Cholesterol Granuloma May Lead to Erroneous Diagnoses of CSF Leakage

Clinical Question

Can cholesterol granulomas mimic cerebrospinal fluid (CSF) leakage by secreting beta-trace protein (BTP)?

Bottom Line

Cholesterol granulomas produce significant quantities of BTP, potentially resulting in erroneous diagnoses of CSF leakage.

Background: Persistent CSF leakage is associated with meningitis and encephalitis risks. A valuable marker for CSF leakage, BTP is widely used for detecting CSF otorrhea or rhinorrhea. Cholesterol granuloma is a chronic inflammatory and foreign body reaction of the mucosa, typically found in the region of the middle ear/petrous bone.

Study design: Cohort study

Setting: Division of Otolaryngology, Head and Neck Surgery, University of Oldenburg, Oldenburg, Germany

Synopsis: Prompted by the case of a patient who was erroneously diagnosed as having CSF otorrhea based on a BTP analysis and operated on twice, and in whom cholesterol granuloma tissue was subsequently identified, researchers looked at 11 other patients (six males; total mean age 58.7 years) undergoing ear surgery with the intra-operative clinical finding of a cholesterol granuloma. Results showed that cholesterol granuloma specimens from all patients were positive for BTP. Authors note that, although BTP is one of the most important polypeptide components of CSF and is a highly sensitive and specific biomarker, it is also found in high concentrations in various body fluids, and the optimal cut-off values for CSF detection remain uncertain. Moreover, increased BTP concentrations were observed in serum and nasal secretions in patients with impaired renal function, whereas lower levels were observed in patients with bacterial meningitis. Findings suggest that the capacity of cholesterol granulomas to produce BTP is a salient factor bearing consequences for clinical management and that, in cases of persistent otorrhea of uncertain origin, CSF diagnostics with BTP should be subjected to critical evaluation and possibly replaced by a ß-2-transferrin test.

Citation: Radeloff A, et al. Cholesterol granuloma mimicking CSF otorrhea by beta-trace-protein production. Otol Neurotol. 2025;46:593-597. doi:10.1097/MAO.0000000000004471.

Comment: This article describes why ß-2-transferrin testing may be preferable to beta-trace protein for the detection of CSF otorrhea, because BTP may be false positive in the presence of cholesterol granuloma. Determining the source of chronic drainage from the ear is a common clinical scenario encountered, and the treatment of CSF otorrhea (i.e., surgery) is different than the treatment of other causes of otorrhea. Rob Hong, MD