A 19 year old college freshman presented, in January of 2004, with a 6 month history of severe recurring global headaches. He had no past medical or travel history. Physical examination was notable for bilateral papilledema. His workup included magnetic resonance imaging (MRI) of the brain and intracranial vessels, which initially did not reveal any abnormalities. Initial examination of the CSF revealed an opening pressure of 50 cm H2O (normal: 10–20 cm), protein of 778 mg/dL (normal: 15–45 mg/dL), glucose of 44 mg/dL (normal: >45 mg/dL), an absolute WBC count of 24/mm3 with 55% lymphocytes and 45% macrophages. A full microbiology workup was negative for organisms. The CSF was negative by polymerase chain reaction (PCR) for enteroviruses and West Nile virus. Flow cytometry showed no evidence of lymphoma or leukemia. Cytologic examination of the CSF was negative for malignant cells, showing predominantly reactive monocytes. The patient was initially managed symptomatically with analgesics and diuretics. By May of 2004, he developed cranial nerve palsies necessitating placement of a VP shunt. The patient sought a medical second opinion at another institution, where a diagnostic biopsy was obtained of an intradural extramedullary lesion at T12/cauda equina via vertebral laminectomy.
The biopsy showed an infiltrating growth pattern of pleomorphic astrocytes. The nuclei were hyperchromatic with irregular borders. Blood vessels were numerous. Dense, wavy collagen bands were noted throughout the tumor, and seemed particularly apparent in the vicinity of blood vessels (Figure ). Necrosis and psammoma bodies were absent. The neoplastic cells had variable amounts of fibrillary cytoplasm which was diffusely positive for glial fibrillary acidic protein (GFAP) (DakoCytomation, Carpinteria, CA, 1:3000 dil; Figure ). A diagnosis of glial neoplasm consistent with leptomeningeal gliomatosis was made. Subsequently, the patient returned for care at our institution. At this time, MRI showed peripheral contrast enhancement of the meninges surrounding the entire spinal cord (Figure ) as well as prominent thickening and enhancement of the cauda equina, consistent with diffuse leptomeningeal disease. Brain MRI study showed only subtle leptomeningeal and subarachnoid spread, without evidence of a primary tumor. He received aggressive craniospinal axis radiation and temozolomide chemotherapy which resulted in clinical improvement for a period of about two months. By August of 2004 the patient developed bilateral lower extremity paraplegia and recurrent seizures. Five months later, he developed massive ascites and an anterior peritoneal mass (Figure ). A computed tomography (CT)-guided FNA of the peritoneal mass was performed. The FNA specimen was processed as air-dried Diff-Quik (DQ) stained and alcohol-fixed Papanicolaou (Pap) stained direct smears, one ThinPrep (TP) slide and a cell block. A diagnosis of VP shunt-related peritoneal spread of PDLG was made.
Figure 1 A. Biopsy of an intradural extramedullary lesion at T12/cauda equina, showing highly pleomorphic cells with a hint of fibrillary cytoplasm growing in an infiltrating fashion (H&E, ×100). B. Diffuse cytoplasmic staining of tumor cells with (more ...)
Figure 2 A. Postcontrast sagittal T1-weighted MR image of the cervical spine shows diffuse leptomeningeal enhancement along the surface of the spinal cord. B. Axial contrast-enhanced CT image through the abdomen demonstrates extensive ascites and an enhancing (more ...)
DQ-stained smears showed pleomorphic malignant cells in poorly formed, somewhat cohesive clusters with haphazard cellular arrangement. The nuclei were hyperchromatic with great variation in size. Cytoplasmic borders were indistinct (Figure ). The TP showed scattered single bizarre, very large multinucleated neoplastic cells with "partial wreath-like" or "horse shoe" nuclear configuration, coarse chromatin clumping, prominent nucleoli, and fibrillary cytoplasmic tails (Figure ). Clusters or nests of smaller, mononuclear neoplastic cells were also seen featuring high nuclear to cytoplasm ratio, scant homogeneous cytoplasm, occasional nuclear clefting and more even chromatin distribution (Figure ). Scattered cytoplasmic GFAP positivity was present in the cell block material from ascites collected 3 days prior to the FNA. Core biopsy of the peritoneal mass was confirmatory.
CT-guided FNA of anterior peritoneal mass, showing a somewhat cohesive large cluster of highly pleomorphic cells (Diff-Quik, ×200).
Figure 4 Cytomorpholgy of primary diffuse leptomeningeal gliomatosis involving the peritoneum. A. Single bizzare multinucleated neoplastic cells display "partial wreath-like" nuclear configuration, coarse chromatin clumping and multiple nucleoli (TP, Pap stain, (more ...)
A repeat CSF specimen was processed as two Cytospin slides, one stained with DQ and one with Pap. It showed a cytomorphology similar to that of the peritoneal mass FNA (Figures and ).
Figure 5 CSF cytology. A. Nests of anaplastic tumor cells are seen with round to oval eccentric nuclei, coarse chromatin, prominent nucleoli and moderate homogeneous cytoplasm (Diff-Quik, ×1000). B. Single giant malignant cells with similar morphology (more ...)
The patient continued to deteriorate clinically. In addition to the non-improving neurologic status, he developed bowel obstruction which was unresponsive to palliative pelvic radiation and peritoneal infusion of phosphorus (P32) radioisotope. He expired in early February 2005, 13 months after initial presentation. An autopsy was declined.