Summary

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.

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Authors

Ludovica Pepe - Department of Human Pathology of Adults and Developmental Age "Gaetano Barresi"

Vincenzo Fiorentino - Department of Human Pathology of Adults and Developmental Age "Gaetano Barresi", Division of Pathology, University of Messina, Messina, Italy.

Antonio Ieni - Department of Human Pathology of Adults and Developmental Age "Gaetano Barresi", Division of Pathology, University of Messina, Messina, Italy.

Mariacarmela Santarpia - Medical Oncology Unit, Department of Human Pathology "G. Barresi", University of Messina, 98122 Messina, Italy.

Antonina Fazio - Department of Human Pathology, Plastic Surgery Unit, University of Messina, Policlinico Hospital.

Mario Vaccaro - Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria, 98124 Messina, Italy.

Francesco Borgia - Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria, 98124 Messina, Italy.

Gerardo Ferrara - Pathology Unit, Istituto Nazionale Tumori di Napoli, IRCCS Fondazione "G. Pascale", via M. Semmola, 80131, Naples, Italy.

Maria Lentini - Department of Human Pathology of Adults and Developmental Age "Gaetano Barresi", Division of Pathology, University of Messina, Messina, Italy.

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Copyright (c) 2026 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology

How to Cite
Pepe, L., Fiorentino, V., Ieni, A., Santarpia, M., Fazio, A., Vaccaro, M., Borgia, F., Ferrara, G., & Lentini, M. (2026). Metastatic melanoma with heterologous bone after neoadjuvant immunotherapy: diagnostic insights. Pathologica - Journal of the Italian Society of Anatomic Pathology and Diagnostic Cytopathology, 118(2). https://doi.org/10.32074/1591-951X-1977
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