Pseudoprogression with Neoadjuvant Immunotherapy for Cutaneous Melanoma

Immune checkpoint inhibitors (ICI) have drastically changed the landscape of metastatic melanoma management, thus significantly improving survival. Clinically, assessing treatment response may be challenging in a portion of cases due to a massive influx of immune cells into the tumor microenvironment, causing a transient increase in the target lesion size. This phenomenon, coined pseudoprogression, can occur in 5-10% of metastatic patients, and it is commonly followed by a tumor regression. Its incidence, however, may be underestimated, given its ephemeral nature and often being documented in visceral metastatic lesions, which are only assessed by imaging scans every 2-3 months. More recently, ICI has been studied in the neoadjuvant setting, yielding durable pathological responses in patients with cutaneous melanoma. Here, we report a case of a large retroauricular melanoma mass with regional lymph node involvement treated with ipilimumab and nivolumab combination therapy that developed pseudoprogression. Initially documented as an increase in size along with inflammatory features, followed by a dramatic clinical improvement. A complete regression was pathologically documented after 3 months and the patient remains disease-free for 14 months after treatment initiation. In conclusion, we document a pseudoprogression case during neoadjuvant ICI treatment and raise the question of whether the incidence of this phenomenon is higher when observed in superficial lesions, which can be assessed by routine physical exam.