Primary T-cell-rich B-cell lymphoma masquerading as a meningioma.

Primary dural lymphoma is rare, and few of the small number of cases reported to date have been classified using immunohistochemical techniques. To our knowledge, we report the first case of T-cell-rich B-cell lymphoma (diffuse mixed small cell and large cell) presenting as a solitary intracranial dural mass. Cytologic and frozen sections prepared during intraoperative consultation revealed a polymorphic population of lymphocytes suspicious for an inflammatory process. Permanent sections of the dura showed a diffusely infiltrating mass composed of mature lymphocytes peppered with large atypical lymphocytes. Immunohistochemical stains identified the small lymphocytes as T cells (CD3 and CD43) and the large atypical lymphocytes as B cells (CD20). Evidence of rearranged immunoglobulin heavy-chain genes demonstrated B-cell monoclonality. Differentiating between inflammatory and neoplastic lymphocytic masses of the dura obviously has important therapeutic and prognostic significance and may require immunohistochemical and molecular techniques.

Atypical skull base paragangliomas.

We present two cases of unusually large skull base paragangliomas. The first tumor was accompanied by marked bony destruction of the central skull base and multiple associated cysts. The second tumor arose along the petrous ridge, with a large intracranial component. The CT, MR imaging, angiographic, histologic, and electron microscopic findings of these unusual lesions are described.

Acquired intracranial herniations: MR imaging findings.

Many of the pathologic processes that increase intracerebral mass may eventually cause brain herniation. It is important to recognize brain herniation, as it can often produce the presenting clinical signs and symptoms and is often the cause of serious neurologic sequelae or death.

Muscle biopsy.

OBJECTIVE: To provide practical guidelines for handling muscle biopsies to be submitted for outside processing and consultation. DESIGN: Review each step of handling a muscle biopsy and provide alternative means of tissue processing when feasible. RESULTS: Practical guidelines are presented for specimen selection, performance of needle biopsy, preparation of tissue for electron microscopy, preparation of tissue for shipping, clinical information to be provided, and submission of tissue for molecular and biochemical studies. CONCLUSIONS: Muscle biopsy samples to be sent to referral centers can be properly handled to avoid the problems noted by the Neuropathology Needs Assessment of the College of American Pathologists.

Possible radiation-induced dural fibrosarcoma with an unusually short latent period: case report.

We report a case of radiation-induced dural fibrosarcoma in a 9.5-year-old male patient who was treated with radiation for medulloblastoma. He received a total dose of 53.2-Gy radiation, delivered at 1.6 and 1.8 Gy per fraction with a 6 MV linear accelerator using the standard cranial-spinal technique. A sequential magnetic resonance image at 15 months after the completion of radiation therapy showed a mass above the cerebral convexity that increased two-fold in size within a period of 4 months. The tumor showed characteristics of a low-grade fibrosarcoma. This case emphasizes the potential risk of early development of a second neoplasm after therapeutic radiation, especially in children, and also documents what is to our knowledge the shortest latent period between the administration of radiation therapy and the development of an intracranial fibrosarcoma that has been reported.

Desmoplastic cerebral astrocytoma of infancy. A case report with immunohistochemical, ultrastructural and proliferation studies.

We present a case of desmoplastic cerebral astrocytoma of infancy (DCAI) in a 7 1/2-month-old girl and include immunohistochemical, ultrastructural and proliferative activity studies. The dural-based cystic tumor showed a biphasic pattern consisting of glial fibrillary acidic protein (GFAP)-positive astrocytes embedded in a desmoplastic stroma. The astrocytic processes were lined with basal lamina at their surface contacting the collagen. Scattered islands of undifferentiated small cells were seen acquiring GFAP positivity at their peripheral zone facing the collagen. Studies with silver nucleolar organizer region and proliferating cell nuclear antigen disclosed a high proliferative activity. Flow cytometric study showed an elevated S phase and 15% hypertetraploid cell population. These findings contrast the favorable prognosis of the tumor at 26 months follow-up. Probably, extracellular-matrix-induced maturation of the undifferentiated cells with the formation of basal lamina may account for this unique disparity.

The short-term effect of low-dose radiation on intracranial germinoma. A pathologic study.

A correlative pathologic and imaging (computed tomography and magnetic resonance imaging) study is reported of a pineal germinoma in a 35-year-old man who died unexpectedly of massive pulmonary embolism on the 8th day during the course of radiation therapy after receiving a total dose of only 1600 cGy. A histologic study of the entire lesion in serial sections revealed no viable tumor cells. The tumor bed was composed of stromal elements with a variable degree of proliferation. The lymphocytic component of the tumor was unaffected by the radiation. This case provided a rare opportunity to show total eradication of tumor cells in a germinoma after a small dose of radiation and supports the notion, based on imaging observations, that histologically proven intracranial pure germinomas may be treated successfully with a much smaller dose of radiation than previously thought.

Occurrence of oligodendrocytes within astrocytes in demyelinating lesions.

We investigated the fine structural details of the presence of apparently newly formed oligodendrocytes within reactive astrocytes in white matter lesions obtained by biopsy from seven cases (3 multiple sclerosis (MS); 3 progressive multifocal leukoencephalopathy (PML); 1 with nonspecific reactive changes next to a sarcoid granuloma). Intact oligodendrocytes were found within astrocytic cytoplasm in two acute MS lesions and also in the reactive white matter lesion. The internalized cells appeared to lie within membrane-bound vacuoles. Formation of rudimentary junctions was observed between the internalized cells and host astrocytes. Sometimes more than one oligodendrocyte was seen in the same astrocyte. Our study suggests that this newly recognized interaction between astrocytes and oligodendrocytes is not restricted to acute MS lesions and probably represents emperipolesis rather than phagocytosis. This apparently nonspecific finding may be expected in any lesion with a proliferation of astrocytes and oligodendrocytes. The precise mechanism of this phenomenon or its functional significance is not entirely clear.

Intraneuronal cylindrical particles in Alzheimer's disease.

In this report we describe an unusual form of intraneuronal cylindrical particles (CP) in the brain of a 69-year-old man with typical Alzheimer's disease (AD). A large number of CP were seen in cortical neurons in the frontal and parietal lobes. The CP were always seen within the cisternae of endoplasmic reticulum, had a 25- to 30-nm-thick trilaminar wall and measured 80-95 nm in cross-sectional diameter. In an occasional neuron, the CP were seen next to filamentous constituents of neurofibrillary tangles. The remaining neurons containing CP appeared normal. A similar finding has been reported in another case of AD and also in two cases with other conditions, thus indicating that the presence of CP is not limited to AD. Morphologically similar intracisternal CP have been observed in the macrophages in certain strain of mice following implantation of dibenzanthracene. The CP in human brains and experimental animals show a remarkable resemblance to rhabdovirus and certain murine endogenous virus particles. The nature of these intraneuronal CP in human brains and their significance, if any, remain undetermined.

Brain lesions in chronic granulomatous disease.

In chronic granulomatous disease (CGD) enzyme-deficient neutrophils and mononuclear cells lack the respiratory burst required for biocidal activity. Recurrent infections lead to granulomas in various organs but brain lesions are rare. In the present case, a 23-year-old male with numerous infections since early childhood died of overwhelming pulmonary aspergillosis. He first began to experience neurological deficits at the age of 17. Computerized tomography and magnetic resonance imaging revealed fleeting white matter lesions that were interpreted as multiple sclerosis (MS). At post mortem, three types of brain lesions were found: (1) Pigmented macrophages in perivascular spaces and the leptomeninges similar to those reported previously. They contained fine, golden-brown, lipofuscin-like material whose chemical composition included a sulfur peak by X-ray analysis. (2) Focal, well-demarcated, "burnt out" white matter lesions with loss of both myelin and axons and intense sclerosis. (3) Diffuse areas of mild pallor in the centrum ovale which spared the U fibers. The pigmented macrophages are characteristic of those seen in the periphery in CGD. The origin of the discrete, destructive white matter lesions is unclear. They may have resulted from: (i) earlier activity by CGD macrophages; (ii) previous infections due to sepsis or embolism; or (iii) possibly post-infectious encephalomyelitis. The more diffuse, mild, white matter lesions are attributed to edema. Evidence for MS, progressive multifocal leukoencephalopathy, or human immunodeficiency virus encephalitis was lacking. This case is presented to alert us to look more carefully for brain lesions in CGD, characterize them and to help determine their cause.

Repetitive high magnetic field stimulation: the effect upon rat brain.

The effect on rat brain of a large number of stimulations with a high strength pulsed magnetic field was investigated in 31 rats: 10 naive controls, 10 anesthetized controls, and 11 stimulated and anesthetized rats. An investigational magnetic stimulating device with a circular 5.5 inch diameter stimulating head was used. The stimulating coil was energized by 1000 V, 8000A, 200 microseconds half sine pulses at a rate of 8 Hz. The peak field strength was 3.4 T, and the peak field flux was approximately 53,000 T/sec. Stimulation was performed for 20 min at a rate of 8/stimuli per second, for a total of at least 10,000 stimulations. The rats were sacrificed after 8 days, and their brains were examined using light microscopy with hematoxylin and eosin staining, or electron microscopy. Histological samples were taken from the neocortex, the hippocampus, the basal ganglia, and the cerebellum. No significant changes were seen.

Interhemispheric cysts in association with agenesis of the corpus callosum.

Two cases of complete agenesis of the corpus callosum each with large interhemispheric cysts are presented. The first case is an adult patient with chronic renal failure secondary to adult polycystic renal disease who was neurologically asymptomatic until she had a seizure during hemodialysis. The second case is an infant, who was diagnosed in utero as hydrocephalic, with severe mental and motor retardation and intractable seizures. The clinicopathologic findings in the two cases are presented, along with a discussion of the possible etiologies and clinical significance.

Intrasellar primitive neuroectodermal tumor (PNET) in familial retinoblastoma: a variant of "trilateral retinoblastoma".

An infant with bilateral familial retinoblastomas was found at age 6 months to have a large mass within the region of the sella turcica. The histology, immunoreactivity and ultrastructure of the tumor showed primitive neuroectodermal cells. A small number of cells showed positive immunostaining to retinal S antigen. This represents a rare form of so-called trilateral retinoblastoma. In most cases of trilateral retinoblastoma, the intracranial non-metastatic tumor is within the pineal gland. The occurrence of such a tumor in the region of sella turcica is very unusual and its possible significance is discussed in regard to our current understanding of the susceptibility to carcinogenesis conferred by inheritance of the mutant retinoblastoma gene, Rb-1.

Malignant transformation of benign cerebellar astrocytoma.

A patient who had a well-differentiated cerebellar astrocytoma resected at 4 years of age, had glioblastoma multiforme of the cerebellum after a symptom-free interval of 28 years. Late malignant transformation of a cerebellar astrocytoma of childhood is rare and previous cases are reviewed. Cerebellar astrocytomas are typically among the most benign of primary brain malignancies with excellent long-term survival rates, sometimes with incomplete resection. This patient indicates that follow-up needs to be long-term because biologic behavior cannot be predicted fully in all cases.

Sterile abscesses in glioma patients treated by intraparenchymal injection of lymphokine-activated killer cells and recombinant interleukin-2: case reports.

Earlier, we conducted Phase I clinical trials to determine any acute toxicity of adoptive immunotherapy with intralesional injections of autologous lymphocytes expressing lymphokine-activated killer (LAK) activity and recombinant interleukin-2 (rIL-2) in patients with malignant glioma. Within six weeks of craniotomy and intralesional injection of autologous LAK cells plus rIL-2, 3 of 29 patients demonstrated a decline in clinical status and evidence on computed tomographic and magnetic resonance imaging scans of edema and mass of unknown character at the site of previous surgery and immunotherapy. Craniotomy was performed to remove the tissue and reduce intracranial pressure. Microscopic examination of the excised material indicated no new tumor growth within the resected mass, but rather that the tissue had the histological characteristics of a chronic sterile abscess including necrosis, fibrosis, and influx of inflammatory cells. Factors that may have contributed to this reaction in the 3 patients were age, Karnofsky score, the extent of tumor excision, and immune status. All 3 had also been treated with greater than average numbers of rIL-2 activated lymphocytes that demonstrated significant in vitro LAK activity. The results suggest that in patients whose clinical status is good and who are not immunosuppressed by corticosteroids, the dose-limiting toxicity of intraparenchymal immunotherapy with LAK cells plus rIL-2 for glioma may be related to the total, absolute number of activated cells injected, and this toxicity develops over time and is manifested by development of a sterile abscess.

Combined effect of respirator-induced ventilation and superoxide dismutase in experimental brain injury.

The function-specific enzyme superoxide dismutase (SOD) was tested for its protective effect in severe experimental fluid-percussion brain injury (4.45 +/- 0.10 atm) in 30 of 60 randomly selected male Sprague-Dawley rats. A respirator was used only in the event of need. The number of animals with permanent resumption of spontaneous breathing (Type I respiratory response) remained essentially the same in each group. However, when Type II apnea (cannot maintain recovery) and Type III apnea (never recovers from the initial apnea) were terminated with a respirator, all rats with Type II responses from each group were successfully converted to a state of sustained spontaneous breathing. In contrast, only five (41.7%) of the 12 rats with Type III response were salvaged in the control group while five (83.3%) of six Type III rats in the SOD-treated group were saved. The results reveal the nature of the therapeutic effectiveness of superoxide radical scavengers in the overall outcome of head injury in this animal model. While SOD alone did not increase the number of spontaneous survivors, the drug shifted a number of animals from the critically injured rats with Type III respiratory response to the less critical Type II condition. Whereas induced respiration as the sole therapy in the control group lowered the mortality rate to 23.3%, respiratory assistance together with SOD treatment reduced the "mortality" to a single animal with Type III apnea (3.3%) which was alive but still required the respirator after 2 hours (p less than 0.001). The results show that respiratory assistance alone accounted for a 33% decrease in mortality rate and that SOD, given in addition to induced ventilation, further decreased mortality by 20%. Since SOD enzymes are reactively specific for superoxide, the increased survival rate of the brain-injured rat must have been due either to preventing or to minimizing pathophysiological changes, probably in the brain stem, caused by oxygen free radicals.

Remyelination in the human central nervous system.

Remyelination, albeit incomplete, has been demonstrated in human central nervous system (CNS). However, information about the initial stage and the final extent of such remyelination is not available. We describe the morphologic findings of a demyelinating lesion with evidence of early remyelination in a biopsy obtained from a 15-year-old boy about two weeks after the onset of neurologic symptoms. The demyelinated area appeared hypercellular with a relatively large number of oligodendrocytes frequently seen in the process of new myelin formation. In addition to the usual reactive changes, the astrocytes were often seen to contain otherwise normal-looking oligodendrocytes within their cytoplasm. In the ensuing months, the patient made apparently total functional recovery accompanied by nearly complete resolution of the white matter lesions demonstrated by the subsequent magnetic resonance studies. These observations suggested that the initial remyelination seen in the biopsy eventually succeeded in producing extensive remyelination in the lesion. Although the exact nature of the demyelinating disorder in our patient remains undetermined, this study indicates that clinically significant remyelination is possible in human CNS. Also, our findings appeared strikingly similar to those described in certain experimental animal models in which widespread remyelination is known to occur.

Epithelial cyst in cerebellopontine angle with xanthogranulomatous changes simulating cholesterol granuloma.

We describe the clinical, radiological, and pathological features of an epithelial lined cyst in the cerebellopontine angle of a 54-year-old man who presented with headaches, ataxia, and multiple cranial nerve dysfunction. The surgically excised lesion showed a cyst lined by ciliated columnar epithelium with copious mucin secretion similar to that seen in colloid cysts of the third ventricle and enterogenous cysts of the spinal canal. In addition the cyst contained brownish material with an exuberant xanthogranulomatous reaction and numerous cholesterol clefts. This lesion closely resembled a cholesterol granuloma by radiographic and pathologic studies. Although two examples of neuroepithelial lined cysts have been described in the cerebellopontine angle, to our knowledge a lesion similar to that in our patient has not been reported previously.

Gliosarcoma with cartilage formation.

A case of gliosarcoma with cartilaginous component is described. Immunohistochemical and electron microscopic studies confirmed the presence of glial and fibroblastic elements. A major part of the sarcomatous tissue was undifferentiated and not labeled by any of the markers used including those for endothelial cells. The cartilage cells also were not labeled either by antiglial fibrillary acidic protein or any other marker. The occurrence and histogenesis of cartilage in gliomas and gliosarcomas have been reviewed.