcifications were seen.
gallbladder specimen and finding gallbladder
wall calcifications.
RESULTS
From 1962 to 1999, there were approximately
25,900 gallbladder specimens analyzed in the
pathology department at Massachusetts General
Hospital. There were 150 patients with gallbladder
cancer who underwent cholecystectomy as part of
their treatment. There were an additional 26
patients with gallbladder cancer diagnosed by eval-
uation of a biopsy specimen from a gallbladder
mass noted at surgical exploration. These latter
patients were excluded from the final analysis
because the entire gallbladder did not undergo
pathologic analysis, and calcifications could have
been missed on the biopsy. However, none of the
biopsy specimens in these patients demonstrated
calcification of the gallbladder wall, and none of
these patients had evidence of gallbladder calcifi-
cation on preoperative radiographic studies. Of the
150 patients who underwent cholecystectomy, 110
were female and 40 were male, supporting the
reported female-to-male ratio of 3-4:1. The average
female age was 71 years with a range of 41 to 98
years. The average male age was 70 years with a
range of 38 to 92 years.
There were 44 patients with calcified gallblad-
ders: 39 women and 5 men, accounting for 0.2% of
all cholecystectomy specimens from our institu-
tion. The average age of these patients was slightly
younger than those with gallbladder cancer, with
Surgery
June 2001
Table I. Symptoms of patients with calcified gall-
bladder
Patients
Presenting symptoms No. (%)
Abdominal pain only 21 (47)
Abdominal pain/nausea/vomiting 7 (16)
Abdominal pain/fever 4 (9)
Anorexia/nausea/vomiting 2 (5)
Abdominal pain/jaundice 2 (5)
Asymptomatic 8 (18)
an average age of 64 years and a range of 24 to 91
years. All of the patients who had a calcified gall-
bladder also had coincident gallstones. Of those
who complained of symptoms, most had symptoms
suggestive of benign biliary tract disease. The most
common presenting symptom was right upper
quadrant or abdominal pain (Table I). Eight of the
patients were asymptomatic. Of these patients, 2
had the incidental discovery of a porcelain gall-
bladder on an x-ray film. The remaining 6 patients
were undergoing an abdominal operation for an
unrelated reason and were noted to have a hard-
ened gallbladder at exploration. There were 2 dis-
tinct types of gallbladder wall calcification
described in the pathology reports: 27 of the 44
gallbladders had focal deposits of calcium in the
gallbladder wall mucosa (selective mucosal calcifi-
cation), and the remaining 17 had diffuse deposi-
tion of calcium in the muscular layer of the gall-
bladder wall (porcelain gallbladder). None of the
pathology reports described the gallbladder as hav-
ing both diffuse intramural calcium and selective
deposits in the mucosa.
There were 2 patients with a diagnosis of both
gallbladder cancer and a calcified gallbladder. The
pathology reports of these 2 patients describe a
focal pattern of calcium deposition in the mucosa
of the gallbladder wall. One patient underwent a
plain film of the abdomen and an abdominal ultra-
sound before surgery; these images were reviewed
and there were no calcifications evident on either
study, although the gallbladder wall was abnormal-
ly thickened on the ultrasound (Fig 1). The second
patient had a chest x-ray and abdominal ultrasound
preoperatively, which were not available for review
but no calcium was noted on the reports of the
studies.
The overall incidence of gallbladder cancer in
patients with gallbladder wall calcifications was 5%
(2/44). The incidence of gallbladder cancer in
gallbladders with focal mucosal calcium deposition
was 7% (2/27). There were no patients with calci-
fication of the muscular layer of the gallbladder
Surgery Stephen and Berger 701
Volume 129, Number 6

A B
Fig 2. Diffuse intramural calcification (A) and selective mucosal calcification (B) of the gallbladder wall as
seen on ultrasonography. A parasagittal sonogram through the gallbladder fossa demonstrates a thin, con-
tinuous, echogenic line with prominent posterior acoustic shadowing (black arrow) in the patient with diffuse
intramural calcification (A). Ultrasonography of the gallbladder with selective mucosal calcification (B) shows
scattered areas of nonshadowing calcium (arrowheads) and several gallstones (white arrow).

wall (porcelain gallbladder) and gallbladder can-
cer. The incidence of gallbladder wall calcification
in patients undergoing cholecystectomy as part of
their treatment for gallbladder cancer was less than
2% (2/150). The results of the Fisher exact test
indicate a significant association between gallblad-
der cancer and a gallbladder wall with mucosal cal-
cification with an odds ratio of 13.89 (P = .01);
these patients had a risk of having gallbladder can-
cer 14 times higher than those without the finding
of gallbladder wall calcification.
DISCUSSION
Gallbladder cancer is a notoriously aggressive
disease that is diagnosed late and carries a poor
prognosis from the time of diagnosis. The average
incidence of gallbladder cancer is estimated to be
between 0.55% and 1.91%.4 Several potential risk
factors have been identified and evaluated (Table
II). There is a well-established association between
gallstones and gallbladder cancer.5 Gallstones are
present in 70% to 90% of patients with gallbladder
cancer, and the epidemiology of the 2 conditions
are similar, with both being more common in older
women. It has also been suggested that large gall-
stones, greater than 3 cm in diameter, increase the
risk of gallbladder cancer more so than small
stones.6
In addition to gallstones, it has long been
reported that a calcified gallbladder is associated
with a high incidence of cancer. Like gallstones and
gallbladder cancer, a calcified gallbladder is most
common in middle-aged women. It is quite rare
and is estimated to occur in 0.06% to 0.8% of gall-
bladder specimens.2 The association between gall-
bladder cancer and calcium deposition in the wall
was first proposed in 1951 in a patient with a carci-
noma arising in a calcified gallbladder.7 In 1959,
the pathology reports on the cholecystectomy spec-
imens at Bellevue Hospital from 1922 to 1956 were
reviewed.8 They found 16 calcified gallbladders, 2
of which harbored carcinoma. This prompted the
researchers to warn of a high incidence of carcino-
matous change in the calcified gallbladder. A sub-
sequent report on the subject from 1962 quoted an
unusually high incidence of gallbladder cancer
arising in a calcified gallbladder.9 The study was
from Argentina and the authors reported the dis-
covery of 78 gallbladder cancers and 26 calcified
gallbladders. Of these, 16 had both gallbladder
cancer and a calcified wall; hence the results
demonstrated a 16/26 incidence of gallbladder
cancer in a porcelain gallbladder. A subsequent
study recommended cholecystectomy for all
patients with a calcified gallbladder; the conclu-
sions drawn in this report were based on the 1962
report from Argentina.2 Since then, there have
only been anecdotal reports of calcified gallblad-
ders with coincidental cancer published in the lit-
erature.10,11
The specimens of the 2 patients in this series
with both cancer and a calcified gallbladder are
described as containing focal deposition of calci-
um. It has long been appreciated that in gallblad-
ders with calcium deposition, there is variation in
the extent and location of the calcification. Sir
William Osler,12 in the 1925 edition of Principles
and Practice of Medicine, described 2 pathologic
types of gallbladder wall calcification: diffuse intra-
mural calcification and selective mucosal calcifica-
702 Stephen and Berger
Table II. Proposed risk factors for gallbladder
cancer
Gallstones
Large gallstones > 3.0 cm
Cholecystoenteric fistula
Anomalous pancreaticobiliary junction
Gallbladder adenoma or polyps
Calcified or porcelain gallbladder
Choledochal cysts
Industrial exposure to carcinogens
Chronic infection with Salmonella typhi
tion. In the first type, a continuous band of calcium
infiltrates and replaces the muscular layer of the
gallbladder wall. It is accompanied by dense fibro-
sis of the entire gallbladder wall, and the mucosal
epithelium is denuded and sloughed away. The sec-
ond type, selective mucosal calcification, is charac-
terized by flecks of calcium in the inner layer, or
mucosa, of the gallbladder wall. The classic descrip-
tion of a porcelain gallbladder was one with a hard-
ened and brittle wall infiltrated and replaced with
calcium. This description is consistent with diffuse
intramural calcium deposition. Selective mucosal
calcification does not confer these characteristics
on the gallbladder. Over time, however, the term
came to be used more generally as a description of
all types of gallbladder wall calcification. Variation
in the use of the term porcelain gallbladder may
account for the different incidence of cancer in dif-
ferent studies. It would perhaps be more appropri-
ate to reserve the term porcelain gallbladder for those
with diffuse intramural calcification and use more
specific pathologic descriptions when describing
selective mucosal calcification.
A limitation of this study was that all 25,900
gallbladder specimens were not re-reviewed; it is
possible there were additional calcifications in the
150 resected gallbladder cancers or in the 25,900
cholecystectomy specimens not noted in the
pathology report. In addition, the calcified gall-
bladders may have contained both diffuse intra-
mural and selective mucosal calcification not
specified in the initial report. The pathology
department at our institution handles gallbladder
specimens by routine sectioning and standard
hematoxylin-and-eosin staining; mineralization of
the gallbladder wall is then apparent on micro-
scopic examination of the stained specimen.
Although specific calcium stains are available,
these stains are not routinely used but could
potentially be helpful when the pattern of calcifi-
cation is not readily apparent.
The radiographic appearance of a calcified gall-
Surgery
June 2001
bladder varies depending on the extent and loca-
tion of the calcifications. Selective mucosal calcifi-
cation is less likely to be identified on a plain film,
whereas diffuse intramural calcification typically
produces a curvilinear or rounded opacity in the
right upper quadrant. The introduction of ultra-
sound and the increasing use of radiologic studies
in the evaluation of patients with abdominal pain
may have led to the earlier identification of patients
with calcified gallbladders and explain earlier
descriptions of more extensively calcified gallblad-
ders that had been diagnosed and removed later.
Because it is a relatively rare and unstudied entity,
the natural history and progression of calcified
gallbladders is unknown, and it is possible that
there is overlap or progression of the different pat-
terns of calcification.
On the basis of ultrasound findings, calcified
gallbladders have been classified as complete and
incomplete types.13 These types correspond to
Osler’s description of diffuse intramural calcifica-
tion and selective mucosal calcification.12 In this
classification system, the ultrasound findings in cal-
cified gallbladders are 1 of 3 possible types: Type I
is characterized by a hyperechoic semilunar struc-
ture with posterior acoustic shadowing, the find-
ings in Type II include a curvilinear echogenic
structure with acoustic shadowing, and in Type III
are irregular clumps of echos with posterior
acoustic shadowing. Type I corresponds to com-
plete intramural calcification of the gallbladder,
and Types II and III correspond to variations of
selective mucosal calcification. Ultrasound exami-
nations of patients with selective mucosal calcifica-
tion and diffuse intramural calcification are shown
in Fig 2. It is also possible, as was the case in the 2
patients in our study with gallbladder cancer and
selective mucosal calcifications, that flecks of
mucosal calcium would not be seen on radiographic
studies but only noted on pathologic examination.
It has been suggested that the 2 patterns of cal-
cification carry different risks of gallbladder can-
cer. A 1989 report demonstrated a significantly
lower incidence of gallbladder cancer in gallblad-
ders with diffuse intramural calcification compared
with incomplete calcification of the mucosa.14 The
authors of the study report an incidence of cancer
in the incomplete type of 25% to 42%; there were
no cancers found in the gallbladders with diffuse
calcification in the muscular layer of the wall. The
incidence, however, of 25% to 42% is higher than
the incidence of cancer found in our study. There
were fewer patients in that report (29 patients with
porcelain gallbladders), and it represented a sam-
pling of patients from the literature (of calcified
Surgery
Volume 129, Number 6
gallbladders with ultrasound findings) and not a
comprehensive review of resected gallbladders
from 1 institution. Furthermore, many patients
with calcified gallbladders predate the introduc-
tion of ultrasound. This could explain the different
incidence of cancer in that study population.
One factor contributing to the poor prognosis
in gallbladder cancer is the lack of specific symp-
toms or signs early in the course of the disease.
There have been efforts made to identify risk fac-
tors for this disease and hence proceed with pro-
phylactic cholecystectomy for those at risk.
Evidence of calcium deposition in the gallbladder
wall, also known as a porcelain gallbladder, has
long been cited as a risk factor for the coincidental
presence of or the future development of gallblad-
der cancer. The identification of calcium deposi-
tion in the gallbladder wall on a radiographic study
in an asymptomatic patient was justification to pro-
ceed with a cholecystectomy. Calcified gallbladders
are mostly found in the elderly population, which
has a higher morbidity and mortality with a surgical
procedure. In addition, the fibrotic wall and brittle
consistency of some porcelain gallbladders makes
them difficult to remove laparoscopically.
The incidence of cancer arising in calcified gall-
bladders is not clearly delineated and current esti-
mates range from 12% to 61%.3 These estimates
are largely based on 1 study from Argentina pub-
lished in 1962.9 In our study, there is a 5% inci-
dence of gallbladder cancer arising in a calcified
gallbladder, indicating that the true incidence is on
the lower end of the quoted range. Although the
numbers are small, this is the largest series from 1
institution on the subject of cancer arising in gall-
bladders with calcified walls. The risk may be fur-
ther assessed by noting the pattern of calcification;
those with flecks of calcium in the gallbladder
mucosa have a significant risk of cancer compared
with those with diffuse, intramural calcification,
which have almost no risk of cancer. There were no
patients in this series with the muscular layer of the
gallbladder wall replaced by calcium and a coinci-
dent gallbladder cancer. The morbidity and mor-
tality of an elective cholecystectomy is low but not
insignificant and increases with age and comorbid
medical conditions. If right upper quadrant calcifi-
cations are identified on a plain film, an ultrasound
examination may further delineate the pattern of
Stephen and Berger 703
calcification by using the description of ultrasound
findings in different patterns of gallbladder wall
calcification as described by Kane et al.13
The results of this study demonstrate that differ-
ent patterns of gallbladder wall calcification have
different risks of developing cancer. The pattern of
calcification can often be identified by ultrasound.
Given these results, the management of an inci-
dentally discovered porcelain gallbladder should
be determined on the basis of a careful assessment
of the individual patient’s overall medical condi-
tion, operative risk, and pattern of calcification,
compared with the risk of harboring a silent carci-
noma.
We thank Dr Mary Jane O’Neill for providing
ultrasound photographs and for assistance in inter-
pretation of the radiologic studies, Dr David
Schoenfeld for his help with the statistical analysis,
Dr David MacLaughlin for critically reviewing the
manuscript, and Barrett Goodspeed for providing
the pathology reports.
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