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A 61-year-old woman with moderate hydrocephalus
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A 61-year-old white woman was initially seen by her primary care physician for slow, tentative gait and problems with visual tracking.
Because of her progressive symptoms, she underwent MRI of her brain, which demonstrated moderate hydrocephalus with a large enhancing lesion that was causing significant aqueductal stenosis. The lesion was homogeneously enhancing and was located between the inferior aspect of the thalamus and the pineal area.
Her medical history was significant for gastroesophageal reflux disease, osteoporosis and hypothyroidism. Her medications include lansoprazole (Prevacid, Takeda), levothyroxine, ibandronate (Boniva, Genentech), nortriptyline, multivitamin, flaxseed oil and calcium.
The patient was referred to neurosurgery, and she had a stereotactic biopsy and ventricular shunt placement.
Immunohistochemistry performed on the tumor showed marked glial fibrillary acidic protein (GFAP) positivity. There was an extensive network of GFAP-positive fibrils associated with the tumor cells, which suggested that the cells present were astrocytic in nature. The tumor cells were negative for chromogranin and AE1/AE3 keratin. Ki-67 staining showed a markedly elevated proliferation rate of more than 50%.
Based on the presence of intensive GFAP positivity, the lesion was considered to be astrocytic. A pineal parenchymal neoplasm would not be expected to show that degree of astrocytic differentiation. The presence of mitotic activity and marked pleomorphism categorized this as an anaplastic astrocytoma (astrocytoma WHO grade III).
Due to the location of the tumor, surgical resection was not feasible.
The patient underwent concurrent chemoradiation with temozolomide. Afterward, she underwent CyberKnife surgery to her residual mass. This was followed by adjuvant temozolomide for 12 months.
Shortly after her completion of treatment, she developed tremors and unsteady gait. She then developed increasing lower extremity weakness, which prompted a visit to the ED. She underwent MRI of lumbosacral spine, which showed diffuse involvement of the leptomeninges consistent with leptomeningeal carcinomatosis. An MRI of her brain also showed progression of disease.
Case discussion
Gliomas comprise a group of primary central nervous system neoplasms with characteristics of neuroglial cells (eg, astrocytes, oligodendrocytes) that express varying degrees of aggressiveness. The slower-growing lesions are commonly referred to as low-grade gliomas, whereas the more rapidly progressive tumors are referred to as high-grade gliomas.
Astrocytomas are divided into diffuse astrocytic tumors, WHO grade II, anaplastic astrocytoma WHO grade III and glioblastoma WHO grade IV.
Anaplastic astrocytomas exhibit higher cellularity, more marked nuclear atypia and hyperchromasia, as well as mitosis, but they do not exhibit endothelial proliferation or necrosis. The low-grade type is more often found in children or young adults, whereas the high-grade types are more prevalent in adults. The prognosis is poor, with a median survival of 18 to 24 months.
Patients with high-grade types usually present with headaches, seizures, memory loss, motor weakness, visual symptoms, neurological deficit and personality changes. Rarely, patients with glioma can present with spinal dissemination. These are not commonly seen with the newer imaging techniques. Prognostic factors that affect the response to treatment include tumor grade, Karnofsky performance status and extent of initial surgical resection.
The mainstay of treatment in patients with anaplastic astrocytoma includes maximal surgical resection with preservation of neurologic function. Although gross total resection is preferred when possible, this may not be possible, depending on the location of the tumor.
After surgery, patients with anaplastic astrocytoma receive adjuvant radiation therapy and chemotherapy using the same approach as in patients with glioblastoma. In recent years, stereotactic surgery using CyberKnife is being employed in areas of the brain where open surgical resection is not possible. This allows increased tumor destruction with preservation of adjacent normal brain tissues. However, this has not been prospectively compared in randomized trials.
Dissemination of astrocytic tumor in the cerebrospinal fluid is considered to be rare. However, autopsy series have shown a higher incidence of multifocal spread of astrocytoma, which indicates that the actual incidence may be underestimated. This also could be due to recent advances in neurosurgical intervention, which allows us increased control of malignant gliomas locally to some extent.
A study by Saito and colleagues published in the Journal of Neuro-Oncology evaluated patients with primary malignant astrocytoma, including 33 patients with anaplastic astrocytoma and 35 patients with glioblastoma. Seventeen patients developed intracranial dissemination.
Six of 17 patients developed spinal dissemination. All patients with spinal dissemination also had intracranial dissemination. Four of the six patients received combination chemotherapy, intrathecal administration of methotrexate and radiation therapy, including spinal irradiation. Local control of the initial lesions was achieved on all patients except one.
Conclusion
Symptomatic spinal dissemination in patients with high-grade astrocytomas may be underestimated.
Leptomeningeal metastases should be suspected in patients with high-grade astrocytomas who present with new or worsening neurological symptoms. This especially applies to patients who are doing well several months after treatment.
Reference:
- Saito R. J Neurooncol. 2003;61:227-235.
For more information:
- Ramya Varadarajan, MD, is a consultant at Regional Hematology and Oncology PA at Helen Graham Cancer Center in Newark, Del. She also is a member of the HemOnc Today Editorial Board.
- Disclosure: Dr. Varadarajan reports no relevant financial disclosures.