Metastatic melanoma with balloon/histiocytoid cytomorphology after treatment with immunotherapy: A histologic mimic and diagnostic pitfall

Epithelioid cells with foamy cytoplasm (histiocytoid features) are typical histopathologic findings among benign and malignant histiocytic neoplasms such as xanthoma and atypical fibroxanthoma. However, these changes are unusual in melanoma, which is typically composed of nested and variably pigmented atypical epithelioid cells. Here, we report a patient with metastatic melanoma in lymph nodes presenting with prominent balloon cell/histiocytoid features expressing melanocytic markers, after treatment with nivolumab. This report suggests that the spectrum of neoplasms with histiocytoid features should be expanded to include melanoma, a pattern that, to the best of our knowledge, is uncommon, especially in the setting of post-neoadjuvant therapy.