Abstract:

Even though the range of histomorphologic diversity among melanomas is well-documented, it often poses diagnostic challenges. This is particularly common in metastatic tumors, with progressive acquisition of spindled morphology, loss of melanocytic markers, acquisition of epithelial and mesenchymal markers and may culminate in heterologous differentiation. The advent of targeted therapies has revolutionized management of patients with metastatic melanoma, but may be associated with several reactive and neoplastic cutaneous adverse effects, as well as changes in pre-existing skin lesions, such as regression of nevi, and rarely, alterations in tumor morphology. Here, we present 3 cases of cutaneous BRAFV600E+ melanoma that displayed histomorphologic changes following neoadjuvant BRAF and MEK inhibitor therapy (BRAFi+MEKi). Case 1: A 32-year-old man with pT4b melanoma of left chest with epithelioid morphology developed axillary lymph node (LN) metastasis. After BRAFi+MEKi, resection revealed small SOX10+ S100+ spindled cells in a desmoplastic background, simulating a scar. Case 2: An 84-year-old man with pT3a melanoma of left parietal scalp with epithelioid morphology developed local recurrence and suboccipital LN metastasis. After BRAFi+MEKi therapy, the tumor showed pronounced nevoid morphology. Case 3: A 75-year-old man with recurrent melanoma of right forearm and axillary nodal metastasis with epithelioid morphology was treated with BRAFi+MEKi. In the lymphadenectomy specimen, the metastatic tumor showed small cell morphology with almost lymphocyte-like appearance and was nearly indistinguishable from the surrounding lymph node. The first 2 patients succumbed to melanoma progression after failing multiple lines of therapy, while the 3rd patient is undergoing BRAFi+MEKi with anti-PD1 therapy. It is essential to consider this rare phenomenon during histologic assessment of melanomas in the neoadjuvant setting for accurate diagnosis and appropriate patient management.

Financial Disclosure: No current or relevant financial relationships exist.

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Kaitlin Vanderbeck, MD