Muir torre syndrome Q87.89

Muir-Torre syndrome (MTS) was first described in 1967 by Muir et al. and, a year later, in 1968, independently by Torre et al.
 

Muir-Torre syndrome is a rare, autosomal dominant disorder that is a phenotypic variant of "hereditary nonpolyposis colorectal cancer (HNPCC)," also known as Lynch syndrome. It is caused by mutations in DNA mismatch repair genes, which lead to microsatellite instability.  The association between mutations in mismatch repair genes and visceral malignancies warrants earlier and more frequent screening for malignancies (see also tumor-associated genodermatoses). The syndrome is characterized by:

• multiple benign and malignant skin tumors (sebaceous gland neoplasms(see also “Sebaceous Gland Hyperplasias”), basal cell carcinomas, keratoacanthomas)

and

• carcinomas of internal organs: colorectal carcinoma (49%), carcinomas of the urogenital tract (20%); breast carcinomas (10%); myeloproliferative disorders (9%), carcinomas of the upper gastrointestinal tract (7%).

It is presumed that Muir-Torre syndrome represents a (deleted) variant ofthe “hereditary nonpolyposis colorectal cancer syndrome” (HNPCC/Lynch syndrome type II), in which mutations occur in the same gene. 

An autosomal dominant genetic disorder.

• A mutation in the MSH2 gene, which is located at the 2p21 genetic locus

and, less commonly,

• theMLH1 gene (genic locus 3p22) and the MSH6 gene

with consequent impairment of DNA mismatch repair (see DNA repair below). It is also conceivable that latent Muir-Torre syndromemay be unmasked during long-term immunosuppressive therapy, e.g., with cyclosporine A.

Skin lesions often appear in early adulthood, usually a decade before the onset of an internal tumor (e.g., colorectal cancer), and represent the most common tumor entity.

The peak age of onset for internal malignancies is 53 years on average.  

Multiple, cutaneous or extracutaneous, primary carcinomas (mainly adenocarcinomas of the gastrointestinal tract, spinocellular carcinoma of the skin) as well as synchronously or metachronously occurring benign and malignant sebaceous gland tumors(sebaceous gland adenomas, sebaceomas, sebaceous gland carcinomas) and basal cell carcinomas. However, emerging sebaceous gland carcinomas behave less aggressively than spontaneously occurring sebaceous gland carcinomas.

Detection of sebaceous gland adenomas or highly differentiated sebaceous gland carcinomas.

MTS is suspected in patients without internal malignancies in the EA if at least 3 of the criteria listed below are present (mod. n. Ko):

• Age: Sebaceous gland tumors aged < 50 years.
• Localization: sebaceous gland tumors outside face and neck.
• Number: 2 or > 2 sebaceous gland tumors.
• FA: Internal malignancies (mainly colorectal or urogenital tumors) in 2 or > 2 first-degree relatives
• Histology: Cystic or keratoacanthoma-like structure.
• Immunohistochemistry: deficiency of MSH2 or MLH1
• Molecular pathology: evidence of microsatellite instability

Ferguson-Smith-type keratoacanthomas

Grzybowski and Witten/Zak-type keratoacanthomas

Timely diagnosis of Torre-Muir syndrome is crucial to initiate preventive measures or necessary surgical procedures.

Screening examinations every 3-6 months, colonoscopy every 2 years (colon carcinomas represent most frequent tumor entity). Avoidance of immunosuppressive therapy (e.g. long-term high-dose administration of glucocorticoids).

Local immunomodulators can lead to a reduction in the incidence of tumours. The use of Imiquimod (e.g. Aldara) 3 times/week has proven successful here. Extensively on the most frequently affected areas, especially on the areas that are freely carried, e.g. the face.

Experiments with isotretinoin (e.g. isotretinoin-ratiopharm; acne normin) to inhibit sebaceous gland proliferation have been described.

Surgical procedure for internal tumors. Excision of the appearing keratoacanthomas as well as the sebaceous gland tumors with histological workup.

The tendency of carcinomas occurring in the context of this syndrome to metastasize is lower than in solitary occurrence. A closely meshed tumour prevention programme (annual endoscopic examinations, urological controls) is necessary.

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