Infantile Congenital Nevus With Atypical Proliferative Nodules and NTRK Gene Fusion

Infantile congenital melanocytic nevus (CMN) is a rare type of benign skin lesion originating from neural crest cells. A proliferative nodule (PN) may develop within CMN, and in some cases, atypical proliferative nodules (APNs) with distinct histopathological features may arise, complicating clinical diagnosis and management. This report describes a case of a giant infantile CMN with APN and novel genetic findings, including TPR::NTRK1 gene fusion and MCL1 amplification. An 8-day-old male presented with a large, uniform, hairless black lesion on the plantar skin. Histological examination revealed nevomelanocytes arranged in a nest-like pattern within the epidermis and dermis. The PN displayed distinct boundaries, with spindle-shaped and oval cells exhibiting pleomorphism, and diffuse infiltration into the subcutaneous fascia and skeletal muscle. Immunohistochemical analysis demonstrated diffuse positivity for HMB45, Melan-A, and S-100 in nevus cells. In the PN, pan-TRK was positive, CD99 showed weak and focal expression, P16 was retained, and PRAME was negative. Genetic analysis revealed a TPR::NTRK1 gene fusion and MCL1 amplification, suggesting a molecular basis for the atypical features observed in the nodule. This case highlights the role of TPR::NTRK1 fusion in driving abnormal melanocyte proliferation and the potential contribution of MCL1 amplification to tumor progression. These findings provide insights into the genetic underpinnings of APN in CMN and suggest potential therapeutic targets for high-risk lesions.