As noted, IPMNs represent a continuum of disease from benign to malignant. In a large series of

resected IPMNs from the Johns Hopkins Hospital,10 the prognosis for the benign forms of the disease

appears to be significantly better than for invasive IPMNs with 1-, 2-, and 5-year actuarial survivals of

97%, 94%, and 77%, respectively. Although invasive IPMNs are associated with disease progression and

death, the prognosis remains markedly better than for invasive ductal carcinoma of the pancreas with

survivals of 72%, 58%, and 43% at 1, 2, and 5 years, respectively. It is unclear if this fact is due to

earlier presentation or differences in tumor biology.

DIAGNOSIS

Table 55-5 Comparison between Mucinous Cystic Neoplasm (MCN) and

Intraductal Papillary Mucinous Neoplasm (IPMN)

2 International consensus guidelines for the management of IPMNs have been developed.11 CT or

MRI with MRCP is recommended for imaging IPMNs. IPMNs are classified as having either “high-risk

stigmata” or “worrisome features.” High-risk stigmata include obstructive jaundice in the setting of a

cyst in the head of the pancreas, a main duct >10 mm, or a cyst with a solid enhancing component in

the wall. Worrisome features include cyst >3 cm, thickened enhanced cyst walls, nonenhanced mural

nodules, main duct size between 5 and 9 mm, abrupt change in the MPD caliber with distal pancreatic

atrophy, and lymphadenopathy. All cysts with “worrisome features” and cysts of >3 cm without

“worrisome features” should undergo endoscopic ultrasonography (EUS), and all cysts with “high-risk

stigmata” should be resected. If no “worrisome features” are present, no further initial work-up is

recommended, although surveillance is still required (Algorithm 55-1).

The goal of surgical therapy for IPMNs should be a complete surgical resection yielding negative

margins for all invasive and noninvasive disease. Unlike those patients with completely resected

noninvasive MCNs (who are routinely cured), patients with completely resected noninvasive IPMNs

should undergo careful follow-up and surveillance for the development of recurrent disease.

Furthermore, patients with resected invasive IPMNs should also undergo careful follow-up and

surveillance as they, too, remain at risk for the development of recurrent disease.

Solid-Pseudopapillary Tumor

Solid-pseudopapillary tumors (SPTs), also termed solid and cystic tumors, papillary cystic tumors,

Hamoudi tumors, and Frantz tumor occur primarily in women in their third to fourth decades of life.

Grossly, the masses range from 5 to 15 cm in diameter. Radiologically, they present as a welldemarcated heterogeneous mass with solid and cystic components, with a peripheral capsule which

rarely shows calcification. EUS-guided fine needle aspiration (FNA) or core biopsy is often diagnostic,

showing uniform cells forming microadenoid structures, branching, and papillary clusters with delicate

fibrovascular cores. Most SPTs exhibit a benign behavior, and even the less than 20% that have vascular

or perineural invasion, lymph node involvement or liver metastases can have a very indolent course.

The overall 5-year survival is close to 97% in patients undergoing surgical resection.

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Algorithm 55-1. International consensus guidelines for the management of IPMNs. From Tanaka M, Fernandez-del Castillo C,

Adsay V, et al. International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatology

2012;12:183–197.

CLINICOPATHOLOGIC STAGING

Accurate pathologic staging of pancreatic cancer is important for providing prognostic information to

patients and for comparing the results of various therapeutic trials. The American Joint Committee on

Cancer (AJCC) staging for pancreatic cancer is shown in Table 55-6. This system, based on the TNM

classification, takes into account the extent of the primary tumor (T), the presence or absence of

regional lymph node involvement (N), and the presence or absence of distant metastatic disease (M).

DIAGNOSIS

Clinical Presentation

Many of the difficulties associated with the management of pancreatic cancer result from our inability

to make the diagnosis at an early stage. The early symptoms of pancreatic cancer include anorexia,

weight loss, abdominal discomfort, and nausea. Unfortunately, the nonspecific nature of these

symptoms often leads to a delay in the diagnosis. Specific symptoms usually develop only after invasion

or obstruction of nearby structures has occurred. Most pancreatic cancers arise in the head of the

pancreas, and obstruction of the intrapancreatic portion of the common bile duct leads to progressive

jaundice, acholic stools, darkening of the urine, and pruritus. Pain is a common symptom of pancreatic

cancer. The pain usually starts as vague upper abdominal or back pain that is often ignored by the

patient or attributed to some other cause. It is usually worse in the supine position and is often relieved

by leaning forward. Pain may be caused by invasion of the tumor into the splanchnic plexus and

retroperitoneum, and by obstruction of the pancreatic duct. Other digestive symptoms are also common

in pancreatic cancer (Table 55-7).

Occasionally, pancreatic cancer may be discovered in an unusual manner. The onset of diabetes may

be the first clinical feature in 10% to 15% of patients. An episode of acute pancreatitis may also be the

initial presentation of pancreatic cancer if the tumor partially obstructs the pancreatic duct. It is

important to consider a pancreatic cancer in patients presenting with acute pancreatitis, especially those

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without an obvious cause for their pancreatitis (alcohol or gallstones).

The most common physical finding at the initial presentation is jaundice (Table 55-8). Hepatomegaly

and a palpable gallbladder may be present in some patients. In cases of advanced disease, cachexia,

muscle wasting, or a nodular liver, consistent with metastatic disease, may be evident. Other physical

findings in patients with disseminated cancer include left supraclavicular adenopathy (Virchow node),

periumbilical adenopathy (Sister Mary Joseph node), and pelvic drop metastases (Blumer shelf). Ascites

can be present in 15% of patients.

STAGING

Table 55-6 American Joint Committee on Cancer Staging of Pancreatic Cancer,

7th Edition

DIAGNOSIS

Table 55-7 Symptoms of Pancreatic Cancer

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Laboratory Studies

In patients with cancer of the head of the pancreas, laboratory studies usually reveal a significant

increase in serum total bilirubin, alkaline phosphatase, and γ-glutamyl transferase indicating bile duct

obstruction. The transaminases can also be elevated but usually not to the same extent as the alkaline

phosphatase. In patients with localized cancer of the body and tail of the pancreas, laboratory values are

frequently normal early in the course. Patients with pancreatic cancer may also demonstrate a

normochromic anemia and hypoalbuminemia secondary to the nutritional consequences of the disease.

In patients with jaundice, the prothrombin time can be abnormally prolonged. This usually is an

indication of biliary obstruction, which prevents bile from entering the gastrointestinal tract and leads

to malabsorption of fat-soluble vitamins and decreased hepatic production of vitamin K–dependent

clotting factors. The prothrombin time can usually be normalized by the administration of parenteral

vitamin K. Serum amylase and lipase levels are usually normal in patients with pancreatic cancer.

A wide variety of serum tumor markers have been proposed for use in the diagnosis and follow-up of

patients with pancreatic cancer. The most extensively studied of these is CA 19–9, a Lewis blood grouprelated mucin glycoprotein. Approximately 5% of the population lacks the Lewis gene and therefore

cannot produce CA 19–9. When a normal upper limit of 37 U/mL is used, the accuracy of the CA 19–9

level in identifying patients with pancreatic adenocarcinoma is only about 80%. When a higher cutoff

value of more than 90 U/mL is used, the accuracy improves to 85%, and increasing the cutoff value to

200 U/mL increases the accuracy to 95%.12 The combined use of CA 19–9 and ultrasonography, CT, or

ERCP can improve the accuracy of the individual tests, so that the combined accuracy approaches 100%

for the diagnosis of pancreatic cancer. Levels of CA 19–9 have also been correlated with prognosis and

tumor recurrence. In general, higher CA 19–9 values before surgery indicate an increased size of the

primary tumor and increased rate of unresectability. In addition, the CA 19–9 level has been used to

monitor the results of neoadjuvant and adjuvant chemoradiation therapy in patients. Increasing CA 19–9

levels usually indicate recurrence or progression of disease, whereas stable or declining levels indicate a

stable tumor burden, absence of recurrence on imaging studies, and an improved prognosis.

DIAGNOSIS

Table 55-8 Signs of Pancreatic Cancer

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Radiologic Investigations

Radiologic imaging plays a crucial role in the diagnosis, staging, and follow-up of patients with

pancreatic cancer. In addition to identifying the primary tumor, the goals of imaging include the

assessment of local and regional invasion, evaluation of lymph nodes and vascular structures,

identification of distant metastatic disease, and the determination of tumor resectability.

Ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI) are all useful

noninvasive tests in the patient suspected of having a pancreatic cancer.

Transabdominal ultrasonography (US) will reveal a pancreatic mass in 60% to 70% of patients with

cancer. Pancreatic cancer typically appears as a hypoechoic mass on US. Ultrasonography may also

demonstrate dilated intrahepatic and extrahepatic bile ducts, liver metastases, pancreatic masses,

ascites, and enlarged peripancreatic lymph nodes. Because helical CT is just as sensitive as

ultrasonography and provides more complete information about surrounding structures and the local

and distant extent of the disease, transabdominal ultrasonography has been largely replaced by CT.

Figure 55-3. Computed tomogram of the abdomen of a patient with adenocarcinoma of the pancreas. A: The obstructed and

dilated common bile duct (light arrow) and pancreatic duct (dark arrow) can be seen. In the adjacent cross section B, a large mass is

present in the head of the pancreas (arrow).

3 Computed tomography (CT) scanning is currently the preferred noninvasive imaging test for the

diagnosis of pancreatic cancer. Pancreas protocol CT should be performed with rapid injection of

intravenous iodinated contrast. Slices should be reconstructed at less than or equal to 3 mm with

overlap. At least two postcontrast acquisitions, in the late arterial (or parenchymal) and venous phases

are useful to assess the arteries (celiac, common hepatic, peripancreatic, and superior mesenteric

arteries) and veins (portal, splenic, and superior mesenteric veins). The parenchymal phase best shows

the tumor as an ill-defined hypodense mass in the pancreatic parenchyma (Fig. 55-3), while the venous

phase is best for detecting liver metastases. Neutral enteral contrast such as water should be given, since

this allows for better identification of the duodenal wall and results in artifact-free reformations. In

many centers, no oral contrast is used. Coronal and sagittal reformations in both arterial and venous

phases increase the sensitivity for determining local invasion. In addition to determining the primary

tumor size, CT is used to evaluate invasion into local structures or metastatic disease.

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