Contributed by Takashi Mizowaki1, Takashi Sasayama1, Shuho Semba2, Ryohei Sasaki3, Kensaku Yasuo4, Satoshi Nakamizo1, Kazuhiro Tanaka1, Katsu Mizukawa1, Yoshito Uchihashi1, Eiji Kohmura1
1Department of Neurosurgery and 2Pathology, 3Radiation oncology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. 4Division of Neurosurgery, Kobe Ekisaikai Hospital, Kobe, Japan
A 40-year-old right-handed female first noticed 6 months ago headache and dizziness. One month later, she complained of repeated vomiting and frequent headache. She was hospitalized at another medical facility. MRI examinations revealed multiple contrast enhanced lesions over the surface of cerebral hemispheres (Figure 1), cerebellum, brainstem (Figure 2) and cervical spinal cord (Figure 3). Laboratory examinations showed no abnormality in the white blood cell (WBC) count, C-reactive protein (CRP), or the tumor markers such as CEA, CA19-9 and SCC. Lumbar punctures revealed an increased opening pressure of 280 mm H2O. Analysis of the cerebrospinal fluid (CSF) disclosed mildly elevated cell counts (22 cells/mm3; 86% mononuclear, 14% polymorphonuclear), a severely decreased concentration of glucose (4 mg/dl) and elevated level of protein (446 mg/dl). A polymerase chain reaction (PCR) test for tuberculosis DNA in the CSF was reported to be normal, and negative result of tuberculosis cultures. No clinical improvement was observed despite a trial of steroid therapy. Because these studies did not reveal a diagnosis and she became tetraparetic, an open biopsy was performed through a left temporal craniotomy 4 months after the onset of initial symptom. At surgery, milky opacification of the leptomeninges was observed at the convexity of the brain and they were biopsied with adjacent brain tissue. Five months after the onset of the disease, she was transferred to our hospital. At this time, she showed tetraparesis (Manual Mascle Test (MMT): Upper extremity=3/5, Lower extremity=1/5), dysphagia, right hearing disturbance, left oculomotor paralysis, sensory disorders of the bilateral lower extremities, and bladder and rectal disturbances. The Karnofsky Performance Scale (KPS) was 40.
Histological examination of H&E stains revealed that the spindle shaped small lesional cells with hyperchromatic and pleomorphic nuclei were spreading and filling the subarachnoid space (Figure 4). These cells extended along the vascular spaces (Virchow-Robin spaces) (Figure 5). In some areas of the lesion, the cells diffusely invaded into the subpial layer of the brain tissue (Figure 4). Several mitotic figures were observed. In immunohistochemistry, most of the cells stained strongly positive for vimentin (Figure 6) and moderately positive for S-100 protein (Figure 7). There were some CD 68 positive cells in the lesion and in the brain close to the lesion. However, spindle tumor cells spreading in the subarachnoid spaces were negative for CD 68 (Figure 8). The MIB-1 index was very high (20~30%). The spindle shaped small lesional cells were also negative for CAM5.2, GFAP, EMA, HMB-45, Leu-7, and LCA. What is your diagnosis?