Int. J. Pancreatol. 9 Copyright 1991 by The Humana Press Inc. All rights of any nature whatsoever reserved. 0169-4197/91/10(2): 161-172/$2.20

CASE REPORT

Multifocal Pancreatic Serous Cystadenoma with Atypical Cells and Focal Perineural Invasion K a t s u h i k o K a m e h *,1 T a k a h i k o F u n a b i k i , ~ M a s a h i r o OchhTi, t H i r o s h i A m a n o , Z M-asao Kasahara,2 a n d T o s h i n o r i S a k a m o t o ~ Departments o f ZSurgery and 2Pathology, Fujita-Gakuen Health University School

of Medicine, Kutsukake-cho Toyoake, Aichi 470-11, Japan; and 3Central Laboratory, Toyota Memorial Hospital, Toyota, Aichi 471, Japan Received March 4, 1991; Revised March 20, 1991; Accepted April 10, 1991

Summary A case of multi focal pancreatic serous cystadenoma with atypical cells is reported. The patient was a 72-yr-old female who complained of jaundice. The distal common bile duct was obstructed, and the proximal bile duct was remarkably dilated on cholangiography. The main portal vein was obstructed and collateral vessels had developed on ~portal angiography. Total pancreatectomy was performed. The resected specimen contained one tumor in the head of the pancreas, five in the body, and one in the tail. The tumors of the head and body were morphologically the same. Microscopically, both contained spongelike multilocular cysts on their cut surfaces. These cysts were covered with low cuboid epithelium containing clear cystoplasm and abundant glycogen. Neural invasion was also found. The tumor cells exhibited an increased N / C ratio, variable nuclear size, irregular nuclear margins, and coarse nuclear chromatin. These tumors had aneuploid nuclear DNA with a DNA index of 1.9 and a proliferation index of 0.28. We feel that it is necessary to reconsider the biological concept of serous cystadenoma.

Key Words: Pancreas; Serous cystadenoma; malignant potential; flow cytometry; DNA, aneuploid. INTRODUCTION T h e p a t h o l o g i c a l c o n c e p t o f p a n c r e a t i c serous c y s t a d e n o m a was established b y C o m p a g n o a n d Oertel (1) in 1978. Case r e p o r t s o f this t u m o r have *Author to whom all correspondence and reprint requests should be addressed.

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increased since then, most of them being benign and single. In 1989, David Ko George (2) reported a case of pancreatic serous cystadenoma with metastases into the liver. We report a case of multifocal pancreatic serous cystadenoma, which caused obstruction of the common bile duct and portal vein and showed atypical cells~ CASE A 72-yr-old female whose chief complaint was jaundice and whose past history and family history were noncontributory is the subject of this case report.

Present Illness Jaundice and abdominal distension developed during October 1988. On October 24, the diagnosis of pancreatic-head tumor was made through abdominal sonography by a local physician. The patient was admitted to the hospital on October 31.

Physical Examination on Admission An abdominal mass of 10 cm in diameter was palpated in the right flank area. Jaundice was evident.

Laboratory Studies on Admission The clinical laboratory data are presented in Table 1. Total and direct bilirubin were elevated. CEA and CA 19-9 were slightly increased. The pancreatic endocrine hormones were within the normal range~

C T Findings A low-density area of 10 cm in diameter with clear margins was seen in the head of the pancreas. A honeycomblike structure with partial calcification was observed in the low-density area. The inferior vena cava was compressed and flattened by the tumor mass (Fig. 1).

M R I Findings A low-intensity area with a reticular septumlike structure was seen in the T-1 weighted image. The tumor showed a high-intensity area in the T-2 weighted image (Fig. 2).

Angiographic Findings The tumor was supplied by the upper and lower pancreatico-duodenal arteries, and by the dorsal pancreatic artery. A remarkable pooling stain of the tumor and abundant "neoplastic" vessels were observed. A 2-cm tumor

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Table 1 Laboratory Studies on Admission WBC: 5800/#L RBC: 388 • 103/#L

Hb: 11.8 g/dL Ht: 35.2% Plat: 35.8 • 103//~L T.P: 7.1 g/dL Alb: 3.3 g/dL T. bil: 11.4 mg/dL D. bil: 8.2 mg/dL GOT: 39 mU/mL GPT: 31 m U / d L LDH: 121 mU/mL

7-GTP: 547 U/mL ALP: 293 m U / m L LAP: 110 m U / m L ChE: 2200 m U / m L AMY: 68 U CEA: 3.1 ng/mL CA 19-9:50 ng/mL Glucagon: 100 pg/mL Insulin: 3.5 uU/mL Somatostatin: 9.8 pg/mL Gastrin: 87 pg/mL

Fig. 1. CT showed a low-density area with calcification in the head of the pancreas. in the tail of the pancreas had a similar appearance. Portal angiography revealed that the main portal vein was blocked and collateral vessels had developed (Fig. 3). Cholangiography and Hypotonic D u o d e n o g r a p h y Cholangiography revealed that the c o m m o n bile duct was obstructed in its distal portion and that the proximal bile duct was remarkably dilated. H y p o tonic d u o d e n o g r a p h y revealed that the descending portion o f the d u o d e n u m was deviated to the right and the C loop was dilated (Fig. 4). A preoperative diagnosis of serous cystadenoma o f the pancreatic head and tail was made based on the above-mentioned findings.

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Fig. 2. a: T-1 weighted image: A tumor of the pancreatic head revealed a towintensity area. b: T-2 weighted image: The tumor showed a high-intensity area.

Operative Findings The pancreatic-head t u m o r could be separated from the vena cava inferior. However, the c o m m o n bile duct and the portal vein were totally involved within the t u m o r . P a n c r e a t o d u o d e n e c t o m y combined with portal-vein resection was performed. Another tumor o f about 0.5 cm in diameter was seen at the resected surface. Through frozen section the tumor of the pancreatic body was diagnosed as serous cystadenoma and the tumor in the tail was diagnosed as an islet-cell t u m o r that was difficult to distinguish as benign or malignant. Therefore, the total residual pancreas was then resected.

Gross Features of the Resected Specimen The t u m o r of the head measured t0 • 10• 8 cm with a clear capsule. The cut surface was brown. Multiple spongy cysts were segmented by white fibrous

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Fig. 3. Angiography. a: The tumor strain was shown in the head and tail of the pancreas, b: The main portal trunk was obstructed and the collateral vessels had developed. tissue (Fig. 5a). Five tumors, each o f 0.5 cm in diameter, were noted in the b o d y . Their margins were distinct. The cut surface was white and solid (Fig~ 5b). The tumor in the tall measured 1.5 cm in diameter and had a clear capsule with a dark-red solid cut surface (Fig. 5c). Consequently, one t u m o r was f o u n d in the head, five in the b o d y , and one in the tail. These tumors were all completely distinct from each other (Fig. 5d).

Histological Findings The tumors of the head and the b o d y were morphologically the same. There were clear margins between the tumors and the pancreatic parenchymal tissue. The tumors formed capsules and consisted o f cysts o f various sizes. Each cyst was lined by a single layer o f flat or cuboid epithelial cells. These had clear cytoplasm with centrally located nuclei. Reticular collagen fibers were observed in the interstitium (Fig. 6a,b). The tumor cells had an increased

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Fig. 4. Cholanglography and hypotonic duodenography: The common bile duct was obstructed in the lower area, N / C ratio, variably sized nuclei, irregular nuclear margins, and coarse nuclear chromatin and atypia (Fig. 6c,d). Neural invasion was also f o u n d on the margin o f the tumor o f the pancreatic head (Fig. 7). The epithelial cells of the tumors of the pancreatic head and body had abundant cytoplasmic PASpositive granules, which were completely digested by diastase. Electron microscopy revealed that the cells covering the internal wall of the cyst were cuboid with numerous microvilli and desmosomes and with massive glycogen granules in the cytoplasm (Fig. 8). The tumor of the tail had a clear margin and formed a capsule. These tumor cells had a trabecular arrangement and the t u m o r had rich capillary vessels in the interstitium. The diagnosis of islet-cell tumor was established based on these observations (Fig. 9a). The pancreatic parenchyma disclosed only a Langerhan's island and remarkable fatty replacement (Fig. 9b).

Nuclear D N A Findings Using the paraffin embedding method, the nuclear DNA histogram was analyzed using a flow cytometer (FACS 440) (3-5). The tumors o f the head and body exhibited aneuploid nuclear DNA with a DNA index of 1.9. The proliferation index was high, having a value of 0.28 (Fig. 10).

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Fig. 8. Electron micrograph showed intracytoplasmic glycogen granules in tumor cells.

DISCUSSION Cystadenoma of the pancreas was classified into two types by Compagno and Oertel (1) and by Hodgkinson et al. (6), one being the serous type and the other the mucinous type. There are clear-cut differences between the two types in both pathological and biological characteristics. There have been many reports of the malignant nature of the mucinous type (7-9). The serous type is commonly benign (1,6,9-14). However, according to an increasing number of case reports, malignancy does occur in the serous type (2,15).

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Fig. 9. a: The tail tumor was an islet-cell tumor, b: The pancreatic parenchyma disclosed only a Langerhan's island and remarkable fatty replacement. We experienced a case o f serous c y s t a d e n o m a o f multifocal origin and with atypical cells. All the images were consistent with previous descriptions o f serous cystad e n o m a (1, 6,9-14,16-19). Five serous cystadenomas in the body, which were f o u n d during the operation, were not observed in these images. It seems that the size of the tumors was too small to be diagnosed by CT or MRI. They were also not observed on angiography. It was felt that this was because the poor capillary vessels o f the t u m o r as found histologically. The islet-celt tumor o f the tail was not seen upon CT or MRI, although a t u m o r with hypervascularity was seen upon angiography. Histopathological findings o f the t u m o r o f the head was similar to that of the five small t~mors in the body. The histological findings were consistent with serous cystadenoma (1, 6). However, the findings o f an increased N / C ratio, a m o r p h o u s nuclei, irregular nuclear margins, coarse nuclear chromatin, and neural invasion suggested that this t u m o r had malignant potential, and

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Fig. 10. The head and body tumors in pancreas showed the same findings with aneuploid nuclear DNA (DI = 1.9) and a high proliferation-index value of 0.28 by nuclear DNA analysis of flow cytometry. these findings were consistent with a case o f malignant serous cystadenoma that was reported by David et al. (2). The portal vein was completely obstructed and involved in the tumor. The common bile duct was also involved in the tumor. However, infiltration o f the portal vein and the common bile duct was not proven histopathologically. The tumor cells o f the head and body had the same findings concerning aneuploid nuclear D N A and a high proliferation-index value o f 0.28. These findings indicated that the biological malignancy and proliferative ability o f these tumors were high. Based on macroscopic and microscopic findings, it seemed that all cystadenomas had developed independently. These findings are different from those of serous cystadenoma previously reported. We suggest that it is necessary to reconsider the concept o f serous cystadenoma. REFERENCES 1 2 3

4

5 6

Compagno J and Oertel JE. Microcystic adenoma of the pancreas(glycogenrich cystadenoma). Am. J. Clin. Pathol. 1978; 69: 289-298. David HG, Fergus M, Roman M, and Brian GU. Serous cystadenocarcinoma of the pancreas: a new entity?. Am. J. Surg. Pathol. 1989; 13: 61-66. Hedley DW, Friedlander ML, Taylor IW, Rugg CA, and Musgrove EA. Method for analysis of cellular DNA content of paraffin-embedded pathological material using flow cytometry. J. Histochem. Cytochem. 1983; 31: 1333-1335. Mcintire TL, Goldey SH, Benson NA, and Braytan RC. Flow cytometric analysis of DNA in cells obtained from deparaffinized formalin-fixed lymphoid tissues. C ytometry. 1987; 8: 474-478. Martin NR. Clinical applications of flow cytometry. Onclogy . 1988; 2: 35-44. Hodgkinson D J, Remine WH, and Weiland LH. Pancreatic cystadenoma. Arch. Surg. 1978; 113: 512-519.

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8 9 10 11 12 13 14 15 16 t7 18 19

K a m e i et al. Compagno J and Oertel JE. Mucinous cystic neoplasms of the pancreas with overt and latent malignancy(cystadenocarcinomaand cystadenoma). Am. J. Clin. Pathol. 1987; 69: 573-580. Hodgkinson DJ, Remine WH, and Weiland LH. A clinicopathologic study of 21 cases of pancreatic eystadenocarcinoma. Ann. Surg. 1978; 188: 679-684. Becker WF, Welsh RA, and Pratt HS. Cystadenoma and cystadenocarcinoma of the pancreas. Ann. Surg. 1965; 161: 845-860. Alpert LC, Truong LD, Bossart MI, and Spjut HJ. Microcystic adenoma(serous-cystadenoma) of the pancreas: a study of 14 cases with immunohistochemial and electromicroscopic correlation. Am. J. Surg. Pathol. 1988; 12: 251-263. Shorten SD, Hart WR, and Petras RE. Microcystic adenoma(serous cystadenomas) of pancreas: a clinicopathological investigation of eight cases with immunohistochemical and ultrastructural studies. A m . J. Surg. Pathol. 1986; 10: 365-372. Nyongo A and Huntrakoon M. Microcystic adenoma of the pancreas with myoepithelial cells. Am. J. Clin. Pathol. 1985; 84: 114-120. Campbell JA and Cruickshank AH. Cystadenoma and cystadenocarcinoma of the pancreas. J. Clin. Pathol. 1962; 15: 432-437. Villar HV, Dawson B. Cystadenoma, microcystic adenomas of the pancreas. Arizo Med. 1981; 38: 602. Zirisnksy K, Abiri M, and Baer JW. Computed tomography decmonstration of pancreatic microcystic adenoma. Am. J. Gastroenterol. 1984; 79: 139-142. Itai Y, Moss AA, and Ohtomo K. Computed tomography of cystadenoma and cystadenocarcinoma of the pancreas. Radiology 1982; 145: 419-425. Freeny PC, Weinstein CJ, and Taft DA. Cystic neoplasms of the pancreas: new angiographicand ultrasonographic findings. A JR 1987; 131: 795-802. Kamei K, Horibe Y, Kuroda M, Tashiro K, Kasahara M, Funabiki T, Ochiai M, Amano H, Hosoda Y, and Shiina E. Two cases of pancreatic serous cystadenoma. J. Jpn. Panc. Soc. 1988; 3: 569-576. Lo JW, Fung CHK, and Yonan TN. Cystadenoma of the pancreas. Cancer 1977; 39: 2470-2474.

International Journal of Pancreatology

Volume 10, 1991

Multifocal pancreatic serous cystadenoma with atypical cells and focal perineural invasion.

A case of multifocal pancreatic serous cystadenoma with atypical cells is reported. The patient was a 72-yr-old female who complained of jaundice. The...
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