BRAF V600E immunohistochemistry as a useful tool in the diagnosis of melanomas with ambiguous morphologies and immunophenotypes

Abstract

We report three melanoma cases in which BRAF V600E immunohistochemistry (IHC) was valuable for diagnosis. Patient 1: In a patient with a history of primary melanoma on the chest and metastatic melanoma to right breast after undergoing multiple local and systemic therapies, a lung metastasis exhibited chondroid differentiation, aberrant myofibroblastic marker expression, and rare pancytokeratin positivity, without melanocytic marker expression. Patient 2: After targeted and immunotherapy for primary melanoma on the scalp as well as regional and distant metastatic melanoma, an omental metastasis showed CDX2‐positive glandular structures that were negative for melanocytic markers. It was initially misdiagnosed as primary gastrointestinal adenocarcinoma. Patient 3: A patient with history of melanoma showing epithelioid morphology on the right thigh presented with multiple soft tissue nodules on skin, lymph nodes and internal organs after being lost to follow‐up for 4 years. A biopsy specimen from the right thigh showed spindled cells with scattered pancytokeratin cocktail positivity and ambiguous staining for melanocytic markers. For melanomas with ambiguous morphologies and/or immunophenotypes in each of the three patients, BRAF V600E expression by IHC was maintained in both primary and metastatic melanoma specimens examined. These cases highlight the utility of BRAF V600E IHC in the diagnosis of melanoma.

Metastatic Nodular Melanoma with Angiosarcomatous Transdifferentiation—A Case Report and Review of the Literature

“…Lastly, despite the valuable role of molecular analysis in dedifferentiated melanomas, such tests are expensive and still not readily available. Consequently, surrogate immunohistochemical markers for the most frequently encountered mutations, BRAF p.V600E and NRAS p.Q61, have been developed and are highly correlated with DNA analysis [42][43][44][45][46][47].…”

Cutaneous Melanoma: A Review of Multifactorial Pathogenesis, Immunohistochemistry, and Emerging Biomarkers for Early Detection and Management

“…In addition to these markers, BRAF V600E immunohistochemical analysis is increasingly performed for primary cutaneous melanomas and metastatic lesions [100,101]. This method is particularly useful for diagnosing dedifferentiated melanomas that lack expression of conventional melanocytic markers and may aberrantly express other markers [102]. Another great advantage of immunohistochemical analysis is its considerably lower costs compared to molecular analysis while the results are similar, with a study reporting a sensitivity of 80.8% and specificity of 100% for immunohistochemistry [103].…”