Papillary Cystic Tumor of the Pancreas

Papillary cystic tumor of the pancreas

Abstract

Two cases of papillary cystic neoplasm of the pancreas (PCNP) diagnosed and treated in Jamaica are presented. Complete excision of PCNP cures the majority of patients. Residual or advanced tumor is treated with surgery, radiotherapy and hormonal therapy.

Introduction

Papillary cystic neoplasm of the pancreas (PCNP) is a recently described exocrine pancreatic tumor. It has excellent prognosis and affects mainly young women (Compagno et al 1979; Sanfey et al 1983; Bombi et al 1984; Kaufman et al 1986; Zinner et al 1991). Less than 100 cases are reported in the English literature. PCNP was diagnosed in two patients who had resection of pancreatic tumors at the University Hospital of the West Indies, Jamaica.

Case I

S.A., a thirty-year-old lady, gave a two-year history of a painful abdominal mass. On physical examination she was anicteric and had a right upper quadrant abdominal mass. Her hematological and chemical investigations were normal. Barium meal examination demonstrated a widened duodenal ‘C’ loop. Ultrasonography and computed tomography showed an 11 cm solid and cystic mass in the head of the pancreas. Fine needle aspiration done under sonographic guidance was not diagnostic. At laparotomy no metastases were identified and a proximal pancreaticoduodenectomy was performed. Three years and seven months after surgery there was no sonographic evidence of tumor recurrence or metastases.

Histopathological examination of the tumor revealed features of PCNP (Fig. 1). The tumor was composed of cuboidal cells with eosinophilic cytoplasm, rounded clear nuclei and small nucleoli. There was central necrosis but peripheral areas showed hemorrhagic cyst-like spaces with papillary protrusions. Other areas were solid with small interspersed vascular channels presenting a pseudo-rosette pattern. Elsewhere there were cystic spaces containing mucinous material. The tumor was limited by a fibrous capsule that had focal invasion but no complete capsular penetration.

Case II

M.D., a thirty-year-old lady, was referred from a neighboring Caribbean island with a one-year history of epigastric pain. Physical examination revealed no abnormality. Hematological and chemical investigations were all normal. Ultrasonography identified a 7- cm mass with solid and cystic areas in the head of the pancreas. Computed tomography showed the cyst to be thick-walled with no evidence of peripancreatic infiltration or intra-abdominal metastases (Fig. 2). Ultrasound-guided fine needle aspiration was not diagnostic. At laparotomy a proximal pancreaticoduodenectomy was performed. Convalescence was uncomplicated allowing the patient early return to her island home.

Histopathological examination of the pancreatic mass showed a thick-walled cystic lesion. The cyst content was necrotic debris and the cyst wall had insular nests of round to ovoid cells with clear cytoplasm. The cells were in sheets or papillary configurations with fibrovascular stalks. Some stalks contained foam cells while others showed mucinous degeneration. These features were those of PCNP.

Discussion

PCNP is diagnosed in less than 1% of pancreatic resection specimens (Sclafani et al 1991; St mmer et al 1991). It affects primarily young women (Komorn et al 1986; Rustin et al 1986) with an average age of 25 years (St mmer et al 1991). Its predilection for females is related to the presence of estrogen and progesterone receptors on the tumor cells (Ladanyi et al 1987; Carbone et al 1989; St mmer et al 1991).

With increased recognition of PCNP, the tumor is now shown to be evenly distributed over head, body and tail of pancreas (Sclafani et al 1991; St mmer et al 1991). Although histogenesis of the tumor remains controversial, immunohistochemical evidence suggests an origin from a totipotential microductular or centroacinar cell allowing ductal, acinar and endocrine differentiation of the tumor cell (Compagno et al 1979; Schlosnagle and Campbell 1981; Ladanyi et al 1987; Matsunou and Konishi 1990; Matsunou et al 1990; Zinner et al 1990; St mmer et al 1991).

The tumor has a growth pattern that is extrapancreatic. It is contained by a fibrovascular capsule. It receives its blood supply from pancreatic vessels (Sanchez et al 1990). Slow growth over years results in a large tumor, occasionally with dystrophic calcification. Intratumoral perivascular sclerosis results in hypoxia which in turn produces cystic areas of necrosis and hemorrhage (Sheen et al 1988; St mmer et al 1991). The tumor therefore displays solid, pseudopapillary and cystic areas (Cappellari et al 1990). Solid areas of tumor have cells in sheets or nests with pseudopapillary and pseudoglandular patterns (Yagihashi et al 1988; Matsunou et al 1990). Within papillary areas, the cells appear as a pseudostratified columnar epithelium covering fine fibrovascular stalks (Compagno et al 1979; Sanfey et al 1983; Kuo et al 1984; Schlosnagle and Campbell 1981; St mmer et al 1991). Occasional histiocytes, foam cells, cholesterol clefts and giant cells are seen in the stroma (Matsunou and Konishi 1990, Yamaguchi et al 1990, St mmer et al 1991).

The tumor has low malignant potential (Compagno et al 1979; Choi et al 1988; Cappellari et al 1990; Matsunou and Konishi 1990). Capsular invasion but no penetration is usually reported (Schlosnagle and Campbell 1981; Sanbey et al 1983; Ladanyi et al 1987; Matsunou et al 1990). Local invasion is found in 16% of tumors (Sclafani et al 1991). Large tumors in older patients are more likely to have metastases (Matsunou and Konishi 1990). A more recently described malignant variety of PCNP is the solid infiltrating variety (SIV) with areas of calcification and ossification (Matsunou et al 1990). It demonstrates capsular penetration, vascular invasion, tissue infiltration and metastases. Reported sites of metastases of PCNP are lymph nodes, liver, lungs and skin (Rustin et al 1986; Zinner et al 1990; Sclafani et al 1991; St mmer et al 1991). Liver metastases occur in 7% of cases (Sclafani et al 1991).

Microscopically the cells of PCNP are polygonal with eosinophilic cytoplasm and round to oval nuclei. There are few mitotic figures and little atypism (Matsunou et al 1990). On electron microscopy mitochondria and Golgi complexes are numerous; cytoplasmic annular lamellate bodies are common; endoplasmic reticulum is occasionally in an onion skin-like arrangement and rough endoplasmic reticulum is often seen. Zymogen granules, lysozomes and dense core neurosecretory type granules have been identified (Schlosnagle and Campbell 1981; Bombi et al 1984; Ladanyi et al 1987; Matsunou et al 1990; St mmer et al 1991). Ruptured granules are found in the malignant variety. The nuclear membrane has characteristic indentations and nucleoli are generally small. Nuclear chromatin is usually condensed as delicate strands. Other features of PCNP include intercellular canaliculi with microvilli and occasional desmosomes (Hamoudi et al 1970). Ruptured basal lamina is described. Cellular atypism, mononucleated and multinucleated tumor giant cells, nuclear pleomorphism, nuclear hyperchromasia, and mitotic figures allow identification of aggressive, malignant tumors. Tumors with metastases demonstrate malignant features primarily in their metastases (Cappellari et al 1990) and the prediction of metastasis or recurrence appears to be impossible from histologic evaluation (Matsunou and Konishi 1990). Immunohistochemical techniques identify 1-antitrypsin, 1-antichymotrypsin, phospholipase A2, P-amylase, neuron-specific enolase, somatostatin, insulin and synaptophysin (Bombi et al 1984; Gould et al 1987; Ladanyi et al 1987; Morohoshi et al 1987; Yagihashi et al 1988; Matsunou and Konishi 1990; Matsunou et al 1990; Zinner et al 1990; Sclafani et al 1991; St mmer et al 1991).

Clinically the low malignant potential of PCNP allows the asymptomatic presentation of large pancreatic masses. The average size of tumors is 10 cms (Sclafani et al 1991; St mmer et al 1991). Case I had a tumor 11 cms and Case II 7 cms in size.

Some patients present with vague or nonspecific gastrointestinal symptoms while others report abdominal pain (Cases I&II). Many patients present with an abdominal mass. Only a few patients present with the incidental finding of calcifications on plain radiography. Hemoperitoneum is a rare presentation. Jaundice is also rare even with tumor in the head of the pancreas (Bombi et al 1984; Sanchez et al 1990; Sclafani et al 1991).

Ultrasonography and computed tomography show the solid and cystic nature of PCNP (Cases I&II) and identify calcifications and metastases. Calcifications are infrequently found lining the cystic wall (Phillips et al 1991). Furthermore, computed tomography confirms the site of tumor origin (Cases I&II) and demonstrates tumor infiltration (Balthazar et al 1984; Choi et al 1988; Friedman and Edmond 1989; Sanchez et al 1990; Yamaguchi et al 1990). Barium meal examination reveals the extra-gastrointestinal origin of PCNP with widening of the duodenal “C” loop (Case I). Diagnostic biopsy features of PCNP are marked cellularity and slender, straight or branching papillary fragments covered by one or two layers of neoplastic cells and perivascular myxoid material. Nuclear folds or grooves are characteristic. Similar fine needle aspiration cytologic features are described by Cappellari et al (1990), Yamaguchi et al (1990) and Zinner et al (1990). Angiography may display abnormal vasculature and ERCP may show a displaced or obstructed pancreatic duct. Without a preoperative diagnosis an exploratory laparotomy with biopsy for frozen-section examination is performed.

Treatment of PCNP is surgical extirpation and cure is expected with complete excision. After surgery local tumor recurrence and metastases are unusual (Compagno et al 1979; Kaufman et al 1986; Rustin et al 1986). Since long-term survival is achieved even with the more malignant variant, recurrent tumor is re-excised and tumor invading vital structures has cytoreduction followed by irradiation of residual tumor (Yagihashi et al 1988). Liver metastases are resected (Rustin et al 1986). Unresectable tumor and metastases are radiated primarily (Sanfey et al 1983; Balthazar et al 1984; Kuo et al 1984; Fried et al 1985; Zinner et al 1990). Alternatively or additionally, patients with advanced tumor are treated with the anti-estrogen tamoxifen (Sclafani et al 1991). Overall prognosis is excellent with only three deaths due to PCNP reported (Matsunou and Konishi 1990; Zinner et al 1990).

Firstly, two case histories of patients who had pancreaticoduodenectomy for PCNP are presented. Then the clinicopathological features of PCNP are described and the low malignant potential of the tumor is emphasized. The clinical diagnosis is to be entertained in young women with large solid and cystic pancreatic masses (Zinner et al 1990; Phillips et al 1991). Importantly surgical excision achieves cure and this justifies a thorough approach to the investigation and pathological examination for accurate diagnosis of PCNP (Komorn et al 1986; Sanchez et al 1990). Finally, cases of PCNP are followed-up indefinitely as recurrent or advanced tumor has further excision, radiation or hormonal therapy.