Japanese Journal of Clinical Oncology 32:206-209 (2002)
© 2002 Foundation for Promotion of Cancer Research
A Long-term Survivor of Intrahepatic Cholangiocarcinoma with Lymph Node Metastasis: a Case Report
1 Department of Surgery, Institute of Gastroenterology, Tokyo Women’s Medical University, Tokyo and 2 Division of Clinical Pathology, National Chiba Hospital, Chiba, Japan
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
|---|
We describe a case of intrahepatic cholangiocarcinoma (ICC) in a 50-year-old man. A well-defined, hypoechoic tumor, 3.5 cm in greatest diameter, was detected in the left medial segment of the liver with ultrasonography. Celiac angiography showed staining at the same location. Computed tomography revealed lymph node swelling around the head of the pancreas. On October 10, 1993, the patient underwent partial hepatectomy with pancreatoduodenectomy and lymph node dissection around the hepatoduodenal ligament and along the common hepatic artery. Postoperative histopathological examination showed a moderately differentiated tubular adenocarcinoma which had metastasized to the dissected lymph nodes at the posterior surface of the head of the pancreas and at the root of the middle colic artery. Eight years after surgery, the patient is alive and well with no sign of recurrence. Immunohistochemical staining showed ductal-type mucin core protein-1 expression in the tumor, which indicates more favorable survival after surgery. Patients with ICC and lymph node metastasis are considered to have poor prognosis; however, further study of the characteristics of ICC with lymph node metastasis is needed.
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
|---|
Lymph node metastasis and curative resection are reported to be prognostic factors in intrahepatic cholangiocarcinoma (ICC) (1–6). Long-term survivors after surgery for ICC with lymph node metastasis are rarely reported in the literature (5–7). Because patients with ICC and lymph node metastasis are considered to have systemic disease, curative resection is not performed. We recently reported that evaluation of mucin core protein-1 (MUC1) expression is useful in predicting surgical outcome in mass-forming ICC (8). We report a long-term survivor of intrahepatic cholangiocarcinoma with lymph node metastasis, in whom MUC1 expression was evaluated retrospectively.
|
CASE REPORT |
|---|
|
TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
|---|
A 50-year-old man was admitted to our hospital on July 7, 1993, because of a tumor in the liver and masses around the head of the pancreas, which had been detected with ultrasonography at another hospital in June 1993. In 1964 the patient had undergone segmental resection of the left upper lobe of the lung for tuberculosis and had received a blood transfusion. Results of laboratory studies were as follows: hepatitis B surface antigen, negative; hepatitis C antibody, positive; hemoglobin, 13.5 g/dl; white blood cell count, 6220/µl; platelet count, 16.6 x 104/µl; total bilirubin, 0.7 mg/dl; albumin, 4.5 g/dl; aspartate aminotransferase, 20 U; alanine aminotransferase, 12 U; and lactate dehydrogenase, 190 U. The serum
-fetoprotein (AFP) level was 1250 ng/ml, the carcinoembryonic antigen level was 15 ng/ml and the carbohydrate antigen 19–9 level was 13 U/ml. Plain computed tomography (CT) showed a well-defined, low-density mass 3.5 cm in greatest diameter in the left medial segment of the liver (Fig. 1a). A rapid sequential series of CT images showed that the liver tumor stained faintly and a delayed CT scan showed irregular enhancement within the tumor. The intrahepatic bile ducts were not dilated and no tumors were detected in the gallbladder, the pancreas or the extrahepatic bile duct. Enlarged lymph nodes were detected at the posterior surface of the head of the pancreas and in the hepatoduodenal ligament (Fig. 1a and b). Celiac angiography showed a faintly stained tumor at the medial segment of the liver. Gastroendoscopy and colonoscopy did not show any other malignant lesion in the upper or lower intestine. The tumor was diagnosed as ICC with lymph node metastasis.
|
The patient underwent partial resection of the medial segment of the liver with pancreatoduodenectomy and lymph node dissection along the common hepatic artery, in the hepatoduodenal ligament and at the root of the superior mesenteric artery because swollen lymph nodes at the posterior surface of the head of the pancreas and at the root of the middle colic artery were detected. However, no lymph nodes in the para-aortic region were dissected because there were no swollen lymph nodes.
Gross examination of the resected specimen showed a white, fibrous, well-defined nodular tumor (Fig. 2) and nodular mass at the posterior surface of the head of the pancreas (Fig. 3). Microscopically, carcinoma cells indicated moderately differentiated tubular adenocarcinoma (Fig. 4). The specimen of the liver was sliced every 5 mm into five pieces and we did not detect hepatocellular elements in any slice. The number of dissected lymph nodes was 10 and moderately differentiated tubular adenocarcinoma cells involved two of the 10 lymph nodes, at the posterior surface of the head of the pancreas and at the root of the middle colic artery. The histopathological findings of the lymph nodes involved were the same as those of the hepatic tumor. No mucin was identified with Alcian Blue and periodic acid–Schiff double staining. Immunohistochemical examination showed positive reactions to carcinoembryonic antigen, cytokeratin 19 and epithelial membrane antigen and a negative reaction to AFP and hepatocyte paraffin 1. The non-cancerous liver tissue showed chronic active hepatitis. We recently evaluated MUC1 expression in the tumor to be of the ductal type (Fig. 5). No other cancer was detected histopathologically in the head of the pancreas, extrahepatic bile duct or gallbladder.
|
|
|
|
In the postoperative period, no anticancer chemotherapy was performed and the patient has been well for 8 years after surgery.
|
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
|---|
Survival after surgery in cases of ICC with lymph node metastasis is reported to be poor (1–6). A few patients with ICC and lymph node metastasis have survived for 5 years or more after surgery (5–7); however, no common factors have been identified in these cases.
In this case, the clinical features, hepatitis C antibody positive, AFP positive, positive tumor stain in arterial phase on imaging and mucin negative, were atypical for ICC.
Yamanaka et al. (9) also reported atypical type ICC cases with chronic liver disease and mild positivity for AFP. The serum AFP levels of Yamanaka et al.’s cases were elevated, but the results of immunostaining for AFP were negative, as in the present case. Some type of ICC has recently been reported to have high association with hepatitis virus infection (9–11). The origin of atypical type ICC was suggested to be the peripheral bile ducts or Hering’s ductule. Histopathologically atypical type ICC consists of tubular adenocarcinoma and is clearly distinguishable from HCC. Patients with atypical type ICC have clinical features associated with the characteristics of HCC (9–11). Yamanaka et al.’s cases had no lymph node metastasis (9) and Kobayashi et al. did not mention lymph node metastasis (11). Kobayashi et al. reported that ICC with hepatitis C virus-related cirrhosis is associated with a relatively poor prognosis (11). Further study of the relation between atypical type ICC and lymph node metastasis and prognosis of atypical type ICC is required.
To determine postoperative tumor biology and prognosis more precisely in cases of ICC, proliferation markers (proliferating cell nuclear antigen, Ki-67, argyrophilic nucleolar organizer regions) and p53 tumor suppressor gene have been studied (7,12–14). However, because these factors have rarely been correlated with prognosis in ICC, they have not been recognized as independent prognostic factors (12–14).
We recently found that the expression pattern of MUC1 is an independent prognostic factor in mass-forming ICC. MUC1 is a membrane-associated glycoprotein and is expressed on the surface of a variety of normal and neoplastic human tissues. Changes in cell surface glycoproteins during malignant transformation and tumor progression are thought to influence the biological behavior of cancer cells (15). It has been reported that MUC1 is an important prognostic factor in other cancers (16,17).
The immunohistochemical staining patterns of MUC1 were classified into three types: negative type, neoplastic cells were not stained (stained parts constituted <5% of whole neoplastic cells); ductal type, the luminal surface membrane of neoplastic cells was stained; and cytoplasmic type, both the luminal surface membrane and the cytoplasm of neoplastic cells were stained, but expression in the cytoplasm was dominant. Expression of MUC1 was detected immunohistochemically in 38 (76%) of 50 cases of m-ICC (ductal type 18, cytoplasmic type 20 and negative type 12). The survival rate of patients with the ductal-type expression was better than that of patients with the other type of expression (8).
In the cases of lymph node dissection, nine of 12 cytoplasmic type cases were positive for lymph node metastasis and one of nine patients survived more than 2 years after surgery. Two of six ductal type cases were positive for lymph node metastasis and these two patients survived more than 2 years after surgery (8). The outcomes after surgery can be predicted by evaluating MUC1 staining patterns even if patients have lymph node metastasis.
We believe that ductal-type MUC1 staining indicates favorable survival after surgery in ICC with lymph node metastasis. However, the biological behavior of ICC needs to be studied in a greater number of cases.
|
FOOTNOTES |
|---|
+ For reprints and all correpsondence: Masakazu Yamamoto, Tokyo Women’s Medical University, 8–1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
|---|
1 Chu KM, Lai ECS, Al-Hadeedi S, Arcilla CE, Lo CM, Liu CL, et al. Intrahepatic cholangiocarcinoma. World J Surg 1997;21:301–6.[Web of Science][Medline]
2 Casavilla FA, Marsh JW, Iwatsuki S, Todo S, Lee RG, Madariage JR, et al. Hepatic resection and transplantation for peripheral cholangiocarcinoma. J Am Coll Surg 1997;185:429–36.[Web of Science][Medline]
3 Yamamoto M, Takasaki K, Yoshikawa T, Ueno K, Nakano M. Does gross appearance indicate prognosis in intrahepatic cholangiocarcinoma? J Surg Oncol 1998;69:162–7.[Web of Science][Medline]
4 Yamamoto M, Takasaki K, Yoshikawa T. Lymph node metastasis in intrahepatic cholangiocarcinoma. Jpn J Clin Oncol 1999;29:147–50.
5 Nakeeb A, Pitt HA, Sohn TA, Coleman J, Abrams RA, Piantadosi S, et al. Cholangiocarcinoma: a spectrum of intrahepatic, perihilar and distal tumors. Ann Surg 1996;224:463–75.[Web of Science][Medline]
6 Pichlmayr R, Lamesch P, Weimann A, Tusch G, Ringe B. Surgical treatment of cholangiocellular carcinoma. World J Surg 1995;19:83–8.[Web of Science][Medline]
7 Izumi R, Shimizu K, Kiriyama M, Yagi M, Matsui O, Nonomura A, et al. Long-term survival of peripheral intrahepatic cholangiocarcinoma with distant metastasis. Am J Gastroenterol 1995;90:505–7.[Web of Science][Medline]
8 Matsumura N, Yamamoto M, Aruga A, Takasaki K, Nakano M. Correlation between expression of MUC1 core protein and outcome after surgery in mass-forming intrahepatic cholangiocarcinoma. Cancer 2002;94:1770–6.[Web of Science][Medline]
9 Yamanaka N, Okamoto E, Ando T, Oriyama T, Fujimoto J, Furukawa K, et al. Clinicopathologic spectrum of resected extraductal mass-forming intrahepatic cholangiocarcinoma. Cancer 1995;76:2449–56.[Web of Science][Medline]
10 Yamamoto M, Takasaki K, Nakano M, Saito A. Minute nodular intrahepatic cholangiocarcinoma. Cancer 1998;82:2145–9.[Web of Science][Medline]
11 Kobayashi M, Ikeda K, Saitoh S, Suzuki F, Tsubota A, Suzuki Y, et al. Incidence of primary cholangiocellular carcinoma of the liver in Japanese patients with hepatitis C virus-related cirrhosis. Cancer 2000;88:2471–7.[Web of Science][Medline]
12 Ohashi K, Nakajima Y, Tsutsumi M, Kanehiro H, Fukuoka T, Hisanaga M, et al. Clinical characteristics and proliferating activity of intrahepatic cholangiocarcinoma. J Gastroenterol Hepatol 1994;9:442–6.[Web of Science][Medline]
13 Ohashi K, Nakajima Y, Kanehiro H, Tsutsumi M, Taki J, Aotatsu Y, et al. Ki-ras mutations and p53 protein expressions in intrahepatic cholangiocarcinoma: relation to gross tumor morphology. Gastroenterology 1995; 109:1612–7.[Web of Science][Medline]
14 Takimoto A, Endo I, Ichikawa Y, Ishikawa T, Togo S, Shimada H. Mode of spreading and biological behavior in bile duct carcinoma. Nippon Geka Gakkai Zasshi 1997;98:472–8 (in Japanese).[Medline]
15 Nakamori S, Ota DM, Clearly KR, Shirotani K, Irimura T. MUC1 mucin expression as a marker of progression and metastasis of human colorectal carcinoma. Gastroenterology 1994;106:353–61.[Web of Science][Medline]
16 Utsunomiya T, Yonezawa S, Sakamoto H, Kitamura H, Hokita S, Aiko T, et al. Expression of MUC1 and MUC2 mucins in gastric carcinomas. Clin Cancer Res 1998;4:2605–14.[Abstract]
17 Hiraga Y, Tanaka S, Haruma K, Yoshihara M, Sumii K, Kajiyama G, et al. Immunoreactive MUC1 expression at the deepest invasive portion correlates with prognosis of colorectal cancer. Oncology 1998;55:307–19.[Web of Science][Medline]
Received December 13, 2001; accepted March 11, 2002
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||