Perineural spread of colorectal carcinoma into the sciatic nerve with positive circulating tumor DNA test: illustrative case.

backgroundPerineural spread (PNS) of colorectal carcinoma (CRC) is a rare and challenging diagnosis. Its clinical and radiological presentation is often subtle and can overlap with radiation-induced neuropathy and malignant nerve tumors, complicating timely diagnosis. The role of circulating tumor DNA (ctDNA) in the detection of PNS has not been previously described. OBSERVATIONS: A 48-year-old man with a history of rectal cancer and perineural invasion presented with progressive, refractory sciatic neuropathic pain. Conventional surveillance imaging was initially negative despite subtle rising of carcinoembryonic antigen and ctDNA levels. Subsequent MRI revealed abnormalities of the lumbosacral plexus and sciatic nerve, and fascicular biopsy confirmed metastatic CRC involving the sciatic nerve, establishing the diagnosis of PNS. LESSONS: This case highlights PNS as a rare but important consideration in patients with focal neuropathic symptoms and prior CRC. Circulating tumor DNA positivity may serve as an early indicator of occult tumor activity even within the nerves when imaging is equivocal. However, currently histopathological confirmation remains the only definitive method to distinguish PNS from alternative diagnoses and is essential to guide appropriate management. https://thejns.org/doi/10.3171/CASE25997.