Individuals with multiple self-healing squamous epithelioma (MSSE) develop multiple invasive skin tumors that undergo spontaneous regression leaving pitted scars. Age at onset is highly variable, ranging from 8 to 62 years. The disorder shows autosomal dominant inheritance, and ... Individuals with multiple self-healing squamous epithelioma (MSSE) develop multiple invasive skin tumors that undergo spontaneous regression leaving pitted scars. Age at onset is highly variable, ranging from 8 to 62 years. The disorder shows autosomal dominant inheritance, and most affected families have originated from western Scotland (Bose et al., 2006). MSSE has been considered to be a variety of multiple keratoacanthoma (Epstein et al., 1957; Haydey et al., 1980).
Ferguson Smith (1934) first described this disorder in a single case, that of a 23-year-old miner, who first developed spots on the legs at age 16 years. The lesions healed spontaneously, but were replaced by others at neighboring ... Ferguson Smith (1934) first described this disorder in a single case, that of a 23-year-old miner, who first developed spots on the legs at age 16 years. The lesions healed spontaneously, but were replaced by others at neighboring sites and later on the face and ears. A depressed scar remained after healing. The lesions resembled squamous carcinoma clinically and histologically. He continued to work except for a few months when lesions on the knees prevented him from kneeling. Ferguson Smith (1948) provided a follow-up of this patient. Treatment of large lesions on his right leg with radium was 'followed by necrosis of the tibia, and ultimately, at the patient's own request...amputation below the knee.' He was wearing a prosthesis to cover an extensive destruction of the nose. Ferguson-Smith (1974) reported that the patient died of 'suppurative meningitis' in December 1948. Autopsy findings were reported by Currie and Ferguson Smith (1952). In addition to the face, ears, arms and legs, the skin of the anus, scrotum and anterior abdominal wall were affected. All tumors were well-differentiated squamous epitheliomata with lymphatic infiltration of the anal and aural lesions. The anal tumor infiltrated the sphincter and muscle coats of the anal canal. Sommerville and Milne (1950) reported 2 cases in each of 2 successive generations. Affected father and son were referred to by Epstein et al. (1957). Degos et al. (1964) described the condition in a woman and 2 daughters. Ereaux and Schopflocher (1965) observed affected brother and sister. Ferguson-Smith et al. (1971), the geneticist son of the dermatologist who first described this condition, reviewed 62 cases in western Scotland. The lesions were found more frequently on exposed areas of the skin. Two girls had their first lesion during their thirteenth year; the oldest onset in a male was at age 56 and in a female at age 55. The mean age of onset in women was 25.5 and in men 26.9. Many examples of male-to-male transmission, equal involvement of the sexes, and precise agreement with the 50:50 segregation ratio proved autosomal dominant inheritance. A single instance of 'skipped generation' was found: the daughter of an affected male and mother of 2 affected daughters had unblemished skin when fully examined at age 57.
In affected members of 18 different families with MSSE, Goudie et al. (2011) identified 11 different heterozygous mutations in the TGFBR1 gene (see, e.g., 190181.0009-190181.0012). The first mutations were found using high-throughput genomic sequencing and exon array capture ... In affected members of 18 different families with MSSE, Goudie et al. (2011) identified 11 different heterozygous mutations in the TGFBR1 gene (see, e.g., 190181.0009-190181.0012). The first mutations were found using high-throughput genomic sequencing and exon array capture of a 24.2-Mb region containing the MSSE locus; additional families were studied by sequencing. One mutation, G52R (190181.0010), was found in 6 Scottish families, including those reported by Ferguson-Smith et al. (1971). The mutations identified by Goudie et al. (2011) occurred in either the extracellular ligand-binding domain or in the serine/threonine kinase domain of the protein, and all were predicted or demonstrated to result in loss of receptor function. Several mutation carriers were unaffected, and tumor tissue from some patients showed loss of heterozygosity for the wildtype allele. Overall, the findings were consistent with wildtype TGFBR1 acting as a tumor suppressor, until somatic deletion by a classic second hit results in carcinogenesis.
Ferguson-Smith et al. (1971) assembled reliable information on 62 cases in western Scotland, and suggested that all the Scottish cases derived from a single mutation which occurred before 1790. The Scottish cases were in 11 independently ascertained families ... Ferguson-Smith et al. (1971) assembled reliable information on 62 cases in western Scotland, and suggested that all the Scottish cases derived from a single mutation which occurred before 1790. The Scottish cases were in 11 independently ascertained families but the genealogic connections of some could be demonstrated.