Muir-Torre Syndrome: Comprehensive Imaging Guide and Clinical Overview
Overview
Muir-Torre Syndrome (MTS) is an autosomal dominant hereditary cancer syndrome, considered a phenotypic variant of Lynch syndrome (hereditary nonpolyposis colorectal carcinoma, HNPCC). It is characterized by the presence of sebaceous skin tumors combined with one or more visceral malignancies, most commonly colorectal carcinoma. The syndrome is caused by germline mutations in DNA mismatch repair (MMR) genes such as MSH2, MLH1, and MSH6, leading to microsatellite instability. Named after Muir and Torre, who described the association with sebaceous neoplasms and internal cancers in the late 1960s, MTS presents clinically with cutaneous sebaceous adenomas, sebaceomas, and carcinomas that may initially resemble benign lesions like sebaceous cysts.
Key Imaging Features
- Presence of visceral malignancies primarily involving the colon and rectum, typically seen as mucinous adenocarcinomas on imaging.
- On cross-sectional imaging (CT, MRI), multifocal or segmental bowel wall thickening with possible luminal narrowing consistent with colorectal tumors.
- Identification of sebaceous tumors on ultrasound or MRI of the skin showing well-circumscribed, lobulated, and heterogeneous lesions typically in the periocular or head and neck soft tissues.
- Possibility of regional lymphadenopathy or distant metastases on PET/CT in advanced malignancies.
- In abdominal imaging, associated malignancies may also include genitourinary tract tumors (e.g., urothelial carcinomas) detected as enhancing masses on CT urography or MRI.
- Skin tumor imaging may reveal heterogeneous signal intensities due to sebaceous content, sometimes with calcifications or cystic degeneration visible on high-resolution MRI.
Pathophysiology
Mutations in DNA mismatch repair genes lead to defective repair of DNA replication errors, causing microsatellite instability and accumulation of mutations in oncogenes and tumor suppressor genes. This genetic instability predisposes individuals to the development of multiple malignancies, particularly colorectal cancer and sebaceous gland tumors. The defective MMR proteins disrupt normal cellular apoptosis and proliferation control mechanisms, facilitating tumorigenesis. The sebaceous tumors arise due to uncontrolled proliferation of sebaceous gland cells, with imaging manifestations reflecting their lobular architecture and sometimes infiltrative growth patterns in carcinomas. The visceral tumors exhibit typical features of their histologic types but tend to occur at a younger age than sporadic counterparts and often show multifocality consistent with a hereditary syndrome.
Differential Diagnosis
- Lynch Syndrome (HNPCC) without cutaneous findings: Presents with similar colorectal and other visceral malignancies but lacks sebaceous tumors; differentiation relies on dermatologic and genetic findings.
- Basal Cell Carcinoma with Sebaceous Differentiation: Skin tumors with some sebaceous features but lacking the systemic malignancy association; histopathology and immunohistochemistry differentiate these from MTS-related tumors.
- Sporadic Sebaceous Tumors: Typically solitary and not associated with visceral malignancies; absence of mismatch repair gene mutations.
- Other Cutaneous Syndromes with Visceral Malignancies (e.g., Gardner syndrome): Distinguished by characteristic skin findings such as epidermoid cysts rather than sebaceous tumors and distinct extracolonic malignancies.
Imaging Protocols and Techniques
Initial imaging for patients suspected of Muir-Torre Syndrome should focus on the evaluation of visceral malignancies and cutaneous lesions:
- Contrast-enhanced CT of the abdomen and pelvis is preferred for colorectal tumor detection and staging, assessing lymph nodes and metastases.
- Pelvic and abdominal MRI offering superior soft tissue contrast aids detailed characterization of tumors, especially mucinous adenocarcinomas frequently associated with MTS.
- High-frequency ultrasound can evaluate superficial sebaceous tumors for size, vascularity, and involvement of adjacent structures.
- Whole-body PET/CT may be employed for staging and surveillance in advanced or recurrent disease, highlighting metabolically active tumors.
- Dedicated dermatologic imaging (including dermoscopy and in some cases MRI) can assist in differentiating benign sebaceous cysts from malignancies.
- Genetic testing and immunohistochemistry (MLH1, MSH2, MSH6, PMS2) complement imaging by identifying loss of mismatch repair proteins and establishing diagnosis.
Imaging pearls: Recognize multifocal colorectal tumors and atypically located sebaceous neoplasms as clues to MTS. Pitfalls include misinterpreting sebaceous carcinomas as benign cysts clinically; thus, biopsy with histopathology is crucial. Monitoring tumor evolution and new lesion development over time on sequential imaging is recommended for surveillance.
Improve Content And Help Your Colleagues!
Found an error in the post? Please let us know using our contact page and we will update it with due credits!
If you wish to contribute radiological images for this case (or any other article on the website), you can submit them here and you will be duly credited: Submit radiology case