Benign non-epithelial neoplasms of the gallbladder and extrahepatic biliary tree are uncommon, accounting for only 6% of biliary tumors, with papilloma and adenomas being the majority, while lesions of a neural origin, such as neurofibromas, are exceedingly rare.¹ Christensen and Ishak’s large series of 180 benign gallbladder tumors and pseudotumors found no neural-origin lesions, emphasizing their scarcity, but traumatic neuromas have been reported in the cystic duct stump post-surgery.^2-5 Neurofibromas of the extrahepatic biliary tree arise from sympathetic and parasympathetic fibers along the CBD wall, which are classified into the following types: traumatic types―more common, resulting from surgical trauma with nerve fiber proliferation outside the epineurium, and primary types―rarer and linked to chronic inflammation, granulomas, infections, or ischemia, with axonal proliferation confined within the epineurium.⁶ The first documented case of isolated gallbladder neurofibroma was reported in 1982, and a literature review revealed eight reported cases in the English literature thus far, four of which were incidental findings during cholecystectomy for nonspecific abdominal symptoms or cholelithiasis and five detected preoperatively via imaging like non-visualization on intravenous cholecystography or as an echogenic mass (Table 1).⁷ Gallbladder neurofibromas typically present at a mean age of 57.9 years (range 32–77), with an equal sex distribution and a 50% association with gallstones, treated effectively by cholecystectomy, while biliary tree neurofibromas, more common in females (2:1 ratio), are often asymptomatic or present with jaundice.⁸ This paper reports the first case of simultaneous primary neurofibroma involving a septate gallbladder and distal CBD in a patient with no prior surgery, presenting with obstructive jaundice. Although the tumor markers were within the normal limits, their limited sensitivity meant that a malignancy could not be excluded. Autoimmune testing was not performed because the clinical and radiological features did not suggest autoimmune disease. The absence of systemic symptoms and focal lesions suggested a neoplastic process. Initially mimicking a dual malignancy (gallbladder carcinoma and distal cholangiocarcinoma) on the clinical, radiological, and intraoperative assessment, this case led to a hepato-pancreatico-duodenectomy (HPD), but histopathological analysis revealed long spindle-shaped cells positive for neurofilament protein and negative for CD117, CD34, and muscle markers, confirming a neurofibroma. A preoperative diagnosis remains challenging because of the imaging similarities to malignant lesions. Endoscopic ultrasound (EUS) was not performed. Although EUS may have aided in a preoperative diagnosis, its unavailability is a limitation. The intraoperative frozen section remains critical in avoiding an extensive resection in such cases.

This case represents an addition to the literature as the first reported instance of simultaneous primary neurofibroma of the gallbladder and distal CBD, expanding the known spectrum of tumors with a neural origin in the biliary system. The rarity of these lesions, which is underscored by their absence in Christensen and Ishak’s extensive series and the limited eight prior gallbladder cases, highlights the diagnostic and therapeutic challenges they pose.² Unlike traumatic neuromas, which are tied to surgical history, this lack of prior intervention in this patient and the histopathological distinction from amputation neuromas align with a primary neurofibroma etiology, possibly driven by chronic inflammatory or ischemic processes. The dual-site involvement and septate gallbladder morphology further complicate the clinical picture, contributing to the preoperative misdiagnosis of a malignancy. This mimicry, evidenced by imaging overlap with gallbladder carcinoma and cholangiocarcinoma, underscores the critical limitation in current diagnostic modalities, as noted in the five prior cases detected preoperatively as echogenic masses or non-visualizing gallbladders. The decision to proceed with HPD reflects the aggressive approach warranted by the suspected malignancy, but the benign histopathology raises the question of whether less invasive management could suffice had the diagnosis been suspected earlier. The literature suggests that cholecystectomy alone is curative for gallbladder neurofibromas, while biliary tree cases, often asymptomatic or jaundice-presenting, may require tailored approaches based on the extent and symptoms. Immunohistochemical confirmation (neurofilament positivity, CD117/CD34 negativity) distinguishes this from other spindle-cell lesions, reinforcing the diagnostic specificity post-resection. This case underscores the need for the heightened awareness of neurofibroma as a differential in biliary tract lesions, particularly in atypical presentations. It supports using intraoperative frozen sections to guide the surgical extent, potentially sparing patients from major procedures like HPD. Further studies could explore the predisposing factors for dual-site neurofibromas and refine imaging techniques to differentiate benign from malignant processes, enhancing the preoperative accuracy in such rare scenarios.