The most common histological type of gallbladder cancer is adenocarcinoma.1–5
The gallbladder carcinosarcoma is extremely rare in clinical practice.6 7
Since Landsteiner et al8
published first case of gallbladder carcinosarcoma in 1907, there have been only about 50 cases reported in the world literature.1 9–12
Because carcinosarcoma contains both malignant epithelial and sarcomatous components, immunohistochemical study appears as an inevitable methodology in differential diagnosis. Diagnosis of carcinosarcoma requires the presence of both components in tissue with various combination and proportion.13
Carcinosarcoma could occur at almost all major organs, such as lung, kidney, upper aerodigestive tract, salivary gland, thyroid, thymus and gastrointestinal tract.1 6
However, the most common site for carcinosarcoma is the uterus, where the tumour is better known as malignant mixed mullerian tumour.14
The gallbladder carcinosarcoma is more common in females with a female to male ratio of 2:1 to 5:1.2 11
The average age range of cancer occurrence is 60–70 years old.2
The disease progress of this neoplasm is extremely aggressive. The median survival time is 5.5 months and the longest postsurgery survival time was 60 months.6 9 11 12 15 16
In a cohort study of 26 gallbladder carcinosarcoma cases, only 3 cases had survival time over 12 months.1
T- and N-staging system proved to be a valuable tool in gallbladder carcinoma prognostic factor stratification.17 18
However, this system has no role in gallbladder carcinosarcoma prognosis stratification. Liu et al
and other groups analysed 48 patients in stages II to IV and demonstrated that the mean survival time was about 2 months regardless of their tumour stage status.11 19 20
Patients with gallbladder carcinosarcoma often present with vague abdominal symptoms, such as dull abdominal pain, nausea, jaundice and weight loss. Occasionally, there is a palpable right upper quadrant mass. About 74% of the gallbladder carcinosarcoma cases are associated with cholecystolithiasis and ultrasounds often show a polypoid mass. Serum CA19.9 level also may be elevated. CT scan can not distinguish gallbladder carcinosarcoma from adenocarcinoma. However, gallbladder carcinosarcoma should be highly suspected if there is speckled calcification within the tumour.21–23
In our case, this patient presented with worsening biliary tract obstruction symptoms associated with a secondary infection. Intraoperative observation demonstrated a sloughing gallbladder tumour mass mixed with calcified gall stones and compressed gallbladder neck, which facilitated tumour emboli formation and obstructed cystic ducts. Because tumour embolus is a rare cause for bile duct obstruction, we report our observation here to raise proper clinical attention.
Gallbladder carcinosarcoma has dual histological differentiations, which include both epithelial and sarcomatous elements. The sarcoma mesenchymal stromal differentiation is an important characteristic evidence for diagnosis of carcinosarcoma. Because sarcomatoid cells express both epithelial membrane antigen and cytokeratin markers, they are considered deriving from mesenchyme of carcinoma cells.24 25
The sarcomatous element simply shows non-specific spindle cell morphology.1
But sometimes, more specific mesenchymal differentiation, which is known as heterogenous elements, can be recognised in certain carcinosarcomas, such as leiomyosarcoma, rhabdomyosarcoma, osteosarcoma and chondrosarcoma. Biologic behaviour of carcinosarcoma is similar to that of advanced sarcoma. Majority of cases manifested as tumour rapid growth and compression to surrounding organs. Exact tumorigenesis mechanism of gallbladder carcinosarcoma is still unknown. One study indicated that certain genetic and gene expression alterations may be relevant to the sarcomatous change/epithelial mesenchymal transition in cholangiocarcinoma cells.26
Another report further linked K-Ras alterations with disrupted cell cycle regulation and gallbladder carcinogenesis.27
Currently, we have very limited experience in managing patients with gallbladder carcinosarcoma. Because of the rarity of this disease, it is impossible to conduct a clinical trial to investigate various therapeutic options at this time. Patients usually receive surgical managements. In general, patients with stage I tumour usually receive cholecystectomy, whereas advanced tumour requires cholecystectomy plus radical regional lymph node excision. If the tumour is limited within submucosa, simple cholecystectomy will be the treatment choice.1 11 12
When tumour is limited within gallbladder, cholecystectomy with excision of liver tissue surrounding gallbladder bed will be sufficient. Similar to other gallbladder tumours, advanced-stage gallbladder carcinosarcoma is often impossible to have a complete excision. Debulking resection can be used for symptom relieving in palliative surgery. Extensive excision of surrounding liver tissue or right hemi-hepatectomy increases only its negative margin but not patient’s survival. Furthermore, radical surgical resection brings more surgery-related risks. Patients with early-stage gallbladder carcinosarcoma may have survival benefit from radical cholecytectomy.1 11 12
There is no role for piece meal excision in surgical management.
There are a few reported cases using single chemotherapy regimen as adjuvant therapy.1 11
However, these adjuvant chemotherapies have not seen adding any remission benefit or survival benefit. 5-Fu is a main chemotherapy regimen in treating gallbladder carcinoma and oxaliplatin (a third-generation platinum analog) is used in treating sarcomas such as soft tissue sarcoma and gynaecological sarcoma. 5-Fu and oxaliplatin combination has been shown a significant survival benefit in treating aggressive colon cancers.28
In this case study, we first report using these two chemotherapy regimens as adjuvant chemotherapy in treating gallbladder carcinosarcoma. We believe that our case and management plan will provide a unique experience in treating gallbladder carcinosarcoma.
- Gallbladder carcinosarcoma is a rare gastrointestinal malignancy with poor prognosis.
- Patient suffering gallbladder carcinosarcoma usually present the symptoms of biliary tract obstruction and mass.
- Morphological and immunohistochemical studies are crucial in diagnosis of gallbladder carcinosarcoma.
- Currently, we still do not have standardised management for gallbladder carcinosarcoma; however, this case report provides a unique experience in treating this kind of patients.