Malignant Transformation of Cellular Blue Nevus in a Lymph Node: A Case Report

Involvement of lymph nodes by benign melanocytic neoplasms is a readily accepted concept in the pathology literature. However, little is known or has been discussed in the literature regarding the concept of malignant transformation of benign melanocytic tumors within lymph nodes. In this report, we describe a 49-year-old woman with a cellular blue nevus on the buttock with no evidence of high-grade atypia or malignancy on both the biopsy and re-excision. She later presented with a palpable lymph node in the left inguinal region. Biopsy of the lymph node showed involvement of the lymph node capsule by the cellular blue nevus that had similar cytomorphology to that in the skin. The parenchyma of the lymph node was completely replaced and expanded by a proliferation of highly atypical and mitotically active melanocytes most consistent with malignant cellular blue nevus. Sequencing studies from the malignant blue nevus in the node and the cellular blue nevus on the buttock demonstrated the same GNAQ p.(Q209L) pathogenic variant. However, the malignant cellular blue nevus also had the following additional pathogenic variants: EIF1AX p.(K3M) and EIF1AX p.(N4S). Pathogenic variants in EIF1AX are well known to play a role in tumor progression of blue melanocytic tumors. These findings are most suggestive of malignant transformation of the cellular blue nevus within the lymph node. We believe this case, including the histologic and molecular findings, provides a novel and unique illustration of the phenomenon of malignant transformation of a melanocytic tumor in a lymph node.