What are the other Names for this Condition? (Also known as/Synonyms)

• Adenoma of Ampulla
• Adenoma of Ampulla of Vater
• Intestinal-type Adenoma of Ampulla of Vater

What is Ampullary Adenoma? (Definition/Background Information)

• Ampullary Adenomas are benign epithelial tumors arising in the ampulla of Vater. The ampulla of Vater is the region around the mouth where the common bile duct and pancreatic duct discharge into the duodenum, which is the upper part of the small intestine
• Ampullary Adenomas are generally considered to be pre-malignant tumors, meaning that these tumors may turn malignant with time. If left untreated, they can develop into small bowel cancer
• Adenomas of Ampulla of Vater are similar to adenomas seen in the small or large bowel. Of the tumors that arise in the ampulla, Ampullary Adenomas are the most common type
• They consists of 3 main types:
  • Tubular Adenoma of Ampulla of Vater
  • Villous Adenoma of Ampulla of Vater
  • Tubulovillous Adenoma of Ampulla of Vater (or mixed pattern, containing both tubular and villous histological features)
• The cause of formation of Ampullary Adenomas is reportedly due to genetic factors. Most adenomas are observed to form sporadically and are generally difficult to diagnose. Some are associated with a variety of syndromes, such as familial adenomatous polyposis or Gardner syndrome
• The signs and symptoms may include obstructive jaundice, abdominal pain, fatigue, and unexplained weight loss. Complications, such as formation of gallstones, or compression of adjacent structures from large-sized tumors may occur
• A majority of Ampullary Adenomas are detected incidentally. The mainstay of treatment is surgical excision of the tumor, which may be performed via an endoscopic procedure or through surgical resection
• If Ampullary Adenomas are detected early enough, they can be removed and the risk of developing into a cancer is low. If, however, they have time to proliferate and grow, the risk for cancer may be high

Who gets Ampullary Adenoma? (Age and Sex Distribution)

• Ampullary Adenoma (sporadic tumors) typically occurs in middle-age to elderly individuals. It is noted in adults between ages 33 and 81 years; average age 61 years
• Both males and females are known to develop these tumors, although a female predominance is noted (female-male ratio is 5:2)
• In the background of familial adenomatous polyposis, the adenomas are seen in younger individuals with 41 years being the average age of presentation. Also, in such cases, no gender preference is noted (female-male ratio is 1:1)
• No racial, ethnic, or geographical predominance is generally noted

What are the Risk Factors for Ampullary Adenoma? (Predisposing Factors)

Common risk factors of Ampullary Adenoma include:

• Aging: Elderly individuals have a higher risk for developing these tumors
• Presence of predisposing genetic conditions, such as familial adenomatous polyposis (FAP) or Gardner syndrome. It is estimated that 50-95% individuals with FAP show Adenomas of Ampulla of Vater
• A family history of Intestinal-type adenomas

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Ampullary Adenoma? (Etiology)

Ampullary Adenoma is caused by genetic mutations that lead to a condition termed dysplasia.

• Dysplasia is the phenomena of disordered growth of the epithelial lining of the small intestine. Genetic mutations lead to cell growths at abnormally high rates. This causes the cells to grow abnormally, forming the tumors characteristic of an adenoma
• Most tumors are noted to appear sporadically; while some appear in the presence of genetic disorders such as familial adenomatous polyposis (FAP) or Gardner syndrome
• The genetic mutations can be either inherited, or caused by exposure to various environmental factors
  • Inherited genetic mutations include those that result from FAP or Gardner syndrome, which are autosomal dominant conditions
  • Environmental factors that cause genetic mutations may include radiation, harmful chemicals in the air, exposure to pollutants, and other such factors

FAP or Gardner syndrome involves germline mutations on the APC gene, located on chromosome 5. In such cases, the risk of formation of adenoma is almost 100%.

• Some FAP tumors show KRAS gene mutations
• BRAF gene anomalies are rarely noted
• Adenomas with high-grade dysplasia may show mutations on TP53 gene
• In 9% of the cases, Ampullary Adenomas show genetic abnormalities such as DNA mismatch repair and/or microsatellite instability (MSI)

17% sporadic tumors show APC gene mutations; while in 40% cases, mutations in the gene KRAS are noted.

What are the Signs and Symptoms of Ampullary Adenoma?

Many Ampullary Adenomas present signs and symptoms, while some are asymptomatic and detected incidentally during an endoscopy. Most adenomatous tumors noted in the small bowel are present around the ampulla in the duodenum (over 80% of them).

The signs and symptoms of Ampullary Adenoma may include:

• Tumors at the ampulla of Vater may cause obstructive jaundice, even at small size
  • Obstruction of the bile ducts leading to jaundice also results in weight loss and pain in the abdomen
  • Yellowing of the skin and eye whites
  • It may also lead to pruritus, an intense itching sensation all over the body
• Inflammation of the pancreas (or pancreatitis) may be noted in some individuals
• Large tumors can frequently cause:
  • Abdominal (cramping) pain and discomfort
  • Swollen abdomen
  • Nausea and vomiting
• Presence of a palpable mass, when tumors are large
• Unexplained weight loss
• Narrowing of the intestine
• Tumors can be present anywhere in the ampullary region and may involve the peri-ampullary and duodenal regions too
• Most sporadic tumors are in the 1-3 cm size range and may appear as soft polyp or as a plaque
• Sometimes, the polyps develop within the common bile duct, at the mouth (called intra-ampullary tumors)
• In the context of a genetic disorder, multiple adenomatous tumors may be noted
• At detection, most tumors in FAP patients are less than 0.5 cm in size

How is Ampullary Adenoma Diagnosed?

A diagnosis of Ampullary Adenoma may include:

• Complete evaluation of family (medical) history, along with a thorough physical examination
• X-ray of the abdomen and pelvic region
• Barium enema X-ray
• Endoscopy: Capsule endoscopy is an effective tool for observing the small intestine along its entire length
• Liver function test
• Test for serum bilirubin levels
• CT or MRI scan of the abdomen and pelvic region
• Abdominal ultrasound scan
• Upper GI endoscopy: An endoscopic procedure is performed using an instrument called an endoscope, which consists of a thin tube and a camera. Using this technique, the radiologist can have a thorough examination of the insides of the gastrointestinal tract
• Endoscopic ultrasonography: During this procedure, fine needle aspiration biopsy (FNAB) can be performed on the affected area. This is good technique for tumor detection including tumor invasion parameters, and whether nearby lymph nodes are affected
• Endoscopic retrograde cholangiopancreatography (ERCP): It is a non-invasive diagnostic tool that can be used to visualize the bile ducts
• Imaging studies, such as MRI scan, scintigraphy, and PET scan, may be performed to detect tumor invasion and metastasis
• Tissue biopsy of the tumor:
  • A tissue biopsy of the tumor is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis
  • Biopsy specimens are studied initially using Hematoxylin and Eosin staining. The pathologist then decides on additional studies depending on the clinical situation
  • Sometimes, the pathologist may perform special studies, which may include immunohistochemical stains, molecular testing, and very rarely, electron microscopic studies to assist in the diagnosis

Note:

• Ampullary Adenomas obstructing the pancreatic and bile duct may present increase in serum levels of compounds such as bilirubin, glutamic transaminase, and alkaline phosphatase
• Sometimes, these tumors are misdiagnosed as reactive atypia, which are changes in the surface of the ampulla due to inflammation or injury that may be mistaken for neoplasia
• Carcinomas around the region may also be mistaken as Ampullary Adenomas (i.e., as invasive carcinomas of the pancreatic and common bile duct), especially on small biopsies
• Individuals with familial adenomatous polyposis (FAP) have an increased risk for colon cancer and development of Ampullary Adenoma. Individuals, who have been diagnosed with colon cancers, often get follow-up upper and lower gastrointestinal endoscopies. Ampullary Adenomas can be diagnosed during such follow-up upper GI endoscopy procedures
• In individuals with FAP, such polyps are discovered incidentally in individuals without any significant symptoms following endoscopic procedures, which are undertaken after the surgical removal of colon (part or entire) as a precautionary measure to prevent colorectal carcinoma
• The signs and symptoms associated with development of an Ampullary Adenoma is usually seen decades (10-15 years) after a colectomy for colon cancer in a majority of individuals

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Ampullary Adenoma?

The complications of Ampullary Adenoma may include:

• Some individuals develop stones in the gallbladder or in the bile duct, due to biliary obstruction caused by the tumor growth
• The tumors may develop to form ampullary adenocarcinomas, if undetected or left untreated
• Complications may arise from the underlying genetic disorder, if any
• Large-sized tumors may compress adjoining tissues and structures resulting in additional complications
• Damage to the muscles, vital nerves, and blood vessels, during surgery
• Post-surgical infection at the wound site is a potential complication

How is Ampullary Adenoma Treated?

Treatment measures for Ampullary Adenoma may include:

• When the tumor is confined to the surface, then endoscopic mucosal/submucosal resection (or surgical removal via endoscopy) is undertaken
• Surgical removal of the entire tumor may be the preferred method of treatment (polypectomy or surgical resection)
• If lesions are large, then it may not be possible to remove through endoscopy. In such cases, they are removed through transduodenal ampullectomy or pancreatoduodenectomy
• Tumors near the pancreatic duct outlet may be treated through a surgical technique termed pancreaticoduodenectomy (or Whipple procedure)
• Undertaking treatment of underlying genetic disorder, as necessary

Regular observation and periodic checkups to monitor the condition is strongly recommended following treatment.

How can Ampullary Adenoma be Prevented?

Currently, there are no known preventative measures against Ampullary Adenoma. However, if the tumor is associated with a genetic disorder, the following points may be considered:

• Genetic counseling and testing: If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Regular health check-ups might help those individuals with a history of the condition in the immediate family and help diagnose the tumor early

Regular medical screening at periodic intervals with blood tests, scans, and physical examinations, are mandatory. Often several years of active vigilance are crucial and necessary.

What is the Prognosis of Ampullary Adenoma? (Outcomes/Resolutions)

With prompt diagnosis and removal of the tumor, Ampullary Adenoma does not develop into cancer and the prognosis is good.

• Intestinal-type adenomas have high risk for development to invasive adenocarcinomas, since these are premalignant lesions
• Generally, there is a greater risk for carcinoma from Ampullary Adenomas than from colonic or duodenal adenomas (of the same size and type)
• Large-sized adenomas in individuals with genetic disorder (such as FAP) and seen with high-grade dysplasia, have a greater potential for adenocarcinoma development

Additional and Relevant Useful Information for Ampullary Adenoma:

The following DoveMed website links are useful resources for additional information:

http://www.dovemed.com/diseases-conditions/cancer/