Muir-Torre Syndrome (MTS) is a rare genetic disorder that is considered a subtype of Lynch Syndrome also known as Hereditary Nonpolyposis Colorectal Cancer (HNPCC). It was first described by Muir et al. in 1967.
It is characterized by the presence of sebaceous skin tumors, mainly sebaceous adenomas and carcinomas, along with an increased risk of certain internal malignancies, particularly colorectal and other gastrointestinal cancers.
Muir-Torre syndrome (MTS) is the fusion of growths on the skin typically sebaceous tumor, sebaceous growth, or sebaceous cancer and an internal cancer.
Epidemiology
Muir-Torre syndrome has been seen in Caucasian individuals from developed nations. It is present in 9.2% of individuals diagnosed with Hereditary Nonpolyposis Colorectal Cancer (HNPCC).
There is a slight preference for males, with a ratio of 3 males to every 2 females. The average age at which malignancy develops is 53 years, with the earliest case reported at 23 years and the latest at 89 years.
MTS is more commonly diagnosed in adults, and there is no significant difference in its occurrence between males and females.
Anatomy
Pathophysiology
MTS is primarily caused by germline mutations in DNA mismatch repair (MMR) genes. These MMR genes play a crucial role in correcting errors that occur during DNA replication.
Microsatellite instability is a characteristic feature of both MTS and Lynch Syndrome. Mutations in these genes lead to a condition known as microsatellite instability (MSI), where repetitive DNA sequences (microsatellites) in the genome are prone to accumulate errors and mutations.
MSI can be detected by analyzing specific DNA markers that are prone to instability due to the defective MMR system. MSI leads to an increased likelihood of mutations in critical genes involved in cell cycle regulation and DNA repair, leading to an increased risk of tumorigenesis.
Etiology
Muir-Torre Syndrome follows an autosomal dominant pattern of inheritance. This means that an affected individual has a 50% chance of passing on the mutated gene to each of their children. If an individual inherits a faulty mismatch repair (MMR) gene from one parent, they have an increased risk of developing MTS and related tumors.
Muir-Torre Syndrome can be associated with mutations in several different MMR genes, including MLH1, MSH2, MSH6, and PMS2. The specific gene affected can influence the severity of the condition and the types of tumors that may develop.
Genetics
Prognostic Factors
The age at which Muir-Torre Syndrome is diagnosed can impact the prognosis. In some cases, early detection of MTS may allow for timely surveillance and intervention, potentially improving outcomes.
The specific types of sebaceous tumors and internal malignancies that develop in an individual with MTS can influence the prognosis. Benign sebaceous adenomas have a better prognosis than malignant sebaceous carcinomas.
When local relapses occur, they typically happen within the initial five years of removal. The rates of relapse are approximately in the range of 30%.
Factors such as smoking, diet, and physical activity can also influence the prognosis in individuals with MTS, as they can impact the risk of cancer development and overall health.
Clinical History
The age at which internal malignancies associated with MTS occur can vary widely. Colorectal cancer and other gastrointestinal cancers, which are common internal malignancies in MTS, typically have a higher incidence in middle-aged and older adults.
The development of sebaceous skin tumors, such as sebaceous adenomas and sebaceous carcinomas, is often one of the initial signs of Muir-Torre Syndrome. These skin tumors can appear at a relatively young age, typically ranging from late childhood to early adulthood.
Physical Examination
Abdominal Examination: The abdomen will be examined for tenderness, masses, or any other abnormalities that may suggest internal malignancies, particularly gastrointestinal tumors.
Rectal Examination: For individuals at an appropriate age, a rectal examination may be performed to check for any abnormalities, such as masses or bleeding, that could indicate colorectal cancer or other gastrointestinal conditions.
Rectal Examination: For individuals at an appropriate age, a rectal examination may be performed to check for any abnormalities, such as masses or bleeding, that could indicate colorectal cancer.
Lymph Node Examination: The healthcare provider may palpate the lymph nodes to check for any signs of enlargement or tenderness. Enlarged lymph nodes could indicate the spread of cancer and may prompt further investigations.
Age group
Associated comorbidity
While colorectal and gastrointestinal cancers are the most common internal malignancies associated with MTS, there is an increased risk of other cancer types as well. These can include cancers affecting the urinary tract, ovaries, uterus, and pancreas.
Some individuals with MTS may have an increased risk of certain endocrine disorders, such as thyroid abnormalities or adrenal gland tumors.
In addition to sebaceous skin tumors, individuals with MTS may be at increased risk of other types of skin tumors, both benign and malignant. These can include basal cell carcinoma, squamous cell carcinoma, and other rare skin cancers.
Associated activity
Acuity of presentation
The development of sebaceous skin tumors, such as sebaceous adenomas and sebaceous carcinomas, is often an early sign of MTS. These skin tumors can appear slowly over time and may be present for a considerable duration before diagnosis.
The onset and acuity of internal malignancies associated with MTS can vary. Colorectal and other gastrointestinal cancers may develop gradually, with symptoms such as changes in bowel habits, abdominal pain, or rectal bleeding becoming apparent over time.
A strong family history of MTS can prompt earlier surveillance and testing, potentially leading to the detection of MTS at an earlier stage.
Differential Diagnoses
Cowden Syndrome: This is another hereditary cancer syndrome caused by mutations in the PTEN gene. It is characterized by multiple hamartomas and an increased risk of various cancers, including breast, thyroid, and endometrial cancers. While it shares some clinical features with MTS, such as skin manifestations, the specific types of skin tumors are different.
Birt-Hogg-Dubé Syndrome: It is a genetic condition caused by mutations in the FLCN gene. It is associated with an increased risk of developing skin tumors called fibrofolliculomas, lung cysts, and kidney tumors. BHD can sometimes be confused with MTS due to the presence of skin tumors, but the types of skin tumors and the specific cancer risks are different.
Brooke-Spiegler Syndrome: Brooke-Spiegler Syndrome is another genetic condition characterized by the development of multiple skin tumors, including cylindromas, spiradenomas, and trichoepitheliomas. While it shares some similarities with MTS regarding skin tumors, the internal cancer risk associated with Brooke-Spiegler Syndrome is not as significant.
Laboratory Studies
Imaging Studies
Procedures
Histologic Findings
Staging
Treatment Paradigm
Surveillance and Screening: Regular surveillance and screening for both sebaceous skin tumors and internal malignancies are essential for individuals with MTS. Surveillance may include Skin Examinations, Colonoscopy and Endometrial Biopsies.
Surgical Management: Surgical removal of sebaceous skin tumors is generally recommended to prevent their progression to more aggressive forms and to address cosmetic concerns.
Management of Malignancies: If internal malignancies are detected during surveillance, appropriate treatment plans will be established. Treatment options may include surgery, chemotherapy, radiation therapy, and targeted therapies.
Avoiding Harmful Exposure: Minimize exposure to environmental factors known to increase cancer risk. This may include limiting exposure to environmental toxins, chemicals, and other potential carcinogens.
Protect from Sun: Since MTS is associated with sebaceous skin tumors, protecting the skin from excessive sun exposure is essential. Encourage the use of broad-spectrum sunscreen with a high SPF, wearing protective clothing, and seeking shade during peak sun hours.
Management of stress: Chronic stress can impact the immune system and overall health. Encourage stress-reduction techniques, such as mindfulness, meditation, yoga, or other relaxation exercises.
Surveillance and Screening: Regular screening and surveillance for both sebaceous skin tumors and internal malignancies are critical in managing MTS. Adhering to the recommended surveillance schedule is essential for early detection and timely intervention.
Healthy Environment: Providing a supportive and understanding environment for the individuals with MTS and their families can help manage the emotional and psychological challenges associated with living with hereditary cancer syndrome.
Use of Retinoids for treating Muir-Torre Syndrome
Retinoids, which are derivatives of vitamin A, have been used in the treatment of various skin conditions, including acne, psoriasis, and certain types of skin cancers. They are known to regulate cell growth and differentiation and can play a role in inhibiting tumor formation and progression.
Isotretinoin: It is taken by mouth that effectively treats severe skin conditions. It is a synthetic 13-cis form of tretinoin (trans-retinoic acid), which is naturally found in the body. Both substances are similar in structure to vitamin A.
Use of Immunotherapy
Immunotherapy is a type of treatment that helps the body’s immune system recognize and attack cancer cells. Immune checkpoint inhibitors are a common type of immunotherapy used in the treatment of various cancers, including some with microsatellite instability (MSI), which is a hallmark feature of MTS-related tumors.
Immunohistochemistry (IHC) examination of sebaceous growths for MMR proteins (MSH2, MLH1, MSH6, and PMS2) is a relatively straightforward technique that can be conducted on formalin-fixed, paraffin-embedded samples as the first screening assay for individuals with suspected Muir-Torre syndrome.
Use of Genetic testing
Genetic testing is utilized to confirm a diagnosis of Muir-Torre Syndrome in individuals suspected to have the condition based on clinical features, such as the presence of sebaceous gland tumors. Identifying the specific MMR gene mutations can help differentiate MTS from other similar conditions and guide appropriate management strategies.
Genetic testing in MTS allows for the assessment of an individual’s risk of developing internal malignancies associated with the syndrome. This information is critical for guiding surveillance strategies and early detection efforts.
Use of Colonoscopy
Individuals with Muir-Torre Syndrome are at a higher risk of developing colorectal cancer compared to the general population. Regular colonoscopies are recommended as a screening tool to detect any abnormalities or precancerous polyps in the colon and rectum.
Colonoscopy: It allows for the early detection of colorectal cancer in individuals with Muir-Torre Syndrome. Detecting cancer at an early stage greatly improves the chances of successful treatment and better outcomes.
A colonoscopy should be performed every one to two years, starting at the age of 20 to 25 years, or two to five years prior to the earliest age at which colorectal cancer has been diagnosed in the family.
Use of Microsatellite instability analysis (MSI)
MSI analysis is part of the diagnostic process for Muir-Torre Syndrome. The presence of microsatellite instability in the tumor tissue can indicate a potential underlying MMR gene mutation, suggesting a diagnosis of MTS.
MSI analysis can provide clues about which MMR gene(s) might be affected by mutations in an individual’s MTS. This information can be helpful for guiding further genetic testing and counselling.
Muir-Torre Syndrome is considered a phenotypic variant of Lynch Syndrome (Hereditary Non-Polyposis Colorectal Cancer or HNPCC). Both conditions are associated with MMR gene mutations. MSI analysis can be used to screen individuals for Lynch Syndrome, even in the absence of skin tumors.
Micrographic Surgery: It is a specialized surgical technique used for the treatment of certain skin cancers, including sebaceous carcinoma. During this procedure, layers of the tumor are removed and examined under a microscope until all cancerous cells are eradicated.
Surgical Excision: Surgical removal is the primary approach for managing sebaceous skin tumors. The goal of excision is to completely remove the tumor along with a margin of healthy surrounding tissue. The extent of excision will depend on factors such as the size, location, and potential for malignancy of the tumor.
Cryotherapy: Cryotherapy involves freezing the tumor using liquid nitrogen or another cryogenic agent. This procedure is commonly used for smaller, benign sebaceous adenomas.
use-of-phases-in-managing-muir-torre-syndrome
Counselling and Testing Phase: The management of MTS begins with the identification of individuals at risk. Genetic counseling is the initial phase, where individuals with a family history of MTS or those who meet, specific clinical criteria are evaluated to determine their risk of carrying germline mutations in DNA mismatch repair (MMR) genes.
Early Intervention and Treatment Phase: If sebaceous skin tumors or internal malignancies are detected during surveillance, early intervention and appropriate treatment are initiated. Surgical management is commonly employed for sebaceous skin tumors to remove the tumors and prevent their progression to more aggressive forms.
Monitoring and Follow-Up Phase: Ongoing monitoring and follow-up are essential for individuals with MTS. Regular assessments and screenings are conducted to monitor the effectiveness of treatments, detect any new tumor developments, and ensure that individuals receive the appropriate care.
Muir-Torre Syndrome (MTS) is a rare genetic disorder that is considered a subtype of Lynch Syndrome also known as Hereditary Nonpolyposis Colorectal Cancer (HNPCC). It was first described by Muir et al. in 1967.
It is characterized by the presence of sebaceous skin tumors, mainly sebaceous adenomas and carcinomas, along with an increased risk of certain internal malignancies, particularly colorectal and other gastrointestinal cancers.
Muir-Torre syndrome (MTS) is the fusion of growths on the skin typically sebaceous tumor, sebaceous growth, or sebaceous cancer and an internal cancer.
Muir-Torre syndrome has been seen in Caucasian individuals from developed nations. It is present in 9.2% of individuals diagnosed with Hereditary Nonpolyposis Colorectal Cancer (HNPCC).
There is a slight preference for males, with a ratio of 3 males to every 2 females. The average age at which malignancy develops is 53 years, with the earliest case reported at 23 years and the latest at 89 years.
MTS is more commonly diagnosed in adults, and there is no significant difference in its occurrence between males and females.
MTS is primarily caused by germline mutations in DNA mismatch repair (MMR) genes. These MMR genes play a crucial role in correcting errors that occur during DNA replication.
Microsatellite instability is a characteristic feature of both MTS and Lynch Syndrome. Mutations in these genes lead to a condition known as microsatellite instability (MSI), where repetitive DNA sequences (microsatellites) in the genome are prone to accumulate errors and mutations.
MSI can be detected by analyzing specific DNA markers that are prone to instability due to the defective MMR system. MSI leads to an increased likelihood of mutations in critical genes involved in cell cycle regulation and DNA repair, leading to an increased risk of tumorigenesis.
Muir-Torre Syndrome follows an autosomal dominant pattern of inheritance. This means that an affected individual has a 50% chance of passing on the mutated gene to each of their children. If an individual inherits a faulty mismatch repair (MMR) gene from one parent, they have an increased risk of developing MTS and related tumors.
Muir-Torre Syndrome can be associated with mutations in several different MMR genes, including MLH1, MSH2, MSH6, and PMS2. The specific gene affected can influence the severity of the condition and the types of tumors that may develop.
The age at which Muir-Torre Syndrome is diagnosed can impact the prognosis. In some cases, early detection of MTS may allow for timely surveillance and intervention, potentially improving outcomes.
The specific types of sebaceous tumors and internal malignancies that develop in an individual with MTS can influence the prognosis. Benign sebaceous adenomas have a better prognosis than malignant sebaceous carcinomas.
When local relapses occur, they typically happen within the initial five years of removal. The rates of relapse are approximately in the range of 30%.
Factors such as smoking, diet, and physical activity can also influence the prognosis in individuals with MTS, as they can impact the risk of cancer development and overall health.
The age at which internal malignancies associated with MTS occur can vary widely. Colorectal cancer and other gastrointestinal cancers, which are common internal malignancies in MTS, typically have a higher incidence in middle-aged and older adults.
The development of sebaceous skin tumors, such as sebaceous adenomas and sebaceous carcinomas, is often one of the initial signs of Muir-Torre Syndrome. These skin tumors can appear at a relatively young age, typically ranging from late childhood to early adulthood.
Abdominal Examination: The abdomen will be examined for tenderness, masses, or any other abnormalities that may suggest internal malignancies, particularly gastrointestinal tumors.
Rectal Examination: For individuals at an appropriate age, a rectal examination may be performed to check for any abnormalities, such as masses or bleeding, that could indicate colorectal cancer or other gastrointestinal conditions.
Rectal Examination: For individuals at an appropriate age, a rectal examination may be performed to check for any abnormalities, such as masses or bleeding, that could indicate colorectal cancer.
Lymph Node Examination: The healthcare provider may palpate the lymph nodes to check for any signs of enlargement or tenderness. Enlarged lymph nodes could indicate the spread of cancer and may prompt further investigations.
While colorectal and gastrointestinal cancers are the most common internal malignancies associated with MTS, there is an increased risk of other cancer types as well. These can include cancers affecting the urinary tract, ovaries, uterus, and pancreas.
Some individuals with MTS may have an increased risk of certain endocrine disorders, such as thyroid abnormalities or adrenal gland tumors.
In addition to sebaceous skin tumors, individuals with MTS may be at increased risk of other types of skin tumors, both benign and malignant. These can include basal cell carcinoma, squamous cell carcinoma, and other rare skin cancers.
The development of sebaceous skin tumors, such as sebaceous adenomas and sebaceous carcinomas, is often an early sign of MTS. These skin tumors can appear slowly over time and may be present for a considerable duration before diagnosis.
The onset and acuity of internal malignancies associated with MTS can vary. Colorectal and other gastrointestinal cancers may develop gradually, with symptoms such as changes in bowel habits, abdominal pain, or rectal bleeding becoming apparent over time.
A strong family history of MTS can prompt earlier surveillance and testing, potentially leading to the detection of MTS at an earlier stage.
Cowden Syndrome: This is another hereditary cancer syndrome caused by mutations in the PTEN gene. It is characterized by multiple hamartomas and an increased risk of various cancers, including breast, thyroid, and endometrial cancers. While it shares some clinical features with MTS, such as skin manifestations, the specific types of skin tumors are different.
Birt-Hogg-Dubé Syndrome: It is a genetic condition caused by mutations in the FLCN gene. It is associated with an increased risk of developing skin tumors called fibrofolliculomas, lung cysts, and kidney tumors. BHD can sometimes be confused with MTS due to the presence of skin tumors, but the types of skin tumors and the specific cancer risks are different.
Brooke-Spiegler Syndrome: Brooke-Spiegler Syndrome is another genetic condition characterized by the development of multiple skin tumors, including cylindromas, spiradenomas, and trichoepitheliomas. While it shares some similarities with MTS regarding skin tumors, the internal cancer risk associated with Brooke-Spiegler Syndrome is not as significant.
Surveillance and Screening: Regular surveillance and screening for both sebaceous skin tumors and internal malignancies are essential for individuals with MTS. Surveillance may include Skin Examinations, Colonoscopy and Endometrial Biopsies.
Surgical Management: Surgical removal of sebaceous skin tumors is generally recommended to prevent their progression to more aggressive forms and to address cosmetic concerns.
Management of Malignancies: If internal malignancies are detected during surveillance, appropriate treatment plans will be established. Treatment options may include surgery, chemotherapy, radiation therapy, and targeted therapies.
Dermatology, General
Lifestyle modification:
Adopting a healthy lifestyle can positively impact overall health and reduce cancer risk.
Follow a balanced and nutritious diet, rich in fruits, vegetables, whole grains, and lean proteins.
Engage in regular physical activity, such as walking, jogging, or other forms of exercise.
Avoiding Harmful Exposure: Minimize exposure to environmental factors known to increase cancer risk. This may include limiting exposure to environmental toxins, chemicals, and other potential carcinogens.
Protect from Sun: Since MTS is associated with sebaceous skin tumors, protecting the skin from excessive sun exposure is essential. Encourage the use of broad-spectrum sunscreen with a high SPF, wearing protective clothing, and seeking shade during peak sun hours.
Management of stress: Chronic stress can impact the immune system and overall health. Encourage stress-reduction techniques, such as mindfulness, meditation, yoga, or other relaxation exercises.
Surveillance and Screening: Regular screening and surveillance for both sebaceous skin tumors and internal malignancies are critical in managing MTS. Adhering to the recommended surveillance schedule is essential for early detection and timely intervention.
Healthy Environment: Providing a supportive and understanding environment for the individuals with MTS and their families can help manage the emotional and psychological challenges associated with living with hereditary cancer syndrome.
Dermatology, General
Retinoids, which are derivatives of vitamin A, have been used in the treatment of various skin conditions, including acne, psoriasis, and certain types of skin cancers. They are known to regulate cell growth and differentiation and can play a role in inhibiting tumor formation and progression.
Isotretinoin: It is taken by mouth that effectively treats severe skin conditions. It is a synthetic 13-cis form of tretinoin (trans-retinoic acid), which is naturally found in the body. Both substances are similar in structure to vitamin A.
Dermatology, General
Immunotherapy is a type of treatment that helps the body’s immune system recognize and attack cancer cells. Immune checkpoint inhibitors are a common type of immunotherapy used in the treatment of various cancers, including some with microsatellite instability (MSI), which is a hallmark feature of MTS-related tumors.
Immunohistochemistry (IHC) examination of sebaceous growths for MMR proteins (MSH2, MLH1, MSH6, and PMS2) is a relatively straightforward technique that can be conducted on formalin-fixed, paraffin-embedded samples as the first screening assay for individuals with suspected Muir-Torre syndrome.
Dermatology, General
Genetic testing is utilized to confirm a diagnosis of Muir-Torre Syndrome in individuals suspected to have the condition based on clinical features, such as the presence of sebaceous gland tumors. Identifying the specific MMR gene mutations can help differentiate MTS from other similar conditions and guide appropriate management strategies.
Genetic testing in MTS allows for the assessment of an individual’s risk of developing internal malignancies associated with the syndrome. This information is critical for guiding surveillance strategies and early detection efforts.
Dermatology, General
Individuals with Muir-Torre Syndrome are at a higher risk of developing colorectal cancer compared to the general population. Regular colonoscopies are recommended as a screening tool to detect any abnormalities or precancerous polyps in the colon and rectum.
Colonoscopy: It allows for the early detection of colorectal cancer in individuals with Muir-Torre Syndrome. Detecting cancer at an early stage greatly improves the chances of successful treatment and better outcomes.
A colonoscopy should be performed every one to two years, starting at the age of 20 to 25 years, or two to five years prior to the earliest age at which colorectal cancer has been diagnosed in the family.
Dermatology, General
MSI analysis is part of the diagnostic process for Muir-Torre Syndrome. The presence of microsatellite instability in the tumor tissue can indicate a potential underlying MMR gene mutation, suggesting a diagnosis of MTS.
MSI analysis can provide clues about which MMR gene(s) might be affected by mutations in an individual’s MTS. This information can be helpful for guiding further genetic testing and counselling.
Muir-Torre Syndrome is considered a phenotypic variant of Lynch Syndrome (Hereditary Non-Polyposis Colorectal Cancer or HNPCC). Both conditions are associated with MMR gene mutations. MSI analysis can be used to screen individuals for Lynch Syndrome, even in the absence of skin tumors.
Dermatology, General
Micrographic Surgery: It is a specialized surgical technique used for the treatment of certain skin cancers, including sebaceous carcinoma. During this procedure, layers of the tumor are removed and examined under a microscope until all cancerous cells are eradicated.
Surgical Excision: Surgical removal is the primary approach for managing sebaceous skin tumors. The goal of excision is to completely remove the tumor along with a margin of healthy surrounding tissue. The extent of excision will depend on factors such as the size, location, and potential for malignancy of the tumor.
Cryotherapy: Cryotherapy involves freezing the tumor using liquid nitrogen or another cryogenic agent. This procedure is commonly used for smaller, benign sebaceous adenomas.
Dermatology, General
Counselling and Testing Phase: The management of MTS begins with the identification of individuals at risk. Genetic counseling is the initial phase, where individuals with a family history of MTS or those who meet, specific clinical criteria are evaluated to determine their risk of carrying germline mutations in DNA mismatch repair (MMR) genes.
Early Intervention and Treatment Phase: If sebaceous skin tumors or internal malignancies are detected during surveillance, early intervention and appropriate treatment are initiated. Surgical management is commonly employed for sebaceous skin tumors to remove the tumors and prevent their progression to more aggressive forms.
Monitoring and Follow-Up Phase: Ongoing monitoring and follow-up are essential for individuals with MTS. Regular assessments and screenings are conducted to monitor the effectiveness of treatments, detect any new tumor developments, and ensure that individuals receive the appropriate care.
Muir-Torre Syndrome | Archives of Pathology & Laboratory Medicine (allenpress.com)
medtigo
Muir-Torre Syndrome
Updated :
October 10, 2023
Muir-Torre Syndrome (MTS) is a rare genetic disorder that is considered a subtype of Lynch Syndrome also known as Hereditary Nonpolyposis Colorectal Cancer (HNPCC). It was first described by Muir et al. in 1967.
It is characterized by the presence of sebaceous skin tumors, mainly sebaceous adenomas and carcinomas, along with an increased risk of certain internal malignancies, particularly colorectal and other gastrointestinal cancers.
Muir-Torre syndrome (MTS) is the fusion of growths on the skin typically sebaceous tumor, sebaceous growth, or sebaceous cancer and an internal cancer.
Muir-Torre syndrome has been seen in Caucasian individuals from developed nations. It is present in 9.2% of individuals diagnosed with Hereditary Nonpolyposis Colorectal Cancer (HNPCC).
There is a slight preference for males, with a ratio of 3 males to every 2 females. The average age at which malignancy develops is 53 years, with the earliest case reported at 23 years and the latest at 89 years.
MTS is more commonly diagnosed in adults, and there is no significant difference in its occurrence between males and females.
MTS is primarily caused by germline mutations in DNA mismatch repair (MMR) genes. These MMR genes play a crucial role in correcting errors that occur during DNA replication.
Microsatellite instability is a characteristic feature of both MTS and Lynch Syndrome. Mutations in these genes lead to a condition known as microsatellite instability (MSI), where repetitive DNA sequences (microsatellites) in the genome are prone to accumulate errors and mutations.
MSI can be detected by analyzing specific DNA markers that are prone to instability due to the defective MMR system. MSI leads to an increased likelihood of mutations in critical genes involved in cell cycle regulation and DNA repair, leading to an increased risk of tumorigenesis.
Muir-Torre Syndrome follows an autosomal dominant pattern of inheritance. This means that an affected individual has a 50% chance of passing on the mutated gene to each of their children. If an individual inherits a faulty mismatch repair (MMR) gene from one parent, they have an increased risk of developing MTS and related tumors.
Muir-Torre Syndrome can be associated with mutations in several different MMR genes, including MLH1, MSH2, MSH6, and PMS2. The specific gene affected can influence the severity of the condition and the types of tumors that may develop.
The age at which Muir-Torre Syndrome is diagnosed can impact the prognosis. In some cases, early detection of MTS may allow for timely surveillance and intervention, potentially improving outcomes.
The specific types of sebaceous tumors and internal malignancies that develop in an individual with MTS can influence the prognosis. Benign sebaceous adenomas have a better prognosis than malignant sebaceous carcinomas.
When local relapses occur, they typically happen within the initial five years of removal. The rates of relapse are approximately in the range of 30%.
Factors such as smoking, diet, and physical activity can also influence the prognosis in individuals with MTS, as they can impact the risk of cancer development and overall health.
The age at which internal malignancies associated with MTS occur can vary widely. Colorectal cancer and other gastrointestinal cancers, which are common internal malignancies in MTS, typically have a higher incidence in middle-aged and older adults.
The development of sebaceous skin tumors, such as sebaceous adenomas and sebaceous carcinomas, is often one of the initial signs of Muir-Torre Syndrome. These skin tumors can appear at a relatively young age, typically ranging from late childhood to early adulthood.
Abdominal Examination: The abdomen will be examined for tenderness, masses, or any other abnormalities that may suggest internal malignancies, particularly gastrointestinal tumors.
Rectal Examination: For individuals at an appropriate age, a rectal examination may be performed to check for any abnormalities, such as masses or bleeding, that could indicate colorectal cancer or other gastrointestinal conditions.
Rectal Examination: For individuals at an appropriate age, a rectal examination may be performed to check for any abnormalities, such as masses or bleeding, that could indicate colorectal cancer.
Lymph Node Examination: The healthcare provider may palpate the lymph nodes to check for any signs of enlargement or tenderness. Enlarged lymph nodes could indicate the spread of cancer and may prompt further investigations.
While colorectal and gastrointestinal cancers are the most common internal malignancies associated with MTS, there is an increased risk of other cancer types as well. These can include cancers affecting the urinary tract, ovaries, uterus, and pancreas.
Some individuals with MTS may have an increased risk of certain endocrine disorders, such as thyroid abnormalities or adrenal gland tumors.
In addition to sebaceous skin tumors, individuals with MTS may be at increased risk of other types of skin tumors, both benign and malignant. These can include basal cell carcinoma, squamous cell carcinoma, and other rare skin cancers.
The development of sebaceous skin tumors, such as sebaceous adenomas and sebaceous carcinomas, is often an early sign of MTS. These skin tumors can appear slowly over time and may be present for a considerable duration before diagnosis.
The onset and acuity of internal malignancies associated with MTS can vary. Colorectal and other gastrointestinal cancers may develop gradually, with symptoms such as changes in bowel habits, abdominal pain, or rectal bleeding becoming apparent over time.
A strong family history of MTS can prompt earlier surveillance and testing, potentially leading to the detection of MTS at an earlier stage.
Cowden Syndrome: This is another hereditary cancer syndrome caused by mutations in the PTEN gene. It is characterized by multiple hamartomas and an increased risk of various cancers, including breast, thyroid, and endometrial cancers. While it shares some clinical features with MTS, such as skin manifestations, the specific types of skin tumors are different.
Birt-Hogg-Dubé Syndrome: It is a genetic condition caused by mutations in the FLCN gene. It is associated with an increased risk of developing skin tumors called fibrofolliculomas, lung cysts, and kidney tumors. BHD can sometimes be confused with MTS due to the presence of skin tumors, but the types of skin tumors and the specific cancer risks are different.
Brooke-Spiegler Syndrome: Brooke-Spiegler Syndrome is another genetic condition characterized by the development of multiple skin tumors, including cylindromas, spiradenomas, and trichoepitheliomas. While it shares some similarities with MTS regarding skin tumors, the internal cancer risk associated with Brooke-Spiegler Syndrome is not as significant.
Surveillance and Screening: Regular surveillance and screening for both sebaceous skin tumors and internal malignancies are essential for individuals with MTS. Surveillance may include Skin Examinations, Colonoscopy and Endometrial Biopsies.
Surgical Management: Surgical removal of sebaceous skin tumors is generally recommended to prevent their progression to more aggressive forms and to address cosmetic concerns.
Management of Malignancies: If internal malignancies are detected during surveillance, appropriate treatment plans will be established. Treatment options may include surgery, chemotherapy, radiation therapy, and targeted therapies.
Dermatology, General
Lifestyle modification:
Adopting a healthy lifestyle can positively impact overall health and reduce cancer risk.
Follow a balanced and nutritious diet, rich in fruits, vegetables, whole grains, and lean proteins.
Engage in regular physical activity, such as walking, jogging, or other forms of exercise.
Avoiding Harmful Exposure: Minimize exposure to environmental factors known to increase cancer risk. This may include limiting exposure to environmental toxins, chemicals, and other potential carcinogens.
Protect from Sun: Since MTS is associated with sebaceous skin tumors, protecting the skin from excessive sun exposure is essential. Encourage the use of broad-spectrum sunscreen with a high SPF, wearing protective clothing, and seeking shade during peak sun hours.
Management of stress: Chronic stress can impact the immune system and overall health. Encourage stress-reduction techniques, such as mindfulness, meditation, yoga, or other relaxation exercises.
Surveillance and Screening: Regular screening and surveillance for both sebaceous skin tumors and internal malignancies are critical in managing MTS. Adhering to the recommended surveillance schedule is essential for early detection and timely intervention.
Healthy Environment: Providing a supportive and understanding environment for the individuals with MTS and their families can help manage the emotional and psychological challenges associated with living with hereditary cancer syndrome.
Dermatology, General
Retinoids, which are derivatives of vitamin A, have been used in the treatment of various skin conditions, including acne, psoriasis, and certain types of skin cancers. They are known to regulate cell growth and differentiation and can play a role in inhibiting tumor formation and progression.
Isotretinoin: It is taken by mouth that effectively treats severe skin conditions. It is a synthetic 13-cis form of tretinoin (trans-retinoic acid), which is naturally found in the body. Both substances are similar in structure to vitamin A.
Dermatology, General
Immunotherapy is a type of treatment that helps the body’s immune system recognize and attack cancer cells. Immune checkpoint inhibitors are a common type of immunotherapy used in the treatment of various cancers, including some with microsatellite instability (MSI), which is a hallmark feature of MTS-related tumors.
Immunohistochemistry (IHC) examination of sebaceous growths for MMR proteins (MSH2, MLH1, MSH6, and PMS2) is a relatively straightforward technique that can be conducted on formalin-fixed, paraffin-embedded samples as the first screening assay for individuals with suspected Muir-Torre syndrome.
Dermatology, General
Genetic testing is utilized to confirm a diagnosis of Muir-Torre Syndrome in individuals suspected to have the condition based on clinical features, such as the presence of sebaceous gland tumors. Identifying the specific MMR gene mutations can help differentiate MTS from other similar conditions and guide appropriate management strategies.
Genetic testing in MTS allows for the assessment of an individual’s risk of developing internal malignancies associated with the syndrome. This information is critical for guiding surveillance strategies and early detection efforts.
Dermatology, General
Individuals with Muir-Torre Syndrome are at a higher risk of developing colorectal cancer compared to the general population. Regular colonoscopies are recommended as a screening tool to detect any abnormalities or precancerous polyps in the colon and rectum.
Colonoscopy: It allows for the early detection of colorectal cancer in individuals with Muir-Torre Syndrome. Detecting cancer at an early stage greatly improves the chances of successful treatment and better outcomes.
A colonoscopy should be performed every one to two years, starting at the age of 20 to 25 years, or two to five years prior to the earliest age at which colorectal cancer has been diagnosed in the family.
Dermatology, General
MSI analysis is part of the diagnostic process for Muir-Torre Syndrome. The presence of microsatellite instability in the tumor tissue can indicate a potential underlying MMR gene mutation, suggesting a diagnosis of MTS.
MSI analysis can provide clues about which MMR gene(s) might be affected by mutations in an individual’s MTS. This information can be helpful for guiding further genetic testing and counselling.
Muir-Torre Syndrome is considered a phenotypic variant of Lynch Syndrome (Hereditary Non-Polyposis Colorectal Cancer or HNPCC). Both conditions are associated with MMR gene mutations. MSI analysis can be used to screen individuals for Lynch Syndrome, even in the absence of skin tumors.
Dermatology, General
Micrographic Surgery: It is a specialized surgical technique used for the treatment of certain skin cancers, including sebaceous carcinoma. During this procedure, layers of the tumor are removed and examined under a microscope until all cancerous cells are eradicated.
Surgical Excision: Surgical removal is the primary approach for managing sebaceous skin tumors. The goal of excision is to completely remove the tumor along with a margin of healthy surrounding tissue. The extent of excision will depend on factors such as the size, location, and potential for malignancy of the tumor.
Cryotherapy: Cryotherapy involves freezing the tumor using liquid nitrogen or another cryogenic agent. This procedure is commonly used for smaller, benign sebaceous adenomas.
Dermatology, General
Counselling and Testing Phase: The management of MTS begins with the identification of individuals at risk. Genetic counseling is the initial phase, where individuals with a family history of MTS or those who meet, specific clinical criteria are evaluated to determine their risk of carrying germline mutations in DNA mismatch repair (MMR) genes.
Early Intervention and Treatment Phase: If sebaceous skin tumors or internal malignancies are detected during surveillance, early intervention and appropriate treatment are initiated. Surgical management is commonly employed for sebaceous skin tumors to remove the tumors and prevent their progression to more aggressive forms.
Monitoring and Follow-Up Phase: Ongoing monitoring and follow-up are essential for individuals with MTS. Regular assessments and screenings are conducted to monitor the effectiveness of treatments, detect any new tumor developments, and ensure that individuals receive the appropriate care.
Muir-Torre Syndrome | Archives of Pathology & Laboratory Medicine (allenpress.com)
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