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Oncology
A case of primary squamous cell carcinoma of the gallbladder
with local invasion of the liver and peritoneum, and
metastasis to the omentum
Asaph C.J. Levya,*, Francisco Casalduc-Cocaa, Saeed Asiryb, Allen Goodmana
aDepartment of Radiology, Northwell Health System, Lenox Hill Hospital, 100 East 77th St, New York, NY 10075 USA
bDepartment of Pathology, Northwell Health System, Lenox Hill Hospital, New York, NY USA
ARTICLE INFO
Article history:
Received 17 August 2017
Received in revised form 11
September 2017
Accepted 25 September 2017
Available online 6 November 2017
Keywords:
Primary
Squamous
Cell
Carcinoma
Gallbladder
Cancer
ABSTRACT
Primary squamous cell carcinoma of the gallbladder is a rare entity that comprises approx-
imately 1%-3% of all primary gallbladder cancers. We report the case of a 37-year-old woman
who was diagnosed with a locally invasive squamous cell carcinoma of the gallbladder. Sur-
gical pathology revealed a predominantly squamous cell carcinoma composition of the tumor
with a few microscopic foci of adenocarcinoma (<1% of tumor). We discuss pertinent clin-
ical features, risk factors, and imaging characteristics to prompt early diagnosis and treatment,
which will ultimately lead to improved patient outcomes.
© 2017 the Authors. Published by Elsevier Inc. under copyright license from the University
of Washington. This is an open access article under the CC BY-NC-ND license (http://
creativecommons.org/licenses/by-nc-nd/4.0/).
Introduction
Gallbladder cancer (GBC) is the fifth most common gastroin-
testinal tract malignancy in the United States, with an incidence
of 6500 cases annually [1]. Known risk factors for GBC include
chronic cholelithiasis, female gender (ratio approximately 3:1),
porcelain gallbladder, adenomatous polyposis of the gallbladder
(GB), carcinogens (eg, miners exposed to radon), Salmonella typhi
infection, and abnormal pancreaticobiliary duct junction [1].
Although only up to 3% of patients with cholelithiasis develop
gallbladder cancer, gallstones are present in 70%-90% of patients
diagnosed with GBC [1]. Chronic irritation of the GB wall related
to gallstones is hypothesized to be the major risk factor for ma-
lignant transformation of the GB epithelium. Approximately
80%-95% of primary gallbladder cancers are adenocarcinoma
(AC) [2]. Other histologic types include small cell cancer, squa-
mous cell carcinoma (SCC), lymphoma, and sarcoma.
Patients with GBC are usually asymptomatic in the absence
of advanced disease. As a result, diagnosis and management
can be challenging. Patients can often present with symp-
toms such as anorexia, abdominal pain, nausea, and vomiting,
Declaration of Interest: We certify that there are no financial or personal relationships with other people or organizations that could
inappropriately influence our work. We certify that this is an original manuscript, which has not been published elsewhere.
*Corresponding author.
E-mail address: asaphlevy@gmail.com (A.C.J. Levy).
https://doi.org/10.1016/j.radcr.2017.09.026
1930-0433/© 2017 the Authors. Published by Elsevier Inc. under copyright license from the University of Washington. This is an open
access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Radiology Case Reports 13 (2018) 269–274
Available online at www.sciencedirect.com
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which may be indistinguishable from those of acute chole-
cystitis [3]. Findings that are more specific for advanced disease
include weight loss, obstructive jaundice (secondary to tumor
invasion of the intrahepatic bile ducts or hepatic metasta-
ses), ascites, palpable abdominal mass, and hepatomegaly.
Computed tomography and ultrasonography results are often
consistent with acute cholecystitis and cholelithiasis.Thus, most
cases are diagnosed intraoperatively.
Case report
A 37-year-old previously healthy Caucasian female pre-
sented initially with progressive right upper quadrant (RUQ)
abdominal pain and pruritus. Her pain became increasingly
worse 2 days prior to presentation. Review of systems re-
vealed jaundice, scleral icterus, pruritus, fatigue, light-colored
stools, and progressive abdominal distension, despite not having
made any dietary modifications. She did not report weight loss,
fever, chills, nausea, or vomiting. Social history reveals social
alcohol consumption and a light tobacco smoking history. On
examination, she was jaundiced, with a palpable RUQ mass.
Her abdomen was soft and nontender. Laboratory findings dem-
onstrated a WBC count of 7100/µL (normal: 3.8-10.5 K/µL), total
bilirubin (T. Bili) of 7.3 mg/dL (Normal: 0.2-1.2 mg/dL), direct
bilirubin (D. Bili) of 5.7 mg/dL (Normal: ≤0.2 mg/dL), alkaline
phosphatase (Alk Phos) of >1000 U/L (Normal: 40-120 U/L), and
Ca 19-9 of 45.0 U/mL (Normal: ≤41.3 U/mL). The initial com-
puted tomography scan of the abdomen was interpreted to
include intrahepatic biliary ductal dilatation, a dilated stone-
filled GB up to 6.4 cm in diameter with an abnormally thickened
wall up to 0.6 cm, and pericholecystic fluid, which was con-
cerning for acute cholecystitis or choledocholithiasis.There was
also an 8.4 cm heterogeneous soft tissue mass within the liver
with an infiltrative component adjacent to the GB fossa (Figs. 1
and 2). A corresponding MRI demonstrated a focal defect in the
Fig. 1 – Coronal contrast-enhanced CT image of the
abdomen demonstrates gallbladder wall thickening,
pericholecystic hepatic lesions (tumor invasion),
intrahepatic biliary ductal dilatation, as well as a soft tissue
peritoneal lesion adjacent to the gallbladder (arrow). CT,
computed tomography.
Fig. 2 – Axial contrast-enhanced CT image demonstrates
large hypodense hepatic lesions, a distended gallbladder
neck with stones (arrow), and intrahepatic biliary ductal
dilatation. CT, computed tomography.
Fig. 3 – Coronal T2-weighted MIP image of the biliary tree
demonstrating CHD obstruction (arrow). CHD, common
hepatic duct; MIP, maximum intensity projection.
270 Radiology Case Reports 13 (2018) 269–274
anterior GB wall adjacent to the right hepatic lobe, likely related
to GB wall necrosis in this region/acute gangrenous cholecys-
titis. Also noted was common hepatic duct (CHD) obstruction
and a large 7.6-cm lesion in hepatic segment 4B, as well as a
second smaller lesion within segment 5, which did not enhance
with gadolinium (Figs. 3-5). As a result, a likely diagnosis of
hepatic abscesses was given with consideration for a super-
imposed infiltrative neoplastic process.
Interventional radiology was consulted for placement of a
cholecystostomy tube and drainage of hepatic abscesses. A cho-
lecystostomy was placed with aspiration of approximately
150 cc of purulent bilious fluid. A large hypoechoic lesion in
hepatic segment 4 was accessed and a drain was placed with
aspiration of only a few cc of purulent fluid. Gram stain and
culture of both specimens showed no growth of organisms.
Despite placement of a cholecystostomy tube and hepatic
drain, T. bili remained elevated up to 7.9 mg/dL over the fol-
lowing 3 days. As a result, an ultrasound was obtained which
redemonstrated a persistently dilated GB with an appropri-
ately positioned cholecystostomy, a thickened GB wall, and
multiple heterogeneous hepatic lesions, which were thought
to be phlegmon or developing abscesses (Fig. 6). Gastroenter-
ology (GI) was consulted and performed an endoscopic
retrograde cholangiopancreatography (ERCP) with placement
of a pancreatic duct stent as well as CHD stent placement for
a visualized stricture. A CHD biliary brushing was performed
at the time which was negative for malignant cells. Follow-
ing the ERCP, her diet was advanced, her T. bili trended down
to 3.3 mg/dL, and her WBC remained in normal range prior to
discharge home.
Fig. 4 – Axial T1-weighted precontrast image demonstrates
heterogeneous, predominantly hypointense hepatic
lesions, a peritoneal lesion (arrow), and cholelithiasis
within the gallbladder.
Fig. 5 – MRI: (A) Axial diffusion-weighted image demonstrates restricted diffusion within the periphery of one of the
hepatic lesions (arrow). There is cholelithiasis within a distended gallbladder neck. (B) Axial T1-weighted contrast
enhanced image (5-minute delay) demonstrates hepatic lesions with peripheral enhancement and central hypointensity
(arrow).
Fig. 6 – Ultrasound images: (A) Markedly dilated intrahepatic biliary ducts within the left hepatic lobe. (B) Marked
gallbladder wall thickening, cholelithiasis, and adjacent hypoechogenic hepatic lesions or invasion.
271Radiology Case Reports 13 (2018) 269–274
She presented again 1 month later with 1 day of severe RUQ
abdominal pain. A repeat ERCP was performed with brushings
of the CHD stricture which returned suspicious for SCC. The
decision was made to perform a laparoscopic cholecystec-
tomy. The previously seen peritoneal soft tissue mass adjacent
to the GB was biopsied and sent for frozen section, which
showed SCC. The gallbladder was resected. Histologic exam-
ination of the GB demonstrated stage T3NxM1 moderately
differentiated invasive SCC with extensive necrosis involving
the entire GB, as well as local invasion to the peritoneum and
metastasis to the omentum (Figs. 7 and 8). A few microscopic
foci of AC were also seen (<1% of total tumor volume). The
patient was discharged to follow-up with another facility for
further treatment.
Discussion
Primary SCC of the gallbladder is a rare entity that comprises
between 1-3% of all primary GB cancers [4,5].There is a poorer
prognosis associated with primary SCC of the gallbladder when
compared to the more common AC variant because it is thought
to be more locally invasive, and is typically diagnosed at a more
advanced T stage [2,4,6]. The overall mean survival rate for pa-
tients with GBC is 6 months, with a 5-year survival rate of 5%
[3]. The gallbladder lacks a serosal layer between the gallblad-
der and liver, which increases susceptibility for local hepatic
tumor invasion.This is why early diagnosis of primary SCC of
the GB is critical for improved patient outcomes.
Song et al. demonstrate in their analysis of 411 patients
with GBC, that there is no statistically significant difference
of percentage of patients with normal or elevated Ca-19-9
levels. It cannot be reliably used as an indicator for disease,
however, a larger number of patients with GBC had a CA-19-9
level >37 (U/mL) [2]. Song et al. also reported a median
follow-up time of 21 months and demonstrated that patients
with mixed adenosquamous carcinoma (ASC)/SCC differenti-
ation had a median survival of 3.3 months compared to 6.0
months in the AC variant [2]. However, Kalayarasan et al.
(136 patients) found no significant difference in survival
rates between patients with SCC/ASC vs AC [6]. A summary
of recently reported cases of SCC of the GB is presented
(Table 1).
Radiographic features suspicious for gallbladder cancer
include: intraluminal mass, diffuse mural thickening, mass re-
placing the gallbladder (present in 40-65% of cases at initial
detection), intra-hepatic biliary ductal dilatation, and hepatic
lesions adjacent to the gallbladder fossa [11]. More advanced
features include peritoneal carcinomatosis, lymphadenopa-
thy, and hepatic/distant metastases. Once we identify suspicious
features, it is important to correlate with the history and
imaging features for suspicious signs and symptoms, as well
as risk factors.
The differential diagnosis for findings suspicious for
gallbladder cancer include: gallbladder polyp, gallbladder
wall thickening/edema (secondary to adenomyomatosis,
portal hypertenion, hepatitis, infectious mononucleosis,
congestive heart failure, renal failure, and pancreatitis), cho-
lecystitis (including acute calculous, acalculous, chronic, and
xanthogranulomatous variants), bile duct tumors, biliary ob-
struction, cholangiocarcinoma, hepatocellular carcinoma,
gallbladder volvulus, and liver abscess.
As radiologists, it is important to keep GBC on the differ-
ential for patients with gallbladder wall thickening, intra-
hepatic biliary ductal dilatation, and/or adjacent hepatic lesions.
It is also important to assess for regional lymphadenopathy.
Although it has been described, regional lymphadenopathy is
Fig. 7 – Microscopic pathology: (A) Nerve (green arrow) is surrounded and invaded by tumor nests (perineural invasion). (B)
Lymphatic channel (green arrow) with tumor nest inside (lymphovascular invasion).
Fig. 8 – Extensive areas of tumor necrosis are identified
(green arrow).
272 Radiology Case Reports 13 (2018) 269–274
Table 1 – Summary of recently reported cases of SCC of the gallbladder
Reference No. of
patients
Age Gender Presentation Imaging findings/diagnostic modality (Dx) Pathology Involvement Survival (mo)
Alpuerto et al.
(2017) [4]
1 75 F RUQ pain, WBC (15,000/µL),
and Normal Liver Function
Tests (LFTs)
CT: GB wall thickening, pericholecystic fluid,
irregular soft tissue mass in GB fundus
US: 3.8 cm Heterogeneous GB fundal lesion
with small calcifications
Dx: Cholecystectomy, duodenal/stomach
resection
Pure 1° SCC of
the GB
T4NxMx
Local invasion of the
liver, duodenum, and
stomach
Alive at the time
of publication
Chandna et al.
(2016) [7]
1 70 F Dyspepsia, RUQ pain,
icterus, and no palpable
mass
CT: Not performed
US: Gallstones with a thickened irregular
GB wall
Dx: Cholecystectomy
Keratinizing SCC
confined to the
serosa
Locally resected tumor
with negative margins
Not reported
Hoshimoto et al.
(2016) [8]
3 SCC
1 ASC
Mean
of 68
2:2
(M:F)
Not reported Imaging findings were not reported SCC (40%-90%)
T2 and T3 stages
Local invasion of the
liver
Not reported
Kalayarasan
et al. (2013) [6]
4 (SCC)
10 (ASCa)
Median
of 49
1:2.5
(M:F)
Abdominal pain, emesis,
and palpable RUQ mass
Imaging was performed but findings are not
reported
Dx: Staging laparoscopy and tumor resection
SCC/ASC stage
T3 (43%) or
T4 (57%)
Local invasion of the
duodenum, CBD, liver,
and colon
Median of 28
Khan et al.
(2012) [9]
1 35 F R-sided abdominal pain,
palpable RUQ mass
CT/US: Enlarged GB up to 8.4 cm, thickened GB
wall up to 0.8 cm, an 8-cm solid hepatic mass
within the right hepatic lobe, and cholelithiasis
Dx: Cholecystectomy and partial hepatectomy
Pure SCC
stage T4N0Mx
Local invasion of the
liver and omentum
Not reported
Mghirbi et al.
(2016) [5]
1 67 F RUQ pain, 15 kg weight
loss, and palpable RUQ
mass
CT: 8-cm solid cystic mass of the GB bed with
intrinsic calcifications and extension into the
adjacent liver parenchyma
US: 10-cm heterogeneous GB mass with
echogenic center and hepatic invasion
Dx: Colonoscopic biopsy of a right colon lesion
SCC of the GB (R
colon biopsy)
T4NxMx
Local invasion of the
liver and right colon
Not reported
Roa et al.
(2011) [10]
8 (SCC)
26 (ASCa)
Mean
of 65
7:27
(M:F)
Specific presenting
symptoms not included
Imaging was performed but findings are not
reported
Dx: Most cases following cholecystectomy for
suspected acute cholecystitis
SCC/ASC stage
T2, T3 (68%), and
T4 at diagnosis
Local invasion of the
duodenum, CBD, liver,
stomach, and colon
ASCamean of 23
Adeno mean
of 50
Song et al.
(2015) [2]
10 (SCC)
24 (ASCa)
Mean
of 61.4
10:24 (M:F) Included abdominal pain,
jaundice, weight loss, and
palpable mass
Imaging was performed but findings are not
reported
Dx: Tumor resection
SCC/ASC stage
T3 (38%) or
T4 (62%)
88.2% with liver
invasion
Median of 3.3
Levy et al. (2017)
(this study)
1 37 F Abdominal pain/distension,
jaundice, pruritus, fatigue,
pale stools, and palpable
RUQ mass
CT: Intrahepatic biliary ductal dilatation, dilated
GB with thickened wall, an 8-cm heterogeneous
liver mass, and cholelithiasis
US: Multiple heterogeneous hepatic lesions
thought to be abscesses
MRI: CHD biliary obstruction and 7.6-cm
nonenhancing hepatic lesion
SCC (<1%
adenocarcinoma)
T3NxM1
Local invasion of the
liver, peritoneum, and
metastasis to the
omentum
Alive at the time
of publication
ASC, adenosquamous carcinoma; CBD, common bile duct; CHD, common hepatic duct; CT, computed tomography; Dx, diagnosis; GB, gallbladder; RUQ, right upper quadrant; SCC, squamous cell
carcinoma; US, ultrasound; WBC, white blood cell.
ASC, adenosquamous differentiation (composed of cases with adenocarcinoma with more than 30%aor 25%b,c of the SCC component).
273Radiology Case Reports 13 (2018) 269–274
seldom reactive secondary to acute cholecystitis.However,there
may be a rare instance where lymphadenopathy is present
secondary to a superimposed infection such as infectious mono-
nucleosis or a systemic lymphoproliferative disorder [12]. Albeit
the SCC variant does not typically demonstrate local lymph
node involvement, the more common AC variant does, and the
presence of lymphadenopathy should increase suspicion for
malignancy. The patient’s risk factors should also be as-
sessed to determine likelihood for GB cancer. Our patient’s
known risk factors are chronic cholelithiasis and female gender.
Care should also be made to obtain as much history as pos-
sible because the provided history is often meager.The synthesis
of both imaging features and clinical history should lead you
to suspect GBC.
Acknowledgments
We would like to acknowledge the departments of Radiology
and Pathology at Northwell Health System’s Lenox Hill Hos-
pital for their collaboration on caring for this patient and
preparation of this report.
Supplementary data
Supplementary data associated with this article can be found
in the online version, at https://doi.org/10.1016/j.radcr.2017
.09.026.
REFERENCES
[1] Whang EE, Duxbury M, Rocha FG, Zinner MJ. Chapter 51.
Cancer of the gallbladder and bile ducts. In: Zinner MJ,
Ashley SW, editors. Maingot’s abdominal operations. 12th
ed. New York (NY): McGraw-Hill; 2013.
[2] Song H-W, Chen C, Shen H-X, Ma L, Zhao Y-L, Zhang G-J,
et al. Squamous/adenosquamous carcinoma of the
gallbladder: analysis of 34 cases and comparison of
clinicopathologic features and surgical outcomes with
adenocarcinoma. J Surg Oncol 2015;112:677–80.
[3] Hundal R, Shaffer EA. Gallbladder cancer: epidemiology and
outcome. Clin Epidemiol 2014;6:99–109. doi:10.2147/CLEP
.S37357.
[4] Alpuerto AC, Mora ME, Robitsek RJ, Schubl SD. Primary pure
squamous cell carcinoma of the gallbladder locally invading
the liver, duodenum, and stomach: a case report and
literature review. Case Reports Surg 2017;2017:2534029.
doi:10.1155/2017/2534029.
[5] Mghirbi F, Ayadi M, Karray W, Yahyaoui Y, Meddeb K,
Mokrani A, et al. Squamous cell carcinoma of the
gallbladder. Transl Gastroenterol Hepatol 2016;1:78.
doi:10.21037/tgh.2016.09.07.
[6] Kalayarasan R, Javed A, Sakhuja P, Agarwal AK. Squamous
variant of gallbladder cancer: is it different from
adenocarcinoma? Am J Surg 2013;206(3):380–5.
[7] Chandna M, Pant L, Garg M, Singh G, Singh S. Primary pure
keratinising squamous cell carcinoma: a rare malignancy
with aggressive behaviour. J Clin Diagn Res 2016;10(9):ED21–
2. doi:10.7860/JCDR/2016/21445.8582.
[8] Hoshimoto S, Hoshi S, Hishinuma S, Tomikawa M,
Shirakawa H, Ozama I, et al. Adenosquamous carcinoma in
the biliary tract: association of the proliferative ability of the
squamous component with its proportion and tumor
progression. Scand J Gastroenterol 2017;52(4):p425–30.
[9] Khan N, Afroz N, Haider N, Khan MA. A case of pure
endophytic squamous cell carcinoma of the gallbladder:
a rare entity with aggressive behaviour. Turkish Journal of
Pathology 2012;28(2):181–3. doi:10.5146/tjpath.2012.01122.
[10] Roa JC, Tapia O, Cakir A, Basturk O, Dursun N, Akdemir D,
et al. Squamous cell and adenosquamous carcinomas of the
gallbladder: clinicopathological analysis of 24 cases
identified in 606 carcinomas. Mod Pathol 2011;24:1069–78.
[11] 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):1440–7.
[12] Iaria C, Arena L, Di Maio G, Fracassi MG, Leonardi MS,
Famulari C, et al. Acute aclculous cholecystitis during the
course of primary Epstein-Barr virus infection: a new case
and a review of the literature. Int J Infect Dis 2008;12(4):391–
5.
274 Radiology Case Reports 13 (2018) 269–274
