Neurology India Medknow Publications on behalf of the Neurological Society of India ISSN: 0028-3886 EISSN: 1998-4022 Vol. 59, Num. 4, 2011, pp. 612-615

Neurology India, Vol. 59, No. 4, July-August, 2011, pp. 612-615

Case Report

Utility of intraoperative fluorescent diagnosis of residual hemangioblastoma using 5-aminolevulinic acid

Satoshi Utsuki, Hidehiro Oka, Chihiro Kijima, Yoshiteru Miyajima, Hiroyuki Hagiwara, Kiyotaka Fujii

Department of Neurosurgery, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
Correspondence Address: Satoshi Utsuki, Department of Neurosurgery, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami, Sagamihara, Kanagawa 252-0473, Japan, utsuki@med.kitasato-u.ac.jp

Date of Submission: 20-Feb-2011
Date of Decision: 31-Mar-2011
Date of Acceptance: 10-Apr-2011

Code Number: ni11182

PMID: 21891945

DOI: 10.4103/0028-3886.84349

Abstract

Keywords: 5-aminolevulinic acid, cyst wall, fluorescence diagnosis, hemangioblastoma, residual tumor

Introduction

Hemangioblastoma, a benign tumor of the cerebellum, often occurs in adults and may recur. ^[1],[2] The recurrence may be from the site of tumor resection bed or distant from the initial tumor resection area. Recurrence in a region other than the area of primary resection may be due to non-visualization of tumor at that site preoperatively or may have been due to a diathesis of easy to occur tumors such as von Hippel-Lindau (VHL) disease. ^[2],[3] The tumor may also relapse and be part of a condition known as hemangioblastomatosis. ^[4] Local recurrence of tumor can be prevented if complete resection is performed during the initial surgery. Intraoperative photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5-ALA) utilizes protoporphyrin IX (PPIX), which is a metabolite of 5-ALA that accumulates in tumor cells. Residual tumor can be detected macroscopically, since red fluorescence is observed when ultraviolet light irradiates PPIX. ^[5] This study investigated whether the residual tumor could be detected when PDD using 5-ALA is performed during surgical removal of hemangioblastomas.

Case Report

Nine patients (four males and five females, mean age 51 years, range 27-69 years) with hemangioblastoma were enrolled for this study between 1995 and 2010. In all the patients, tumor resection was done using intraoperative PDD with 5-ALA. All patients had detailed examination to exclude any phakomatosis, retinal angioma and abdominal mass lesions. Genetic studies for VHL disease done in two patients were negative. Of the nine patients, two had local recurrent lesion. Magnetic resonance imaging (MRI) showed one or more peritumoral cysts in all the patients. One of the nine hemangioblastomas with peritumoral cyst showed thin enhancement of the cyst (case 1) [Figure - 1]. However, at this point of time, we could not study further the histological characters of this cyst as the patient refused to have surgery. During the subsequent 15 months of follow-up, the cyst increased in size, but contrast enhancement of the cyst wall disappeared except near the tumor attachment site; at this time, the patient agreed for surgery [Figure - 2]. All patients received 1 g of orally administered 5-ALA, 2 hours prior to the introduction of an anesthetic. Tumor masses were excised under microscope, and the tumor bed was irradiated with 405 nm of excitation light using a semiconductor laser device (VLD-V1 version 2; M and M Co. Ltd., Tokyo, Japan). The presence of PPIX fluorescence was observed through a low-cut filter (cut 420 nm, M and M Co. Ltd.). The fluorescence of the PPIX waveform was confirmed by spectrometer and accessory software (BW-Spec V3.09; B and W TEK, Inc., Newark, DE, USA). This was necessary as all the visualized red fluorescent light may not have been the fluorescence of PPIX. The PPIX fluorescence spectrum has two peaks, a sharp peak at 636 nm and a slightly broader peak at 705 nm.

Results

Fluorescence of PPIX was observed in the tumor mass in all the patients. After tumor resection with microscope, the region was observed under a laser beam of 405 nm. The fluorescence of PPIX was not observed at the point of attachment of the tumor mass in the brain. Of the nine tumors, fluorescence of PPIX was observed in two peritumoral cysts. One of the fluorescent peritumoral cysts was a recurrent tumor (case 1) [Figure - 2] and [Figure - 3]b ^[5] and the other was a first occurrence tumor (case 2) [Figure - 4] and [Figure - 5]b. The two fluorescent peritumoral cyst walls did not show any macroscopic abnormality [Figure - 3]a and [Figure - 5]a and histological examination of the resected fluorescent cyst walls confirmed the presence of tumor cells [Figure - 6] and [Figure - 7]. The part was the cystic wall with PPIX fluorescence of the macroscopy normality with the distance from tumor attachment. In these two cases after the cyst walls were resected, tumor cyst wall bed did not reflect the fluorescence of PPIX [Figure - 5]c, which does not have a waveform that creates a sharp peak at 636 nm on spectrometer. No tumor cells were seen in the tissue [Figure - 8]. The fluorescence of PPIX was not observed in the cyst wall of the other seven hemangioblastomas. A part of these cyst walls was also resected, but tumor cells were not seen histopathologically. Cyst walls with other cases are composed of collagen fiber, astrocytic gliosis and Rosenthal fibers and are devoid of tumor cells.

Discussion

Hemangioblastoma is a benign tumor with a surrounding border clear of tumor. Recurrence of hemangioblastoma is unusual if the tumor resection is complete. The reported recurrence rates with long-term follow-up varied between 15% and 27%, ^[1],[2] even with the complete resection of the tumor. Risk factors for recurrence are: Young age at the time of diagnosis, VHL disease, and multicentric tumors. Recurrence of tumor in patients with incomplete resection can be treated by surgical resection with no further recurrences. Intraoperative PDD using 5-ALA is mainly performed while resecting malignant tumors such as malignant glioma, and outcomes are better as this allows better resection rates. ^[6],[7]

A small amount of residual benign tumor may be hard to detect. There are limited reports on the use of intraoperative PDD using 5-ALA in the detection of residual benign tumor. ^[8],[9] Jagannathan et al. ^[10] reported that recurrence of tumor can be minimized by checking all hemangioblastoma cyst walls, including peritumoral cysts, and further resecting the lesion like tumor after hemangioblastoma removal. We have used PDD using 5-ALA in hemangioblastoma surgery. Fluorescence of PPIX was found in two of nine peritumoral cyst walls after resection of the tumor, and a residual tumor was found in this study. Our results suggest that objectively, intraoperative PDD using 5-ALA is useful in finding residual tumor in hemangioblastoma surgery.

MRI studies suggest that cysts of hemangioblastoma are intratumoral cysts and peritumoral cysts in location. ^[11] The mechanisms of formation of intratumoral and peritumoral cysts are different. Intratumoral cysts are a result of tumor necrosis, while peritumoral cysts develop as a result of a tumor interstitial process that begins with the occurrence of edema. ^[12],[13] These peritumoral cysts are organized in gliosis and Rosenthal fibers without tumor cells and are located in the brain tissue adjacent to hemangioblastomas. ^[14] This observation does not warrant resection of the cyst walls of hemangioblastoma, and excision of the cyst wall may result in new neurologic deficits. However, there are cases of hemangioblastoma recurrence due to infiltration of tumor cells into brain parenchyma or cyst walls. ^[15] These peritumoral cysts might be intratumoral cysts in imitation of peritumoral cysts. The cyst wall of an intratumoral cyst might appear like that of a peritumoral cyst because the cyst wall becomes thin with an increase in size. ^[5],[15] As seen in one of our patients, there was an enhancement of the cyst wall with the initial recurrence of hemangioblastoma. At first, this cyst was judged to be an intratumoral cyst. In the follow-up, there was change in the morphology of the cyst and was like the peritumoral cyst as seen in hemangioblastoma, and the cyst wall did not enhance with contrast with increase in cyst size. This case illustrates that the peritumoral cysts of hemangioblastoma can have the imaging characteristics of intratumoral cysts. The other mechanism of recurrence is implantation of floating tumor cells consisting of gliosis and Rosenthal fibers in the cyst wall in the peritumoral cyst. Though rare, there is a report of a hemangioblastoma appearing similar to an arachnoid cyst without the mural nodule and enhancement effect of the cyst wall on MRI. ^[16] To prevent recurrence of hemangioblastomas such as these, it is necessary to resect the entire cyst wall, which tumor cells can infiltrate. PDD using 5-ALA contributes to thorough resection of hemangioblastomas.

References

Copyright 2011 - Neurology India

The following images related to this document are available:

Photo images