Metastatic melanoma with heterologous bone after neoadjuvant immunotherapy: diagnostic insights

We report a BRAF V600E-mutated cutaneous melanoma (pT3b) with nodal metastases treated with neoadjuvant anti-PD-1 therapy. Axillary lymph node dissection demonstrated residual viable melanoma intimately associated with extensive heterologous lamellar bone formation within the post-treatment tumor bed. Histologic assessment supported a melanoma-related heterologous component rather than a purely reactive stromal phenomenon, underscoring a relevant diagnostic pitfall in treated specimens. The observation also has practical implications for pathological response evaluation after neoadjuvant immunotherapy: in this case, the osseous component was integrated into the viable tumor compartment to avoid underestimation of residual disease. Overall, this case exemplifies the evolving morphobiological spectrum of melanoma in the immunotherapy era, and emphasizes that careful correlation of morphology with the clinical context remains the mainstay to avoid misinterpretation, particularly when uncommon heterologous or metaplastic patterns emerge after immune checkpoint blockade.