Multiple self-healing squamous epitheliomas of Ferguson-Smith
What are multiple self-healing squamous epitheliomas?
Multiple self-healing squamous epitheliomas (MSSE) is a rare inherited skin condition characterised by the sudden appearance of recurrent skin cancers resembling well differentiated squamous cell carcinomas (SCC) or keratoacanthomas (KA) clinically and histologically. The SCC/KA-like lesions tend to spontaneously regress, leaving pitted scars.
MSSE was first described in 1934 by the Scottish Dermatologist J Ferguson-Smith, who reported a young man who had developed multiple self-healing squamous tumours. It was later reported in the patient’s daughter, and in 1971, Malcolm A Ferguson-Smith (the geneticist son of the dermatologist) presented information on 62 cases of MSSE from the West of Scotland, including pedigrees compatible with an autosomal dominant pattern of inheritance.
Other names for the disorder are:
- Familial multiple keratoacanthomas
- Ferguson-Smith multiple keratoacanthomas
- Ferguson-Smith disease
What are the clinical features of MSSE?
In MSSE, SCC/KA like-lesions tend to appear for the first time during the second or third decade of life. They arise in crops or singly, most commonly in sun-exposed areas and at sites of trauma. The lesion begins as a dull red macule that soon becomes a papule, and grows rapidly over 2–4 weeks. It may reach 2–3 cm in diameter, and remain stable for up to 2 months before involuting, leaving a pitted scar.
Patients may have up to one hundred lesions over time.
What are the genetics of MSSE?
Cases of MSSE have been identified in a wider geographical area, in Japan, America and Denmark, suggesting that the disease is more common than originally thought. In some families, the phenotype is milder, and the onset of disease later than in other families.
MSSE was initially thought to be caused by a founder mutation. Although the disease is inherited in an autosomal dominant fashion (from parent to half of his or her children), it is not fully penetrant, as there are reports of obligate carriers showing no clinical symptoms. Eleven different heterozygous mutations have been identified in the Transforming Growth Factor Beta Receptor 1 (TGFBR1) gene located on Chromosome 9q22.
It is thought that wildtype TGFBR1 acts as a tumour suppressor, until somatic deletion of the wildtype gene by a classic second "hit" results in carcinogenesis.
How is MSSE diagnosed?
Familial multiple keratoacanthomas should be considered in patients presenting with SCC/KA-like lesions at a young age with a positive family history.
The characteristic histology of the familial type differs from usual KA, as there is no marked ‘shouldering’, and leucocyte abscesses are absent. They appear to be aggressive SCC histologically yet they usually heal by themselves.
The differential diagnosis of familial multiple keratoacanthomas includes:
- Non-familial SCCs and KAs
- KAs in Muir-Torre syndrome
- Generalised eruptive KAs of Grzybowski syndrome
- Xeroderma pigmentosum
DNA samples from blood or oral rinse can be obtained to perform linkage studies and haplotype analysis, looking for mutations in the TGFBR1 gene on chromosome 9q22. A heterozygous loss-of-function mutation in this gene leads to susceptibility to familial multiple keratoacanthomas.
In areas of high ultraviolet (UV) exposure and high prevalence of SCCs, the diagnosis of MSSE may be delayed or easily missed. Patients with early onset of histologically aggressive squamous cell carcinomas in young patients with a family history of other affected members should be investigated for possible MSSE.
What is the treatment for MSSE?
Although individual SCC/KA-like lesions will generally resolve spontaneously, treatment can hasten this and also improve cosmetic outcome. Mostly, the lesions are removed surgically by excision or curettage and cautery. Other reported treatments are:
Whilst radiotherapy has been used for MSSE, this can lead to further development of new lesions within the treated field, so is best avoided.
Patients with MSSE should be advised to protect their skin from exposure to the sun.