How Common is Cowden Disease?

Cowden disease is estimated to affect around 1 in 200,000 people.

What are signs and symptoms of Cowden Disease?

Signs and symptoms of Cowden Syndrome include: - Development of tumors called hamartomas in any organ, which can potentially become malignant or cancerous. - Skin changes, with more than 80% of patients showing symptoms affecting the skin. These changes often appear in the second or third decade of life and may include: - Oral lesions with a bumpy or cobblestone-like pattern in the mouth. - Warty papules on the face, varying from skin-colored to yellow-brown. - Well-defined skin bumps or nodes known as sclerotic fibromas. - Skeletal system abnormalities, such as a high-arched palate, curvature of the spine (scoliosis), or an abnormally large head size (macrocephaly). - Gastrointestinal polyps, which are present in about 85% of patients and may increase the risk of colon cancer. - Uterine and ovarian cysts in women, leading to irregular periods and an increased risk of endometrial cancer by 20% to 30%. - Elevated risk of breast cancer in women, with as many as 85% developing the disease at some point. Breast cancer has also been reported in men. - Benign and malignant thyroid conditions. - Lhermitte-Duclos disease, a specific type of benign cerebellum tumor. - Increased likelihood of renal or kidney cancer in up to 30% of patients. - 5% incidence of melanoma skin cancer.

What else can Cowden Disease be?

The doctor needs to rule out the following conditions when diagnosing Cowden Disease: - Birt-Hogg-Dube syndrome - MEN 1 or Tuberous Sclerosis - Heck disease, Goltz Syndrome, or MEN 2B - Bannayan-Riley-Ruvalcaba syndrome

What kinds of test are needed for Cowden Disease?

The types of tests that are needed for Cowden Disease include: - Skin biopsy to examine any unusual skin growths - Complete blood count to check for any abnormalities - Thyroid function tests to assess thyroid health - Stool test to detect hidden blood - Imaging tests to identify any potential cancer or tumors - Urine analysis to evaluate kidney function and detect any abnormalities Additionally, the International Cowden Syndrome Consortium has established criteria for diagnosing Cowden Disease, which include major and minor criteria. These criteria involve specific conditions and abnormalities such as Lhermitte-Duclos disease, macrocephaly, thyroid cancer, breast cancer, urinary or genital tumors, lipomas, fibromas, mental delay, fibrocystic disease of the breast, gastrointestinal hamartomas, and thyroid abnormalities. Furthermore, the presence of certain skin or nail abnormalities can also contribute to the diagnosis of Cowden Disease.

How is Cowden Disease treated?

Treatment for Cowden disease involves a team of healthcare professionals and is specially tailored based on each patient's symptoms. Skin lesions, a common symptom of Cowden disease, can be treated with a variety of methods including surgery, medication like 5-fluorouracil, investigational treatments like mTOR inhibitors, laser therapy, isotretinoin, or other methods designed to remove the lesions. Genetic counseling can also be beneficial since this disease can run in families.

Cowden Disease

What is Cowden Disease?

Cowden disease, also known as Cowden syndrome or multiple hamartoma syndrome, is a rare inherited skin condition first identified in 1963. This disease inherits from parents in a dominant manner, meaning that an affected individual only needs a changed gene from one parent to inherit the disease. It falls under a group of disorders associated with changes in a particular gene known as the phosphatase and tensin homolog gene, also known as PTEN. Cowden syndrome is most commonly known to cause harmless, abnormal growths, termed “hamartomas,” which can appear in any organ.

Typical symptoms of Cowden syndrome include the development of skin and mucous membrane lesions, and an unusually large head size. It is important to note that most people who have this disease will later develop a harmful tumor in the thyroid, endometrium, or breast. Managing Cowden syndrome typically requires a team effort from healthcare professionals and often involves proactive monitoring for any signs of cancer. Current research on potential medications for treating this condition is showing promising results.

What Causes Cowden Disease?

Cowden disease is caused by inherited changes or mutations in a gene that usually protects the body from forming tumors, known as the PTEN gene. This mutation is passed down in families, meaning it’s from one generation to the next. Other conditions like Bannayan-Riley-Ruvalcaba syndrome and a syndrome called SOLAMEN (which stands for Segmental Overgrowth Lipomatosis Arteriovenous Malformation Epidermal Nevus) also have this same PTEN gene mutation.

Risk Factors and Frequency for Cowden Disease

Cowden syndrome tends to be more commonly found in females according to some studies, and is predominantly found among white individuals. The occurrences of this syndrome are somewhat rare, and it is estimated to affect around 1 in 200,000 people.

Signs and Symptoms of Cowden Disease

Cowden syndrome is a disorder that is mainly marked by the development of tumors called hamartomas. These can occur in any organ, and although often benign, they hold the potential to become malignant or cancerous. Persons with this disease typically start showing signs on their skin and inside their mouth relatively early in life. More than 80% of patients show symptoms affecting the skin, with visible changes often appearing in the second or third decade of their lives.

Oral lesions can form in the mouth, often having a bumpy or cobblestone-like pattern, usually matching the color of the surrounding skin tissue. They can appear on the tongue, lips, or any other part of the mouth. The skin may develop warty papules, varying from skin-colored to yellow-brown, especially on the central face. Another more specific finding is well-defined skin bumps or nodes, representing a type of skin tumor known as sclerotic fibromas.

Oral lesions, often with a bumpy or cobblestone-like pattern
Warty papules on the face
Dermal papules or nodules

The disease also affects various body systems and can manifest in several ways other than on the skin. For example, it can impact the skeletal system resulting in a high-arched palate, curvature of the spine or scoliosis, or an abnormally large head size or macrocephaly. About 85% of patients experience symptoms in the form of gastrointestinal polyps. There may be an increased risk of colon cancer in such patients. Women may develop uterine and ovarian cysts which can cause irregular periods and increase the risk of endometrial cancer by 20% to 30%. Furthermore, women with Cowden syndrome face an elevated risk of breast cancer, with as many as 85% developing this disease at some point. Unusually, instances of breast cancer have also been reported in men.

Several other abnormalities and increased cancer risks are associated with Cowden Syndrome. These include benign and malignant thyroid conditions, a specific type of benign cerebellum tumor known as Lhermitte-Duclos disease, an increased likelihood of renal or kidney cancer in up to 30% of patients, and a 5% incidence of melanoma skin cancer.

Testing for Cowden Disease

If doctors suspect a person might have Cowden disease, they might run several tests. If there are any unusual skin growths present, a skin biopsy (a test where a small piece of skin tissue is removed for testing) can be extremely helpful. Other useful tests might include a complete blood count, checking thyroid function, testing stool for hidden blood, undergoing imaging tests, or a urine analysis. These tests help detect any potential cancer or tumors related to Cowden disease.

The International Cowden Syndrome Consortium has set certain criteria to diagnose Cowden disease. These include “major criteria” and “minor criteria”.

To be diagnosed with Cowden disease, a person must meet at least two major criteria. However, one of these must either be Lhermitte-Duclos disease (a rare, non-cancerous brain tumor) or macrocephaly (an overly large head). The other major criteria include thyroid cancer and breast cancer.

Alternatively, a person can be diagnosed with Cowden disease by meeting one major and three minor criteria, or four minor criteria. These minor criteria include urinary or genital tumors or abnormalities, lumps of fatty tissue under the skin (lipomas), fibromas (non-cancerous tumors), mental delay, fibrocystic disease of the breast (non-cancerous lumps in the breast), growths in the stomach or intestines (gastrointestinal hamartomas), and other thyroid abnormalities such as an enlarged thyroid (goiter).

In addition, if a person has six or more specific types of skin or nail abnormalities (mucocutaneous lesions or palmoplantar keratosis), that alone can be enough to meet the criteria for Cowden disease.

Treatment Options for Cowden Disease

Treatment for Cowden disease involves a team of healthcare professionals and is specially tailored based on each patient’s symptoms. Genetic counseling can be beneficial since this disease can run in families. Skin lesions, a common symptom of Cowden disease, can be treated with a variety of methods. This might include surgery, medication like 5-fluorouracil, investigational treatments like mTOR inhibitors, laser therapy, isotretinoin, or other methods designed to remove the lesions.

Due to the wide-ranging effects of Cowden disease, it’s crucial for patients to see specialists suited to their individual health concerns. These could include doctors specializing in women’s health (obstetricians/gynecologists), digestive health (gastroenterologists), hormonal health (endocrinologists), skin conditions (dermatologists), brain and nervous system conditions (neurologists), or diagnostic imaging (radiologists). These professionals can help with screening and tests related to their specialty.

Certain inherited conditions can exhibit symptoms similar to Cowden syndrome, making it tricky to diagnose accurately. Some of these illnesses involve changes in specific genes, noted as SDHB/C/D, and can also lead to thyroid, breast, and kidney cancers.

Birt-Hogg-Dube syndrome: This condition might manifest similar skin issues, such as fibrofolliculomas or non-cancerous bumps on the skin.
MEN 1 or Tuberous Sclerosis: These might also show identical skin features, such as angiofibromas which appear as red or skin-colored bumps.
Heck disease, Goltz Syndrome, or MEN 2B: These conditions might have similar mouth issues such as growths or bumpy areas in the mouth (oral papillomas) that also appear in Cowden syndrome.

Another condition that can closely resemble Cowden syndrome is Bannayan-Riley-Ruvalcaba syndrome. This disorder shares many similar features with Cowden syndrome, with the unique characteristic of spots on the genital areas. This syndrome is associated with changes in the same gene as Cowden syndrome (PTEN gene), reinforcing its shared similarities.

What to expect with Cowden Disease

The outlook is generally positive, especially if cancer is detected early. In such cases, patients might potentially live almost as long as those without the disease.

Preventing Cowden Disease

The PTEN Hararmatoma Tumor Syndrome Foundation is a useful platform where patients and their families can find support. Regular health check-ups are advised for these patients. It’s also important for them to limit their exposure to the sun to safeguard their health.