Acta Pathol. Jpn. 35(3) : 687-691, 1985

GRANULAR CELL TUMOR OF THE GALLBLADDER Report of a Case

Koji YAMAGUCHI, Shoji KUROKI, Yutaka DAIMARU, Hiroshi HASHIMOTO, and Munetomo ENJOJI

Second Department of Pathology, F m l t y of Medicine, Kyushu University, Fukuoka

A rare case of granular cell tumor of the gallbladder in a 58-year-old Japanese man is presented. This is the third report of such a tumor arising in the gallbladder. The immunohistochemical study demonstrated the localiza- tion of the nervous-system-specific protein (S-100 protein) in the granular component cells, thereby supporting the Schwann cell origin of this tumor. ACTA PATHOL. JPN. 35 : 687-691, 1985.

Introduction Granular cell tumor, previously termed granular cell myoblastoma, was first

described as myoblastic myoma in 1926 by ABRIKOSSOFF.~ The tumor occurs most frequently on the tongue and less frequently in the skin and subcutaneous tissue, but rarely involves the alimentary passages, such as the stomach, the extrahepatic biliary tract and the gallbladder. To our knowledge, only two cases of this tumor occurring in the gallbladder have been reported in the English literature.2J0 Although the origin of the cells in this tumor has been debated, recent immunohistochemical studies on the presence of 5-100 protein in the granular cell tumor of various sites have led to the view that the tumors are derived from Schwann c e l l ~ . ’ ~ J ~ The purpose of this brief paper is to report the third case of granular cell tumor of the gallbladder, with reference to immunohistochemical localization of 5-100 protein.

Case Report

The patient, a 68-year-old Japanese man, was admitted to the Fukuoka Red Cross Hospital because of right hypochondral pain of five year duration. The patient was jaundiced four years ago, and later had tenderness to palpation in the right upper quadrant of the abdomen. Routine laboratory studies were normal, including com- plete blood cell count, blood sugar, and blood nitrogen, except for slight elevation of alkaline phosphatase and y-glutamyltranspeptidase. An intravenous cholangiogram

Accepted for publication August 25, 1984.

Mailing address : Kyushu University 60, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812, JAPAN.

CLla P--, z7K #q, 93. 8, %* R , BB+ %:5w Dr. M. ENJOJI, Second Department of Pathology, Faculty of Medicine,

688 GRANULAR CELL TUMOR OF THE GALLBLADDER Acta Pathol. Jpn

35(3) : 1985 K. YAMAGUCHI et at. 689

Fig. 4. Demonstration of S l O O protein in the granular cells and the peripheral nerve bundles Both the nuclei and cytoplasm of the granular cells (arrows).

are positively stained for 5-100. PAP method, x 12. Inset :

PAP method, x320.

failed to visualize the gallbladder and ultrasonograms were interpreted as showing a dilated common bile duct containing two calculi and a collapsed gallbladder. Endoscopic retrograde cholangiogram demonstrated the dilatation of the common bile duct containing two calculi and an internal fistula between the gallbladder and the duodenum.

Cholecystectomy, choledocholithotomy, choledocho-jejunostomy with Roux-en Y method and closure of the fistula were performed on Dec. 10 1979. The patient made an uneventful recovery and was discharged on the 60th postoperative day. He has been well for these four years.

The resected gallbladder measuring 5 x 4 cm had a fibrosed and thickened wall. A spherical tumor, 0.7cm in diameter, was located in the body of the organ, was non-capsulated, yellow-white in color, homogeneous in appearance and rubbery in consistency and mainly occupied the subserosal layer of the wall rather diffusely with extension into upper layers (Fig. 1).

Fig. 1.

Fig. 2. Fig. 3.

Granular cell tumor of the gallbladder.

Nests of granular cells are separated by thin fibrous bands. H.E., ~ 3 2 0 . A peripheral nerve bundle is encircled by granular cells, the distinction between these

An ill-defined mass is located mainly in the subserosal layer, extending into the upper muscular and subepithelial layers. H.E., x 27.

two elements being difficult. H.E., x 220.

6 9 U GRANIJLARCELLTUMOROFTHEGALLBLADDER Acta Pathol. Jpn.

Microscopically, the tumor was composed of large round or polygonal cells of uniform size, with distinct cell boundaries and a small dark and faintly eosinophilic granular cytoplasm. The cytoplasmic granules were abundant, coarse to fine and eosinophilic or brownish yellow, on the conventional sections stained with hematox- ylin and eosin (H.E.). These cells were arranged in small groups separated by thin bundles of fibrous structures which were probably pre-existing (Fig. 2). At the periphery of the tumor, the granular cells infiltrated singly or in groups, but did not destroy the muscle coat or other surrounding structures. A striking feature was that suggesting connection of the tumor cells with the nerve. Hypertrophic nerve bundles were found frequently in and around the tumor, the granular cells tightly encircling the bundles and existing within them (Fig. 3).

The cytoplasmic granules were positive for periodic acid-Schiff reaction and were resistant to digestion by diastase. The immunohistochemical staining for S-100 protein using a PAP method* produced a distinct deposit in these granular cells. Both nuclei and cytoplasm of the granular cells were positively stained, and the reaction deposit appeared either granular or diffuse (Fig. 4).

Discussion

The occurrence of granulm cell tumor in the extrahepatic biliary tract is uncom- mon and that in the gallbladder is exceedingly rare. In the available documents there were 31 cases of granular cell tumor involving the extrahepatic biliary tract. These include 19 occurring in the common bile duct, 12 in the cystic duct and only 2 in the gallbladder. The previous reports 5,7~11*12~17 showed that granular cell tumors of the biliary tract occur more often in females and in blacks. Although the tumor was single in our patient, a patient reported by AISNER, et a1.2 had multiple tumors in the biliary tract. The present patient with a single lesion, however, was a Japanese male and is the second case of this tumor involving the gallbladder, in a Japanese.

There is much controversy concerning the origin of granular cell tumor. Striated muscle,' histiocyte,'j perineural fibroblast,15 undifferentiated mesenchymal cells,4 and Schwann c e l l ~ ~ 9 ~ have been suggested as precursors of this tumor, together with the possibility of a multicellular origin.3 Recent immunohistochemical studies 13,14,16

have shown the location of S-100 protein in a granular cell tumor with a close correspondence of peripheral nerve myelin proteins (P2 and PO proteins). This would give rise to characteristic PAS-positive granules, seen on the serial ~ect ions, '~ these findings supporting the hypothesis of Schwann cell origin of the tumor. In the present case, there was a close association of nerve bundles with granular cells, and the 5-100 protein was amply demonstrated in most of the granular cells.

Clinical signs and symptoms in patients with this tumor vary with the site of the tumor and the presence of the associated lesions. The tumor involving the gallbladder often mimics cholelithiasis and the common bile duct tumor easily leads to the

* The anti-bovine S-100 protein rabbit IgG was kindly provided from Dr. Takashi Nakashima, National Cancer Center Research Institute, Tokyo." It was diluted 1 : 300.

35(3) : 1985 K. YAMAGUCHI et d. 691

association of jaundice. Our patient had right hypochondralgia and jaundice both caused by real choledocholithiasis and the granular cell tumor of the gallbladder WBS

rather an incidental event.

Acknowledgments: We thank Mariko OHARA for comments on the manuscript, and Dr. Takashi NAKAJIMA, National Cancer Center Research Institute, Tokyo for kindly providing the anti-bovine 5-100 protein IgG.

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