| treatment = Surgical excision, regular cancer surveillance
| medication =
| medication =
| prognosis =
| prognosis = Good with early detection and management
| frequency =
| frequency = Rare
| deaths =
| deaths = Usually related to complications from malignancies
}}
}}
'''Muir–Torre syndrome''' is a rare hereditary, [[autosomal dominant]] [[cancer syndrome]]<ref name="Andrews">{{cite book |author1=James, William D. |author2=Berger, Timothy G. |title=Andrews' Diseases of the Skin: clinical Dermatology |publisher=Saunders Elsevier |location= |year=2006 |pages= |isbn=978-0-7216-2921-6 |oclc= |doi= |display-authors=etal}}</ref>{{rp|663}} that is thought to be a subtype of [[HNPCC]]. Individuals are prone to develop cancers of the colon, genitourinary tract, and skin lesions, such as [[keratoacanthoma]]s and [[Sebaceous carcinoma|sebaceous tumors]]. The genes affected are [[MLH1]], [[MSH2]], and more recently, MSH6, and are involved in [[DNA mismatch repair]].
'''Muir–Torre syndrome''' ('''MTS''') is a rare, hereditary [[autosomal dominant]] [[cancer syndrome]], considered a subtype of [[Lynch syndrome]] (Hereditary Non-Polyposis Colorectal Cancer, [[HNPCC]]). Individuals with this syndrome have an increased susceptibility to cancers of the colon, genitourinary tract, and distinct skin lesions, including [[keratoacanthoma]]s and sebaceous tumors such as [[sebaceous adenoma]], sebaceous epithelioma, and [[sebaceous carcinoma]].
== Symptoms ==
== Signs and Symptoms ==
Muir–Torre syndrome is characterized by both:<ref name="Am Journal">{{cite journal |vauthors=Cohen PR, Kohn R, Kurzrock R |title=Association of sebaceous gland tumors and internal malignancy: The Muir–Torre syndrome |journal= The American Journal of Medicine|volume=90 |issue=5 |pages=606–13 |date=May 1991 |doi= 10.1016/S0002-9343(05)80013-0 |pmid=2029018}}</ref>
Characteristic features include:
# At least a single sebaceous gland tumor (either an adenoma, an epithelioma, or a carcinoma)
* Presence of at least one sebaceous gland tumor (adenoma, epithelioma, or carcinoma)
# A minimum of one internal malignancy
* Occurrence of at least one internal malignancy, commonly colorectal or genitourinary cancers
The [[Amsterdam criteria]] are frequently used to diagnose Lynch syndrome and Muir–Torre syndrome. They include the following:
== Genetics ==
* 3 or more relatives with an HNPCC-associated cancer (i.e., colorectal, cancer of the endometrium, small bowel, ureter, or renal pelvis)
Muir–Torre syndrome is caused primarily by mutations in the [[MLH1]], [[MSH2]], and more recently identified [[MSH6]] genes. These genes are critical for the [[DNA mismatch repair]] pathway. Mutations result in defective DNA repair mechanisms, increasing the risk of developing cancers.
* 2 or more successive generations affected by cancer
* 1 or more persons with cancer is a first-degree relative of the other 2, at least 1 case of colorectal cancer younger than age 50 years, a diagnosis of familial adenomatous polyposis has been excluded, tumors are verified by histologic examination
Muir–Torre syndrome is a genetic condition. Mutations in [[MLH1]] and [[MSH2]] are linked with the disease. These genes code for DNA mismatch repair genes, and mutations increase the risk of developing cancerous qualities.{{cn|date=April 2020}}
== Diagnosis ==
Diagnosis typically involves:
* Clinical evaluation of sebaceous skin tumors and internal malignancies
* Genetic testing for mutations in DNA mismatch repair genes
* Immunohistochemical analysis for mismatch repair proteins
* Application of the [[Amsterdam criteria]], widely used to diagnose Lynch syndrome and Muir–Torre syndrome, which include:
** At least three relatives affected by Lynch-associated cancers (colorectal, endometrial, small bowel, ureter, renal pelvis)
** Cancer affecting at least two successive generations
** At least one individual diagnosed before age 50
** Exclusion of familial adenomatous polyposis
The Mayo Muir–Torre risk score was developed to enhance diagnostic accuracy, distinguishing true cases from sporadic sebaceous tumors.
Many patients who have sebaceous neoplasms with mutations in MSH2 and MLH1 do not in fact have Muir–Torre syndrome. The Mayo Muir–Torre risk score was devised to improve the positive predictive value of immunohistochemistry and reduce the false positive rate.<ref name="Roberts ME 2014">{{cite journal | author = Roberts ME, Riegert-Johnson DL, Thomas BC | display-authors = etal | year = 2014 | title = A clinical scoring system to identify patients with sebaceous neoplasms at risk for the Muir–Torre variant of Lynch syndrome | url = | journal = Genetics in Medicine| volume = 16 | issue = 9| pages = 711–16 | doi = 10.1038/gim.2014.19 | pmid = 24603434 | doi-access = free }}</ref><ref>{{cite journal | author = Roberts ME, Riegert-Johnson DL, Thomas BC | display-authors = etal | year = 2013 | title = Screening for Muir–Torre syndrome using mismatch repair protein immunohisochemistry of sebaceous neoplasms | url = | journal = J Genet Counsel | volume = 22 | issue = 3| pages = 393–405 | doi = 10.1007/s10897-012-9552-4 | pmid = 23212176 }}</ref>
== Management ==
The Mayo Muir–Torre Risk score assigns points based several characteristics. A score of 2 or greater has a high positive predictive value of Muir–Torre syndrome. A score of 1 or lower is less likely to be Muir–Torre syndrome.<ref name="Roberts ME 2014"/>
Treatment strategies involve:
* Surgical removal of skin lesions
* Regular screening and surveillance for internal malignancies (colonoscopies, genitourinary screenings)
* Genetic counseling for patients and their families
Age of onset of first sebaceous neoplasm: <60 years = 1 point, otherwise 0 points
== Prognosis ==
Total number of sebaceous neoplasms: 1 = 0 points, >2 = 2 points.
With appropriate management and regular surveillance, the prognosis for individuals with Muir–Torre syndrome can be favorable. Early detection and treatment of malignancies significantly improve outcomes.
Personal history of Lynch related cancers: No = 0 points, Yes = 1 point
Family history of Lynch-related cancer: No = 0 points, Yes = 1 point
The most common internal malignancies associated with Muir–Torre syndrome are: Colorectal (56%), Urogenital (22%), Small Intestine (4%), and Breast (4%). A variety of other internal malignancies have been reported.<ref>{{cite journal | author = Akhtar S, Oza KK, Khan SA | display-authors = etal | year = 1999 | title = Muir–Torre syndrome: a case report of a patient with concurrent jejunal and ureteral cancer and a review of the literature | url = | journal = J Am Acad Dermatol | volume = 41 | issue = 5| pages = 681–6 | doi = 10.1016/s0190-9622(99)70001-0 | pmid = 10534628 }}</ref>
== Prevention ==
Preventive measures focus on:
* Early genetic screening and counseling for at-risk families
* Frequent surveillance for early detection of malignancies
==Cause==
Muir–Torre syndrome remains a rare condition, requiring multidisciplinary care involving dermatologists, geneticists, oncologists, and surgeons.
=== Genetic overlap with Turcot syndrome ===
A couple studies have been conducted on patients with both Muir–Torre syndrome and [[Turcot syndrome]]. It is thought that the two may have some genetic overlap. Both have been associated defects in [[MLH1]] and [[MSH2]] genes.<ref name="Dermatology Online">{{cite journal |vauthors=Kleinerman R, Marino J, Loucas E |title=Muir–Torre Syndrome / Turcot Syndrome overlap? A patient with sebaceous carcinoma, colon cancer, and a malignant astrocytoma |journal=Dermatology Online Journal |volume = 18|issue=5 |pages=3 |date=May 2012 |pmid= 22630573 |url=}}</ref>
In one study, a patient with defective [[MSH2]] and [[MSH6]] mismatch repair genes exhibited both syndromes. This is the first case where a patient with genotypic changes consistent with [[HNPCC]] has been properly diagnosed with an overlap of both syndromes. Along with neoplasms of the sebaceous gland, this patient developed cerebral neoplasms, characteristic of Turcot syndrome.<ref name="Surgical Neurology International">{{cite journal |vauthors=Grandhi R, Deibert CP, Pirris SM, Lembersky B, Mintz AH |title=Simultaneous Muir–Torre and Turcot's syndrome: A case report and review of the literature |journal=Surg Neurol Int |volume = 4|issue=52 |date=April 2013 |doi=10.4103/2152-7806.110512 |pmid=23646262 |pmc=3640225 |url= |pages=52}}</ref>
==Diagnosis==
A person is suspected to have Muir-Torre syndrome (MTS) if he/she has one or more of the following:
* History of one or more [[Sebaceous tumor|sebaceous tumors]]
* Age younger than 60 years at first presentation of sebaceous tumors
* Personal history of Lynch-related cancers
* Family history of Lynch-related cancers
* The presence of specific skin tumors in MTS may lead to the correct diagnosis even in the absence of a clear family history.
* A person diagnosed with MTS can also have [[genetic testing]] to see if they have a mutation in one of the genes known to cause MTS.
* However, not everyone with Muir-Torre syndrome will have a detectable mutation in one of these genes.
* Other, unidentified genes may also play a role in the development of the condition.
== Treatment ==
Immunohistochemistry is now being used more often to diagnose patients likely to have Muir–Torre syndrome. Sebaceous neoplasms are only infrequently encountered, and immunohistochemistry is reliable and readily available, so researchers have recommended its use. Routine immunohistochemical detection of DNA mismatch repair proteins help identify hereditary DNA mismatch repair deficiency.<ref name="Immunohistochemistry">{{cite journal |vauthors=Orta L, Klimstra DS, Qin J, etal |title= Towards identification of hereditary DNA mismatch repair deficiency: sebaceous neoplasm warrants routine immunohistochemical screening regardless of patient's age or other clinical characteristics |journal=Am J Surg Pathol |volume=33|issue=6|pages=934–44 |year=2009|pmid=19342947|doi=10.1097/PAS.0b013e318199edca|url=}}</ref>
Treatment of Muir–Torre syndrome normally consists of oral [[isotretinoin]]. The drug has been found to prevent tumor development.<ref name="Isotretinoin">{{cite journal |vauthors=Graefe T, Wollina U, Schulz H, Burgdorf W |title= Muir–Torre Syndrome – Treatment with Isotretinoin and Interferon Alpha-2a Can Prevent Tumour Development |journal=Dermatology |volume=200|issue=4 |pages=331–3 |date=March 2000 |doi= 10.1159/000018399|url= http://nbn-resolving.de/urn:nbn:de:bvb:19-epub-16903-5|pmid=10894967}}</ref><ref name="Oral isotretinoin">{{cite journal |vauthors=Spielvogel RL, DeVillez RL, Roberts LC |title= Oral isotretinoin therapy for familial Muir–Torre syndrome |journal=J Am Acad Dermatol |volume=12|issue=3 |pages=475–80 |date=March 1985|pmid=3857234|url= |doi=10.1016/S0190-9622(85)70066-7}}</ref>
Patients with Muir–Torre syndrome should follow the same stringent screening for colorectal carcinoma and other malignancies as patients with Lynch syndrome. This includes frequent and early colonoscopies, mammograms, dermatologic evaluation, and imaging of the abdomen and pelvis.<ref>{{cite journal | author = Ponti G, Pnz de Leon M | year = 2005 | title = Muir–Torre syndrome | url = | journal = Lancet Oncol | volume = 6 | issue = 12| pages = 980–87 | pmid = 16321766 | doi = 10.1016/S1470-2045(05)70465-4 }}</ref>
== Incidence ==
Muir–Torre was observed to occur in 14 of 50 families (28%) and in 14 of 152 individuals (9.2%) with Lynch syndrome, also known as [[HNPCC]].<ref name="Oxford Journal">{{cite journal |vauthors=South CD, Hampel H, Comeas I, Westman JA, Frankel WL, Chapelle A |title=The Frequency of Muir–Torre Syndrome Among Lynch Syndrome Families |journal= Oxford Journal|volume=100 |issue=4 |pages=277–81 |date=February 2008 |pmid=18270343 |doi= 10.1093/jnci/djm291|url=|doi-access=free }}</ref>
The 2 major MMR proteins involved are hMLH1 and hMSH2. Approximately 70% of tumors associated with the MTS have microsatellite instability. While germline disruption of hMLH1 and hMSH2 is evenly distributed in HNPCC, disruption of hMSH2 is seen in greater than 90% of MTS patients.<ref name="J Invest Dermatol">{{cite journal |vauthors=Ponti G, Losi L, Pedroni M |title= Value of MLH1 and MSH2 mutations in the appearance of Muir–Torre syndrome phenotype in HNPCC patients presenting sebaceous gland tumors or keratoacanthomas. ||journal=J Invest Dermatol|volume=126|issue=10|pages=2302–7|date=October 2006|pmid=16826164|url= |doi=10.1038/sj.jid.5700475|doi-access=free}}</ref>
Gastrointestinal and genitourinary cancers are the most common internal malignancies. Colorectal cancer is the most common visceral neoplasm in Muir–Torre syndrome patients.<ref name="PubMed">{{cite journal |vauthors=Okan G, Vural P, Ince U, Yazar A, Uras C, Saruc M |title=Muir–Torre syndrome: a case report and review of the literature |journal=Turk J Gastroenterol |issue=4 |pages=394–8 |date=August 2012 |pmid= 22965514 |url= |volume=23|doi=10.4318/tjg.2012.0411 }}</ref>
== Eponym ==
== Eponym ==
It is named for EG Muir and D Torre. A British physician, Muir noted a patient with many keratoacanthomas who went on to develop several internal malignancies at a young age. Torre presented his findings at a meeting of the New York Dermatologic Society.<ref name="pmid6020987">{{cite journal |vauthors=Muir EG, Bell AJ, Barlow KA |title=Multiple primary carcinomata of the colon, duodenum, and larynx associated with kerato-acanthomata of the face |journal=Br J Surg |volume=54 |issue=3 |pages=191–5 |date=March 1967 |pmid=6020987 |doi= 10.1002/bjs.1800540309|url=}}</ref><ref name="pmid5684233">{{cite journal |author=Torre D |title=Multiple sebaceous tumors |journal=Arch Dermatol |volume=98 |issue=5 |pages=549–51 |date=November 1968 |pmid=5684233 |doi= 10.1001/archderm.98.5.549|url=}}</ref>
It is named for EG Muir and D Torre. A British physician, Muir noted a patient with many keratoacanthomas who went on to develop several internal malignancies at a young age. Torre presented his findings at a meeting of the New York Dermatologic Society.
It was not until the 1980s when Creighton professor Henry Lynch noted a clustering of Muir–Torre syndrome patients in families with Lynch syndrome.<ref>{{cite journal | author = Lynch HT, Fussaro RM, Roberts L | display-authors = etal | year = 1985 | title = Muir–Torre syndrome in several members of a family with a variant of the Cancer Family Syndrome | url = | journal = Br J Dermatol | volume = 113 | issue = 3| pages = 295–301 | doi = 10.1111/j.1365-2133.1985.tb02081.x | pmid = 4063166 }}</ref>
== See also ==
== See also ==
* [[List of cutaneous conditions]]
* [[List of cutaneous conditions]]
* [[List of cutaneous conditions associated with increased risk of nonmelanoma skin cancer]]
* [[List of cutaneous conditions associated with increased risk of nonmelanoma skin cancer]]
== References ==
{{Reflist}}
== External links ==
== External links ==
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{{Tumors of skin appendages}}
{{Tumors of skin appendages}}
{{DNA repair-deficiency disorder}}
{{DNA repair-deficiency disorder}}
{{stub}}
{{DEFAULTSORT:Muir-Torre syndrome}}
{{DEFAULTSORT:Muir-Torre syndrome}}
[[Category:Epidermal nevi, neoplasms, and cysts]]
[[Category:Epidermal nevi, neoplasms, and cysts]]
[[Category:DNA replication and repair-deficiency disorders]]
[[Category:DNA replication and repair-deficiency disorders]]
Sporadic sebaceous tumors, other hereditary cancer syndromes
Prevention
Regular screening, genetic counseling
Treatment
Surgical excision, regular cancer surveillance
Medication
Prognosis
Good with early detection and management
Frequency
Rare
Deaths
Usually related to complications from malignancies
Muir–Torre syndrome (MTS) is a rare, hereditary autosomal dominantcancer syndrome, considered a subtype of Lynch syndrome (Hereditary Non-Polyposis Colorectal Cancer, HNPCC). Individuals with this syndrome have an increased susceptibility to cancers of the colon, genitourinary tract, and distinct skin lesions, including keratoacanthomas and sebaceous tumors such as sebaceous adenoma, sebaceous epithelioma, and sebaceous carcinoma.
Muir–Torre syndrome is caused primarily by mutations in the MLH1, MSH2, and more recently identified MSH6 genes. These genes are critical for the DNA mismatch repair pathway. Mutations result in defective DNA repair mechanisms, increasing the risk of developing cancers.
With appropriate management and regular surveillance, the prognosis for individuals with Muir–Torre syndrome can be favorable. Early detection and treatment of malignancies significantly improve outcomes.
It is named for EG Muir and D Torre. A British physician, Muir noted a patient with many keratoacanthomas who went on to develop several internal malignancies at a young age. Torre presented his findings at a meeting of the New York Dermatologic Society.
