The woman was in her 60s when dermatologists finally figured things out.
Breast cancer. Colon cancer. An enlarged thyroid gland. A family history of tumors and cancers as well. It wasn't until the woman developed an annoying case of dry mouth that doctors put it all together. By then, she was in her 60s.
According toa new case study in JAMA Dermatology, the woman presented to a dermatology clinic in Spain after three months of oral unpleasantness. They noted the cancers in her medical history. When she opened wide, doctors immediately saw the problem: Her tongue was covered in little wart-like bumps that resembled a slippery, flesh-colored cobblestone path. (Imagehere.)
Such a cobblestone tongue is a telltale sign of a rare genetic condition calledCowden syndrome. It's caused by inherited mutations that break a protein, called PTEN, leading to tumors and cancers.
PTEN, which stands for phosphatase and tensin homolog, generally helps keep cells from growing out of control. Specifically,PTEN deactivates a signaling lipid called PIP3(phosphatidylinositol 3,4,5-trisphosphate), and that deactivation blocks a signaling pathway (the PI3K/AKT/mTOR pathway) involved in regulating cell growth, survival, and migration. When PTEN is broken, PIP3activity ramps up, and tumors can grow unchecked.
In Cowden syndrome, PTEN mutations lead to noncancerous tumors or masses called hamartomas, which can occur in any organ. But, people with the syndrome are also at high risk of developing a slew of cancerous growths—most commonly cancers of the breast, thyroid, and uterus—over their lifetime. That's why people diagnosed with the condition are advised to undergo intensive cancer screenings, including annual ultrasounds of the thyroid starting at age 7 and annual mammograms and MRIs (magnetic resonance imaging) starting at age 30 at the latest.
For Cowden syndrome patients who aren't aware that the autosomal dominant condition runs in their family, most figure it out in their teens or 20s. Cowden syndrome typically starts with small masses on the skin or mucus membranes, often in the mouth and particularly on the tongue. About 80 percent of cases start with those skin and mucus membrane masses showing up in the second or third decade of life. However, the woman in Spain didn't seem to have problems with her tongue until she reached her 60s, which may have been why her doctors didn't diagnose her condition sooner.
Also, Cowden syndrome is rare. Researchers estimate that Cowden syndrome, first identified in the 1960s, occurs in about 1 in 200,000 people. But while the inherited condition is rare, mutations in PTEN are not rare in cancers generally. PTEN mutations can also occur sporadically, meaning they are not inherited. Overall, mutations in PTEN areamong the most common mutations in sporadic cancers. Sporadic PTEN mutations are often found driving cancers of the lung, prostate, and pancreas, as well as melanoma.
For the patient in Spain, genetic testing confirmed she had a PTEN mutation, and her Cowden syndrome diagnosis was confirmed. Unfortunately for her and other patients, there's no specific treatment for the genetic disease. Some drugs that inhibit the mTOR pathway have shown some promise, and noncancerous masses can be treated with things like surgery and laser treatments. However, the condition is managed by a team of clinicians who rigorously monitor and treat any tumors or cancers that may occur.
