Introduction

It is summer, and many people are soaking up the sunshine – be it relaxing at the beach, hiking under clear skies or simply enjoying the warmth. For most of us, sunlight means joy, freedom and fun. But for some people, the sun can be a deadly threat.

Individuals with De Sanctis-Cacchione syndrome (DSCS) are extremely sensitive to light. Even brief exposure to sunlight can lead to aggressive skin cancers.¹ In addition to this photosensitivity, people with DSCS could also suffer severe neurological impairments, developmental delays and early-onset cancers.¹ 

So, how do we treat skin cancer in someone highly sensitive to light? In this article, we will explore both surgical and nonsurgical approaches to treating skin cancers in DSCS, highlighting the challenges, treatment options and ways to care for some of the most vulnerable patients in dermatology and oncology.

De Sanctis-Cacchione syndrome 

What is it?

De Sanctis-Cacchione Syndrome (DSCS) is an extremely rare genetic disorder caused by an autosomal recessive genotype. DSCS is classified as a form of the genetic skin condition xeroderma pigmentosum (XP).^2,3  

Characteristics of DSCS

Both DSCS and XP cause cells in the body to lose the ability to repair DNA that has been damaged by ultraviolet (UV) radiation from sunlight.⁴ Those with DSCS suffer from extreme sensitivity to sunlight and are at an increased risk of developing skin cancers.⁵

More than sensitivity to the sun

DSCS does not just affect the skin. Along with photosensitivity, people with DSCS can also experience a range of neurological impairments and developmental delays, making their everyday life a little harder.⁴

Neurological symptoms can include:⁴

• Problems with movement and motor skills
• Difficulties with learning and memory
• Cognitive deficits, motor skill challenges and a variety of other developmental obstacles  that can affect the person's growth and independence

Between the light sensitivity issues and developmental challenges, DSCS is a particularly challenging condition which needs careful and specialised medical attention.

Surgical treatments for skin cancers caused by DSCS

Surgeries are a common and effective option to remove tumours and manage skin cancers in patients with DSCS. For example:^6,7  

• Excisional surgery: to guarantee that all malignant cells are eliminated, it involves the total removal of the tumoir together with a margin of healthy tissue
• Mohs micrographic surgery: with this method, the tumour is removed layer by layer. Doctors examine each layer under a microscope to make sure the tumour has been completely removed
• Curretage and electrodessication: for more superficial lesions, the tumour is scraped off the skin and the area is cauterised (heated) to destroy remaining cancer cells

Risks of surgery

Although these surgeries can effectively remove tumours, it is important to understand the potential drawbacks before deciding on a treatment approach:^6,7

• Excisional surgery can lead to scarring and employs anaesthesia, which can carry additional risks for children and individuals with neurological impairments
• Mohs micrographic surgery is an accurate method, but it requires a highly trained and specialised doctor, so it's not easy to get an appointment
• Curettage and electrodessication work against small (e.g., face) tumours, but they may not be effective for more complex, aggressive tumours

Before deciding which surgery to get, people with DSCS should be mindful of the extra challenges that they may face due to their condition.

For example:⁸

• They may need repeated surgeries, which can become physically draining
• Wounds may heal more slowly because of the pre-existing skin sensitivity or the neurological symptoms of DSCS

Nonsurgical treatments for skin cancer caused by DSCS

Nonsurgical treatments offer alternative options for managing skin cancers in patients with DSCS, but their effectiveness can be influenced by the unique characteristics of the condition.¹ Topical therapies, such as Imiquimod (an immune response modifier) and 5-Fluorouracil (5-FU,  a chemotherapeutic cream), are commonly used for superficial basal cell carcinoma or squamous cell carcinoma.^9,10 Imiquimod stimulates the immune system to target cancer cells, whereas 5-FU directly destroys cancerous tissue. These treatments are most effective for smaller, less aggressive tumours, but they can sometimes lead to skin irritation or inflammation, particularly in patients with sensitive skin.¹⁰

Photodynamic Therapy (PDT) is another nonsurgical option that uses light-activated drugs to destroy cancer cells.¹⁰ The drug is applied to the tumour and then a special light is used to activate it, targeting the cancerous tissue. While PDT can be effective for some skin cancers, it is generally not recommended for DSCS patients due to their increased photosensitivity, which may lead to more severe reactions to the treatment.¹⁰

For patients with more advanced or metastatic skin cancers, systemic therapies can be used. Retinoids, like isotretinoin, have been shown to help prevent the development of new cancers and manage existing lesions.¹¹ Additionally, targeted therapies are specifically designed to attack cancer cells and can be used for tumours that have spread or are resistant to other treatments.¹² However, these therapies can have significant side effects, including skin dryness or irritation, which may be more pronounced in DSCS patients.¹²

Radiation therapy is typically avoided in DSCS due to the increased radiosensitivity associated with the syndrome.¹³ Exposure to radiation may cause more severe side effects, including tissue damage, which can be particularly challenging for DSCS patients with delicate skin.

Finally, experimental treatments such as gene therapy and immunotherapy are emerging options in clinical trials.^14,15 These therapies hold promise for future treatment regimens, especially for more resistant or advanced skin cancers, but they are not yet widely available and are considered on a case-by-case basis.

Given the complexity of DSCS and its impact on skin and healing, nonsurgical treatments must be carefully selected and monitored, ensuring they address both the skin cancer and the patient's broader health needs.

FAQs

How important is regular monitoring for DSCS patients in preventing skin cancer?

Regular monitoring for patients with DSCS is crucial in preventing skin cancer, as individuals with this condition are at a heightened risk due to genetic mutations that impair DNA repair, particularly in response to UV damage.¹ DSCS patients also experience increased sensitivity to sunlight, which further elevates the risk of UV-induced skin damage. This combination makes regular skin exams essential for detecting early signs of skin cancer or precancerous lesions. 

Early detection is key, as it allows for timely intervention, significantly improving prognosis and treatment outcomes.¹ Dermatologists may recommend more frequent skin checks, including total body skin exams and may use dermoscopy or other imaging techniques to identify suspicious lesions. Beyond cancer detection, patients with DSCS may also face other skin issues like dry skin, eczema and pigmentation problems, all of which require ongoing attention.

Are there any preventive strategies for DSCS patients to reduce the risk of skin cancer?

Yes, photoprotection is key for reducing the risk of skin cancer in DSCS patients.¹ Using strict sun protection is one of the most crucial tactics. DSCS patients should avoid direct sun exposure, particularly during peak UV hours and wear sun-protective clothing (e.g. long sleeves, wide-brimmed hats and UV-blocking apparel). Daily application of broad-spectrum sunscreen is essential, and UV-blocking sunglasses are important to protect the eyes from UV-related damage. Additionally, the use of topical antioxidants like vitamin C, vitamin E and niacinamide may help reduce oxidative stress caused by UV exposure, offering further skin protection.¹⁶ DSCS patients should also avoid tanning beds as they emit UV radiation that exacerbates the risk of skin cancer.¹⁷ 

Summary 

There is no one-size-fits-all way to treat skin cancer when you have DSCS. Due to the complexity of DSCS, each patient's treatment plan must address their specific needs, considering factors like skin sensitivity, neurological concerns and overall health. A thorough understanding of the patient's condition is crucial for determining the best course of action.

Finding the right balance between aggressive treatment and maintaining the patient's quality of life is critical. While effective cancer treatment is essential, it is equally important to minimise side effects that may affect the patient's daily functioning and well-being. Treatments should aim not only to manage the cancer but also to improve or maintain the patient's overall quality of life.

To conclude, ongoing research is vital to discovering safer, more effective therapies for genetically vulnerable populations like those with DSCS. Advancements in targeted therapies, genetic treatments and other innovative options hold promise for providing better outcomes with fewer risks. Continued research and clinical trials are key to improving the standard of care for DSCS patients, ultimately offering hope for more personalised and effective treatment options in the future.