Tim H. Moss

A medical research council randomized trial in patients with primary cerebral non-Hodgkin lymphoma

The role of chemotherapy in the treatment of patients with primary central nervous system lymphoma (PCL) remains unclear, with no randomized trials available to aid in the interpretation of the current data. The Medical Research Council therefore conducted the current randomized trial to assess the impact on survival of postradiotherapy chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in nonimmunocompromised adult patients with pathologically proven PCL.

The mononuclear cell infiltrate compared with survival in high-grade astrocytomas

SummaryFrozen samples from 92 malignant astrocytomas were stained with a panel of monoclonal antibodies directed against macrophages and lymphocytes. A follow-up to death was available on 68 cases which form the basis of this study. Large numbers of macrophages were found in all cases; T lymphocytes, mostly of the CD8 phenotype were also seen in moderate numbers in 70% of cases. CD4-positive cells were present in small numbers in 32% and B cells were seen in only 8% of cases. Analysis of the survival showed no demonstrable correlation between the numbers of macrophages or CD4 lymphocytes and survival. The survival curves for parencymal CD8 infiltration diverged after 9 months suggesting increased survival for those patients without such an infiltration but the difference failed to reach statistical significance (P=0.37). No correlation between lymphocytic cuffing and survival was seen after studying all paraffinembedded material. We conclude that there is no significant statistical correlation between survival and the various types of mononuclear cell infiltrating malignant astrocytomas.

An MRI and neuropathological study of a case of fatal status epilepticus

We report a case of fatal status epilepticus of unknown origin resulting in acute neuropathological changes in the hippocampus and claustrum. The case history, brain magnetic resonance images, and results of neuropathological study of the whole brain were obtained. The subject was a 35 year old male with no significant previous medical history who presented with generalized epileptic seizures progressing to status epilepticus. He died 6 days after developing status epilepticus. Magnetic resonance imaging (MRI) brain scans were performed before and four days after developing status epilepticus. The first scan was normal and the second showed high signal lesions on T2 weighted images in the medial aspects of both temporal lobes and in the right claustrum. Neuropathological studies showed severe neuronal loss in the Sommer section of both hippocampi with early glial reactive changes. Similar changes were seen in the claustrum on both sides. There was no evidence of other causes of brain injury such as infectious encephalitis or global hypoxic-ischaemic change. The patient died of status epilepticus for which no underlying cause was found despite extensive investigation. In this case the radiological and pathological changes found bilaterally in the claustrum and hippocampus appear to be the direct result of the status epilepticus.

Differentiation in embryonal neuroepithelial tumors of the central nervous system

Ninety‐six embryonal neuroectodermal tumors were studied histologically and immunohistologically with a panel of antibodies including glial, neuronal, epithelial, mesodermal, and myelin markers. In 71 tumors there was glial and neuronal differentiation and expression both of an S (photoreceptor) antigen and vimentin. In five tumors there was only glial differentiation and in 20 tumors only neuronal differentiation. No reactivity for myelin and epithelial markers was found. Histologic and immunohistologic findings identified various degrees of differentiation in different tumors, which was bipolar (glial and neuronal) in most tumors and unipolar in the remainder. The authors suggest that their findings may be the result of normal or aberrant oncogenic differentiation, agreeing with the nomenclature of the World Health Organization classification for these tumors with and the inclusion of a category for ependymoblastoma.

Mononuclear cell infiltrate and HLA-DR expression in low grade astrocytomas

SummaryFrozen samples from 23 low grade (grade I and II) astrocytomas were studied by means of a panel of monoclonal antibodies to macrophages, lymphocytes (and their subsets) and HLA-DR antigens. Macrophages were present in low to moderate numbers in 38%–86% of cases, the variance in figures depending on the antibody used. T lymphocytes, the majority of CD8 phenotype, were detected in low numbers in 78% of tumours. B lymphocytes were scanty in 22% (5/22) and totally absent in the remaining cases. HLA-DR antigen was expressed by tumour cells in 35% (6/17) of cases. These findings indicate that in some low grade astrocytomas there is a mononuclear cell infiltrate with macrophages and secondarily CD8+lymphocytes playing the major role. The significance of these findings remains speculative at present.

Direct Injection of 90Y MoAbs into Glioma Tumor Resection Cavities Leads to Limited Diffusion of the Radioimmunoconjugates into Normal Brain Parenchyma: A Model to Estimate Absorbed Radiation Dose

PURPOSE Previously we have demonstrated that radioimmunoconjugates can be injected into glioma resection cavities to deliver a boost of radiation to the cavity edge with little toxicity to the normal brain. In the mathematical models we have previously published to assist in the development of this strategy we assumed that antibody remains associated with the cavity edge and no diffusion occurs. However, moderate diffusion might be beneficial while, if this were excessive, it would decrease the therapeutic index markedly. METHODS AND MATERIALS Selected individuals with relapsed malignant glioma underwent further surgical debulking; 90Y MoAb radioimmunotherapy; and open biopsy to determine the extent to which the conjugate diffuses from the cavity edge. Samples from these patients were taken in radial tracts and the corrected activity in each sample was plotted against distance from the cavity wall to determine appropriate diffusion constants. RESULTS Our data indicates that diffusion of radioimmunoconjugate from the edge of a glioma resection cavity appears to be an exponential process. The mean Ro for each patients data set ranged from 0.48-0.63 (overall mean 0.6) cm. A dosimetric model was developed that translates these measurements into estimates of radiation dose. Applying the clinical data to this model indicates that, in each patient, the peak dose is delivered 0.16-0.18 cm below the cavity margin, and the mean dose at 2 cm deep is 5.3% (4.4-5.8%) of the peak. CONCLUSION The model described can be used to translate diffusion constants measured by any method into estimates of absorbed radiation dose. Assuming similar diffusion kinetics, it can also be used to predict the dose deposited if alternative radionuclides are linked to MoAb, although the effect of dose rate should also be considered. In the future, it may be possible to manipulate diffusion by using either different antibodies or antibody fragments for intracavity radioimmunotherapy. Before this can be done, however, further data are needed and a noninvasive approach to measuring diffusion would clearly be optimal.

Malignant transformation of posterior fossa epidermoid cyst

The authors report the case of a 45-year-old man who presented with a short duration of a painful ophthalmoparesis. Initial magnetic resonance imaging revealed an extraaxial petroclival mass characteristic of an epidermoid cyst, with the exception of a contiguous contrast-enhancing lobule. A subtotal resection was performed with the histopathological diagnosis revealing malignant transformation of an epidermoid cyst. Despite aggressive postoperative adjuvant therapy, the patient developed leptomeningeal metastasis and died shortly thereafter. The presence of contrast enhancement at the site of an epidermoid cyst combined with an acute, progressive neurological deficit should alert the treating physician to the possibility of a malignant transformation. When transformation does occur, the clinical and radiological course is quite aggressive as compared with the indolent growth of epidermoid cysts. Treatment options include surgery with adjuvant chemotherapy or radiotherapy. We review the pertinent features of this case along with the relevant literature regarding primary intracranial squamous cell carcinomas.

Tophaceous gout of the spine causing spinal cord compression

Tophaceous gout of the spine rarely causes spinal cord compression. Only eight cases have been reported previously. We report a further case presenting with progressive quadriparesis caused by gouty tophi at C1, treated successfully by decompressive laminectomy and internal fixation. This case and the previously reported cases are reviewed.

Comparison of three silver stains for demonstrating neurofibrillary tangles and neuritic plaques in brain tissue stored for long periods.

SummaryThree methods were compared to find a reliable method for demonstrating neurofibrillary tangles (NFTs) and neuritic plaques (NPs) in brain tissue stored for long periods in formalin or as paraffin blocks. The short-term fixation of tissue, e.g. up to 6 months in formalin does not usually present a problem using any of the three methods tried, e.g. Gallyas, modified Palmgren, or modified Bielschowsky, but once the time lengthens to 6 years or more the demonstration of NFTs and NPs is not so reliable using the first two methods. The modified Bielschowsky method, however, demonstrates well both NFTs and NPs in material stored in formalin or as paraffin blocks for long periods, e.g. 7 years, and also compares favourably with the other methods on freshly processed material and fixed tissue, stored for shorter periods. We also noted as a consistent trend, irrespective of the staining technique employed, the detection of fewer plaques and tangles in material stored in formalin, as opposed to that stored as blocks embedded in paraffin wax.

Cervical lymph nodes metastases from a pituitary carcinoma

The authors report a case of a pituitary carcinoma which was locally invasive and which metastasized to cervical lymph nodes more than 9 years after the initial presentation. Cells from the tumour and metastasis immunostained with antibodies to prolactin and growth hormone, even though there was no clinical or biochemical evidence that the tumour was secreting prolactin or growth hormone. In addition, ultrastructural studies showed a monomorphic tumour with secretory granules much smaller than those normally associated with prolactin and growth hormone secretion. The clinical and pathological features suggest that the tumour is probably an acidophil stem cell adenoma, which although known to be aggressive in its clinical behaviour has not been previously reported to metastasize.