Ampullary Carcinoma Workup

Updated: Aug 24, 2022
  • Author: Ayana Allard-Picou, MD, FACS; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
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Approach Considerations

In the workup of ampullary carcinoma, diagnostic modalties of choice are as follows [33] :

  • Endoscopic ultrasound (EUS)
  • Endoscopic retrograde cholangiopancreatography (ERCP)
  • Fine-needle aspiration cytology (FNAC)

Staging of ampullary carcinoma requires computed tomography (CT) of the chest, abdomen, and pelvis. Endoscopic ampullectomy may be part of the diagnostic process and may be curative in highly selected cases (eg, early ampullary carcinoma, in situ carcinoma, low-grade dysplasia). [33]


Laboratory Studies

Routine laboratory studies include the following:

  • Complete blood cell count
  • Electrolyte panel
  • Liver function studies (prothrombin time, bilirubin [direct and indirect], transaminases, alkaline phosphatase)
  • Cancer antigen 19-9 (CA 19-9)
  • Carcinoembryonic antigen (CEA)

A rising bilirubin level due to obstructive jaundice often is the sole presenting sign.

CA 19-9 is a serum tumor marker that is often elevated in pancreatic malignancies and might have a role in assessing response to therapy, predicting tumor recurrence, or both.

CEA is another nonspecific tumor marker that sometimes is elevated in pancreatic malignancies. Measurement of CEA might have a role in assessing response to treatment or predicting tumor recurrence. Because CEA also is elevated in patients with other gastrointestinal malignancies (in particular, colon and rectal cancer), the possibility of a second primary tumor needs to be excluded in these patients.


Imaging Studies


Abdominal ultrasound is the initial study to evaluate the common bile duct or pancreatic ducts. Dilatation of these ducts essentially is diagnostic for extrahepatic obstruction and can explain abdominal pain, even in patients with localized and noninvasive disease. However, 10-15% of patients with normal common bile duct findings on ultrasonography demonstrate extrahepatic biliary obstruction on a computed tomography (CT) scan. Both ultrasound and CT can help reveal metastatic disease in the liver or regional lymph nodes.

Computed tomography

Obtain a CT scan image to evaluate the local region of interest (abdomen, pelvis, or both) and evaluate for possible metastases. CT scan often demonstrates a mass but is not helpful in differentiating ampullary carcinoma from tumors of the head of the pancreas or periampullary region. If the lesion is smaller than 2 cm, pancreatic or bile duct dilation might be the only abnormalities noted on CT scan. Such findings are highly suggestive of pancreatic malignancy and require further evaluation, usually with endoscopic retrograde cholangiopancreatography (ERCP).

Dynamic CT scanning (ie, high-speed scans obtained during rapid intravenous administration of iodinated contrast material) can reveal tumor involvement of the vasculature. Some centers still rely on angiography to help identify patients with potentially resectable disease.

Ampullary multidetector computed tomography (MDCT) can be useful to differentiate pancreatobiliary and intestinal subtypes of ampullary adenocarcinoma preoperatively, provided the duodenum is optimally distended at imaging. [34]

Endoscopic ultrasound

Endoscopic ultrasound (EUS) is often used as a part of the local staging. EUS allows visualization of the duodenal wall, ampulla, bile duct, and pancreatic duct, as well as regional lymph nodes. EUS can facilitate biopsy of the tumor via fine needle aspiration (FNA) and is also used to evaluate regional lymph nodes for lymph node metastasis. Lastly, EUS allows visualization of celiac and superior mesenteric vessels to evaluate for vascular invasion.

In one series comparing the accuracy of EUS and CT for staging of ampullary cancer, EUS demonstrated a better sensitivity, specificity, positive predictive value, and negative predictive value stage for stage. [35]

Intraductal ultrasonography has been reported by some to more accurately visualize tumor infiltration into the duodenal wall and ampulla.

Endoscopic retrograde cholangiopancreatography

Obtain ERCP to evaluate the ductal architecture further. The following findings on ERCP suggest pancreatic cancer:

  • Irregular pancreatic duct narrowing
  • Displacement of the main pancreatic duct
  • Destruction or displacement of the side branches of the duct
  • Pooling of contrast material in necrotic areas of tumor

Chest radiograph

Obtain a chest x-ray film to complete the workup (ie, for staging purposes).

Positron emission tomography

Positron emission tomography (PET) or PET-CT scans have been widely adopted in the author's clinic as a means of imaging the metabolic activity of a particular tumor. PET or PET-CT scans can detect metastases that are too small to be reliably detected on a CT scan.



Over the years, multiple systems for staging this tumor have been proposed. Martin proposed a 4-stage system, as follows:

  • Stage I - Vegetating tumor limited to the epithelium with no involvement of the sphincter of Oddi

  • Stage II - Tumor localized in the duodenal submucosa without involvement of the duodenal muscularis propria but possible involvement of the sphincter of Oddi

  • Stage III - Tumor of the duodenal muscularis propria

  • Stage IV - Tumor of the periduodenal area or pancreas, with proximal or distal lymph node involvement

The classification system of Yamaguchi and Enjoji is similar to the Martin classification. [36]

Talbot et al devised a system that scored tumors according to the degree of infiltration (from 1-4 according to increasing infiltration) and according to tumor differentiation (from 1-3 for well, moderately, and poorly differentiated tumors), the sum of which separated the patients into 2 groups (scores 2-4 and scores 5-7). [37]

The currently accepted American Joint Committee on Cancer staging system (8th edition) for ampullary carcinoma emphasizes the importance of pancreatic invasion and lymph node metastases (see below and see Table 1, below). Size has little impact on tumor stage. The definition of primary tumor (T), regional lymph node (N), and remote metastases (M) for classification and staging of cancer of the ampulla of Vater is provided below. [38]

Primary tumor is defined as follows [38] :

  • TX – Primary tumor cannot be assessed
  • T0 – No evidence of primary tumor
  • Tis – Carcinoma in situ
  • T1a – Tumor limited to ampulla of Vater or sphincter of Oddi
  • T1b – Tumor invades beyond the sphincter of Oddi (perisphincteric invasion) and/or into the duodenal submucosa
  • T2 – Tumor invades duodenal wal
  • T3a – Tumor invades pancreas (up to 0.5 cm)
  • T3b – Tumor extends more than 0.5 cm into the pancreas, or extends into peripancreatic tissue or duodenal serosa without involvement of the celiac axis or superior mesenteric artery
  • T4 – Tumor involves the celiac axis, superior mesenteric artery, and/or common hepatic artery, irrespective of size

Regional lymph nodes are defined as follows:

  • NX – Regional lymph nodes cannot be assessed
  • N0 – No regional lymph node metastases
  • N1 – Metastasis to one to three regional lymph nodes
  • N2 – Metastasis to four or more regional lymph nodes

Distant metastases are defined as follows:

  • MX – Presence of distant metastases cannot be assessed
  • M0 – No distant metastases
  • M1 – Distant metastases

Table 2. Staging of Ampullary Cancers by the TNM System. [38] (Open Table in a new window)





Stage 0




Stage I




Stage IB




Stage IIA




Stage IIB




Stage IIIA




Stage IIIB


Any T

Any N




Stage IV

Any T

Any N