Tubular Adenomatosis (TA) is a rare genetic disorder caused by mutations in the Klinefelter’s syndrome gene. T.A occurs when one or both copies of the Klinefelter’s syndrome gene are deleted from chromosome 21 resulting in incomplete development of male reproductive organs and testes, and absence of ovaries and uterus. Approximately 1 in every 100,000 males have the condition. There is no cure for T.A but there are treatments available such as hormone replacement therapy and surgery to remove the affected tissue.
The most common form of T.A is tubular adenomyosis (TA). TA involves abnormal growth of lymphoid tissues within the tunica albuginea, which produces small nodules called tubules (Figure ).
These tubules may grow up to 5 mm in diameter and contain lymphoid cells. They may also produce fluid (cysts) or pus (ulcers).
In some cases, the growth of these tubercles becomes so large it causes deformities such as spina bifida. The disease is usually diagnosed during childhood. Treatment includes removing the affected tissue and/or surgically removing the affected body part(s), if necessary.
Tubular adenomas of the colon are hamartomas of the serosa of the colonic mucosa. They may be associated with Gardner’s syndrome and Peutz-Jeghers syndrome.
They are benign but multiple tubular adenomas and villous adenomas have been associated with familial adenomatous polyposis and juvenile polyposis, respectively.
These types are also hamartomas of the submucosa. They are usually asymptomatic and are detected during a colonoscopy performed for other reasons.
These adenomas are classified into three groups: tubular, villous, and mixed tubular-villous. They are classified according to the histological appearance of the cells lining the tubular structures.
Tubular adenomas are the most common type. Tubules are lined by columnar epithelium and filled with fluid. The cytoplasm of these epithelial cells may contain vacuoles (Figure ).
Adenomas are benign neoplasms that have the capacity to cause symptoms or become life-threatening. They are more common in the colon than in other parts of the gastrointestinal tract. The most common types are listed in the Table.
A hyperplastic polyp is a type of adenoma that has more features of a normal colonic crypt than an adenoma. An example would be a group of cells that replaces a single lost colonic epithelial cell.
Villous adenomas are relatively uncommon and resemble villi found in the small intestine. Cyst formation is common and often there is hyperkeratosis.
Villous-adenomas are usually solitary, surrounded by a fibrous sheath, and located in the rectosigmoid region. They resemble small villi, hence their name. They have finger-like projections that contain epithelial cells and range in size from 1 to 3 millimeters in diameter.
A tubular adenoma is a hamartomatous (benign) neoplasm found in the colonic subepithelium. They are lined by simple columnar epithelium that contains one or more large fluid filled tubes. The cytoplasm of these epithelial cells may contain vacuoles (hollow).
They are usually solitary and range in size from 1 to 5 millimeters in diameter.
Colonic adenomas, like all benign neoplasms, grow slowly and are usually asymptomatic. Most adenomas do not cause any adverse symptoms unless they become very large, when they may cause abdominal distention and pain. Large adenomas may also twist or rupture, which can lead to life-threatening hemorrhage.
The natural history of adenomas is not well understood. They are not known to metastasize, but they may precede the development of a more serious neoplasm. For this reason, the presence of adenomas is considered premalignant and treated like a malignant tumor.
Many factors influence the risk of developing adenomas or other neoplasms. These include diet, smoking, and infection with specific bacteria.
Most epidemiological studies have focused on dietary factors. Two such studies in the UK showed an increased risk of adenomas among people with low intake of saturated fat and those with high-fat dairy consumption.
There is evidence that a diet high in meats increases the risk of colorectal neoplasms, while a diet high in fruits and vegetables has a protective effect. This has led some to believe that certain food additives may be partly responsible. Two such additives widely used in the USA, but not in the EU, are sulpheric acid and polydimethylsiloxane.
Sulphur dioxide has been shown to cause adenomas in rats and mice.
The presence of inflammatory bowel disease (ulcerative colitis or Crohn’s disease) also increases the risk of developing colorectal adenomas.
Studies have shown that infection with a specific strain of “Campylobacter” can cause an increase in colorectal adenomas in mice. This relationship has been confirmed in humans, and researchers believe that this common food-borne bacterium is a potential factor in the development of colorectal adenomas.
It is well known that cigarette smoking increases the risk of cancer, but its role as a risk factor for adenomas is less clear.
The most common symptom of an adenoma is the presence of microscopic (micro) tumors in the intestines. The adenomas are usually found during a scan or during a colonoscopy. The location, size and number of adenomas, as well as the presence of any inflammatory bowel disease, will help the physician decide upon further action.
Many adenomas never become malignant, however for precautionary reasons they are removed by surgery. The location, size and number of adenomas removed will be based upon the patient’s age and medical history and may also take family history into account.
Follow up will be determined by the extent of the surgery and any post-operative adjuvant therapy. Patients with a family history of colon cancer or inflammatory bowel disease should undergo periodic screening (usually every 1 to 3 years) with flexible sigmoidoscopy or regular CT Scans. Most patients with sporadic adenomas will be followed by a colonoscopy, where the entire colon is visualized, every 5 years.
Adenomas can be easily detected in the colon using a number of techniques. The most common method for adenoma detection is flexible sigmoidoscopy, during which the physician pushes a tube with an attached light and camera (called a “sigmoidoscope”) through the patient’s bottom and into the rectum and sigmoid colon. This allows the physician to look for abnormalities inside the rectum and lower colon.
During the examination, the physician can take a small tissue sample (biopsy) of any growths inside the rectum or lower colon. The patient is then able to go home shortly after the procedure.
Alternatively, a CT colonography may be used. During this procedure, the patient is placed on a table and x-rays of the pelvis and abdomen are taken. This procedure can easily detect polyps and adenomas throughout the colon and rectum.
The patient does not require sedation and can go home shortly after the procedure.
These methods are both effective at detecting adenomas but flexible sigmoidoscopy is less expensive. It is recommended that people between the ages of 50-75 be screened yearly.
The adenoma-carcinoma sequence is a common cause of colon cancer. The term is used to describe how a genetic predisposition to high levels of DNA damage causes an accumulation of adenomas in the colon. These adenomas can develop into cancer over time.
Because the sequence includes adenomas, interventions to reduce DNA damage can be used to prevent the development of colon cancers in people with this genetic predisposition. This includes eating a diet low in red meats and processed foods and high in fruits and vegetables, and also possibly using supplements that protect against DNA damage (such as Sulforaphane).
The adenoma-carcinoma sequence was first described in 1988. It is currently the most accepted theory to explain how long-standing mutations in DNA lead to colon cancer. Specifically, a defect in the “APC” gene leads to a loss of apoptotic activity, which causes a buildup of adenomas in the colon.
APC stands for “adenomatous polyposis coli” and is a tumor suppressor gene located on the short arm of chromosome 5. The protein produced from the “APC” gene suppresses the formation of tumors by causing programmed cell death (apoptosis) in abnormal cells.
The adenoma-carcinoma sequence involves the following series of steps:
If this theory holds true, then DNA damage and adenomas will eventually develop in the colon of all people with the defective “APC” gene. It has been established that most people with familial adenomatous polyposis (FAP) develop colonic cancer by the age of 40. The average age for people with hereditary non-polyposis colorectal cancer (HNPCC or Lynch syndrome) to develop colon cancer is 55.
It is important to note that not everyone with these defects will get colon cancer and people can have these defects and never develop colon cancer.
The reason for this is probably because other factors such as diet, nutrition, exercise, and body weight affect the rate of adenoma formation, size of adenomas formed and risk of developing colon cancer. Although people with a defective “APC” gene are at greater risk of developing colon cancer, this process can take many years to develop. Because it takes years for an adenoma to become cancerous, screening methods such as sigmoidoscopy and colonoscopy are very effective in the prevention of colon cancer in these individuals.
If these methods were not available, the prevalence of colon cancer would be much higher.
There are other steps in the adenoma-carcinoma sequence that are not yet well defined. This includes the exact nature of the defect in the “APC” gene and how a loss of apoptotic activity leads to the buildup of colorectal tumors. It is known that apoptosis does not take place in cells with a defective “APC” gene, but it is not known why these cells fail to undergo apoptosis.
The adenoma-carcinoma sequence involves not only the loss of apoptotic activity, but also an increase in DNA damage. This may lead one to believe that cancer would occur in people with defective “APC” genes, but this does not seem to be the case. Instead, numerous steps are involved and an adenoma must form and grow to a certain size before it can progress to cancer.
The average size of adenomas in people with FAP is about 4 millimeters before they become malignant. In people with hereditary non-polyposis colorectal cancer (HNPCC), the average size of adenomas is about 10 millimeters before they become malignant. These larger adenomas are more likely to undergo mutations that will lead to colon cancer.
Sources & references used in this article:
Polyp size measurement at CT colonography: what do we know and what do we need to know? by RM Summers – Radiology, 2010 – pubs.rsna.org
Con: High-grade dysplasia and villous features should not be part of the routine diagnosis of colorectal adenomas by HD Appelman – American Journal of Gastroenterology, 2008 – journals.lww.com
A randomized surveillance study of patients with pedunculated and small sessile tubular and tubulovillous adenomas: the Funen Adenoma Follow-up Study by OD Jørgensen, O Kronborg… – Scandinavian journal of …, 1995 – Taylor & Francis