Radiation-induced spinal cord glioblastoma with cerebrospinal fluid dissemination subsequent to treatment of lymphoblastic lymphoma
In May 2001, a 21-year-old male diagnosed with Stage IVB T-cell lymphoblastic lymphoma, and underwent half-CHOP chemotherapy. In November 2001, he underwent focal irradiation for a residual anterior mediastinal lymphadenopathy, consisting of a total of 30 Gy in 20 fractions, with a maximum dose of 37.8 Gy and mean dose of 9.2 Gy to the spinal cord []. In February 2002, he underwent a peripheral blood stem cell transplantation using cells donated by his identical twin, resulting in complete remission. He had not visited a hospital for 9 years.\nIn January 2012, he was referred to us with a 2-month history of progressive weakness in his right lower extremity. Motor examination revealed mild weakness in the right lower extremity (manual muscle testing, 4/5), and he required a crutch to walk. Sensory examination revealed no sensations for pain or temperature below the T4 dermatome on the left side, 30-50% reduction in touch sensation at the T4-T11 dermatome on the right side, complete loss of all sensation at the T5-T6 dermatome bilaterally, mild reduction of position sense in his right lower extremity, and loss of vibration sense in the bilateral lower extremities. Deep tendon reflexes were hyperactive in the right lower extremity. No bladder or rectal functional disruptions were observed, and there was no evidence of lymphadenopathy.\nGadolinium-enhanced magnetic resonance (MR) imaging of the spine revealed an intramedullary tumor with irregular enhancement extending from the C6 to the T6 level, corresponding to the previous radiation portal [Figures and ]. Moreover, the surface of the spinal cord and the dura mater were diffusely enhanced, suggesting dissemination of the CSF. Although we planned to perform a biopsy of the spinal lesion to establish a definitive diagnosis, the patient refused any kind of spinal surgery to avoid worsening of neurological deficits. Cytological examination of the CSF obtained by lumbar puncture revealed large atypical cells with nuclear grooves or clefts [], suggesting the recurrence of lymphoblastic lymphoma. Thus, we planned to start chemotherapy for recurrent lymphoblastic lymphoma. However, gadolinium-enhanced brain MR imaging revealed periventricular enhanced lesions [Figures and ] and diffuse enhancement of the ventral surface of the pons and the medulla oblongata.\nFor more accurate diagnosis, we obtained a sample of the periventricular lesion along the right anterior horn with a stereotactic biopsy through the right frontal lobe without ventricular puncture. Histopathological examination of this sample showed diffuse proliferation of anaplastic glioma cells with hyperchromatic nuclei on a fibrillary background, along with a tendency for perivascular accumulation []. Microvascular proliferation was also noted. Immunohistochemistry revealed that the tumor cells were positive for S-100 protein and Olig2 [] and negative for leukocyte common antigen (LCA), T-cell markers (CD45R0 and CD3), and B-cell markers (CD20 and CD79a) []. The MIB-1 staining index was 25.1%. The histopathological diagnosis was glioblastoma. Because there was a discrepancy between the CSF cytology and the histopathology of the intracranial disseminated lesion, CSF cytology and immunocytochemistry were again performed after biopsy. These assays revealed that the atypical cells with enlarged hyperchromatic delicate irregular nuclei in the CSF were positive for Olig2 [] but negative for LCA []. In contrast, the LCA+/Olig2− lymphocytes showed relatively uniform, smaller roundish nuclei [Figures and ], suggesting that the LCA+ cells in the CSF were nonneoplastic lymphocytes such as reactive lymphocytes rather than lymphoma cells. Finally, we diagnosed the spinal tumor as a radiation-induced glioblastoma with CSF dissemination.\nThe patient was treated with radiotherapy plus concomitant and adjuvant temozolomide. He received 30 Gy whole-brain radiation and then boost 30 Gy radiation to the periventricular lesion in 40 fractions, as well as 30 Gy whole-spine radiation and boost 22.5 Gy local radiation to the cervicothoracic spinal cord in 35 fractions. Concomitant temozolomide therapy was administered at a dose of 75 mg/m2/day, 7 days/week from the first day of radiotherapy until the last day of radiotherapy. After radiotherapy, the spinal tumor was markedly reduced in size, and the dissemination disappeared []. However, reduction in touch sensation at the T4-T11 dermatome on the right side worsened and extended to the entire leg, and sensations for pain and temperature at the T4-T11 dermatome on the right side decreased by 20-30%. In contrast, sensations for pain and temperature at the T5-T12 dermatome on the left side increased by 20-50%. The mild weakness in the right lower extremity remained unchanged. CSF cytology showed an absence of Olig2-immunopositive cells, although lymphocytes were still present in the CSF. Then, the patient was discharged from the hospital. He continued to receive oral temozolomide therapy and underwent follow-up MRI every 3 months. Temozolomide was administrated orally at 150 mg/m2/day on days 1-5 for the first cycle. The dose was increased to 200 mg/m2/day beginning with the second cycle. Treatment cycles were repeated every 28 days. The patient has been followed for 9 months after the radiotherapy and received total nine cycles of temozolomide therapy. A 9-months follow-up MRI showed no regrowth of the spinal tumor and no disseminated lesions. The patient showed no marked changes in his neurological status. He is now undergoing outpatient temozolomide therapy.