Case Reports

763

@ 1991 The Japanese Society of Pathology

Solid and Cystic Tumor of the Pancreas in an Adult Male

Tsukasa Tsunoda', Toshifumi Eto', Takahito Tsurifune', Shigeki Tokunaga', Tatsuhiro Ishii', Koichi Motojima', Teiji Matsumoto', Tohru Segawa', Kazuhide Ura', and Hiroshi Fukui2

A solid and cystic tumor (SCT) was located at the head of the pancreas in a 43-year-old Japanese male, and pan- creatoduodenectomy was performed on the suspicion of papillary carcinoma or cystadenocarcinoma of the pan- creas. The lesion, which measured 4.5 x4.5 x4.0 cm, was clearly demarcated by connective tissue. The cut surface showed solid grayish-white areas with central cystic degen- erative changes. The solid areas consisted of small round cells proliferating in a small solid or a pseudopapillary pattern. The tumor cells partially invaded the surrounding normal pancreatic parenchyma. lmmunohistochemical studies revealed positive staining for alpha-1-antitrypsin and neuron-specific enolase, but no staining for known pancreatic hormones. Moreover, ultrastructural studies showed the absence of zymogen granules and the presence of anullate lamellae and neurosecretory granules. On the basis of these findings, a diagnosis of SCT of the pancreas was established. In order to clarify the histogenesis and biological behavior of the tumor, it is necessary to accumu- late and analyze similar cases, an endeavor which in turn w i l l contribute to the successful management of this dis- ease. Acta Pathol Jpn 41 : 763-770, 1991.

Key words: Solid and cystic tumor, Pancreas, Immunohisto- chemical study, Ultrastructural study

INTRODUCTION

Solid and cystic tumor (SCT) of the pancreas is a rare

Received February 15, 1991. Accepted for publication July 22, 1991. 'Second Department of Surgery, Nagasaki University School of Medicine, Nagasaki and 2Department of Surgery, Nagasaki Memorial Hospital, Nagasaki. Mailing address : Tsukasa Tsunoda, M.D., Second Depart- ment of Surgery, Nagasaki University School of Medicine, 7-1 Sakamoto, Nagasaki 852, Japan.

tumor characterized by occurrence in young females and a favorable prognosis when completely resected (1). The tumor has been gradually accepted as a clinico- pathological entity since it was reported by Kloppel et a/. in 1981 (2). In spite of extensive pathological examina- tions, however, there is still controversy as to whether it is derived from exocrine, endocrine, or more primitive cells of the pancreas(2-5). Recently, SCT of the pan- creas was observed in an adult man in our department.

The purpose of this paper is to report this extremely rare case with detailed pathological information, includ- ing the results of immunohistochemical and ultra- structural studies.

CASEREPORT

On April 23, 1989, a 43-year-old Japanese man was admitted to Nagasaki Memorial Hospital complaining of upper abdominal pain and vomiting after drinking. No particular family or past history were given. Physical examination showed mild tenderness in the upper abdo- men. No abnormal mass was palpated. Blood cell counts and blood chemistry were all within normal limits except for leukocytosis. Ultrasonography revealed a hypoechoic lesion in the head of the pancreas with an accompanying echo-free space in the center of the mass (Fig. 1). Abdominal computed tomography confirmed a 4.5x4.0 cm low density mass, the peripheral area of which was enhanced by contrast medium (Fig. 2). There were no calicifications in the mass. Endoscopic retro- grade pancreatography revealed that the pancreatic duct in the head of the pancreas was displaced to the upper right side by the mass. Selective celiac angiography showed that the mass was a hypovascular lesion and that the mass compressed the pancreatic arcades of the

764 Solid and Cystic Tumor of the Pancreas (Tsunoda et a/.)

Figure 1. Ultrasonography shows a hypoechoic lesion in the head of the pancreas. An echo-free space is par- tially shown in the center of the mass.

Figure 2. Abdominal computed tomo- graphy shows a 4 . 5 x 4 . 0 c m mass lesion in the head of the pancreas The peripheral area of the tumor IS

enhanced by contrast medium No calcifications are detected in the mass.

arteries. Fine-needle biopsy of the mass was done mass with a clear border was found in the head of the under ultrasound guidance and the result was reported to pancreas without ascites or invasion to surrounding be class IV, raising the suspicion of papillary adenocar- organs. The regional lymph nodes were swollen but cinoma (Fig. 3). The patient was referred to the Second soft. Pancreatoduodenectomy was performed. The Department of Surgery, Nagasaki University School of postoperative course was uneventful. The patient was Medicine. On April 24, 1989, a laparotomy was per- discharged on the 30th postoperative day and has been formed on the suspicion of possible papillary carcinoma well ever since. or cystadenocarcinoma of the head of the pancreas. A

Acta Pathologica Japonica 41 (10): 1991 765

METHODS

Light microscopy

Resected specimens were fixed in 10% formalin and processed for paraffin sections. The paraffin-embedded sections were cut and stained with hematoxylin and eosin (HE) and periodic acid-Schiff (PAS).

I mmunohistochemical studies

Staining by the peroxidase anti-peroxidase method was applied to deparaffinized sections by the use of

Figure 3. Aspiration cytological ex- amination of the tumor by fine-needle biopsy (Papanicoloau stain). The tumor cells show slight nuclear pleomorphism, raising the suspicion of papillary adenocarcinoma (Class IV).

antibodies to alpha-1 -antitrypsin (AAT, Dako, Santa Fe, CA), neuron-specific enolase (NSE, Dako), insulin, glucagon, somatostatin and pancreatic polypeptide (Da ko).

Electron microscopy

Twenty samples of the resected specimen were imme- diately fixed in 2% glutaraldehyde and postfixed in 2% osmium tetroxide. Ultrathin sections from tissues em- bedded with Epon were stained with uranyl acetate and lead citrate, and processed for electron microscopic examination.

Figure4. The cut surface of the re- sected specimen. The tumor consists of a solid gray-whitish mass with cystic changes in the center.

766 Solid and Cystic Tumor of the Pancreas (Tsunoda et a/.)

Acta Pathologica Japonica 41 (10): 1991 76 7

F i g u r e 5 Microscopic features. (a) In the solid area, proliferation of the tumor cells shows a pseudopapillary pattern (HE). (b) The tumor cells invade the surrounding pancreatic tissue (HE). (c) At the periphery of the tumor, tumor cells invade the small vein (arrows) (HE).

PATHOLOGICAL FINDINGS

Gross features

Measwing 4 . 5 x 4 . 5 x 4 . 0 cm, the tumor mass was clearly demarcated by connective tissue from the sur- rounding: normal pancreatic tissue, but no definite fibrous capsule formation was observed. The cut surface was solid grayish-white with cystic degenerative changes in the center of the tumor (Fig. 4). No calcifications were found in the mass.

Microscopic features

The solid area consisted of small round cells showing slight nuclear pleomorphism or atypism. The tumor cells proliferated in a small solid or a pseudo-papillary pattern (:Fig. 5a). The cystic area in the center of the tumor displayed degenerative changes such as hemor- rhage, necrosis and scattered cholesterol deposits or cholesterol granulomas. The tumor cells partially invad-

ed the surrounding normal pancreatic tissue (Fig. 5b) and veins (Fig. 5c). PAS-positive materials were not seen in the cells. No metastasis was detected in any of the resected regional lymph nodes.

I mmunohistochemical features

Most of the tumor cells stained positive for NSE, while a few positive for AAT. No positivity was detected for i nsuli n, g I ucago n, somatostatin or pa ncrea t ic po I y pep tide.

U I t ra st ruct ura I features

Mitochondria were well developed in the cytoplasm of the tumor cells. No zymogen granules were observed in any cells and a few neurosecretory granules were detect- ed in a small number cells by extensive examination (Fig. 6a). Annulate lamellae were noted in some cells (Fig. 6 b).

Figure 6. Ultrastructural examinations. (a) No zymogen granules are demonstrated. A few neurosecretory granules are found (arrows) (X2,500). (b) Annulate lamellae are detected in some cells (x8,OOO).

768 Solid and Cystic Tumor of the Pancreas (Tsunoda et a/.)

Acta Pathologica Japonica 41 (10): 1991 769

DISCUSSION

SCTs o f the pancreas are extremely rare in adult men. Cubilla and Fitzgerald reported that SCT of the pancreas occurred mainly in adolescent girls and young women and that only about 5% were observed in men(6). Sixty-one cases of SCT of the pancreas collected from Japanese literature consisted of 57 women and 4 men (7).

In the past, SCT of the pancreas was often mis- diagnosed as a non-functioning islet cell tumor (8). We also suspected a non-functioning islet cell tumor in our case on the basis of the pathological findings by light microscopic examination. However, i mmu no h is t o- chemical studies did not reveal any staining for insulin, glucagoii, somatostatin or pancreatic polypeptide. Furthermore, neurosecretory granules, one of the charac- teristic findings of islet cell tumors, were seldom detected in the ultrastructural studies, thus resulting in rejection of the islet cell tumor diagnosis. AAT and NSE were stained immunohistochemically in our case. Positive staining for AAT has often been reported in SCT, but its positivity is also revealed in normal islets, acinar cell carcinomas, pancreatoblastoma and so forth (3, 9). NSE has been stained in tissues other than SCT, such as normal pancreatic tissue, acinar cell carcinomas, pan- creatoblastoma and so forth (10). Positivity for AAT and NSE per se is one of the characteristics of SCT, but it does riot constitute a specific marker for SCT (1 1).

Ultras.tructural studies have revealed that zymogen granules and abundant mitochondria were present in many cases of SCT (2), and that neurosecretory gran- ules were present in some cases(l2). In our case, no zymogeri granules were detected, while mitochondria, annulate lamellae and a few neurosecretory granules were dernonstrated.

There are many views about the cell origin of SCT. These iriclude acinar cells (2, 3), ductular cells (4, 13) and multipotential stem cells (primordial cells) that can differentiate toward both acinar and islet cells (5, 14). In our case, the detection of annulate lamellae(l5) and neurosecretory granules by ultrastructural examination was considered to be indicative of acinar cell and islet cell differentiation, respectively. Absent, however, were zymogeri granules, which most often indicate acinar cell differentiation in SCT. Therefore, the stage of differ- entiation in our case did not seem to be sufficiently advanced for the appearance of zymogen granules.

The treatment of choice was complete resection of the tumor, a procedure that yielded favorable results. This has also been shown in male patients(8). However, SCT should be recognized as a low-grade malignancy because, although occurring only in a few cases, local

recurrence, metastasis to other organs and peritonitis carcinomatosa have been reported (4, 6, 16). In our case, the presence of invasion to the surrounding pancre- atic tissue and veins was observed and even though the affected area was completely resected, the findings in- dicated the necessity for a strict and lengthy follow-up.

In conclusion, in order to clarify the histogenesis and biological behavior of SCT, it is necessary to accumulate and analyze similar cases, an endeavor which in turn will contribute to the successful management of this rare tumor.

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770 Solid and Cystic Tumor of the Pancreas (Tsunoda et a/.)

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