What is Muir-Torre Syndrome?
Muir-Torre syndrome (MTS) is a condition first recognized by Muir and others in 1967 and Torre and others in 1968. This syndrome is a hereditary disorder, meaning it gets passed down through families. It’s closely related to a condition called Lynch syndrome, which is formally known as hereditary non-polyposis colorectal cancer (HNPCC). The cause of Muir-Torre syndrome is changes or mutations in specific genes that help fix mistakes in DNA. However, when these mutations occur, it often results in instability in short repeated patterns in DNA, which is called microsatellite instability.
This condition is characterized by certain features like special types of skin tumors (sebaceous neoplasms) and internal cancers (visceral malignancies), the most common being colon cancer. Given the association of certain gene mutations and internal cancers, individuals with this syndrome are typically advised to have regular health checks from a young age and more frequently to detect any potential cancers early.
What Causes Muir-Torre Syndrome?
Muir-Torre syndrome is caused by a change or defect in certain genes that are responsible for fixing mistakes in the DNA. This syndrome is usually inherited, which means it’s passed down from parents to their children. The genes most often changed in this condition include MLH1, MSH2, MSH6, and PMS2.
Interestingly, there have also been cases where the disease is inherited differently and doesn’t cause a common feature of the syndrome known as microsatellite instability. This happens when there’s a defect in another gene named MYH that’s involved in repairing the DNA. These cases, which make up about 35% of all Muir-Torre syndrome cases, have been given the name MTS II.
There are also some cases of Muir-Torre syndrome that aren’t inherited but occur sporadically. These tend to happen when a person’s immune system is suppressed, often due to medications like tacrolimus and cyclosporine.
Risk Factors and Frequency for Muir-Torre Syndrome
Muir-Torre syndrome is most commonly reported in Caucasian patients from developed countries, but we don’t have much data from other parts of the world. More men seem to have this syndrome than women, with a ratio of about 3 men for every 2 women. The average age when a person with this syndrome develops cancer is 53 years, but cases have been reported as early as 23 years old and as late as 89 years old. This syndrome is observed in 9.2% of patients with HNPCC, a similar genetic condition.
Signs and Symptoms of Muir-Torre Syndrome
Muir-Torre syndrome is a condition where various types of skin tumors appear. These include sebaceous adenomas, sebaceous epitheliomas, sebaceous carcinomas, cystic sebaceous tumors, basal cell carcinomas with sebaceous differentiation, and keratoacanthomas displaying some sebaceous differentiation. Among these, sebaceous adenomas are the most common.
To diagnose this syndrome, a person should have at least one sebaceous tumor and at least one internal cancer at any point in their life, provided there are no other causes like radiotherapy or immunosuppression. The diagnosis can also be given if there are multiple keratoacanthomas, a visceral malignancy, and a family history of Muir-Torre syndrome. However, sebaceous hyperplasia and nevus sebaceus of Jadassohn are not considered features of this syndrome.
The number and types of visible tumors can vary, ranging from one to hundreds, due to differences in the expression of certain genes called mismatch repair genes. These tumors often appear as slow-growing, painless, yellowish bumps or lumps that may or may not have ulceration. They are most commonly found on the face, but can appear on any part of the skin that has a sebaceous gland. Tumors occurring below the neck can signal Muir-Torre syndrome, as these are rarely seen in patients without the syndrome. Like their single appearing counterparts, keratoacanthomas can also appear singularly or in multiple numbers.
When evaluating a patient suspected of having Muir-Torre syndrome, a thorough medical history needs to be taken. Although colon carcinoma is the most common associated cancer, it’s been reported alongside a number of other cancers such as those affecting the endometrium, cervix, ovaries, breasts, small intestine, bones, liver and bile duct, brain, pancreas, upper uroepithelial tract, blood (lymphoma and leukemia), and lungs.
Testing for Muir-Torre Syndrome
If you have growths in the oil-producing glands, known as sebaceous neoplasms, doctors may use a technique called Immunohistochemistry (IHC) to detect certain gene defects. These defects could be a sign of Muir-Torre syndrome, a rare genetic disease that can lead to skin tumors and other types of cancer.
However, this IHC test isn’t perfect. Sometimes it can detect gene defects in the sebaceous neoplasms, but not in other cell types in the body. When this happens, it usually means that these changes are happening only in specific cells and not across the whole body. As a result, those patients with such mutations are not necessarily at higher risk for developing other types of cancer.
Because IHC alone can’t definitively diagnose the syndrome, doctors usually combine it with a careful review of your personal and family medical history. If the IHC test shows gene defects, the next step is usually genetic testing to confirm the presence of Muir-Torre syndrome.
Once someone is diagnosed with Muir-Torre syndrome, regular annual checks for cancer are recommended. Because sebaceous tumors can look very similar to harmless skin conditions, doctors are typically more likely to perform a biopsy just to be safe for patients with Muir-Torre syndrome. This is especially true for sebaceous neoplasms near the eye, as this is a typical location for sebaceous carcinoma, a form of skin cancer. But remember, sebaceous carcinomas can come from any oil-producing gland in the body.
Treatment Options for Muir-Torre Syndrome
If you are diagnosed with Muir-Torre syndrome, it’s important to get checked every year for signs of internal and skin-related cancers. You’ll need to regularly get an upper and lower gastrointestinal endoscopy – a test that uses a flexible tube to look inside your digestive tract. Starting from the age of 18, you should have regular colonoscopies, which are inspections of your colon (a part of your digestive system). From 25 to 30 years old, you should also start getting upper endoscopies (which inspect your esophagus, stomach, and small intestine).
Men should have yearly exams to check their testicles and prostate, while women should have yearly breast and pelvic examinations. Women may also need a transvaginal ultrasound and checks of their endometrium (the lining of the uterus) if anything unusual is found in regular checks.
Yearly chest x-rays, tests for early signs of cervical cancer and bladder cancer, tests for proteins associated with tumor development, checking for blood in your stool, liver function tests, and complete check-ups of your blood may also be done.
On the outside, Muir-Torre syndrome can lead to many sebaceous neoplasms – which are usually benign or non-cancerous growths in your sebaceous glands. These glands produce an oil called sebum, which lubricates your skin and hair. These growths can be distressing due to their potential number and how they can change your appearance. So, doctors will often recommend:
1. Having the non-cancerous ones removed if you want (this can be done through local excision or cryotherapy which uses extreme cold), and
2. More aggressive treatments for sebaceous carcinomas (cancerous sebaceous glands), which includes wide local excision (surgically removing a large area of tissue around the growth), or Mohs surgery (a precise surgical procedure to remove skin cancer layer by layer while sparing the surrounding healthy tissue).
It’s important to note that radiation therapy, which uses high-energy particles or waves to destroy or damage cancer cells, should only be used after surgery, and not on its own, for this type of skin cancer. Using radiation alone has been linked to higher death rates and chances of the cancer coming back.
In addition to these treatments, doctors may also suggest medications like interferon-alpha and oral isotretinoin, as they can often help to reduce the development of skin and internal cancers associated with Muir-Torre syndrome.
What else can Muir-Torre Syndrome be?
When diagnosing Muir-Torre syndrome, doctors should consider a range of other conditions that also cause multiple skin bumps or nodules on the face and body. Some of these conditions include:
- Cowden syndrome
- Birt-Hogg-Dube syndrome
- Tuberous Sclerosis
- Brooke-Spiegler syndrome
- Gorlin syndrome
Conditions like Grzybowski-type generalized eruptive keratoacanthomas and Ferguson-Smith-type multiple eruptive keratoacanthomas should also be considered, especially in patients with numerous keratoacanthomas. Also, isolated cases of sebaceous tumors and keratoacanthomas could be possible, although these are rare in the general population. It’s important to note, sebaceous neoplasms commonly occur on the head, while it’s rare to find them below the neck. Finding sebaceous tumors below the neck could indicate the likelihood of Muir-Torre syndrome.
