Cholangiocarcinoma accompanied by desmoid-type fibromatosis

Chengdu, China

Cholangiocarcinoma accompanied by desmoid-type fibromatosis

Nan Xu, Zhe-Yu Chen, Lu-Nan Yan, Jia-Ying Yang, Wen-Tao Wang and Shu-Guang Jing

Chengdu, China

BACKGROUND: Cholangiocarcinoma complicated by intraabdominal desmoid-type fibromatosis (DTF) is uncommon. There are no reports on patients with this type of fibromatosis, in which the pre-operative treatment (including diagnosis), surgical approach, post-operative pathologic reports, and prognosis are discussed.

METHOD: The clinicopathological features of a 49-year-old man were retrospectively analyzed.

RESULTS: Cholangiocarcinoma located in the inferior segment of the bile duct was considered pre-operatively on the basis of clinical findings. At the time of pancreaticoduodenectomy, the mesojejunum was stiff without nodules or a mass at a distance of approximately 80 cm from the ligament of Treitz. Complete excision of the entire lesion of the intestinal mesenteric contracture and its subsidiary was performed. Post-operative pathologic findings confirmed an adenocarcinoma located at the extremity of the common bile duct and infiltrating the full thickness of the common bile duct as well as the deep muscular layer of the duodenum. The contracted jejunal mesentery was shown to have DTF. The patient was alive with no evidence of recurrence after a follow-up of 6 months.

CONCLUSIONS: The patient had a rare hereditary disease with intra-abdominal DTF, which manifests the characteristics of an aggressive growth pattern and a high rate of local recurrence; conservative therapy is recommended. Complete excision of the fibromatous lesion during pancreaticoduodenectomy may maximally decrease the risk of local recurrence.

(Hepatobiliary Pancreat Dis Int 2011; 10: 214-217)

cholangiocarcinoma; desmoid-type fibromatosis; diagnosis; pancreaticoduodenectomy; pathology

Introduction

Intra-abdominal desmoid-type fibromatosis (DTF) is a relatively rare disease. Owing to a lack of characteristic manifestations on iconography, few cases have been diagnosed before surgery. By presenting a rare case of jejunum DTF combined with cholangiocarcinoma, we discuss the controversy of a therapeutic scheme for DTF and emphasize the significant relationship between complete resection and post-operative recurrence.

Case report

A 49-year-old male patient was admitted to the hospital with a history of "right upper quadrant" pain for 5 months, and icterus of the sclera and skin for 1 month. Physical examination revealed mild-to-moderate staining of the sclera and skin, a soft abdomen without tenderness or rebound tenderness, and muscle tension. Laboratory examination showed the following: total bilirubin, 234.1 μmol/L; direct bilirubin, 176.9 μmol/L; serum alanine aminotransferase, 1058 IU/L; serum aspartate aminotransferase, 169 IU/L; alkaline phosphatase, 705 IU/L; and γ-glutamyltranspeptidase, 1793 IU/L. The CA19-9 level was significantly increased to 53.51 U/ml. Ultrasonography showed common bile duct intraluminal filling with an abated echo and cholangiectasis of the intra- and extra-hepatic bile ducts. Magnetic resonance cholangiopancreatography showed the bottom of the common bile duct wall to be thickened with slight enhancement, and intra- and extra-hepatic cholangiectasis, suggesting the possibility of a cholangiocarcinoma (Fig. 1). Hepato-protective and supportive treatment significantly improved liver function. Pre-operatively and after a laparotomy, no ascites was found and the tumorhad not metastasized to the liver, mesangium, omentum, or other abdominal organs. The cystic duct converged into the common bile duct at the posterior side of the superior segment of the duodenum; a small mass was palpable behind the posterior portion of the descending duodenum. Uplift lesions were found in the inferior extremity of the common bile duct through an intraoperative choledochoscope. Frozen sections revealed mildto-moderate atypical hyperplasia. The decision was made to perform a pancreaticoduodenectomy. Intraoperative reconstruction of the digestive tract at a distance of 80 cm away from the ligament of Treitz was performed; the surrounding tissues were stiff without nodules or masses, and the intestines were normal. Complete resection of the intestinal mesenteric contracture and its subsidiary was performed, and the distal jejunum was closed. A side-to-side anastomosis was made between the jejunum and gastric remnant before the transverse colon was performed, while an end-to-side anastomosis (Roux-en-Y) of the intestines was made 20 cm beneath the anastomotic stoma. The operation was uneventful without complications. Post-operative pathologic findings confirmed an adenocarcinoma ranging from moderately differentiated to well-differentiated in the common bile duct infiltrating the full thickness of the common bile duct as well as the deep muscular layer of the duodenum (Fig. 2). No infiltration or metastasis was observed in the stumps of the enteron, hepatoduodenal ligament, and nearby lymph nodes. The contracted jejunal mesentery was shown to be a DTF (Fig. 3). The patient recovered quite well. After follow-up for 6 months, the patient was healthy. MRI showed no recurrent lesions in the biliary system and intestines, as well as the accessory configurations.

Fig. 1. MRI showing thickening of the bottom of the common bile duct wall, slight enhancement, and intra-hepatic and extrahepatic cholangiectasis.

Fig. 2. Microscopic examination showing adenocarcinoma infiltrating the full-thickness of the common bile duct as well as the deep muscular layer of the duodenum (HE, original magnification ×400).

Fig. 3. Microscopic examination showing the jejunal mesentery was DTF that did not infiltrate the intestinal canal (HE, original magnification ×400).

Discussion

Cholangiocarcinoma is a rare neoplasm, which accounts for approximately 3% of gastrointestinal cancers worldwide.[1]It affects both sexes equally but is more prevalent in individuals aged 50-70 years. Two-thirds arise at the confluence of the hepatic ducts (Klatskin tumors), and one-fourth arise in the distal extrahepatic duct; the remainder are intrahepatic. Progressive jaundice is the most common and usually the first sign of obstruction of the extrahepatic biliary system. In the later course of cholangiocarcinoma, pain in the right upper abdomen with radiation into the back is usually present. Laboratory examination, especially magnetic resonance cholangiopancreatography, may be helpful. For treatment considerations, curative surgery such as pancreaticoduodenectomy is recommended if the tumor is well localized.[2,3]

DTF, also known as aggressive fibromatosis, is a low-grade malignant tumor classified between benign fibromas and fibrosarcomas. The morbidity of DTF is 0.03% in solid tumors body-wide and 3.6% in solid tumors of fibrous tissue.[4]DTF can appear throughout the body. According to the anatomic location ofoccurrence, DTF can be divided into 3 categories: extraabdominal, abdominal wall, and intra-abdominal. Intra-abdominal DTF is rare and often associated with familial adenomatous polyposis. It has been reported that the incidence of DTF in familial adenomatous polyposis is 10%-25%.[5]Familial adenomatous polyposis-associated desmoids reportedly result from germline mutation to the adenomatous polyposis coli (APC) gene followed by somatic inactivation of the wildtype APC allele. Sporadic desmoids may also contain mutations in the APC gene, but are best characterized by mutations in the beta-catenin/Wnt signaling pathway. In the Wnt-APC-beta-catenin pathway, the stabilization of beta-catenin is the key factor in the pathogenesis of aggressive fibromatosis.[6-8]The case reported here involving a carcinoma of the bile duct combined with DTF is seldom seen, even without a family history of familial adenomatous polyposis. Hence we assume that it belongs to the sporadic desmoids which also have the pathogenesis of APC gene mutations.

The early diagnosis of DTF is significantly different based on location.[9]Kreuzberg et al[10]reported 4 DTF patients detected by CT or MRI with post-operation pathologic findings as a reference for comparison. Only abdominal wall DTF is accurately diagnosed pre-operatively, while internal DTF has a high rate of misdiagnosis. The current case showed little abnormality within the space contracture lesions in the jejunum mesenteric area, which did not lead to special features, therefore it was not diagnosed by pre-operative MRI.

Histologically, DTF is composed of fibroblastic and myofibroblastic cells and has the potential for local invasion, with the following characteristics: 1) welldifferentiated fibroblasts; 2) invasive growth pattern; 3) proliferation of a large number of cells with the presence of collagen; 4) lack of characteristics of malignant cells, and rarely or non-mitotic; and 5) repeated local recurrence with distant metastasis.[11]The Kouho study[12]found that patient age and vascular-rich areas in the tumor was closely related to recurrence and that the age of patients and the location of the tumor in hypervascular areas were highly associated with tumor recurrence. Fluorescencein situhybridization is used to detect trisomy 8 in relapsed cases; the incidence rate is 72.7%, which is much higher than 12.5% of cases that do not relapse.[13]Therefore, the use of fluorescencein situhybridization to detect trisomy 8 expression in formalin-fixed, paraffin-embedded tissue specimens may predict local recurrence of DTF.

There is much discussion about the treatment of DTF. Dalén et al[14]reported that only the local compression caused by tumor enlargement requires surgery, and conservative treatment can be considered for asymptomatic patients. Sturt and Clark[15]also think abdominal wall DTF should be preferred for surgery and there is risk with surgery for intra-abdominal DTF because of the chance of sacrificing a significant portion of normal bowel. Smith et al[16]prospectively studied 24 patients with pathologically-confirmed DTF, and found that the survival rate was not significantly different between complete excision of the lesion and a non-cutting procedure (P=0.73). However, patients with complete surgical resection had a higher incidence of postoperative complications than patients with non-resections, especially those who had the entire small intestine resected. More multi-center clinical studies are needed to assess the effects of surgical treatment of intra-abdominal DTF. In our case, complete excision of early-stage fibromatous lesion during pancreaticoduodenectomy was a reasonable choice to balance both exhaustive therapy and utmost normal preservation of function.

At present, radiotherapy is frequently used. The reported local control rate for surgery alone is 61%, for surgery combined with radiotherapy 75%, and for radiotherapy alone 78%.[17]The difference among them is statistically significant. Guney et al[18]stated that the results of radiotherapy depend on tumor location, tumor characteristics, and the general health of the patient. But still rare cases have received radiotherapy for DTF, and the effects of the therapy need further confirmation. Rosato et al[19]suggested high-dose chemotherapy with tamoxifen for those patients whose illness is relatively stable but unsuitable for surgical treatment.

Our patient had a cholangiocarcinoma associated with jejunum DTF, which is fairly rare. The mesenteric contraction at the jejunum did not involve the intestine, therefore a cure was feasible by complete resection of the entire lesion, the mesentery, and the subsidiary intestines. However, a long-term post-operative followup is necessary as local recurrence of lesions is possible and comprehensive treatment is needed.

Funding: None.

Ethical approval: Not needed.

Contributors: XN and CZY wrote the first draft of this commentary. All authors contributed to the intellectual context and approved the final version. YLN is the guarantor.

Competing interest: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.

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Received February 25, 2010

Accepted after revision August 28, 2010

Author Affiliations: Department of Liver and Vascular Surgery (Xu N, Yan LN, Yang JY, Wang WT and Jing SG), and Department of Hepato-biliarypancreatic Surgery (Chen ZY), West China Hospital, Sichuan University, Chengdu 610041, China

Zhe-Yu Chen, MD, PhD, Department of Hepatobiliary-pancreatic Surgery, West China Hospital, Sichuan University, Chengdu 610041, China (Tel: 86-28-85422476; Fax: 86-28-85423724; Email: chenzheyu71@sina.com.cn)

? 2011, Hepatobiliary Pancreat Dis Int. All rights reserved.