Benign nonepithelial tumors of the gallbladder (GB), such as neurofibromas, are rare, with neurofibroma often linked to NF-1. An isolated neurofibroma of the GB and common bile duct (CBD) is exceptionally uncommon and challenging to diagnose preoperatively because they resemble malignancies like gallbladder carcinoma and cholangiocarcinoma. Most are discovered incidentally following cholecystectomy on histopathology. This paper reports a rare case of primary neurofibroma involving a septate GB and distal CBD, presenting as a diagnostic challenge by mimicking malignancy.

This patient is a 32-year-old male who presented with a two-month history of right upper quadrant abdominal pain, jaundice associated with severe pruritus, and clay-colored stools. Importantly, there was no history of fever, anorexia, or weight loss, which are often associated with infections or advanced malignancies. The patient was initially evaluated at another hospital, where endoscopic retrograde cholangiography (ERC) with biliary stent placement was performed to relieve an obstruction caused by suspected Mirizzi’s syndrome. The patient’s symptoms improved after stenting, but further evaluations were required because of the ongoing concerns regarding the underlying etiology. Subsequent imaging studies, including magnetic resonance cholangiopancreatography (MRCP) (Fig. 1A) and contrast-enhanced computed tomography (CECT) (Fig. 1B), revealed a double/septate GB stone in the neck of the GB, eccentric mural thickening in the GB body with a loss of fat planes with the liver, and annular thickening of the distal CBD raising concerns for a malignancy. Based on these findings, a preoperative diagnosis of carcinoma GB involving the CBD or a dual malignancy (carcinoma of the GB along with distal cholangiocarcinoma) was considered. These were the most likely causes of the patient’s symptoms and imaging findings. The tumor markers (CA 19-9, CEA) were within the normal limits. The patient underwent an exploratory laparotomy. Intraoperatively, the following findings were noted: septate gall bladder and nodular growth in the neck of the anterior wall of GB extending to the distal CBD. These findings aligned with the preoperative suspicion of a malignancy. The patient underwent a hepato-pancreatic-duodenectomy under the clinical suspicion of a malignancy and the anatomical involvement of the GB, CBD, and surrounding structures. The gross findings showed a 1×0.5×0.5 cm sized grey–white nodular lesion in the distal CBD and a 0.4 cm lesion at the neck of the septate gall bladder (Fig. 2A, 2B). The histopathological evaluation revealed both lesions to be composed of spindle cells arranged in sheets and fascicles (Fig. 2C, 2D). These spindle cells surrounded the nerve fascicles and ductular structures, pointing towards a neural origin. The cells had elongated, ovoid to kinked nuclei and moderate eosinophilic cytoplasm, typical of neurofibromas. Immunohistochemistry showed that the spindle cells were strongly positive for S100 and neurofilament protein (NFP). These findings confirmed the diagnosis of a neurofibroma. All 47 lymph nodes examined exhibited reactive changes with no evidence of a malignancy. The final diagnosis was a neurofibroma of the septate gall bladder and distal CBD, a benign neural tumor. The patient experienced a bile leak post-operatively, which was managed conservatively without further intervention. The patient was discharged on the 17th post-operative day after an uneventful recovery. He remained asymptomatic with no evidence of recurrence on regular follow-ups, with the last follow-up at 24 months

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.