5-ALA-induced fluorescence as a marker for diagnostic tissue in stereotactic biopsies of intracranial lymphomas: experience in 41 patients

Neurosurg Focus. 2018 Jun;44(6):E7. doi: 10.3171/2018.3.FOCUS1859.

Abstract

OBJECTIVE Stereotactic needle biopsies are usually performed for histopathological confirmation of intracranial lymphomas to guide adequate treatment. During biopsy, intraoperative histopathology is an effective tool to avoid acquisition of nondiagnostic samples. In the last years, 5-aminolevulinic acid (5-ALA)-induced fluorescence has been increasingly used for visualization of diagnostic brain tumor tissue during stereotactic biopsies. Recently, visible fluorescence was reported in the first cases of intracranial lymphomas as well. The aim of this study is thus to investigate the technical and clinical utility of 5-ALA-induced fluorescence in a large series of stereotactic biopsies for intracranial lymphoma. METHODS This prospective study recruited adult patients who underwent frameless stereotactic needle biopsy for a radiologically suspected intracranial lymphoma after oral 5-ALA administration. During biopsy, samples from the tumor region were collected for histopathological analysis, and presence of fluorescence (strong, vague, or no fluorescence) was assessed with a modified neurosurgical microscope. In tumors with available biopsy samples from at least 2 different regions the intratumoral fluorescence homogeneity was additionally investigated. Furthermore, the influence of potential preoperative corticosteroid treatment or immunosuppression on fluorescence was analyzed. Histopathological tumor diagnosis was established and all collected biopsy samples were screened for diagnostic lymphoma tissue. RESULTS The final study cohort included 41 patients with intracranial lymphoma. Stereotactic biopsies with assistance of 5-ALA were technically feasible in all cases. Strong fluorescence was found as maximum level in 30 patients (75%), vague fluorescence in 2 patients (4%), and no visible fluorescence in 9 patients (21%). In 28 cases, samples were obtained from at least 2 different tumor regions; homogenous intratumoral fluorescence was found in 16 of those cases (57%) and inhomogeneous intratumoral fluorescence in 12 (43%). According to histopathological analysis, all samples with strong or vague fluorescence contained diagnostic lymphoma tissue, resulting in a positive predictive value of 100%. Analysis showed no influence of preoperative corticosteroids or immunosuppression on fluorescence. CONCLUSIONS The data obtained in this study demonstrate the technical and clinical utility of 5-ALA-induced fluorescence in stereotactic biopsies of intracranial lymphomas. Thus, 5-ALA can serve as a useful tool to select patients not requiring intraoperative histopathology, and its application should markedly reduce operation time and related costs in the future.

Keywords: 5-ALA = 5-aminolevulinic acid; 5-aminolevulinic acid; HIV = human immunodeficiency virus; NPV = negative predictive value; PCNSL = primary central nervous system lymphoma; PPV = positive predictive value; PpIX = protoporphyrin IX; diagnostic tissue; fluorescence; intracranial lymphoma; stereotactic biopsy.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aminolevulinic Acid* / administration & dosage
  • Biopsy / methods
  • Brain Neoplasms / diagnostic imaging*
  • Brain Neoplasms / pathology
  • Brain Neoplasms / surgery
  • Female
  • Humans
  • Lymphoma / diagnostic imaging*
  • Lymphoma / pathology
  • Lymphoma / surgery
  • Male
  • Middle Aged
  • Monitoring, Intraoperative / methods*
  • Optical Imaging / methods*
  • Prospective Studies
  • Stereotaxic Techniques*

Substances

  • Aminolevulinic Acid