Pleomorphic Carcinoma of the Pancreas: Reappraisal ofSurgical Resection

K. Yamaguchi, M.D., K. Nakamura, M.D., S. Shimizu, M.D., K. Yokohata, M.D., T. Morisaki, M.D.,K. Chijiiwa, M.D., and M. Tanaka, M.D.

Department of Surgery I, Kyushu University Faculty of Medicine, Fukuoka, and Department of Surgery, Kyushu Rosai Hospital,Kitakyushu, Japan

Pleomorphic carcinoma is a rare variant of pancreaticexocrine carcinoma. The aim of this communication is toreappraise surgical resection of pleomorphic carcinomaof the pancreas. Clinicopathological findings of four Jap-anese patients with pleomorphic carcinoma of the pan-creas were reviewed and compared with those of 24Japanese patients with adenocarcinoma of the pancreasto clarify possible surgical implications of pleomorphiccarcinoma. Of the four patients, three were female andone male, aged 64, 65, 66, and 74 yr, respectively. Twocarcinomas were located in the head of the pancreas, onein the body, and the other in the tail. Ultrasonographydemonstrated a well defined hypoechoic mass measuring5–10 cm, with central necrotic area in all of the patients.Computed tomography showed a low density tumor withsharp margin and heterogenous internal structure in all.On angiography, three tumors were hypervascular andanother was hypovascular. Extensive vascular encase-ment was observed in all. Pancreatoduodenectomy wasdone in two patients and distal pancreatectomy in theother two. Multiple liver metastases occurred 1 monthafter surgical resection in two patients and local recur-rence 1 month in one and 2 months in the other, leadingto death either 2 (2 patients) or 3 months (2 patients)after pancreatectomy. Significantly differentiating fea-tures of the four pleomorphic carcinomas of the pan-creas and the 24 adenocarcinomas of the pancreas werethe mean diameter (6.66 1.3 cm vs 3.5 6 0.3 cm,p 50.0007), margin of the tumor (expansive in the fourpleomorphic carcinomasversusinfiltrative in 21 of the24 adenocarcinomas,p 5 0.003) and vascularity on an-giography (hypervascular in three of the four pleomor-phic carcinomas versus hypovascular in 21 of the 23adenocarcinomas,p 5 0.013). The 1-yr and 3-yr survivalrates of the four patients with pleomorphic carcinomawere 0% and 0%, whereas those of the 24 patients withadenocarcinoma of the pancreas were 42% and 13%,respectively (p < 0.0001). These findings suggest that theclinical course of patients with pleomorphic carcinomaof the pancreas is so poor even after surgical resection

that pleomorphic carcinoma of the pancreas is not acandidate for pancreatectomy despite its locally expan-sive growth. (Am J Gastroenterol 1998;93:1151–1155. ©1998 by Am. Coll. of Gastroenterology)

INTRODUCTION

Pleomorphic carcinoma of the pancreas is an unusualvariant of pancreatic exocrine carcinoma and constitutes0.5–7% of carcinoma of the pancreas (1–3). This disease ischaracterized by a loss of cohesiveness of cancer cells,showing a sarcomatoid structure by histology. It is com-posed of varying mixtures of anaplastic mononuclear cells,pleomorphic multinucleated giant cells, and atypical spindlecells. Since the first report by Sommers and Meissner (4),pleomorphic carcinoma of the pancreas has been reportedunder various names including pleomorphic adenocarci-noma (5), sarcomatoid carcinoma (6), pleomorphic giantcell carcinoma, pleomorphic carcinoma (7), and giant cellcarcinoma (8). To our knowledge, only a few articles (5–9)or case reports (10, 11) have focused on pleomorphic car-cinoma of the pancreas because of the rarity of this condi-tion. Regarding the imaging findings, only one article (12)reviewing six cases of pleomorphic carcinoma of the pan-creas has been available with regard to computed tomo-graphic (CT) findings. Few articles have mentioned theclinical course of pleomorphic carcinoma of the pancreasafter a surgical resection. We herein describe the clinico-pathological findings of the four patients with pleomorphiccarcinoma of the pancreas and compare them with those ofthe 24 Japanese patients with adenocarcinoma of the pan-creas to reappraise the surgical implications of pleomorphiccarcinoma of the pancreas.

PATIENTS

This series is composed of four Japanese patients withpleomorphic carcinoma of the pancreas and 24 with adeno-carcinoma of the pancreas. Of the four patients, three un-derwent surgical resection at the Department of Surgery I,Kyushu University Hospital, Fukuoka, Japan, from 1986 toReceived Aug. 26, 1997; accepted Jan. 19, 1998.

THE AMERICAN JOURNAL OF GASTROENTEROLOGY Vol. 93, No. 7, 1998Copyright © 1998 by Am. Coll. of Gastroenterology ISSN 0002-9270/98/$19.00Published by Elsevier Science Inc. PII S0002-9270(98)00232-9

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1995 and the remaining patient at the Department of Sur-gery, Kyushu Rosai Hospital, Kitakyushu, Japan, in 1987. Inaddition, 24 patients underwent surgical resection at theDepartment of Surgery I, Kyushu University Hospital, from1986 to 1995. Clinical charts were available for all 28patients. The imaging findings were obtained as follows:abdominal x-ray, ultrasonography, CT in all, endoscopicretrograde cholangiopancreatography in 25, and angiogra-phy in 27. Of the four patients with pleomorphic carcinomaof the pancreas, two underwent pancreatoduodenectomy andthe other two distal pancreatectomy and splenectomy. Of the24 patients with adenocarcinoma of the pancreas, 16 under-went pancreatoduodenectomy, and the remaining eight un-derwent distal pancreatectomy either with (six patients) orwithout (two patients) splenectomy. Follow-up CT was ob-tained in two patients with pleomorphic carcinoma of thepancreas and follow-up ultrasonography in the other twowith pleomorphic carcinoma of the pancreas.

The distribution of the patients was measured by thex2

test and the mean values were compared by the Student’sttest. The clinical follow-up was updated as of June 30, 1997.Follow-up data were available for all 28 patients. The cu-mulative survival rates were examined and the differencesamong the rates were measured by the log rank test. Thesurvival curves were examined by the Kaplan-Meier methodand the differences between the curves were determined bythe generalized Wilcoxon test.

RESULTS

Clinical findings of pleomorphic carcinoma of thepancreas

The four patients consisted of three women and one manwith a mean age of 67.3 yr (range, 64–74 yr). Three patientscomplained of abdominal pain and another jaundice. Onepatient with obstructive jaundice had had external cholecys-tostomy in a nearby hospital. One of the four patients had ahistory of right mastectomy for breast cancer 2 yr ago, andanother of distal partial gastrectomy with Billroth II recon-struction for duodenal ulcer 15 yr previously. One patienthad been diagnosed as having lung cancer and had beentreated with radiation and chemotherapy. The lung cancershowed no interval growth. Therefore, pancreatic tumor andlung tumor were considered to be independent from eachother. On palpation, a mass was evident in the left upperquadrant in one, whereas no mass was present in the otherthree. Laboratory data showed elevation of the white bloodcell count in one of the four patients. Serum levels ofcarcinoembryonic antigen (CEA) and carbohydrate antigen(CA) 19-9 were not elevated in all four patients.

Imaging findings of pleomorphic carcinoma of thepancreas

A plain x-ray film showed a tumor shadow in one of thefour patients. There was no abnormal calcification. Ultra-sonography showed a well defined hypoechoic mass, mea-

suring 5–10 cm, in the head of the pancreas in two patientsand in the body-tail in the other two. CT showed a lowdensity mass with sharp margin, measuring 3.5–10 cm at thegreatest diameter, in the four patients. The internal densityof the mass was heterogenous in all. Magnetic resonanceimaging showed a tumor with central necrosis as evidencedon T2 in two patients examined. Endoscopic ultrasonogra-phy demonstrated a hypoechoic mass in the body to tail ofthe pancreas in two patients studied. Endoscopic retrogradecholangiopancreatography showed a complete obstructionof the main pancreatic duct in one of the two patientsexamined and a double duct sign in the other. Celiac an-giography showed a hypovascular mass in one and a hyper-vascular tumor in the other three. All four patients hadextensive vascular encasement of the splenic artery in one,dorsal pancreatic artery in one, anterior superior pancre-atoduodenal artery in one, and splenic artery and vein in theother.

Operative findings of pleomorphic carcinoma of thepancreas

Pancreatectomy was done because of apparently expan-sive growth despite the huge size and rapid enlargement.The preoperative diagnosis was mucinous cystadenocarci-noma in one and pancreatic carcinoma in the other three.Pancreatoduodenectomy was done in two, and distal pan-createctomy and splenectomy with partial gastrectomy andwedge resection of the portal vein in one and with partialresection of the transverse colon in the other. Intraoperativeradiation therapy (25 Gy and 30 Gy) was performed in twoof the four patients.

The cut-surface of the tumor was yellowish white andhemorrhagic necrosis was present. Histopathologically, thetumor showed expansive growth (Fig. 1). The tumor wascomposed of various amounts of a solid proliferation ofpleomorphic mononucleated or multinucleated malignantgiant cells with bizarre nuclei (Fig. 2) and a proliferation of

FIG. 1. Expansive growth of pleomorphic carcinoma of the pancreas(hematoxylin and eosin,310).

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spindle-shaped malignant cells (Fig. 3). Foci of malignantglandular structures (Fig. 4) were present within the tumorin two of the four tumors. Lymphatic and venous invasionwas prominent and the surgical margins were affected bymalignant cells in the four. The lymph node metastasis wasevident in three of the four: around the common hepaticartery in one, splenic artery in one and pancreatic head in theother. The histopathologic diagnosis of the resected speci-men was pleomorphic carcinoma of the head of the pancreasin two and pleomorphic carcinoma of the body-tail of thepancreas invading the subserosal layer of the stomach in oneand the transverse colon in the other.

Clinical outcome of pleomorphic carcinoma of thepancreas

Early liver metastasis was present 1 month after surgeryin two patients and local recurrence was evident 1 monthafter surgical resection in 1 and 2 months in the other two.

Of the four patients, two died of liver metastasis 2 monthsafter operation and the two others local recurrence 3 monthsafter surgery. Unfortunately, autopsy was not done in all thepatients.

Differentiating features of pleomorphic carcinoma fromadenocarcinoma

Patient age, sex, and location of the tumor were notdifferent. The mean diameter of the four pleomorphic car-cinomas was significantly larger than that of the 24 adeno-carcinomas of the pancreas (6.66 1.3vs3.56 0.3 cm,p 50.0007). The tumor margin on US and/or CT was expansiveand well defined in all four pleomorphic carcinomas,whereas it was infiltrative in 21 of the 24 adenocarcinomasof the pancreas (p , 0.0003). On angiograms, three of thefour pleomorphic carcinomas were hypervascular, whereasonly two of the 23 adenocarcinoma examined were hyper-vascular (p 5 0.013). Vascular encasement was evident inall four patients in pleomorphic carcinoma and in 17 of the23 patients with adenocarcinoma. The 1-yr and 3-yr surviv-als of the four patients with pleomorphic carcinoma of thepancreas were 0% and 0%, whereas those of the 24 patientswith adenocarcinoma of the pancreas were 42% and 13%,respectively (p , 0.0001). The survival curve of the fourpatients with pleomorphic carcinoma of the pancreas wassignificantly worse than that of the 24 patients with adeno-carcinoma of the pancreas (p , 0.0001).

DISCUSSION

Kamisawaet al. (13) reviewed 66 reported cases (63nonresected and three resected) of pleomorphic carcinomaof the pancreas, excluding osteoclast-type giant cell tumorof the pancreas. The mean age of the 66 patients was 63 yr.There were 49 men and 17 women, showing a male pre-ponderance of 2.8. Of the 66 pancreatic tumors, 28 werelocated in the head of the pancreas, 32 in the body or tail,

FIG. 2. A proliferation of pleomorphic mono-nucleated or multi-nucle-ated malignant giant cells with bizarre nuclei (hematoxylin and eosin,3220).

FIG. 3. A proliferation of spindle-shaped malignant cells in short fasci-cles (hematoxylin and eosin,3200).

FIG. 4. Foci of malignant glandular structures are present within thetumor (hematoxylin and eosin,3130).

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and the remaining four diffusely involved the pancreas. Thediameter of the 66 tumors ranged from 3 to 30 cm, with amean diameter of 10 cm. Central bleeding or necrosis wasoften encountered.

Clinical symptoms are similar between pleomorphic car-cinoma and adenocarcinoma of the pancreas (9, 14), includ-ing epigastralgia, body weight loss, back pain, anorexia, andvomiting. The incidence of icterus in patients with pleomor-phic carcinoma is lower than that with adenocarcinoma, theincidence of jaundice being reported to be 29% in pleomor-phic carcinoma (13). At the time of clinical diagnosis,pleomorphic carcinoma of the pancreas is sometimes pal-pated as a huge abdominal mass in the left upper quadrantas in one of the four patients in our series.

Few papers have reported imaging findings of pleomor-phic carcinoma of the pancreas (11, 12). In the present seriesof four patients, ultrasonography (US) and/or computedtomography showed an expansive and well defined marginof the tumor with a central necrosis. Follow-up imagingsshowed a rapid growth. Angiography demonstrated a hy-pervascular mass with extensive involvement of the pancre-atic vessels in three of the four patients. Possible differen-tiating features of pleomorphic carcinoma fromadenocarcinoma of the pancreas was the huge size, a welldefined margin, and prominent vascularity.

In patients with pleomorphic carcinoma of the pancreas,the internal structure of the pancreatic mass is heteroge-neous on imaging techniques. A pleomorphic carcinomashould be differentiated from a mucinous cystadenocarci-noma and a solid and cystic tumor of the pancreas. Thedifferentiation is important, because the clinical course ofthe latter two entities are favorable after surgical resection.In pleomorphic carcinoma, there is extensive vascular inva-sion, whereas the solid and cystic tumor is usually seen in ayoung woman and hardly shows vascular encasement. Inthose with mucinous cystadenocarcinoma, the papilla ofVater is usually enlarged and mucin is secreted therefrom.

Histopathologically, cancer cells in pleomorphic carci-noma of the pancreas show little or no attachment with eachother and marked lymphatic, venous, and perineural infil-tration, and lymph node metastasis. Pleomorphic carcinomaof the pancreas is divided into three types: giant cell, spindlecell, and round cell. Pleomorphic carcinoma of the pancreasmay contain a focal area of adenocarcinoma, the rate of theconcomitance being reported to be 63% (13). In the presentseries, foci of adenocarcinoma were evident in two of thefour patients. This finding suggests that pleomorphic carci-noma of the pancreas may derive from preexisting adeno-carcinoma of the pancreas.

Effects of chemotherapy and radiation therapy remainpessimistic in pleomorphic carcinoma as well as adenocar-cinoma of the pancreas. At present, surgical resection is theonly effective strategy against pancreatic adenocarcinomaand pleomorphic carcinoma of the pancreas. According toKamisawa’s review of 66 patients with pleomorphic carci-noma of the pancreas, only three tumors were surgically

resected (13). The mean survival was only about 5 monthsafter the clinical diagnosis was made, when resection wasnot performed. In the present study, pancreatectomy wasperformed in the four patients because US and/or CTshowed a well-defined margin from the surrounding organsand tissues, although the tumor was huge and surgical re-section was expected to provide the only chance for longterm survival. All four patients, however, developed localrecurrence and/or liver metastasis within their hospital stay.The survival curve of the four patients with pleomorphiccarcinoma of the pancreas was significantly worse than thatof the 24 patients with adenocarcinoma of the pancreas. Theclinical outcome of pleomorphic carcinoma was terriblydismal after surgical resection. Tschanget al. (9) reported ahigh incidence of hematogenous spread of pleomorphiccarcinoma of the pancreas to the liver (87%), lung (73%),adrenal gland (60%), kidney (47%), bone (40%), heart(33%), and thyroid gland (20%). The incidence of hema-togenous metastasis of pleomorphic carcinoma of the pan-creas seems to be higher than that of adenocarcinoma of thepancreas, where hematogenous spread is also often the case(15, 16).

Pleomorphic carcinoma of the pancreas is characterizedby a locally expansive, huge pancreatic mass with a centralnecrosis and extensive vascular invasion. When a hugeexpansive pancreatic tumor showing rapid growth is en-countered, the surgeon should be well aware of pleomorphiccarcinoma of the pancreas as a differential diagnosis. Whenthe diagnosis of pleomorphic carcinoma of the pancreas ishighly suspected, the surgeon should abandon the notion ofan extensive pancreatic resection, because the clinical out-come of patients with pleomorphic carcinoma of the pan-creas is dismal even after surgical intervention.

Reprint requests and correspondence: Koji Yamaguchi, M.D., Depart-ment of Surgery I, Kyushu University Faculty of Medicine, 3-1-1 Mai-dashi, Higashi-Ku, Fukuoka 812-8582, Japan.

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