Proton relative biological effectiveness (RBE) for survival in mice after thoracic irradiation with fractionated doses.

PURPOSE: This study aims at providing relative biological effectiveness (RBE) data under reference conditions accounting for the determination of the "clinical RBE" of protons. METHODS AND MATERIALS: RBE (ref. (60)Co gamma-rays) of the 200 MeV clinical proton beam produced at the National Accelerator Centre (South Africa) was determined for lung tolerance assessed by survival after selective irradiation of the thorax in mice. Irradiations were performed in 1, 3, or 10 fractions separated by 12 h. Proton irradiations were performed at the middle of a 7-cm spread out Bragg peak (SOBP). Control gamma irradiations were randomized with proton irradiations and performed simultaneously. A total of 1008 mice was used, of which 96 were assessed for histopathology. RESULTS: RBEs derived from LD50 ratios were found not to vary significantly with fractionation (corresponding dose range, approximately 2-20 Gy). They, however, tend to increase with time and reach (mean of the RBEs for 1, 3 and 10 fractions) 1.00, 1.08, 1.14, and 1.25 for LD50 at 180, 210, 240, and 270 days, respectively (confidence interval approximately 20%). alpha/beta ratios for protons and gamma are very similar and average 2.3 (0.6-4.8) for the different endpoints. Additional irradiations in 10 fractions at the end of the SOBP were found slightly more effective ( approximately 6%) than at the middle of the SOBP. A control experiment for intestinal crypt regeneration in mice was randomized with the lung experiment and yielded an RBE of 1.14 +/- 0.03, i.e., the same value as obtained previously, which vouches for the reliability of the experimental procedure. CONCLUSION: There is no need to raise the clinical RBE of protons in consideration of the late tolerance of healthy tissues in the extent that RBE for lung tolerance was found not to vary with fractionation nor to differ significantly from those of the majority of early- and late-responding tissues.

Lafora-body disease with optic atrophy, macular degeneration and cardiac failure.

A 17-year-old boy was admitted to hospital in acute cardiac failure and psychosis. The clinical course, EEG records and tissue diagnosis, including biopsies of brain, skin, skeletal muscle, peripheral nerve and liver were compatible with Lafora-body disease (LBD). Unusual features were those of optic atrophy and macular degeneration, signs generally regarded as negative criteria for the diagnosis of this disease. We also present the findings on endomyocardial biopsy which was performed because cardiac failure as an early symptom of LBD has not been previously described. The patient died in status epilepticus a few months after discharge from hospital.

Microcystic meningiomas.

Four patients (two male and two female) underwent surgery for the removal of tumors with clinical and radiographic features typical of a meningioma. Despite an incorrect intraoperative frozen section diagnosis in two cases, the tumors were totally resected because the surgeon was convinced of the meningiomatous nature of the lesion. Subsequent histology revealed features of a microcystic meningioma and careful scrutiny of paraffin sections showed that each of the tumors contained occasional typical meningothelial cellular whorls which were a helpful diagnostic clue. Ultrastructural examination and the absence of GFAP confirmed the diagnosis. Close liaison with the neurosurgeon, on the part of the pathologist and an awareness of this unusual variant of meningioma should prevent misdiagnosis and inappropriate treatment of a potentially curable tumor.

Alexander's disease: a case report with brain biopsy, ultrasound, CT scan and MRI findings.

Alexander's disease is reported in a 6-month-old infant. The clinical course was characterized by hydrocephalus, irritability and psychomotor retardation, with subsequent seizures and spasticity. Findings on ultrasound examination, computerized tomography, magnetic resonance imaging and brain biopsy are presented. The glial nature of the Rosenthal fibers was confirmed by immuno-gold staining. Clinical classification and differential diagnosis are discussed.

Acute stroke in a child with miliary tuberculosis.

Neurological symptoms in childhood miliary tuberculosis are generally caused by underlying tuberculous meningitis (TBM), since the 2 conditions commonly occur concurrently. Cerebral infarction, a well-recognized complication of TBM, usually results from tuberculous periarteritis and secondary thrombosis. Neuropathological studies have demonstrated that the anterior cerebral circulation is more commonly affected than the arteries of the vertebro-basilar system, and basilar artery occlusion as a presenting manifestation of childhood miliary tuberculosis or TBM has not been described before. We report a 13-month-old infant who presented with fever and convulsions, terminating in acute decerebration after a second prolonged seizure 1 week after the onset of symptoms. Magnetic resonance (MR) imaging demonstrated density changes compatible with acute vertebro-basilar ischemia as well as multiple cerebral granulomas. A chest radiograph showed diffuse miliary tuberculosis. Postmortem examination confirmed this diagnosis and revealed acute occlusion of the basilar artery by an infected (septic) thromboembolus showing granulomatous inflammation, which most likely arose from an endocardial vegetation with identical histology.

Phenotypic and genotypic characterization of glioblastoma multiforme with epithelial differentiation and adenoid formations.

Rare examples of high-grade gliomas show focal epithelial differentiation, which may require distinction from colliision tumors. These epithelial constituents are not well-characterized immunophenotypically and have rarely been subjected to genotyping. We describe a case of a 54-year-old female with a short history of hemiparesis who was found to have an absolute lymphocytosis and a heterogeneously enhancing frontotemporal tumor. Cytological and histological examination of brain biopsies confirmed the presence of a glioblastoma multiforme also containing CAM5.2/CK7/BerEP4/CEA/EMA-immunopositive and GFAP-immunonegative nests of epithelial cells with a high proliferative index and focal glandular differentiation. Hematological investigations confirmed a diagn of chronic lymphocytic leukemia (CLL) with no demonstrable CNS involvement. Genetic analysis using microsatellite markers and specimens obtained by laser capture microdissection of the CNS tumor and normal brain tissue, showed that both the glial and epithelial components of the brain tumor had identical losses of 2/2 informative markers on chromosome 17p13 and 5/5 informative markers on chromosome 10q22-26. The glial and epithelial components also shared an identical 2 base pair deletion in the TP53 gene at codon 209, exon 6, introducing a stop codon at codon 214. No losses at any of the above loci and no TP53 mutation were detected in the leukemic cells. These results suggest both components of the brain tumor, although differing in phenotype, share the same genetic lineage.

Semiquantitative postembedding characterization of intermediate filaments in central nervous system lesions using immunoelectron microscopy.

Standardized postembedding immunoelectron microscopy was performed to demonstrate glial fibrillary acidic protein (GFAP) and vimentin in individual intermediate filaments to determine the diagnostic value of demonstrating ultrastructural and immunophenotypic characteristics of intermediate filaments in routine brain biopsy specimens. Dual expression of GFAP and vimentin was observed in the astroblastoma and astrocytes of Alexander's disease. The antigen availability for vimentin, however, was too low to allow reliable assessment of the GFAP:vimentin ratio in individual intermediate filaments and/or filament bundles. In meningioma, only vimentin positive intermediate filaments were found. GFAP positive intermediate filaments were present in all other specimens except the oligodendroglial components of the mixed glioma, which were devoid of intermediate filaments. GFAP positivity in the filamentous periphery and electron-dense core of Rosenthal fibers was demonstrated. Technical and tissue processing factors had a significant effect on particle density values obtained for individual specimens. Although the number, distribution, and density of glial intermediate filaments varies in different astroglial entities, correlation of particle density values determined by immunoelectron microscopy with relative GFAP concentrations in different lesions requires utmost caution. Nevertheless, application of the postembedding approach to routinely fixed biopsy specimens indicated an association of different entities with the exclusive presence of GFAP and/or vimentin in individual intermediate filaments, thus emphasizing the diagnostic value of intermediate filament typing for pathological characterization.

Amoebic meningo-encephalitis due to a free-living amoeba. A case report.

A 47-year-old man developed an undiagnosed encephalitic illness and died within 12 days. Autopsy showed focal granulomatous lesions associated with a necrotizing vasculitis. Light microscopy revealed the presence of free-living amoebae morphologically resembling Acanthamoeba species. The pathology of this form of meningo-encephalitis is contrasted with that caused by Naegleria fowleri infection, and attention is drawn to its existence within the RSA.

Autopsy-confirmed multiple sclerosis in a white South African. A case report.

The clinical and autopsy findings of a 31-year-old white South African woman with multiple sclerosis are described. Diagnostic, epidemiological and therapeutic aspects are discussed.

Pineal tumours at Groote Schuur Hospital, 1976-1984.

Since 1976, surgical approaches to the pineal region have been undertaken at Groote Schuur Hospital. Thirty cases presenting with a clinical and investigative diagnosis of pineal tumour have been reviewed with respect to epidemiology, surgery, histological subtypes and metastatic pattern. The postoperative management with radiotherapy in the different histological subtypes is discussed. The prognosis for germ cell and benign tumours is good, with 100% control, but pineal parenchymal tumours and astrocytomas have not fared as well.

Medicolegal aspects of cerebral amyloid angiopathy. A case report.

Autopsy examination performed on a 75-year-old woman who had been in a minor road traffic accident revealed an occipital lobar hematoma with subdural extension. Histological examination of brain tissue showed the presence of severe cerebral amyloid angiopathy. Diagnostic techniques and correlation and interpretation of these findings are discussed.

Chordomas--ultrastructure and immunohistochemistry: a report based on the examination of six cases.

Six chordomas (three classic and three chondroid) were examined ultrastructurally and with a panel of monoclonal antibodies. The three classic tumours showed the presence of desmosomes and intermediate filaments on electron microscopy, findings which gave a direct positive correlation when the tumours were stained with monoclonal antibodies against low molecular weight cytokeratin proteins. These results suggest that chordomas are essentially epithelial neoplasms and underline the fact that monoclonal antibodies to cytokeratins cannot be used in the differential diagnosis of classic chordoma vs carcinoma. Furthermore, the epithelial characteristics are lost as the tumour undergoes chondroid differentiation.

Xanthogranuloma of the choroid plexus of lateral ventricle, presenting with parosmia and parageusia.

Xanthogranulomas of the choroid plexus are usually asymptomatic. We present a short case report of a 60-year-old male whose symptoms of parosmia and parageusia have been relieved following surgical removal of a xanthogranuloma situated in the right lateral ventricle. Previous case reports and correlation of symptomatology and pathology are discussed.

Metastasizing pineal germinoma. A case report and review.

A patient with biopsy-proven pineal germinoma was treated successfully by craniospinal irradiation. Lung and hilar node metastases developed 22 months after therapy. These were subtotally resected and further cis-platinum, vinblastine and bleomycin chemotherapy given with control 8 months later. Twenty cases of metastases from pineal tumours are documented. The role of chemotherapy as adjuvant therapy, and in recurrent and metastatic disease is reviewed.

Cutaneous leishmaniasis in Southern Africa. A case report.

The microscopical findings in a case of cutaneous leishmaniasis from South West Africa are presented in order to highlight the pathology of this disease and facilitate its recognition, should unsuspected cases occur in the Republic of South Africa. In addition, the ultrastructural findings confirm the presence of typical Leishmania which occur in the cytoplasm of macrophages where they are undergoing destruction. This adds a further dimension to the characterization of this disease in southern Africa.

Shotgun pellet embolism to the brain.

This report describes the autopsy findings in a young man who died after having been shot with a shotgun from about 30 m. Although not suspected clinically, a right middle cerebral artery territory infarct was found; its cause was shown to be a shotgun pellet embolus that had lodged just proximal to the trifurcation of the right middle cerebral artery. The case underscores the importance of performing a thorough postmortem examination, including a careful study of cerebral vasculature, in instances of brain infarction.

Malignant glioma following radiotherapy for unrelated primary tumors.

Four cases are documented where a glioma was histologically verified in the irradiation field of a previously treated malignancy of a different cell line. Radiation-induced neoplasia in the central nervous system now has been established in the induction of meningioma and sarcoma. The association between therapeutic irradiation and glioma in the reported cases lends to the evidence that a causal relation does exist. This incidence is small and does not detract from the overall benefit of irradiation as a therapeutic modality.

Cerebrotendinous xanthomatosis: a defect in cellular sterol biosynthetic control.

A mentally retarded woman with tendon xanthomata and normal serum cholesterol concentration was found to have raised cholestanol concentrations in the serum and in a xanthoma. This confirmed the diagnosis of cerebrotendinous xanthomatosis (CBX). No specific lipoprotein fraction was found to transport cholestanol. For the first time cultured fibroblasts from a patient with CBX were found to accumulate cholestanol.

Cerebral infarction and intracranial arterial dissection in closed head injury.

This report describes the autopsy findings in three cases of closed head injury dying of cerebral infarction, with brain swelling and herniation. In each instance the cause of the infarct was found to be subintimal dissection involving intracranial anterior circulation arteries. The autopsy findings underscore the value of histological examination of vessels that macroscopically appear thrombosed. We discuss factors that impact on the reported incidence and make brief mention of problems surrounding the true pathogenesis of this lesion.