First Clinical Report of the Intraoperative Macro- and Micro-Photodiagnosis and Photodynamic Therapy Using Talaporfin Sodium for a Patient with Disseminated Lumbar Medulloblastoma

Abstract

Photodiagnosis (PD) and photodynamic therapy (PDT) using the second-generation photosensitizer talaporfin sodium together with an exciting laser for primary intracranial malignant tumors is well recognized in Japan, and many medical institutions are introducing this new therapeutic option. In particular, intraoperative PDT using talaporfin sodium for infiltrating tumor cells in the cavity walls after the resection of malignant glioma is now covered by health insurance after receiving governmental approvement, and this method has been recommended in therapeutic guidelines for primary malignant brain tumors in Japan. On the other hand, experimental and clinical studies on the development of novel therapeutic strategies for malignant spinal cord tumors have not been reported to date, although their histological features are almost identical to those of intracranial malignant tumors. Therefore, the clinical outcomes of malignant spinal cord tumors have been less favorable than those of malignant brain tumors. In this report, we performed the PD and PDT using talaporfin sodium on a patient with a metastatic lumbar lesion that was detected on magnetic resonance image (MRI) 50 months after the resection of cerebellar medulloblastoma who presented with lumbago and sciatica. We were able to detect the target lesion in the conus medullaris using a surgical microscope, and detected the disseminated medulloblastoma cells floating in the cerebrospinal fluid using a compact fluorescence microscope. Furthermore, we performed PDT to the resected lumbar lesion with the adjuvant platinum-based chemotherapy, and the patient survived a meaningful life for more than 2 years after the lumbar surgery. This report describes the first case of a human patient in whom the efficacy of PD and PDT was demonstrated for a malignant spinal cord tumor.

Keywords: malignant spinal cord tumor; photodiagnosis; photodynamic therapy; talaporfin sodium.

Figure 1

Radio-pathological findings of the patient before the lumbar surgery. (A,B): Preoperative gadolinium-enhanced T1-weighted MRI images of the brain displayed a heterogeneously enhanced tumor in the cerebellar vermis accompanied with obstructive hydrocephalus. (C): The histopathological diagnosis of the tumor was a classic type medulloblastoma with abundant typical Homer-wright rosette in the hematoxylin and eosin stain (×100). (D): Postoperative gadolinium-enhance T1-wegihted MRI image of brain displayed subtotal resection of the cerebellar tumor. (E,F): Gadolinium-enhanced T1-weighted image of lumbar spine displayed a nodular enhanced mass ((F): white arrow) with enhancement of meninges of cauda equina ((E): white arrow).

Figure 2

Intraoperative findings of the lumbar surgery and practice of PD and PDT for the tumor located in the conus medullaris. (A): Intraoperative finding of an intradural lumbar lesion demonstrating a gelatinous pink tumor located in the conus medullaris between the cauda equina (white arrow). (B): Intraoperative PD using a surgical microscope demonstrated weak fluorescencefrom the tumor (white arrow). (C): Piece by piece resection of the tumor. (D,G): Intraoperative fluorescence cytology of sediment from the CSF (D) and resected tumor tissue (G) under white light demonstrated a cluster of tumor cells. (E,H): Intraoperative fluorescence cytology of the sediment from the CSF (E) and resected tumor tissue (H) demonstrated strong fluorescence of talaporfin sodium in the cytoplasm of the cluster of tumor cells with a high N/C ratio. (F): Giemsa stain (×400) of the sediment from the CSF demonstrated a cluster of tumor cells. (I): We performed a single shot of irradiation of PDT to the conus medullaris. The magnification of histological images: (D,E,G): ×200, (F,H): ×400.

Figure 3

Radio-pathological course of the patient after the lumbar surgery. (A,B) Histopathological findings of the resected tumor in the conus medullaris demonstrated a cluster of small round cell tumor cells with a high N/C ratio (×400). (C): Postoperative gadolinium-enhanced T1-weighted image of the lumbar spine displayed a faint tumor nodule (white arrow) in the conus medullaris without enhancement of the meninges of the cauda equina. (D,E) Gadolinium-enhanced T1-weighted MRI of the lumbar spine (D) and cervical spine (E) taken 2 months after the lumbar surgery. The lumbar lesion displayed faint tumor enhancement ((D): white arrow), and the heterogeneous enhanced intramedullary mass was located between the C3 and C7 levels ((E): white arrow).