Meredith McMahon, Medical Student IV; Cecylia Mizera, Surgery Resident, Department of Surgery; Russell Brown, Associate Professor, Department of GI Medicine; N. Joseph Espat, Associate Professor, Department of Hepatobiliary and Oncology Surgery, University of Illinois at Chicago, Chicago, IL
Meredith McMahon, BS
Medical Student IV
Cecylia Mizera, MD
Department of Surgery
Russell Brown, MD
Department of GI Medicine
N. Joseph Espat, MD, MS
Department of Hepatobiliary and Oncology Surgery
University of Illinois at Chicago
Intraductal papillary mucinous neoplasms (IPMNs) are the most commonly resected cystic tumors of the pancreas. These tumors are characterized by the endoscopic triad of a bulging ampulla of Vater, mucin secretion, and a dilated pancreatic duct. The present consensus is that IPMN represents a premalignant lesion, with approximately half of all cases found to have invasive components at the time of resection. The authors report a case of an IPMN and discuss the prognostic factors and management strategies regarding these lesions.
Cystic neoplasms of the pancreas account for fewer than 10% of pancreatic neoplasms, with the most commonly identified subtypes being serous cystadenomas (32% to 39%), mucinous cystic neoplasms (10% to 45%), intraductal papillary mucinous neoplasms (IPMN; 21% to 33%), and solid pseudopapillary neoplasms (less than 10%).1-3 Accurate delineation of the type of cystic neoplasm is necessary from a prognostic and management standpoint, because more than one third of these lesions are discovered incidentally and only mucinous cystic neoplasms and IPMNs have malignant potential.1 Despite advances in imaging techniques, such as the advent of computed tomography (CT) scanning and magnetic resonance imaging (MRI), there is still limited ability to preoperatively differentiate between these lesions and determine whether malignant disease is present.4,5 While additional diagnostic modalities, such as endoscopic retrograde cholangiopancreatography (ERCP), endoscopic ultrasonography, and cystic fluid aspiration analysis, can provide a more detailed morphology of pancreatic lesions, these modalities also lack the ability to define them accurately. Consequently, surgical resection is recommended for any potentially malignant cystic lesion and remains the only means of obtaining a definitive histopathological diagnosis.
IPMNs were first described by Ohhashi and colleagues in the Japanese literature in 1982.6 The disease, however, was not histologically categorized by the World Health Organization (WHO) until 1996.7 Since their categorization, IPMNs have been increasingly recognized and are now the most commonly resected cystic tumor of the pancreas. These neoplasms are composed of columnar, mucin-containing epithelium, with or without papillary projections, and are characterized by cystic dilatation of either the main or side branches of the pancreatic duct.8 IPMNs are historically characterized by the endoscopic triad of a bulging ampulla of Vater, mucin secretion, and a dilated pancreatic duct. Histologically, the WHO divides these tumors into three groups: benign (adenomatous), borderline (moderate dysplasia), and malignant (carcinoma in situ and invasive cancer).9,10 Approximately 50% of resected cases have progressed to invasive carcinoma, leading to the current consensus that IPMN represents a premalignant lesion.11 Because of their malignant potential, IPMNs should be surgically resected, with a goal of removing all disease. Usually this can be achieved with a partial pancreatectomy. Patients with IPMNs will benefit from resection for three reasons: the presence of invasion is not known until after resection; if found to be benign, the risk of malignant degeneration is avoided; and, if found to be invasive, the best chance for cure begins with resection.8
A 63-year-old man with a distant history of alcohol abuse and chronic pancreatitis came to our institution because of epigastric abdominal discomfort and a weight loss of approximately 20 lb. He had been evaluated for pancreatitis 7 years earlier, and ERCP at that time showed a small stricture with associated dilation of the distal pancreatic duct. Brushings of the duct were negative for malignancy. His pancreatitis had resolved completely, and he was started on pancreatic enzymes to counter weight loss. He sought no further medical care, because his symptoms had resolved.
On physical examination, the patient was thin and had a soft, scaphoid abdomen with a palpable, 8- to 10-cm mass in the mid-epigastrium. He was evaluated by CT scanning, which demonstrated a markedly dilated pancreatic duct containing a marble-sized concretion of what appeared to be calcified mucin (Figure 1). There were also multiple fluid collections associated with the body and tail of the pancreas. The radiographic appearance of the pancreas demonstrated a complex cystic mass orginating from the mid-portion of the body and involving the tail. The mass abutted the splenic hilum and stomach and was draped by the transverse mesocolon. Although the superior mesenteric artery and portal vein appeared to be grossly uninvolved with the mass, there was distortion of the surrounding structures, limiting our ability to ensure resectability. There did appear to be a surgical plane between the splenic vein and the left renal vein. ERCP demonstrated a wide-open ampulla of Vater and mucus and debris emanating from within the massively dilated pancreatic duct (Figure 2). Mucus was collected for cytologic evaluation, which revealed ductal epithelial cells in a papillary configuration, raising the suspicion of an IPMN. Endoscopic ultrasonography was performed, identifying a dilated pancreatic duct with no evidence of mural nodules, but was unable to further define the internal structure of the duct.
Given the appearance of the pancreas, the cytologic diagnosis, and the patient’s history of chronic pancreatitis, we were almost certain the lesion was an IPMN. With the patient’s recent recurrence of symptoms and weight loss, the concern was that pancreatic adenocarcinoma was already present.
A staging laparoscopy to evaluate for occult metastatic disease was negative. Laparotomy was performed, which immediately revealed the bulk of the mass. The pancreatic duct was remarkable for a diameter greater than 1 cm and contained the solid, marble-sized ball of calcified mucin that was previously identified on CT scanning (Figure 3). The surgical plane identified on preoperative CT scanning was developed, and the pancreas was mobilized and resected up to the neck to remove all visible disease. As previously suspected, the superior mesenteric artery was grossly uninvolved in the mass. The duct was irrigated free of inspissated mucus, and an antegrade pancreatogram demonstrated even filling of the pancreatic duct, retrograde filling of the common bile duct, and prompt emptying into the duodenum.
A postoperative CT scan demonstrated marked improvement at the previous location of the tumor. Pathology evaluation showed that the resected specimen and lymph nodes were negative for malignancy. The patient was discharged from the hospital on postoperative day 5. He received pancreatic enzyme replacement therapy, which allowed him to tolerate a regular diet. At 6-month follow-up, there was no radiographic evidence of recurrence, and the patient had gained 10 lb. He had also resumed his normal daily activities, including employment as a carpenter.
Before the WHO recognized IPMNs as an entity in 1996, they were reported under a variety of names in the literature, including villous adenomas or intraductal papillary neoplasms, mucin-producing tumors or intraductal mucin-hypersecreting tumors, and mucinous duct ectasia or ductectatic mucinous cystic neoplasms. The histologic overlap of these entities prompted the development of a single category to describe these lesions.12 Since 1996, much has been learned about IPMNs regarding diagnosis, course of the disease, and management; however, determining malignant degeneration preoperatively is still limited, and the general consensus is that all patients with IPMNs who are surgical candidates should undergo resection to avoid the risk of malignancy.
Several factors have been identified as indicators for the development of malignant disease, some of which were identified in our case. It is commonly thought that malignant tumors are larger than benign ones. In Navarro and colleagues’ retrospective study, malignant tumors averaged 5.3 cm versus 2.8 cm for benign lesions ( < 0.0002).13 Our patient’s tumor was large, measuring 8 x 7.5 x 5.8 cm, but it was benign. The study by Navarro and colleagues also showed that men are more likely to have benign tumors than women and that benign tumors are more likely to be located in the body or tail of the pancreas and more likely to present with pancreatitis. All of these findings are consistent with our case. Gross mucus observed on endoscopy, as was found in our patient’s case, also has been associated with benign disease.11 Another interesting aspect of our case is that 7 years elapsed between initial presentation and surgical resection of the benign lesion, whereas several authors have noted a lag time of approximately 5 years between presentation of benign IPMN and development of invasive carcinoma.11
Factors identified as predictors of malignant disease include the presence of mural nodules, dilatation of the main pancreatic duct greater than 15 mm, main pancreatic duct tumor origin as opposed to tumors arising from pancreatic duct side branches, advancing age, steatorrhea, recent onset of or deterioration from diabetes, solid component on imaging studies, jaundice, and elevated carcinoembryonic antigen in pure pancreatic juice.11,14-17 These characteristics, however, are not conclusive indicators of malignancy, and their value in making management decisions yet to be seen.
When formulating a plan for postoperative surveillance, clinicians should keep in mind that recurrence rates following resection of noninvasive IPMNs have been reported as ranging from 0% to 8%. Whether these recurrences are due to lesions that are missed at the time of initial resection or are new lesions that developed after resection is unknown.8 While there are no specific guidelines for postoperative surveillance, recommendations include semiannual to annual CT scans and office visits every 3 months for 2 years and every 6 months thereafter.8,11 Our patient’s follow-up will be determined based on his symptoms and routine CT scans at 6 months and 1 year.
IPMN represents a spectrum of disease from the benign to aggressively malignant. For patients demonstrating clinical or imaging hallmarks of IPMN, resection is recommended to ascertain the exact diagnosis (benign versus malignant) and to preclude progression to adenocarcinoma.
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