Journal of Clinical and Aesthetic Dermatology • Hot Topics in Melanoma July 2025 • CASE STUDY SPOTLIGHT

Three cases of melanoma are presented here, with discussion from Dr. Angela Wingfield on how the 31-GEP test helped to inform decisions on each patient’s treatment plan.

Case Discussions

Case 1: A 52-year-old male patient with a lesion on the right preauricular cheek.

Case discussion. This patient presented to us with a pink nodule on his preauricular cheek. It was biopsied, and it came back as a malignant melanoma. The depth was 1.5mm—that’s a pretty deep lesion on the face, and it was ulcerated. Based upon that depth and his age, we immediately got him to an ear, nose, and throat (ENT) surgeon who does sentinel lymph node biopsy. We were pleased to see that the sentinel lymph node was negative. A lot of people would just leave it at that—the sentinel node was negative, so we’ll just follow him. However, though the patient was node negative, he had risky clinicopathological features, such as the lesion’s depth and ulceration, so we ordered the 31-gene expression profile (31-GEP) test to help guide our management decisions.

The 31-GEP test returned a Class 2B result, the highest-risk result. We used that information to get some imaging for him. After imaging, a salivary gland metastasis noted on the positron emission tomography (PET) scan prompted surgical removal, and the surgeon did a neck dissection in which all the nodes were negative. The patient went on to see a medical oncologist and was treated with combined nivolumab and ipilimumab for four cycles, then continued on monthly nivolumab for maintenance.

This was a case where the 31-GEP test result really helped us to confidently order the imaging that we thought we needed because he was a Class 2B, which found metastatic disease in an interesting location.

Case 2: A 42-year-old female patient with a lesion on the right posterior shoulder.

Case discussion. This patient presented with a firm, nondescript, flesh-colored bump on her arm. Initially the lesion was not concerning, but the patient said it was getting bigger. Whenever we can’t put a name on something and explain why it’s growing, we usually just biopsy it. Very surprisingly, the biopsy came back as a malignant melanoma. It was deep (1.9mm) but not ulcerated. It didn’t appear to be ulcerating or bleeding. The mitotic rate was 3/mm². It was positive all the way to the deep margin. Pathologically, it was a stage pT2a.

This one was really caught us all by surprise because of her age. The patient was 40 years old at the time of the biopsy. She experienced a lot of anxiety upon receiving her diagnosis. I sent her for a sentinel lymph node biopsy. In addition, considering her age, I also ordered the 31-GEP test to provide her with more information about her tumor molecular risk.

The patient had positive sentinel node. That was concerning, and we referred her to an oncology office. When the 31-GEP test came back it was a Class 1A—the lowest risk result. I tried to reconcile how this deep lesion came back with positive sentinel node but only a Class 1A result. I think what was going on with this lesion is that it started deep in the dermis. The pathologist called me with a concern that it might be a metastatic lesion because she did not see any connection to the epidermis, and all of the action was pretty deep in the dermis. She was worried that this was a cutaneous metastasis from another melanoma. I think this one must have began deep in the dermis, and it took a while for us to see it on the surface as that bump, because it had to push so much tissue upward to get attention. I think the reason it ended up in the lymph node was not due to its aggressiveness, but due to how long it had gone unnoticed due to how deeply it began in the dermis. The oncologist decided to get a PET scan. There were no other foci anywhere, which was reassuring. However, this patient was young with three young children and particularly anxious about this diagnosis. Therefore, they decided to treat her with nivolumab for one year without any side effects or autoimmune problems. Now, we follow her closely and biopsy anything new that appears in order to quell her nervousness. However, when we got that Class 1A result back, I felt much more comfortable that the patient was going to have a good outcome. Luckily, there have been no events and nothing has shown up on her PET scans. This is a really interesting case just because of the presentation, and it’s another one of those cases where the 31-GEP test helped us make some important decisions.

Case discussion. The lesion on this patient’s calf was mostly pink with some pigment at one edge. This is a patient who had multiple basal cell carcinomas over the years. I see him every three months and remove two or three. We thought this might be a pigmented basal cell carcinoma, but to our surprise, it came back from the biopsy as a malignant melanoma, and the depth was deep (1.5mm). That’s unusual for a lesion that’s been there for a short period of time, so I was concerned. There was no ulceration on the pathology report, and the mitotic rate was 3 to 4/mm². Pathologically, the stage was pT2a.

It’s policy at our clinic to order a 31-GEP test for any melanoma with a Breslow’s thickness over 0.3mm in patients aged 65 and older. In this patient, the 31-GEP came back as a Class 1A, the lowest risk result. Even at a depth of 1.5mm, a patient older than 65 years with a Class 1A result is likely to have a very good outcome. After speaking with the patient, we decided that it was probably overkill to do a sentinel lymph node biopsy. I just excised that primarily in my office, and because he’s a Class 1A, I did not offer him any imaging. After two and a half years, we continue to follow him closely as we had done before this event. He’s done well now at two and a half years. This is a good illustration of a patient over 65 years old with a deep melanoma but with a very good 31-GEP score that had a good outcome.

Case discussion. This case involves a patient who was referred to me after her surgery was completed. She had come from a general surgeon who performed a wide local excision with sentinel lymph node biopsy, and her melanoma, which was on her shoulder in the upper arm area, was 3.7mm deep, which makes everyone’s heart sink when you see a report like that. It was ulcerated, the mitotic rate was 8/mm², and it had lymphatic invasion. All of those things make you think this is going to go very poorly.

Her sentinel lymph node biopsy was negative. She was stage IIB after that surgery, but I immediately knew when I saw her that this was going to be bad. The patient had decided that because the sentinel lymph node was negative, that she was going to be fine. I ordered the 31-GEP test so I could use that information to help me guide her. It came back as a Class 2B, which is very high risk. I tried to use this information to convince her to get a PET scan. She refused the PET scan, but said she would think about it and then ended up returning after six months for another skin exam. At that point, I had been thinking about her, just knowing that something bad was going to happen. I was finally able to convince her to get a PET scan.

She ended up having some pulmonary metastases on that scan. She was referred to medical oncology, but delayed her appointment. The patient did not want to believe what was there. They finally got her biopsied and proved that it was metastatic melanoma and started her on chemotherapy. She went through four different types of regimens. She kept getting new metastases on the next scan. One would shrink, one would get bigger, and it finally devolved into some brain metastases. She made it about a year and a half after I met her and 11 months after PET scan.

This case just breaks my heart because I know if this patient had received early detection and proper care from the beginning, she would’ve had a much lower tumor burden and probably would’ve done much better on all of the new medications and immunotherapies that we have. As soon as I saw her original pathology report, I knew it was going to be a battle. Sometimes, as in this case, we use the 31-GEP test to provide information that emphasizing the need for imaging. It’s one more piece of information to communicate your level of concern to a patient.

Watch Dr. Wingfield discuss these cases and additional patients in the “Cases with Castle” video series.