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For SCC, legs are a high-risk anatomic site in women



When Maryam M. Asgari, MD, reviewed results from a large population-based study published in 2017, which found that a large proportion of cutaneous squamous cell carcinomas were being detected on the lower extremities of women, it caused her to reflect on her own clinical practice as a Mohs surgeon.

Dr. Maryam M. Asgari, professor of dermatology, Harvard Medical School; Massachusetts General Hospital department of dermatology, Boston

Dr. Maryam M. Asgari

“I was struck by the number of times I was seeing women present with lower extremity SCCs,” Dr. Asgari, professor of dermatology, Harvard Medical School, Boston, said during a virtual forum on cutaneous malignancies jointly presented by Postgraduate Institute for Medicine and Global Academy for Medical Education. “When female patients push you for a waist-up skin exam, try to convince them that the legs are an important area to look at as well.”

In an effort to ascertain if there are sex differences in the anatomic distribution of cutaneous SCC, she and her postdoctoral fellow, Yuhree Kim, MD, MPH, used an institutional registry to identify 618 non-Hispanic White patients diagnosed with 2,111 SCCs between 2000 and 2016. They found that men were more likely to have SCCs arise on the head and neck (52% vs. 21% among women, respectively), while women were more likely to have SCCs develop on the lower extremity (41% vs. 10% in men).

“When we looked at whether these tumors were in situ or invasive, in women, the majority of these weren’t just your run-of-the-mill in situ SCCs; 44% were actually invasive SCCs,” Dr. Asgari said. “What this is getting at is to make sure that you’re examining the lower extremities when you’re doing these skin exams. Many times, especially in colder weather, your patients will come in and request a waist-up exam. For women, you absolutely have to examine their lower extremities. That’s their high-risk area for SCCs.”

The incidence of keratinocyte carcinomas (KCs), which include SCCs and basal cell carcinomas (BCCs), is higher than all other cancers combined, she continued. According to 2020 data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results SEER program, the incidence of KC in the United States is estimated to be 3.5 million cases per year, while all other cancers account for approximately 1.8 million cases per year.

To make matters worse, while the incidence of many other cancers have plateaued or even declined over time in the United States, data from a population-based cohort at Kaiser Permanente Northern California show that the incidence of BCCs rose between 1998 and 2012, estimated to occur in about 2 million Americans each year.

Dr. Asgari noted that the incidence of KCs can be difficult to quantify and study. “Part of the reason is that they’re not reported to traditional cancer registries like the SEER program,” she said. “You can imagine why. The sheer volume of KC dwarfs all other cancers, and oftentimes KCs are biopsied in dermatology offices. Sometimes, dermatologists even read their own biopsy specimens, so they don’t go to a central pathology repository like other cancers do.”

The best available research suggests that patients at the highest risk of KC include men and women between the ages of 60 and 89. Dr. Asgari said that she informs her patients that people in their 80s have about a 20-fold risk of BCC or SCC compared with people in their 30s. “I raise this because a lot of time the people who come in for skin cancer screenings are the ‘worried well,’ ” she said. “They can be at risk, but they’re not our highest risk subgroup. They come in proactively wanting to have those full skin screens done, but where we really need to be focusing is in people in their 60s to 80s.”

Risk factors can be shared or unique to each tumor type. Extrinsic factors include chronic UV exposure, ionizing radiation, and tanning bed use. “Acute UV exposures that give you a blistering sunburn puts you at risk for BCC, whereas chronic sun exposures puts you at risk for SCC,” she said. “Tanning bed use can increase the risk for both types, as can ionizing radiation, although it ups the risk for BCCs much more than it does for SCCs.” Intrinsic risk factors for both tumor types include fair skin, blue/green eyes, blond/red hair, male gender, having pigment gene variants, and being immunosuppressed.

By race/ethnicity, the highest risk for KC in the United States falls to non-Hispanic Whites (a rate of 150-360 per 100,000 individuals), while the rate among blacks is 3 per 100,000 individuals. “In darker skin phenotypes, sun exposure tends to be less of a risk factor,” Dr. Asgari said. “They can rise on sun-protected areas and are frequently associated with chronic inflammation, chronic wounds, or scarring.”

In a soon-to-be published study, Dr. Asgari and colleagues sought to examine the association between genetic ancestry and SCC risk. The found that people with northwestern European ancestry faced the highest risk of SCC, especially those with Irish/Scottish ancestry. Among people of Hispanic/Latino descent, the highest risk of SCC came in those who had the most European ancestry.

Global Academy for Medical Education and this news organization are owned by the same parent company.

Dr. Asgari disclosed that she receives royalties from UpToDate.

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