Intraoperative 5-aminolevulinic acid–induced fluorescence in primary central nervous system lymphoma

Case report

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The authors report a case of primary CNS lymphoma located in the floor of the fourth ventricle that showed intense fluorescence after preoperative administration of 5-aminolevulinic acid. The authors believe that this is the first demonstration of a 5-aminolevulinic acid–induced fluorescence pattern in primary CNS lymphoma.

Abbreviations used in this paper:PCNSL = primary CNS lymphoma; UV = ultraviolet; 5-ALA = 5-aminolevulinic acid.

The authors report a case of primary CNS lymphoma located in the floor of the fourth ventricle that showed intense fluorescence after preoperative administration of 5-aminolevulinic acid. The authors believe that this is the first demonstration of a 5-aminolevulinic acid–induced fluorescence pattern in primary CNS lymphoma.

Orally administered 5-aminolevulinic acid (5-ALA)–induced fluorescence has been commonly used in glioma surgery in recent years.5–7 One randomized controlled multicenter Phase III study has shown that its use is associated with increased extent of resection and prolongation of progression-free survival in patients with malignant gliomas.5 The 5-ALA passes through the intact blood-brain barrier and is metabolized intracellularly by tumor cells to form the fluorescent molecule protoporphyrin IX.2,6 We present a case of 5-ALA–induced fluorescence in a primary CNS lymphoma (PCNSL) located in the fourth ventricle. To the best of our knowledge this is the first demonstration of 5-ALA–induced fluorescence in PCNSL depicting the infiltrative nature of this tumor in the brain.

Case Report

History and Examination

This 66-year-old man with an 8-year history of chronic lymphocytic leukemia presented to our neurosurgical department for evaluation of progressive gait disturbances and diplopia. Physical examination revealed mild left hemiparesis and dysmetria, an unstable wide gait, and a positive Romberg test. Complete blood count tests showed 156,000 leukocytes and 76% lymphocytes, which were unchanged from complete blood count results in the previous years. Brain MRI sequences revealed an exophytic 13 × 12–mm intraaxial mass located on the left side of the floor of the fourth ventricle. The tumor was hypointense on T1- and T2-weighted sequences and showed a homogeneous enhancement after contrast injection. The tumor was associated with edema involving the cerebellar peduncle and pons (Fig. 1). Diffusion-weighted MRI sequences showed mild fluid restriction. Whole-body CT as well as PET-CT scans showed no systemic involvement.

Fig. 1.
Fig. 1.

Preoperative axial MRI sequences. A: A Gd-enhanced T1-weighted view. B: A FIESTA study. C: A diffusionweighted MRI study. D: A T1-weighted MRI study. E: A FLAIR study. These MRI studies demonstrate a homogeneously enhancing mass on the left side of the floor of the fourth ventricle, with mild restriction on diffusion-weighted MRI sequences.

Operation

Tumor resection took place after oral administration of 5-ALA according to a previously described protocol.5 Via a suboccipital midline approach, the tumor was identified on the left side of the floor of the fourth ventricle (Fig. 2 left). Blue-light illumination of the tumor revealed the typical red fluorescence under a 440-nm ultraviolet (UV) light source (violet-blue light, an optical component of the OPMI Pentero microscope; Carl Zeiss AG) (Fig. 2 right). The fluoresced tumor tissue was resected in a piecemeal fashion after identification and preservation of the pontine cranial nerves. The intensity of fluorescence gradually diminished over distance from the main tumor bulk, suggesting an infiltrating zone in the floor of the ventricle.

Fig. 2.
Fig. 2.

Intraoperative views. Left: The tumor mass bulging from the floor of the fourth ventricle under a white light source of the intraoperative microscope. Right: The tumor showing charcoal-red fluorescence under a 440-nm UV light source of the intraoperative microscope. The arrows and letters indicate the following: a) tumor mass; b) medullary stria of fourth ventricle; c) midline of fourth ventricle; and d) infiltrating zone of the floor of the fourth ventricle by the tumor.

Histopathological Findings

Histopathological examination of the tumor revealed sheets of large anaplastic and pleomorphic tumor cells with a B-cell immune phenotype and a high proliferation index, findings that were compatible with a large B-cell CNS lymphoma (Fig. 3). The patient was referred for further oncological treatment for his disease.

Fig. 3.
Fig. 3.

Photomicrographs. A: H & E staining demonstrating sheets of large anaplastic and pleomorphic tumor cells. B: Immunostaining with CD20 demonstrating tumor cells with a B-cell immune phenotype. C: Immunostaining with CD3 demonstrating intermingling of small reactive T lymphocytes. D: Immunostaining with MIB1 demonstrating a high proliferation index. Original magnification ×40 in all panels.

Discussion

Accumulation of photosensitive protoporphyrin IX in glioma cells is observed after oral administration of 5-ALA. This phenomenon has been used in recent years to identify infiltrating glioma, to discriminate between normal and tumor tissue, and to improve the extent of tumor resection in gliomas. The use of 5-ALA–based fluorescence has been recently described in brain metastases4 and meningiomas.1 There is one report describing a stereotactic biopsy specimen of a deep-seated lesion in the thalamus3 that showed 5-ALA–induced fluorescence and was found to be a large B-cell lymphoma.

In the present report, the preoperative MRI results suggested an intraaxial tumor reminiscent of a high-grade glioma. The open resective approach to this tumor allowed us to observe the macroscopic appearance of 5-ALA–induced fluorescence in PCNSL. Interestingly, the fluorescence intensity gradient as seen through the intraoperative UV light microscope correlated with the tumor extension and infiltration as demonstrated by the MRI FLAIR sequence.

In this report we show for the first time the fluorescence pattern of PCNSLs in the brain. This observation may be of importance considering the recent published report indicating a survival advantage when PCNSL is resected rather than biopsied.8 It appears that intraoperative tools to enhance resection may apply to lymphoma in a similar way to what has been shown in glioma surgery. The knowledge that this phenomenon of tumor fluorescence is not exclusive to high-grade glioma, but may occur in the same pattern in PCNSLs, should be taken into account during tumor resection and, as previously noted, cannot assist in differentiating among various tumor types.

Disclosure

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Author contributions to the study and manuscript preparation include the following. Conception and design: Grossman, Ram. Acquisition of data: Grossman, Nossek, Raz. Analysis and interpretation of data: Grossman. Drafting the article: Grossman, Ram. Critically revising the article: all authors. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Grossman. Administrative/technical/material support: Grossman, Nossek. Study supervision: Grossman, Ram.

References

  • 1

    Coluccia DFandino JFujioka MCordovi SMuroi CLandolt H: Intraoperative 5-aminolevulinic-acid-induced fluorescence in meningiomas. Acta Neurochir (Wien) 152:171117192010

    • Search Google Scholar
    • Export Citation
  • 2

    Duffner FRitz RFreudenstein DWeller MDietz KWessels J: Specific intensity imaging for glioblastoma and neural cell cultures with 5-aminolevulinic acid-derived protoporphyrin IX. J Neurooncol 71:1071112005

    • Search Google Scholar
    • Export Citation
  • 3

    Moriuchi SYamada KDehara MTeramoto YSoda TImakita M: Use of 5-aminolevulinic acid for the confirmation of deep-seated brain tumors during stereotactic biopsy. Report of 2 cases. J Neurosurg 115:2782802011

    • Search Google Scholar
    • Export Citation
  • 4

    Schucht PBeck JVajtai IRaabe A: Paradoxical fluorescence after administration of 5-aminolevulinic acid for resection of a cerebral melanoma metastasis. Acta Neurochir (Wien) 153:149714992011

    • Search Google Scholar
    • Export Citation
  • 5

    Stummer WPichlmeier UMeinel TWiestler ODZanella FReulen HJ: Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol 7:3924012006

    • Search Google Scholar
    • Export Citation
  • 6

    Stummer WStepp HMöller GEhrhardt ALeonhard MReulen HJ: Technical principles for protoporphyrin-IX-fluorescence guided microsurgical resection of malignant glioma tissue. Acta Neurochir (Wien) 140:99510001998

    • Search Google Scholar
    • Export Citation
  • 7

    Stummer WStocker SWagner SStepp HFritsch CGoetz C: Intraoperative detection of malignant gliomas by 5-aminolevulinic acid-induced porphyrin fluorescence. Neurosurgery 42:5185261998

    • Search Google Scholar
    • Export Citation
  • 8

    Weller MMartus PRoth PThiel EKorfel A: Surgery for primary CNS lymphoma? Challenging a paradigm. Neuro Oncol 14:148114842012

    • Search Google Scholar
    • Export Citation

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Article Information

Address correspondence to: Rachel Grossman, M.D., Department of Neurosurgery, Tel-Aviv Sourasky Medical Center, 6 Weizmann St., Tel-Aviv 64239, Israel. email: rachelgr@tasmc.health.gov.il.

Please include this information when citing this paper: published online October 18, 2013; DOI: 10.3171/2013.9.JNS131076.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    Preoperative axial MRI sequences. A: A Gd-enhanced T1-weighted view. B: A FIESTA study. C: A diffusionweighted MRI study. D: A T1-weighted MRI study. E: A FLAIR study. These MRI studies demonstrate a homogeneously enhancing mass on the left side of the floor of the fourth ventricle, with mild restriction on diffusion-weighted MRI sequences.

  • View in gallery

    Intraoperative views. Left: The tumor mass bulging from the floor of the fourth ventricle under a white light source of the intraoperative microscope. Right: The tumor showing charcoal-red fluorescence under a 440-nm UV light source of the intraoperative microscope. The arrows and letters indicate the following: a) tumor mass; b) medullary stria of fourth ventricle; c) midline of fourth ventricle; and d) infiltrating zone of the floor of the fourth ventricle by the tumor.

  • View in gallery

    Photomicrographs. A: H & E staining demonstrating sheets of large anaplastic and pleomorphic tumor cells. B: Immunostaining with CD20 demonstrating tumor cells with a B-cell immune phenotype. C: Immunostaining with CD3 demonstrating intermingling of small reactive T lymphocytes. D: Immunostaining with MIB1 demonstrating a high proliferation index. Original magnification ×40 in all panels.

References

  • 1

    Coluccia DFandino JFujioka MCordovi SMuroi CLandolt H: Intraoperative 5-aminolevulinic-acid-induced fluorescence in meningiomas. Acta Neurochir (Wien) 152:171117192010

    • Search Google Scholar
    • Export Citation
  • 2

    Duffner FRitz RFreudenstein DWeller MDietz KWessels J: Specific intensity imaging for glioblastoma and neural cell cultures with 5-aminolevulinic acid-derived protoporphyrin IX. J Neurooncol 71:1071112005

    • Search Google Scholar
    • Export Citation
  • 3

    Moriuchi SYamada KDehara MTeramoto YSoda TImakita M: Use of 5-aminolevulinic acid for the confirmation of deep-seated brain tumors during stereotactic biopsy. Report of 2 cases. J Neurosurg 115:2782802011

    • Search Google Scholar
    • Export Citation
  • 4

    Schucht PBeck JVajtai IRaabe A: Paradoxical fluorescence after administration of 5-aminolevulinic acid for resection of a cerebral melanoma metastasis. Acta Neurochir (Wien) 153:149714992011

    • Search Google Scholar
    • Export Citation
  • 5

    Stummer WPichlmeier UMeinel TWiestler ODZanella FReulen HJ: Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol 7:3924012006

    • Search Google Scholar
    • Export Citation
  • 6

    Stummer WStepp HMöller GEhrhardt ALeonhard MReulen HJ: Technical principles for protoporphyrin-IX-fluorescence guided microsurgical resection of malignant glioma tissue. Acta Neurochir (Wien) 140:99510001998

    • Search Google Scholar
    • Export Citation
  • 7

    Stummer WStocker SWagner SStepp HFritsch CGoetz C: Intraoperative detection of malignant gliomas by 5-aminolevulinic acid-induced porphyrin fluorescence. Neurosurgery 42:5185261998

    • Search Google Scholar
    • Export Citation
  • 8

    Weller MMartus PRoth PThiel EKorfel A: Surgery for primary CNS lymphoma? Challenging a paradigm. Neuro Oncol 14:148114842012

    • Search Google Scholar
    • Export Citation

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