Melanoma is a dangerous and potentially life-threatening skin cancer. While it is rare in children, pediatric melanoma often behaves very differently than adult melanoma, making it more difficult to recognize, diagnose, and treat. Certain types of melanomas are more common in children, particularly those that arise from congenital melanocytic nevi (moles present at birth) and Spitzoid tumors, which can appear benign but may, in rare cases, present as melanoma. Because the precursor lesions (spitzoid lesions or congenital nevi) often look non-threatening, the standard medical approach has been to monitor them over time rather than remove them or conduct advanced genetic testing. This proposal was inspired by one of my own patients—a child who had a mole biopsied at age four. Fortunately, the pathology was considered benign at the time, and no genetic testing was performed, which is in line with standard care. The mole was watched for years without significant change, but during puberty, it suddenly became ulcerated. When it was removed, it was diagnosed as melanoma. Genetic testing revealed serious mutations, and unfortunately, the disease progressed rapidly. Had we known earlier what was happening at the molecular level, it’s possible that a more proactive treatment plan could have been offered—one that might have changed the outcome. Today, genetic testing is typically only done for melanomas. As a result, we know little about the precursor lesions which may have early molecular changes or otherwise signal a higher risk for progression. This project aims to bridge that gap by studying preserved tumor tissue from pediatric patients who had congenital nevi, spitzoid lesions, or melanomas biopsied in the past—which were never genetically analyzed. Using advanced sequencing technologies, we will look for hidden genetic changes that could help distinguish between harmless and high-risk tumors. Our study will examine archived cases of pediatric melanoma that were never tested using modern genomic tools. We will also study Spitzoid tumors, which are often difficult to classify, to better understand whether certain genetic signatures are associated with more aggressive behavior or have recognized genetic patterns. Finally, we will analyze congenital moles to see whether some of them carry genetic markers that could guide future care, including earlier intervention or targeted therapies that are already showing promise in related conditions. By combining decades of carefully collected tissue samples with modern genetic techniques, this research seeks to change how we understand and manage pediatric melanocytic tumors. Rather than relying solely on how a tumor looks under the microscope, we hope to identify genetic information that can help doctors make more informed decisions—leading to earlier diagnoses, better treatments, and improved outcomes for children at risk of melanoma.  

Pediatric melanoma, a rare but aggressive form of skin cancer in children and young adults, poses a unique challenge for diagnosis and treatment, as it does not present with the same clinical criteria as adult melanoma. Standard recommendations for diagnosis and treatment of melanoma in this patient population are crucial, but an understanding of the biological mechanisms, and how this compares to adult melanoma, is lacking. One mechanism by which cancer cells grow uncontrollably is by preventing their DNA’s protective caps, called telomeres, from getting shorter as they should with each cell division. Research has shown that telomere maintenance may play a pivotal role in the development and progression of pediatric melanoma. This project will explore the role of specific genetic mutations within the telomeres, and the proteins they bind to, in melanoma prognosis in pediatric and adolescent/young adult patients. By elucidating genomic drivers of disease in these patients, we will provide groundwork for subsequent standardization of prognosis and treatment recommendations in this patient population.

Pediatric melanomas are a rare and deadly form of skin cancer. Melanomas in adults have better studied than the pediatric variant due to the rarity of melanomas arising in children. Most of the information available about pediatric melanomas are from smaller studies, and the medical literature is sparse on information about factors that are associated with more aggressive disease. Disease staging is an important predictor for how long a patient is expected to live. Patients with localized disease generally have better outcomes than those with advanced disease that have spread to the brain, lungs, liver, among other organs. In adults, staging criteria are well defined, and factors such as tumor size, how deep a tumor invades into the tissue, and how a tumor looks under the microscope, have been helpful in identifying whether a melanoma will behave aggressively and spread to distant tissues. In children, these factors are well less defined given the rarity of the disease, and current studies suggest that pediatric melanomas may behavior differently than those that arise in adults. Our study aims to use a national database of pediatric melanoma patients to address these uncertainties in the medical literature. We performed a preliminary analysis that demonstrates that different subtypes of pediatric melanomas behave differently. We demonstrate that epithelioid/spindle cell and melanoma arising from a previous mole are more aggressive than other subtypes. We additionally found that nodular melanoma and epithelioid/spindle cell subtypes have higher rates of having metastatic disease. In our study, we aim to identify high-risk features that increase the probability of a child developing metastatic melanoma. We additionally want to create a risk calculator to help clinicians quantify this risk to help them decide as to whether a child with melanoma requires further studies, such as lymph node evaluation or clinical imaging to assess whether advanced disease is present.

We know that there are often differences in the way that pediatric melanoma looks on the skin. We also know that parents and doctors often do not know that children can get melanoma. Children often have better outcomes than adults with melanoma, though we don’t know how to predict which children may have their melanoma spread to other parts of their body and cause death. Because of these differences, pediatric melanoma is often caught late and even once diagnosed, doctors often aren’t sure how to treat it. This is a problem because we know that catching melanoma early is very important and can lead to the cancer being an earlier stage and patients requiring less treatment and having better outcomes.

Since pediatric melanoma makes up such a small number of overall melanomas, it has been difficult to study. The goal of this research project is to now study the information from hundreds of pediatric melanoma patients over many years from different hospitals from our retrospective database that we created so that we can better understand pediatric melanoma and be able to create pediatric melanoma treatment guidelines. Our improved understanding and standardization of care will lead to better outcomes for the patients diagnosed with this cancer.

The second part of this study will focus on growing our research groundwork through the creation of a “prospective database” to be able to continually study pediatric melanoma as changes and improvements are made in the care of adult melanoma. We will be able to collect patient information when first diagnosed and over time as they are treated and monitored by their medical team. Pediatric melanoma patients from all over the nation will be able to participate in this important research. We will also include very important information from the patient and parent perspective by asking participants to complete surveys about their experience with melanoma. We believe it is very important not only to increase our ability to treat pediatric melanoma, but to also understand the patient/parent experience during the process. The study will be further enhanced by including access to melanoma tumor samples, as well as photography documentation of the skin lesions before and after treatment, to fully pave the way for ongoing research and improvement of our care of pediatric melanoma.

Career Development Award – Brittani Seynnaeve, MD