Hamartomas and Choristomas of Nerve: Similarities, Differences and Opportunities

Rochester, MN, USA

Hamartomas and choristomas are rare benign congenital disorders that may affect nerves. Hamartomas have abnormal tissue found in abnormal amounts in normal sites, while choristomas have normal tissue in abnormal locations. Lipomatosis of nerve (LN, also known as fibrolipomatous or lipofibromatous hamartoma) has abundant adipose tissue within nerve and neuromuscular choristoma (NMC) has muscle (frequently, skeletal) within nerve. Based on an experience with a large number of patients (75 with LN and 20 with NMC), I offer perspectives on recent advances that highlight the similarities and differences between the two entities and translational opportunities. Patients with LN and NMC tend to present with symptoms or signs of neuropathy (i.e., pain, paresthesias, weakness/atrophy) by adolescence or young adulthood. LN most commonly occurs in the median and digital nerves in the wrist/palm but can occur at many other sites; NMC typically occurs in proximal nerves such as the sciatic nerve or brachial plexus. LN is part of the PIK3CA-related overgrowth spectrum (PROS) and is associated with bony (macrodactyly) or soft tissue overgrowth (lipomas) in the nerve territory; NMC has been associated with CTNNB1 mutations and nerve-territory undergrowth, including hip dysplasia, limb length shortening and foot (cavovarus) deformity. MRIs show fusiform enlargement of nerve segments: LN tends to have MRI signaling features of the predominant fatty component and NMC, of the muscle component. Both lesions can be diagnosed based on the pathognomonic appearance of MRI, but the imaging features may be misinterpreted or subtle. Biopsy is usually not necessary, may not be diagnostic and may have sequelae: exuberant circumferential fibroproliferative neuromas in patients with LN or desmoid type fibromatosis in patients with NMC (NMC-DTF). Treatment of LN has been focused on nerve decompression and addressing the bony/soft tissue overgrowth in LN. In patients with NMC, a “no touch” technique has been recommended given the occurrence of NMC-DTF following percutaneous or open procedures. The natural history for both conditions is being described, but there has not been any case reported with malignant transformation. Evaluating these 2 pathologies in tandem could provide a model of proliferation and inhibition, one that could be replicated in the laboratory to further our understanding of mesenchymal growth. Basic and clinical research using animal models and targeted molecular therapies could be considered.