Biliary Duct Granular Cell Tumor: A Rare But Surgically Curable Benign Tumor

Granulosa cell tumors are rare benign tumors which may be found throughout the body. Rare cases are isolated within the biliary tree. If completely resected, surgical excision is curative. A case of biliary duct granulosa cell tumor is presented with review of the world’s literature on this topic.


INTRODUCTION
The etiology of biliary obstruction may occasionally be obscured by the presence of a benign tumor. Benign tumors of the extrahepatic biliary tract are uncommon, and in the USA the incidence is reported at 1 to 2 cases per 100,000 population 1. These benign tumors consist primarily of hyperplastic (adenomatous and adenomyomatous), polypoid and granular cell tumors. Abrikossoff first described granular cell tumors (GCT) in 1926 and attributed their origin to striated muscle cells2. Granular cell tumors constitute only 1.1% of all benign tumors of the biliary tract and are considered rare in any location3. However, these nonmetastasizing lesions have been found in the oral cavity, skin or subcutaneous tissue, female reproductive tract4, breast5, pituitary gland6, gastrointestinal tract7, and bronchi.
Granular cell tumors occur in the biliary tree. They are most commonly seen in young black women, and generally arise at the confluence of the cystic, hepatic, and common bile duct leading to obstruction. The majority of patients present with abdominal pain and jaundice. A significant proportion however, present with painless jaundice or pruritus alone. Work up of obstructive lesions of the bile ducts generally includes radiologic visualization of the biliary system via percutaneous transhepatic cholangiogram (PTC) or endoscopic retrograde cholangiopancreaticogram (ERCP). In the case of GCT, a concentric smooth narrowing intrinsic to the bile duct is demonstrated. This finding is generally interpreted erroneously to represent a cholangiocarcinoma or primary sclerosing cholangitis. Misdiagnosis can lead to inadequate resection of a curable lesion, and result in treatment failure.
Forty-two cases of granular cell tumor of the biliary tree have been reported in the literature9-4. In this paper we report the forty-third case and only the third such case of a granular cell tumor isolated to the common hepatic duct.

CASE REPORT
A twenty-seven year old white female was transferred from a Boston area hospital to the Hepatobiliary Service at the Deaconess Hospital for evaluation of bile peritonitis. The patient presented with nausea, vomiting, fever, diarrhea, abdominal pain and acholic stool. Her past medical history was unremarkable with the exception of a documented case of hepatitis A eleven months prior, with elevated bilirubin and alkaline phosphatase levels. Follow-up liver function testing revealed an elevated bilirubin of 2.5 mg/ml and an alkaline phosphatase of 2100 IU/L (nl < 39 IU/L). A percutaneous liver biopsy demonstrated a nonspecific cholestatic picture with periportal fibrosis and bile duct proliferation. Post biopsy, the patient developed abdominal distension and signs of peritoneal irritation. A dimethyliminodiacetic acid (HIDA) scan demonstrated extrahepatic excretion of contrast and a subhepatic collection which proved to be bile by paracentesis.
On admission, she was mildly jaundiced without stigmata of chronic liver disease. She was afebrile. Her abdomen was distended with the liver edge 3 cm below the right costal margin. The spleen was 2 cm below the left costal margin. Abdominal exam elicited diffuse tenderness, rebound and shifting dullness. Laboratory findings included a normal prothrombin time but an elevated bilirubin of 2.9 mg/ml. The serum asparate aminotransferase was 69 U/ml (nl< 40 U/ml); alkaline phosphatase 458 IU/L (n1<39 IU/L); and a white blood cell count of 12.600 per cubic millimeter. Paracentesis in the right anterior axillary line produced 2.5 liters of bile. Ultrasound and computerized tomography suggested a lesion in the upper biliary tract. ERCP was then performed, which revealed a concentric area of narrowing in the common hepatic duct (Figure 1). Dye was reflexed beyond the stratum and demonstrated the bile leak from the site of liver biopsy. During this procedure, a nasobiliary stent was placed in the common hepatic duct resulting in a fall in the bilirubin to 1.5 mg/ml; alkaline phosphatase to 279 IU/L and serum asparate aminotransferase to 33 U/ml. At operation, a 2 cm smooth, oval tumor was found to involve the proximal common hepatic duct. The tumor had a firm, yellow, filamentous quality. Frozen section diagnosed the lesion as a granular cell tumor. Due to the lesion's proximal location, a Roux-en-Y hepaticojejunostomy was performed to assure adequate proximal resection margins. Distally, resection of the biliary system was extended to the level of the pancreas where frozen section confirmed the margins to be free of tumor. Permanent histologic examination of the specimen showed the resection margins to be free of tumor. The tumor was composed of large polygonal cells with distinct cell borders, small nuclei and an acidophilic granular cytoplasm. These granules were periodic acid-Schiff positive. Staining for S-100 protein was not performed.
The patient did well post operatively and was discharged home with normal liver functions six days post operatively. She remains in good health one year later.

DISCUSSION
Granular cell tumors were first described by Abrikossoff in 1926 and Coggins reported the first case involving the biliary tree in 19522'9. Since that time only forty-two cases of biliary involvement have been reported with only two isolated in the common hepatic duct17'39. In review, 95 percent of cases occurred in females41, while 65 percent of all cases were in blacks. Two females were Asian, nine white, and four unspecified. The mean patient age was 33 (range 11 to 61). Duration of symptoms prior to the tissue diagnosis ranged from one week to six years.
Clinical symptoms at presentation are related to the anatomical location of the lesion. Plain (62%) and jaundice (36%) are the most commonly reported presenting symptoms. The vast majority of biliary GCTs involve the cystic, hepatic, and common bile duct ( Figure 2). The only case of multifocality within the biliary tree involved the gallbladder, cystic duct, and common hepatic duct 32 (Table 1).
Synchronous extra biliary lesions have also been described in six cases with five involving skin and a single lesion found in the stomach. Five cases have been reported to involve the pancreatic duct 9"30"42"43"44 While only a single case was found alone-. Previously, two patients have had isolated to involve the gallbladder involvement of the common hepatic duct 7,40. Our case therefore is the third case of granular cell tumor isolated to the common hepatic duct in the literature. Fourteen of the 43 patients (35%) reported were worked up with transhepatic cholangiography or endoscopic retrograde cholangiopancreatography in which an area of circumferential narrowing in the biliary tree was demonstrated. Of note, correct diagnosis was not suspected in any of these cases preoperatively. Intraoperative  Evidence to support this theory came from the demonstration of the presence of S-100 protein within the tumors. S-100 protein has been found outside the central nervous system in the Schwann cells of the autonomic ganglia as well as in the granules of granular cell tumors. Despite persistent controversy, the Schwann cell theory of origin remains the predominant theory. In summary, granular tumors of the biliary tree are rare, benign tumors that most often occur in black females and present with pain or jaundice. Diagnostic procedures such as ERCP and PTC are sensitive in identifying lesions and their location but are nonspecific and unable to identify granular cell tumors. Due to confusion between diagnosis of granular cell tumors and cholangiocarcinoma it is essential to perform a frozen section and histologically confirm the