Muir-Torre Syndrome Clinical Presentation

• A positive family history of Muir-Torre syndrome (MTS) can be found in roughly 50% of patients.
• There is an association with a family history of colon cancer.
• Cutaneous sebaceous neoplasms can precede or follow a diagnosis of visceral malignancy.^[7]
• MTS is associated with HNPCC, an autosomal dominant cancer genetic syndrome.^[8] The diagnostic criteria (Amsterdam criteria) include the following^[9] :

  • Three or more relatives with an HNPCC-associated cancer (ie, colorectal, cancer of the endometrium, small bowel, ureter, or renal pelvis)
  • Cancer affecting at least 2 successive generations
  • One person 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

Criteria for the diagnosis of Muir-Torre syndrome (MTS) include the presence of at least one sebaceous adenoma, sebaceous epithelioma, or sebaceous carcinoma (sebaceous hyperplasia and nevus sebaceus of Jadassohn are generally excluded), and at least one visceral cancer. Keratoacanthoma, squamous cell carcinoma, and multiple follicular cysts are sometimes included in the cutaneous tumors. In general, sebaceous neoplasms occurring below the neck are more strongly associated with MTS than those lesions arising around the eye or ear.^[10] Non–head and neck lesions are more commonly associated with alterations of the epidermal growth factor receptor.^[11]

The skin lesions may precede the presentation of internal malignancy, although they often develop later. Cutaneous nodules occurring on the face, the trunk, and the extremities are found in various other disorders, including Gardner syndrome, Cowden syndrome, multiple trichoepitheliomas, basal cell nevus syndrome, eruptive keratoacanthomas, and tuberous sclerosis. Many of these syndromes are also associated with visceral tumors.

• Sebaceous adenoma is the most characteristic marker of MTS. These fairly rare benign tumors usually appear as yellow papules or nodules in adult patients. In the sporadic cases, most tumors are located on the head (particularly on the face, the scalp, and the eyelids), with the remaining minority scattered over the rest of the body. In MTS, lesions on the trunk may be more common. The clinical features of sebaceous epithelioma are similar. The nomenclature for sebaceous neoplasms is controversial. Some authors use the term "sebaceoma" for indolent tumors composed of mature sebocytes and a predominance of undifferentiated basaloid germinative cells. This subset of tumors corresponds to lesions traditionally classified as sebaceous epithelioma.
• Sebaceous carcinomas most commonly occur on the eyelids, where they generally arise from the meibomian glands and the glands of Zeiss. They may also occur almost anywhere on the skin, including the ears, the feet, the penis, and the labia. On the eyelids, the tumor appears as a firm, yellow nodule with a tendency to ulcerate, as shown in the images below. Clinically, these lesions are often mistaken for chalazia, chronic blepharoconjunctivitis, or carbuncles. Sebaceous carcinoma of the eyelid can invade the orbit and can frequently metastasize and cause death. Extraocular tumors can also metastasize but are less likely to cause death. Sebaceous carcinoma of the upper eyelid. Courtesy of Mark S. Brown, MD, University of South Alabama Medical Center. Sebaceous carcinoma as viewed from the conjunctival side. Courtesy of Mark S. Brown, MD, University of South Alabama Medical Center. Gross image of an ear resection due to a deeply invasive sebaceous carcinoma
• The distinction of sebaceous carcinoma and adenoma/epithelioma is usually based upon the architecture of the lesion (infiltrative in carcinoma versus circumscribed in adenoma/epithelioma). However, some lesions may have circumscribed borders but do show frank cytologic atypia,^[12] while the authors have seen lesions without any degree of cytologic atypia diffusely infiltrating the subcutaneous tissue.
• Keratoacanthoma, whether solitary or multiple, is frequently seen in MTS. Keratoacanthoma usually starts as a red papule that rapidly grows to become a skin-colored, shiny nodule with telangiectases and a central horny plug covered by a crust. Common sites of involvement include the face and the dorsum of the hands, but they can occur anywhere on the body. The tumors have a tendency to regress, ultimately leaving a scar. Those keratoacanthoma cases with sebaceous differentiation are strongly associated with MTS.
• The most common visceral neoplasm in MTS is colorectal cancer, occurring in almost one half of patients. The tumors are usually proximal to the splenic flexure. The second most common site is the genitourinary tract, representing approximately one quarter of visceral cancers. A wide variety of other cancers, including breast cancer, lymphoma and rarely leukemia, salivary gland tumors, lower and upper respiratory tract tumors, and chondrosarcoma, are reported. Intestinal polyps occur in at least one quarter of patients. Other benign tumors described in MTS include ovarian granulosa cell tumor, hepatic angioma, benign schwannoma of the small bowel, and uterine leiomyomas.

See Pathophysiology. The main anomaly detected in Muir-Torre syndrome (MTS) patients is the alteration in the mismatch repair genes, particularly MSH2 on chromosome 2 and MLH1 on chromosome 3.^[13] Other genes are MSH-6, MLH-3, and PMS-2. Loss of 2 of the retinoid receptors (RXR-beta and RXR-gamma) seems apparent in sebaceous carcinoma.^[14]