Muir-Torre Syndrome - Causes, Symptoms, Diagnosis, and Treatment

Introduction

Muir-Torre syndrome (MTS) was initially identified by Muir et al. in 1967 and independently by Torre et al. in 1968. Hereditary non-polyposis colorectal cancer (HNPCC), often known as Lynch syndrome, has a phenotypic form known as Muir-Torre syndrome, an autosomal dominant condition. The genitourinary and gastrointestinal tracts are the two most often afflicted internal sites, with colorectal cancer occurring in about half of those affected. Before or after an internal cancer diagnosis, skin lesions can appear. MTS has an autosomal dominant inheritance pattern and is passed on by mutations in the MLH1 or MSH2 genes. A person has a higher lifetime risk of getting skin abnormalities and cancer types linked to the illness if they have a genetic mutation in either of these genes.

What Causes Muir-Torre Syndrome?

The inheritance of Muir-Torre syndrome is typically autosomal dominant and is due to a genetic deficiency in the mismatch repair genes. Muir-Torre syndrome is most frequently caused by mutations in the genes MLH1, MSH2, MSH6, and PMS2. More recently, several autosomal recessive Muir-Torre syndrome cases have been identified that are caused by mutations in the MYH gene, a base excision repair gene, and do not exhibit microsatellite instability. These cases, known as MTS II, are thought to make up about 35 percent of Muir-Torre syndrome cases. Sporadic occurrences have been reported; they are typically linked to immunosuppression, with Tacrolimus and Cyclosporine as the main offenders.

How Is Muir-Torre Syndrome Inherited?

The majority of genes have two copies in each person. The number of copies of a gene that must contain a disease-causing variation determines how a disease is passed down through the family. The pattern of inheritance for this illness is autosomal dominant.

X or Y chromosomes, which represent the sex chromosomes, are not present in autosomal diseases. Like chromosomes, genes frequently exist in pairs. Dominant refers to the fact that just one copy of the illness-causing change (pathogenic variant) on the causative gene (causal gene) is required for a person to have the condition. Pathogenic variants are sometimes referred to as "mutations."

Sometimes a parent with the genetic disorder passes on the harmful variation to their child. In other instances, there is no known family history of the disease, and the condition develops due to a novel harmful mutation (de novo) in the causative gene.

There is a 50 percent (one in two) chance that the variation and the disease will be inherited by each child of a person with an autosomal dominant disease. Children who inherit a dominant variant typically develop the condition, though it may affect them less or more severely than their parents did. A person may occasionally carry a pathogenic variation for an autosomal dominant disease without displaying any symptoms or signs of the illness.

What Are the Symptoms of Muir-Torre Syndrome?

The following are some of the symptoms of the Muir-Torre syndrome:

• The presence of a sebaceous adenoma that develops in skin cells that secrete sebum.

• Abnormal growth of skin tissue known as skin neoplasm.

• Colon cancer.

• Abnormal growth of cells in the stomach.

• Breast cancer.

• A cancer of the uterine cavity's mucous lining, the endometrium is endometrial cancer.

• Neoplasms that are found in the lymphatic and bone marrow, two tissues that produce blood are Hematological Neoplasm.

• Laryngeal cancer.

• Liver cancer.

• Malignant neoplasm of the genitourinary tract.

• Renal cancer.

• Salivary gland neoplasm.

How Is Muir-Torre Syndrome Diagnosed?

1. Criteria:

• At least one sebaceous gland tumor, such as a carcinoma, adenoma, or epithelioma.

• A minimum of one internal cancer. Sebaceous hyperplasia alone is typically seen as insufficient for the first criteria.

2. History:

• Obtain a thorough family cancer history, taking into account colorectal (colon), hepatobiliary (liver, bile ducts, and gallbladder), endometrial (inner lining of the uterus), and urogenital (the urinary and genital tract) malignancies (cancer). Contrary to sporadic occurrences, colon cancer is typically located at or close to the splenic flexure, similar to other familial colon cancer syndromes.

• Sebaceous neoplasms, such as sebaceous adenomas, epitheliomas (also known as sebaceous), carcinomas, basal cell carcinomas (BCCs) with sebaceous differentiation, and sebo acanthomas, may run in one's personal or family history.

• Sebaceous tumors can occur before, at the same time as, or most frequently after visceral cancer.

• With a frequency of 68 percent, sebaceous adenoma is the most prevalent cancer, followed by carcinoma (30 percent) and epithelioma (27 percent).

3. Physical Examination:

Pink or yellow papules or nodules that usually appear on the eyelid or nose are painless and slow to expand. Both central umbilication and ulceration are possible. It is less likely that lesions detected below the neck are random tumors. Additionally, sebaceous neoplasms should be suspected if there are several keratoacanthomas (skin cancers), whether they are present concurrently or not.

4. Diagnostic Procedures:

• Histopathological Examination: Sebaceous tumors are thought to have "mulberry cells," which are cells with a starry nucleus and a cytoplasm that is coarsely vacuolated. Epithelial membrane antigens will cause immune responses in sebaceous cells.

  • Sebaceous Adenoma: A sebaceous adenoma is made up of several sebaceous lobules with uneven shapes and poor differentiation that are encircled by a layer of tiny basaloid cells. Because it lacks a central drainage duct, sebaceous hyperplasia can be distinguished from it.

  • Sebaceoma: Sebaceoma, a subtype of sebaceous adenoma with greater than or equal to 50 percent basaloid epithelial cells, is a benign growth.

  • Carcinoma: Cellular atypia, strong mitotic activity, infiltrative development, etc., are characteristics of carcinomas that are more typical of malignancy. Contrary to BCC (basal cell carcinoma), peripheral palisading and cleft development are typically absent. This diagnosis may be supported by positive fat staining. Sometimes the epidermis will show signs of pagetoid spread.

  • Keratoacanthoma: In regions of sebaceous proliferation, keratoacanthoma and BCC with sebaceous differentiation will react to epithelial membrane antigens in addition to their own characteristic features.

• Lab Tests:

  • Complete blood count (CBC).

  • Cancer antigen 125 (CA-125).

  • Carcinoembryonic antigen (CEA).

  • Fecal occult blood test (FOBT).

  • Urinalysis.

• Immunohistochemistry: In one study, mutations in MLH-1 had a positive predictive value (PPD) of 88 percent, compared to 55 percent and 67 percent for MSH-2 and MSH-6, respectively, and 100 percent for MLH-1 and MSH-6 combinations. A different recent study recommended combining or excluding MSH-2 and using MLH-1, MSH-6, and PMS2. Since these mutations might occur randomly, a diagnosis also requires the presence of clinical evidence or a history of a related visceral malignancy.

How Is Muir-Torre Syndrome Managed?

Due to the possible number and potential for disfigurement that multiple sebaceous neoplasms can create, treating the cutaneous signs of Muir-Torre syndrome can be challenging.

• Local Excision and Cryotherapy: Benign lesions should be given reassurance. Patients who want benign lesions removed may undergo local excision and cryotherapy. Additionally, local excision should be used to manage keratoacanthomas conservatively. Sebaceous carcinomas should be treated more aggressively with wide local excision with margins of 5 to 6 millimeters or Mohs micrographic surgery since they have the potential for local and distant metastases.

• Radiation: Radiation may be used, but only as adjuvant therapy following the excision of a recurrent sebaceous carcinoma or a localized metastasis. For primary cutaneous sebaceous carcinoma, radiation as a single treatment has been linked to greater death and recurrence rates.

• Drugs: Interferon-alpha and oral Isotretinoin have also been shown to reduce the occurrence of cutaneous and visceral cancers.

How Is the Muir-Torre Syndrome Follow-up Carried Out?

Patients with Muir-Torre syndrome should have annual screenings for cutaneous and visceral cancer after the diagnosis has been made. Endoscopies of the upper and lower gastrointestinal tracts must be done. While upper endoscopy is advised between the ages of 25 and 30, colonoscopy can start as early as 18 years old. Annual testicular and prostate exams are recommended for men, whereas annual breast and pelvic exams, transvaginal ultrasounds, and endometrial sampling are recommended for women. Chest X-rays, cervical and urine cytology, carcinoembryonic antigen levels, fecal occult blood testing, liver function tests, and complete blood counts are other procedures that could be helpful.

Conclusion

The type and stage of the tumor that forms determine the Muir-Torre syndrome prognosis. Regular medical examinations can aid in the early detection of malignancies, which, when properly treated, can lengthen life expectancy.