Abstract:

BRAF V600E immunohistochemistry (IHC) is typically utilized to assess mutational status of BRAF in melanoma, important for prognostic and therapeutic purposes. Herein, we report three cases where BRAF V600E IHC was essential for diagnosis of de-differentiated melanoma. Case #1: A 27-year-old female was diagnosed with primary melanoma on the chest, metastatic to breast after five years of surveillance. Both specimens expressed melanocytic markers and focal glandular differentiation. After multiple BRAF and MEK inhibitor therapies, a lung lesion showed prominent chondroid differentiation, no expression with melanocytic markers, and aberrant expression of myofibroblastic markers with rare pankeratin positivity. BRAF V600E IHC positivity was consistent with metastatic melanoma. Case #2: A 23-year-old female was diagnosed with a cytologically heterogeneous, BRAF V600E-mutated melanoma on the scalp. Five months after targeted therapy, biopsy of an omental tumor showed glandular structures negative for melanocytic markers, leading to an initial misdiagnosis of primary gastrointestinal adenocarcinoma. Diffuse expression of BRAF V600E by IHC instead supported the diagnosis of metastatic melanoma. Case #3: A 46-year-old female was diagnosed with melanoma on the right thigh with epithelioid morphology and expression of melanocytic markers. The patient was lost to follow-up but returned several years later with multiple masses. A right thigh mass specimen showed spindled cells, with scattered positivity for pancytokeratin cocktail and ambiguous staining with melanocytic markers. BRAF V600E IHC was positive, and a diagnosis of melanoma was rendered. These cases highlight the utility of BRAF V600E IHC in the diagnosis of de-differentiated melanoma in addition to its role in guiding therapy.

Financial Disclosure:
No current or relevant financial relationships exist.

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Aimi Rothrock, MD