Diagnostic Utility of Molecular Profiling in a Giant Cellular Blue Nevus

Giant cellular blue nevi (CBN) are rare melanocytic proliferations that may mimic melanoma, posing diagnostic challenges. We report a case of a 22-year-old woman with a 6-cm bluish-gray mass on the left medial buttock that had been present since childhood. An incisional punch biopsy performed at an outside facility demonstrated a dermal proliferation of heavily pigmented and densely cellular spindled and epithelioid melanocytes that were negative for PRAME. Comprehensive molecular profiling showed a low tumor mutational burden and identified an activating GNAQ p.Q209L mutation with no alterations in BRAF , NRAS , or KIT . Further workup at our institution included a pelvic MRI that showed no evidence of invasion into adjacent muscle or bone; however, the lesion's size warranted complete surgical excision. Final pathology analysis demonstrated a large circumscribed neoplasm consisting of both spindled and epithelioid melanocytes with no significant pleomorphism, a low proliferative index, and BRAF and PRAME negativity, though perineural involvement was noted. In the context of the imaging and molecular study results, a diagnosis of giant cellular blue nevus was made. This case highlights a rare presentation of giant CBN and the utility of integrating next-generation sequencing with histopathologic evaluation to distinguish the latter from melanoma and support clinical decision making.