CASE 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.

DIAGNOSIS

Carcinoma of the gallbladder with sarcomatoid degeneration

IMAGING FINDINGS

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 differentiation.

DISCUSSION

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 carcinoma.1

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

Conclusion

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 postoperative follow-up.