Summary: An 87-year-old woman with a history of hypertension and
hypothyroidism was admitted to the hospital for a urinary tract
infection. Computed tomography (CT) scan (figure 1) and ultrasound
examinations (figure 2) were performed. Laproscopic exploration
revealed a large, hard mass of the gallbladder fossa, completely
obliterating the gallbladder and infiltrating the duodenum and
liver, and a biopsy was taken. The patient died of massive
pulmonary emboli 2 weeks following the surgery.
Carcinoma of the gallbladder with sarcomatoid degeneration
CT scan (figure 1) and ultrasound examinations (figure 2)
demonstrated a 4-cm right upper-quadrant mass in the gallbladder
fossa. The normal gallbladder was not visualized. Mild biliary duct
dilation was present and there were bilateral large pleural
effusions with adjacent atelectasis.
Microscopic examination of the gallbladder biopsy (figure 3)
revealed no gland formation and areas of spindle cells and strips
of mildly atypical epithelium consistent with remnants of normal
biliary mucous. There is abundant tumor necrosis.
Immunohistochemistry showed the tumor to be positive for both
mesenchyma and epithelium. The above findings are compatible with
the diagnosis of a poorly differentiated carcinoma with sarcomatoid
Carcinoma of the gallbladder has an unusual geographic and
demographic distribution, as it is more common in Israel, Bolivia,
and Chile and in Native Americans in the southwestern United
States. Risk factors include chronic cholecystitis, porcelain
gallbladder, choledochal cysts, significantly high body mass index,
female gender, age, smoking, history of cholecystectomy,
postmenopausal women, and hysterectomy.1,2
More than 90% of gallbladder carcinomas are adenocarcinomas.
Undifferentiated gallbladder carcinoma is extremely rare, and fewer
than 30 cases have been reported since the first well-documented
description.3,4 Carcinosarcoma (CS) is a rare tumor characterized
by malignant epithelial and mesenchymal elements and is usually
found in the uterine body or in the pelvic structures of Mullerian
origin.4 Gallstones are frequently associated with CS (74%).
Histologically, these tumors are composed of admixed epithelial and
sarcomatous elements, and classified into three types according to
the components: 1) small cell type; 2) pleomorphic cell type; and
3) spindle cell or pseudosarcomatous type.5 Clinically, fever and
jaundice were seldom present.4 Diagnosis has not yet been made
preoperatively. Ultrasound usually reveals a polypoid mass
protruding into the lumen with an irregular, thickened wall. Study
of the gallbladder wall is of particular importance to
differentiate CS from a simple polyp.
The prognosis of patients with undifferentiated carcinoma of the
gallbladder is dismal and is poorer than that of patients with
differentiated adenocarcinoma.5 However, the natural history of
gallbladder CS resembles that of gallbladder carcinoma.4 The tumor
progressively invades the liver through the serosa and cystic
lymphatic nodes and distant metastases are rare. Cholecystectomy is
the operation of choice when the tumor does not involve the serosa,
and open cholecystectomy is more suitable than the laparoscopic
procedure. It appears that if resected at an early stage,
gallbladder CS may be curable with long-term survival comparable to
that for carcinoma. P53 protein overexpression and P53 mutation may
be related to increased grade of cytological atypia and to
invasiveness. K-ras gene mutation occurs in both dysplasia and
Ultrasound, CT, and MRI can generally provide accurate
diagnostic staging. Ultrasound has been proven to possess superior
ability to characterize gallbladder abnormalities.6 CT can not only
demonstrate gallbladder abnormalities, but also depict their
relationship to adjacent organs, the presence of lymphadenopathy,
and remote metastases. Therefore CT offers accurate staging of
gallbladder carcinoma. Magnetic resonance cholangio-pancreaticogram
(MRCP) has been reported to be superior to ERCP in some cases.7 In
addition, MRCP provides excellent anatomic delineation of the
gallbladder and surrounding soft-tissue structures, especially the
liver, pancreas, and duodenum. MRI imaging may be able to provide
important information in the diagnosis of adenomyomatosis,
differentiating it from gallbladder carcinoma.8
Early gallbladder carcinoma (stage 1), limited to the mucosa or
muscularis proper without lymph node metastases, is often difficult
to diagnose because of the high incidence of inapparent carcinoma,
gallstones, and inflammatory changes of the vesicular wall.
However, differentiation grade and infiltration level are the most
reliable prognostic factors in gallbladder carcinoma. It is
difficult to diagnose early gallbladder carcinoma, but it is also
essential to improve the survival of these patients. Gallbladder
carcinoma tends to be missed when gallstones were present.10
Preoperative diagnosis of the flat-type gallbladder carcinoma is
difficult. Tumor location also does not always correlate the
preoperative diagnosis. Even the protruding type of gallbladder
carcinoma was misdiagnosed in 50% of cases with ultrasound and CT
and were not visualized clearly by drip infusion cholangiogram.
Using a combination of imaging modalities with other more specific
diagnostic tools is extremely important in diagnosis of early
gallbladder carcinoma, since cytology is sensitive and P53 is
expressed only in early carcinoma, not in adenoma or dysphasia.
Therefore, even in the presence of gallstones or cholecystitis, any
abnormal findings should make one suspicious of gallbladder
carcinoma. Of interest is that a recent report provides evidence
that increased serum alpha-fetoprotein may be associated with
undifferentiated and poorly differentiated gallbladder carcinoma
and could be particularly useful in documenting metastatic
recurrence of gallbladder carcinoma.11
In summary, we report a gallbladder carcinosarcoma without
distal metastases. This type of gallbladder neoplasm is extremely
rare and has a dismal prognosis. Early diagnosis is critical to
lengthen long-term survival. Ultrasound is superior to CT and MRI
in characterizing gallbladder abnormalities. However, combining
multi-imaging modalities and other diagnostic tools is important
for diagnosing early gallbladder neoplasm, tumor staging, and
- Levin B:Gallbladder carcinoma. Ann Oncol
10(Suppl 4):129-130, 1999.
- Khan ZR, Neugut AI, Ahsan H, Chabot JA: Risk
factors for biliary tract cancers. Am J Gastroenterol 94:149-52,
- Diebold-berger S, Vaiton JC, Pache JC, d'Amore
ESG: Undifferentiated carcinoma of the gallbladder. Arch
Pathol Lab Med 119(March):279-282, 1995.
- Fagot H, Fabre JM, Ramos J, et
al:Carcinosarcoma of the gallbladder-A case report and
review of the literature. J Clin Gastroenterol 18:314-316,
- Guo KJ, Yamaguchi K, Enjoji M:
Undifferentiated carcinoma of the gallbladder. A clinicopathologic,
histochemical, and immunohistochemical study of 21 patients with a
poor prognosis. Cancer 61:1872-1879, 1988.
- Versaci A, Terranova M, Rossitto M, et al:
Authors' experience with the role of preoperative ultrasonography
in the study of benign lesions of the gallbladder [in Italian].
Gior Chirurg 20:354-358, 1999.
- Hatano S, Kondoh S, Akiyama T, Okita K:
Reevaluation of MRCP compared to ERCP in the diagnosis of biliary
and pancreatic duct [in Japanese]. Japan J Clin Med 56:2874-2879,
- Yoshimitsu K, Honda H, Jimi M, et al: MR
diagnosis of adenomyomatosis of the gallbladder and differentiation
from gallbladder carcinoma: Importance of showing
Rokitansky-Aschoff sinuses. AJR Am J Roentgenol 172:1535-1540,
- Roa I, Araya JC, Villaseca M, et al:
Gallbladder cancer in a high risk area: Morphological features and
spread patterns. Hepat Gastroenterol 46:1540-1546, 1999.
- Onoyama H, Yamamoto M, Takada M, et al:
Diagnostic imaging of early gallbladder cancer: Retrospective study
of 53 cases. World J Surg 23:708-712, 1999.
- St. Laurent M, Esterl RM Jr., Halff GA, Speeg
KV: Gallbladder carcinoma producing alpha-fetoprotein. J
Clin Gastroenterol 28:155-158, 1999.