In the present case, the tumor consisted of mainly spindle-shaped and giant cells without any apparent differentiation, showed both epithelial and mesenchymal immunoreactivities, and was finally diagnosed to be spindle and giant cell type undifferentiated carcinoma of the proximal bile duct. Only 9 cases of this type of undifferentiated carcinoma arising in the extrahepatic bile duct have been published in the English language literature (table ).
The reported cases of undifferentiated carcinoma, spindle and giant cell type, of the extrahepatic bile duct
The preoperative diagnosis of undifferentiated carcinoma of the extrahepatic biliary system is considered to be difficult because the exact diagnosis could not be reached before surgical intervention in the previously reported 9 cases as well as the present case. A polypoid or nodular configuration was shown in 9 of the 10 cases with undifferentiated carcinoma of the extrahepatic bile duct, including the present case. Therefore these tumors occluded the bile duct and caused obstructive jaundice in most of the cases, but these findings are not sufficient to differentiate between usual adenocarcinoma and undifferentiated carcinoma. Furthermore, there are no peculiar radiographic features reported so far associated with this neoplasm. If an exact preoperative diagnosis is requested to decide the treatment modality, a sufficient volume of biopsy specimen should be obtained.
In the literature, the prognosis of patients with undifferentiated carcinoma is very poor. The reported one-year survival rate for patients with undifferentiated carcinoma of the gallbladder was 18% [13
], and the mean survival time for patients with undifferentiated carcinoma of the pancreas was estimated to be only 5 months [14
]. The outcome of patients with this type of carcinoma of the extrahepatic bile duct is still uncertain because of the limited number of reported cases. In the 7 previous reports including follow-up studies, 2 patients died of postoperative complications (liver failure [5
] and pulmonary infarction [10
]) and 1 patient died 10 months after the operation due to local recurrence [6
]. Nevertheless 4 patients were recurrence-free for 7–60 months since the surgical treatment [4
]. The present patient has also been doing well for 16 months after the surgery. Hence, these outcomes seem to be better than those of the gallbladder and pancreas. The reason why patients with undifferentiated carcinoma of the extrahepatic bile duct have a relatively better prognosis may be due to the early appearance of jaundice, consequently such cases may be diagnosed at a resectable stage before further tumor progression. However, this does not necessarily mean that there is a better surgical outcome of undifferentiated carcinoma of the extrahepatic bile duct, because the durations of observation are not long enough in cases without disease relapse.
On the other hand, the recurrence-free cases showed a lack of any nodal involvement and a lack of any venous or lymphatic permeation. In contrast, the case that developed local recurrence had venous and lymphatic infiltration as well as perineural invasion, in spite of the fact that there was no metastasis to the regional lymph nodes [6
]. This demonstrates that these invasion-related factors might be prognostic factors for patients with undifferentiated carcinomas. In our case, adjuvant chemotherapy was administered due to the detection of perineural invasion, and thus the patient has survived without recurrence since the surgical treatment, although continuation of careful follow-up is necessary. The most suitable adjuvant chemotherapeutic regimen is still the subject of much debate even for bile duct cancer, and this is the first report suggesting the possibility that a curative resection combined with adjuvant chemotherapy may contribute to prolonging the survival rate for this type of malignancy.
At present, there is no optimal therapy for undifferentiated carcinoma of the extrahepatic bile duct. A favorable prognosis can be expected with curative resection for the locally invasive cases of this type of carcinoma. However, surgical resection alone is not sufficient to produce a radical cure in cases with any nodal involvement or vessel invasion. Therefore, it is conceivable that multidisciplinary therapy, including chemotherapy and/or radiotherapy, might be indispensable for such cases. To approach the establishment of an optimal treatment for this type of carcinoma, a further accumulation of cases and discussions, as well as a better understanding of its biological features, is required.