1 December 2022

Red flags for repeated melanomas 

Cancer dermatology

A family history and a higher number of moles at age 21 puts people at the highest risk of another primary melanoma. 


People with a greater number of moles and a genetic predisposition to melanoma are at the highest risk of developing a second primary melanoma, according to a new study. 

Findings of a population-based prospective cohort study have revealed that a second case of primary melanoma was more likely to occur in patients with a high genetic predisposition to skin cancer and in those with many moles at age 21. 

Second primary melanoma was also more strongly associated with a history of multiple skin cancer excisions than first melanomas, the study of almost 40,000 middle-aged Queenslanders found. 

Researchers analysed self-reported information on demographics, pigmentary and phenotypic characteristics, sun exposure and sun protection, family history, general medical history and history of skin cancer and other skin lesion treatments, taken between 2011 and 2018. 

Overall, 3.1% of participants had only one primary melanoma diagnosis and 0.6% had two or more primary melanoma diagnoses over the study period.  

“While the associations between most phenotypic factors and risk of first and second melanomas were similar in magnitude, the factors that differed statistically significantly between first and second melanomas were high self-reported nevus counts and a high genetic predisposition for melanoma (as determined by polygenic risk score),” the authors wrote. 

“We also noted a significantly higher hazard ratio for second than first primary melanoma associated with numbers of previous excisions for skin cancer.” 

The researchers found that nevus phenotype was strongly associated with second primary melanoma than first primary melanoma. 

“Many ‘classic’ phenotypic and pigmentary factors previously reported for cutaneous melanoma were significantly associated with both first and second melanomas and had risk estimates of similar magnitude,” the authors wrote. 

Factors such as age, sex, hair colour, tanning ability, burning tendency and family history of melanoma did not appear to play more or less of a role in how likely someone was to get an additional primary melanoma.  

A high melanoma polygenic risk score was far more influential in the development of the second melanoma than it was with first primary melanoma.  

People who developed second primary melanomas were older at baseline than those who only ever developed one primary melanoma and were more likely to have a sun-sensitive phenotype and a self-reported history of skin cancer excisions. 

Second primary melanomas were also more commonly in situ and of a thin morphology (? 1mm) for invasive tumours than first melanomas. 

The authors stressed the importance of regular surveillance to detect recurrent disease. This would allow subsequent primary melanomas, which may otherwise go unnoticed, to be identified. 

“Clinical practice guidelines recommend periodic screening for patients after a diagnosis of melanoma; the frequency of screening is guided by the characteristics of the primary tumour, including thickness, stage, presence of ulcerations, and number of mitoses,” they said. 

“Patients with melanoma with high nevus counts have more potential targets for biopsy during follow-up, which may also contribute to higher detection rates. 

This heightened surveillance among patients with melanoma possibly leads to detection of second melanomas early in their course, resulting in lower morbidity and risk of mortality, but it may also contribute to the overdiagnosis of second primary melanomas that may otherwise have followed an indolent course.” 

JAMA Dermatology 2022, online 23 November