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ABSTRACT: Using guinea pigs, we previously demonstrated that pneumoperitoneum during pregnancy produces behavioral deficits in the offspring. In the current study, the purpose was to determine if CO(2) pneumoperitoneum during the early postnatal period also produced behavioral anomalies.
Following delivery, guinea pig pups were randomly assigned to one of three treatment groups: CO(2) pneumoperitoneum (P), laparotomy (L), or isolation control (I). Surgeries were performed on postnatal day (PND) 5 under isoflurane anesthesia; control pups were isolated from the dams for an equivalent period of time. On PNDs 10, 20, 40, and 60, behavior was assessed by monitoring locomotor and exploratory activity.
A total of 29 animals were studied. We observed no immediate morbidity or mortality and the manipulations did not appear to affect postnatal growth. On PND 10, pups in group P exhibited lower levels of locomotor activity compared to L and I neonates, but this difference resolved as the animals got older. Histologic assessment of the adult offspring brains revealed no evidence of neurologic injury.
These data suggest that unlike insufflation during pregnancy, neonatal pneumoperitoneum does not produce behavioral deficits.
Surgical Endoscopy 06/2005; 19(5):715-9. · 4.01 Impact Factor
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ABSTRACT: To investigate similarities and differences between Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), we undertook a demographic analysis of 277 patients from the Kathleen Price Bryan Brain Bank with an antemortem diagnosis of probable AD. Patients with additional, possibly confounding clinical and pathologic diagnoses such as infarcts, hematomas, neoplasms, and other neurodegenerative disorders, were excluded from the analysis. Neuropathologically, AD alone was present in 192 subjects (69%), and DLB was found in 85 subjects (31%). All of the DLB cases had neuropathologic evidence of AD sufficient to meet CERAD criteria for a diagnosis of definite AD plus nigral Lewy bodies. Gender, apolipoprotein E (APOE) genotype, brain weight, age at death, duration of disease and Braak stage were compared between the two groups. Statistical analyses were performed using Fisher's exact test for comparisons of categorical data and Student's t-test for comparison of means for continuous outcomes. The proportion of males and females was balanced in the combined AD and DLB populations. There was a highly statistically significant increased frequency of APOE 3/4 in males with DLB (P = 0.007). We found higher brain weights in males with DLB versus males with AD (P = 0.012). AD was more frequent in females and DLB was more frequent in males (P = 0.019). Our findings with respect to age at death, duration of disease and Braak stage within diagnostic groups confirm previously reported findings. These data suggest that Lewy bodies are more common in males affected with dementia, especially those with the APOE 3/4 genotype.
Acta Neuropathologica 01/2002; 102(6):621-6. · 9.32 Impact Factor
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ABSTRACT: Endodermal cysts are rare congenital intracranial lesions. Although histologically benign, they can become symptomatic as a result of mass effect and cause neurological deficits. We report a 30-year-old woman who presented with paresis of her right oculomotor nerve. Magnetic resonance imaging showed a 13 x 8-mm cystic lesion originating from the right oculomotor nerve at its exit from the mesencephalon. She underwent craniotomy, biopsy, slit resection, and drainage of the cyst. To our knowledge, endodermal cysts have not been previously described in relation to the oculomotor nerve.
Neuroradiology 01/2002; 43(12):1063-6. · 2.82 Impact Factor
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ABSTRACT: The Bryan Alzheimer's Disease Research Center Rapid Autopsy Program at Duke University Medical Center obtains postmortem human brain tissue for experimental investigations. We evaluated 19 brains for RNA integrity and mRNA gene expression. Nine were from patients diagnosed with Alzheimer's disease, and ten were from nondemented controls. In all cases, the following variables were recorded: postmortem procurement delay (range, 1 hour and 10 minutes to 14 hours), pH of cerebrospinal fluid, premortem fever or sepsis, provision of supplemental oxygen in the agonal period, and temporal relation to time of death (either sudden death or protracted illness). Total RNA was extracted, quantified, and evaluated by agarose gel electrophoresis and quantitative gene expression analysis of 18S rRNA and edg-1 using TaqMan technology. All samples appeared to yield intact RNA without significant degradation, and expression of the edg-1 gene was detected by the real time reverse transcriptase polymerase chain reaction in all cases. We conclude that intact RNA can be obtained from postmortem human brain tissue, even in patients with severe premortem illnesses and delayed postmortem tissue procurement intervals. However, we caution that the successful expression of certain genes from postmortem brain tissue may require enhanced procurement efforts to maximize RNA integrity.
Modern Pathology 12/2001; 14(11):1157-61. · 4.79 Impact Factor
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ABSTRACT: Intracranial solitary fibrous tumors (SFTs) are typically dural-based, CD34-positive neoplasms of uncertain histogenesis. We examined ten cases of meninges obtained at autopsy from patients with no history of neurological illness, head trauma, or neurosurgical intervention, and ten cases of typical meningiomas with attached dural margins not involved by tumor. All cases were immunostained with CD34. CD34 reactivity was noted in the long, thin delicate processes of dural fibroblasts preferentially located in the meningeal portion of the dura rather than the periosteal portion. No CD34 reactivity was identified in the arachnoid or pia mater, except in some endothelial cells. One supratentorial dural-based fibrous nodule and one SFT within the confines of the fourth ventricle showed strong and diffuse reactivity to CD34, bcl-2, and vimentin, and were negative for epithelial membrane antigen (EMA), S-100 protein, glial fibrillary acidic protein, smooth muscle actin, and desmin. We also describe a meningothelial meningioma within which a well circumscribed SFT-like nodule was embedded. The SFT-like nodule was strongly CD34 positive and EMA negative, and the meningioma was strongly EMA positive and CD34 negative. Fibroblasts of the dural border cell layer are attached to the underlying arachnoid, and their inclusion with arachnoidal stromal elements and pial-based tela choroidea during formation of choroid plexus interstitium may account for intraventricular SFTs. Our results suggest that SFTs and dural-based fibrous nodules derive from CD34-positive dural-based fibroblasts, and that CD34 reactivity in meningiomas may result from inclusion of dural fibroblasts within the neoplasm.
Acta Neuropathologica 11/2001; 102(4):349-54. · 9.32 Impact Factor
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ABSTRACT: The March COM: A 16 year old female presented with headaches and cerebellar dysfunction. MR images showed a mass lesion of the right cerebellar hemisphere with mass effect on the medulla. The mass exhibited a striated pattern of alternating isointense and hypointense zones on T1-weighted images that did not contrast enhance. The lesion was hyperintense on T2-weighted images, and also showed a striated appearance. A suboccipital craniotomy and resection of the lesion was performed. Microscopically, the specimen consisted of widened folia and a disorganized cerebellar architectonic pattern in which the internal granular cell layer was occupied by a population of large dysmorphic nerve cell bodies. Patient's diagnosed with Lhermitte-Duclos disease must be adequately evaluated for Cowden's syndrome.
Brain Pathology 08/2001; 11(3):391-3. · 3.99 Impact Factor
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ABSTRACT: Classic diagnostic neuropathologic teachings have cautioned against making the diagnosis of neoplasia in the presence of a macrophage population. The knowledge of macrophage distribution should prove useful when confronted with an infiltrating glioma containing macrophages.
To identify macrophages in untreated, infiltrating gliomas using the monoclonal antibody HAM56, and to confirm their presence in an untreated glioblastoma multiforme (GBM) with the serial analysis of gene expression (SAGE) method.
We evaluated the presence of macrophages in 16 cases of untreated, supratentorial infiltrating gliomas with the macrophage monoclonal antibody HAM56. We performed SAGE for one case of GBM and for normal brain tissue.
In World Health Organization (WHO) grade II well-differentiated astrocytoma and oligodendroglioma, HAM56 reactivity was noted only in endothelial cells, and unequivocal macrophages were not identified. In WHO grade III anaplastic astrocytoma and anaplastic oligodendroglioma, rare HAM56-positive macrophages were noted in solid areas of tumor. In WHO grade IV GBM, HAM56-positive macrophages were identified in areas of solid tumor (mean labeling index, 8.6%). In all cases of GBM, nonquantitated HAM56-positive macrophages were identified in foci of pseudopalisading cells abutting necrosis and in foci of microvascular proliferations. In none of the cases were granulomas or microglial nodules found, and there was no prior history of surgical intervention, radiation therapy, chemotherapy, or head trauma in these cases. By SAGE, the macrophage-related proteins osteopontin and macrophage-capping protein were overexpressed 12-fold and eightfold, respectively, in one untreated GBM compared with normal brain tissue. In this case, numerous HAM56-positive macrophages (labeling index, 24.5%) were present in the solid portion of tumor, and abundant nonquantified macrophages were identified in foci of pseudopalisading cells abutting necrosis and in foci of microvascular proliferations.
This study confirms the utility of the monoclonal antibody HAM56 in identifying macrophages within untreated infiltrating gliomas. The overexpression of macrophage-related proteins in one case of GBM as detected by SAGE signifies that macrophages may be present in untreated GBMs.
Archives of pathology & laboratory medicine 06/2001; 125(5):637-41. · 2.58 Impact Factor
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ABSTRACT: A 25-yr-old male presented with a cerebellar mass, underwent a suboccipital craniotomy, and was diagnosed with medulloblastoma. Six months later he developed a large mass in the right iliac crest. Fine-needle aspiration biopsy (FNAB) confirmed the diagnosis of metastatic medulloblastoma. The diagnosis of metastatic medulloblastoma is usually suspected clinically or radiographically, and is uncommonly confirmed by cytologic evaluation. Here we report on a rare case of FNAB used to diagnose metastatic medulloblastoma.
Diagnostic Cytopathology 06/2001; 24(5):361-3. · 1.16 Impact Factor
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Archives of pathology & laboratory medicine 03/2001; 125(2):299-300. · 2.58 Impact Factor
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ABSTRACT: A 51-yr-old male presented with an 8-mo history of lower back pain. Computerized axial tomography (CT) and magnetic resonance imaging (MRI) studies showed a 3.5 X 3.0 cm sacral mass within the spinal canal in the region of the left S2 nerve root. A fine-needle aspirate biopsy (FNAB) was performed under CT guidance. The cytologic findings included a spindle-cell population with a fibrillary background arranged in a vaguely streaming pattern, wavy nuclei with mild atypia, wispy cytoplasm, rare intranuclear inclusions, and dilated vascular spaces. Some cells contained a nonrefractile granular brown pigment consistent with melanin. Also identified were calcified concentric laminations typical of psammoma bodies. Immunohistochemically, the neoplastic cells were strongly immunoreactive for S-100 protein and HMB-45. A diagnosis of psammomatous melanotic schwannoma was rendered. No stigmata of Carney's complex were identified on physical examination. The patient has declined the recommendation of surgical excision of the mass. We herein describe a case unequivocally diagnosed as psammomatous melanotic schwannoma by FNAB.
Diagnostic Cytopathology 08/2000; 23(1):55-8. · 1.16 Impact Factor
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ABSTRACT: We report a rare case of the plasma cell variant of Castleman's disease confined to the leptomeninges in a 42-year-old female. Flow cytometry demonstrated a minor monoclonal kappa light chain population, and conventional Southern blotting confirmed clonal rearrangement of the J(H) immunoglobulin heavy-chain gene. Polymerase chain reaction for Epstein-Barr virus and Kaposi's sarcoma-associated herpes virus was negative. The patient is disease-free five years after surgical resection. To our knowledge, clonal gene rearrangement has not been previously reported in the plasma cell variant of localized intracranial Castleman's disease.
Annals of clinical and laboratory science 08/2000; 30(3):278-82. · 0.96 Impact Factor
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Journal of Neurosurgery 06/2000; 92(5):909-10. · 2.96 Impact Factor
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ABSTRACT: Alzheimer's disease is the most common cause of dementia It is associated with genetic risk factors and at least three autosomal dominant mutations. Community pathologists are frequently asked by families to evaluate autopsy material for Alzheimer's disease. Neuropathologic diagnosis is based on technically difficult silver impregnation stains that may not be readily available to community-based pathologists. Because immunohistochemical techniques are more widely accessible, we evaluated the practical utility of using a single immunohistochemical stain for diagnosing Alzheimer's disease. The ubiquitin antigen was selected because of its presence in morphologically distinct deposits characteristic of several neurodegenerative diseases. Paraffin blocks were obtained from the Bryan Alzheimer's Disease Research Center Brain Bank, a repository of approximately 900 brains. Tissues from 16 individuals who exhibited the entire range of Alzheimer's-type neuropathology were selected. Ubiquitin immunostains, evaluated blindly and independently by four pathologists ranging from first-year resident trainee to experienced neuropathologist, reliably stained both neuritic plaques and neurofibrillary tangles essential for diagnosing and staging Alzheimer's disease. Nondemented controls with early Alzheimer's-type changes were easily distinguished from cases of definitive Alzheimer's disease. The stains also highlighted characteristic inclusions of Parkinson's disease or Lewy body dementia Ubiquitin immunohistochemistry is a reliable, reproducible, and readily available diagnostic aid for distinguishing Alzheimer's disease from other causes of dementia.
Modern Pathology 05/2000; 13(4):420-6. · 4.79 Impact Factor
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ABSTRACT: Gliomas of the optic nerve, although typically of pilocytic (WHO grade I) histology, can present within the spectrum of astrocytic neoplasia including glioblastoma (WHO grade IV). In certain cases, histologic features alone make the distinction between pilocytic and diffuse astrocytomas difficult. We reviewed 22 cases of optic nerve gliomas, 19 of which were pilocytic astrocytomas (PA), and 3 of which were diffuse, non-pilocytic astrocytomas. The cases were evaluated for their clinical course, radiographic appearance, histologic grade, and proliferation indices as detected by MIB-1 (Ki-67) and p53 antibodies. Of the 19 PA, 14 showed no tumor growth by magnetic resonance imaging, and had Ki-67 and p53 labeling indices (LI) of < 1%. The other 5 PA exhibited aggressive behavior manifest by marked diffuse infiltrative tumor growth causing death in 2 patients, 1 of whom was diagnosed with neurofibromatosis type 1 (immunoperoxidase and radiographs not available), and marked local growth with an average time to growth of 39.3 months, a Ki-67 LI of 2-3%, and a p53 LI of < 1% in three others. Three of the five aggressive PA histologically demonstrated a finely reticulated pattern, a pattern that appears as an exaggeration or expansion of the normal neuroglia of the optic nerve, and may simulate a diffuse low-grade astrocytoma. Two demonstrated the coarsely reticulated pattern, with the biphasic and microcystic pattern typical of PA. Three diffuse astrocytomas (2 anaplastic astrocytomas and 1 glioblastoma) originated clinically and radiographically from the optic nerve, and revealed a Ki-67 LI of 2-12%, a p53 LI of 2-8%, and an average time to growth of 8 months. We conclude that the majority of PA of the optic nerve are non-aggressive, stabilize radiographically, and have Ki-67 and p53 LI < 1%. However, a subpopulation of PA has a propensity for aggressive behavior, and are identified by a Ki-67 LI of 2-3% and a p53 LI of < 1%. Diffuse astrocytomas have both Ki-67 and p53 LI > 2%. Thus, in cases of aggressive optic nerve tumors in which the histologic review of biopsy material cannot confidently confirm the diagnosis of pilocytic or diffuse fibrillary glioma, a p53 LI of > 1% appears to favor the diagnosis of diffuse astrocytoma.
Acta Neuropathologica 05/2000; 99(5):563-70. · 9.32 Impact Factor
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ABSTRACT: Cerebral sparganosis, a parasitic disease, rarely produces a chronic active inflammatory response in the brain. Clinically and radiographically the process may mimic a neoplasm. We report a 30-year-old man who underwent surgical exploration for a mass in the insular cortex. Histology revealed a densely fibrotic mass heavily infiltrated with plasma cells and lymphocytes, in which were embedded parasitic forms consistent with sparganosis. We describe the MRI appearances and pathologic features. Intracranial mass lesions secondary to sparganosis must be considered in patients with a history of travel to endemic areas, especially Asia.
Neuroradiology 04/2000; 42(3):206-8. · 2.82 Impact Factor
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ABSTRACT: The embryologic histogenesis of cartilage is not well characterized. While cranial cartilage is believed to be derived from pluripotential precursor cells of the neural crest, chondrocytes found elsewhere in the body are thought to be derived from mesoderm. As such, soft tissue tumors with cartilaginous differentiation may be related to neural crest or mesoderm. Peripherin is an intermediate filament encoded on chromosome 12, involved in growth and development of the peripheral nervous system. Peripherin is apparently expressed exclusively in cells derived from the neural crest and neural tube. A group of six soft tissue tumor types was selected because they are either of controversial differentiation or cytogenetically related to chromosome 12. A total of 41 cases was evaluated with antibodies against the intermediate filament peripherin. A panel of neural and neuroendocrine differentiation markers was used in selected cases. Three of five extraskeletal myxoid chondrosarcomas showed strong cytoplasmic reactivity with anti-peripherin. No peripherin expression was noted in any of eleven epithelioid sarcomas, eight liposarcomas, seven conventional chondrosarcomas, four neurothekeomas, three alveolar soft part sarcomas, or three clear cell sarcomas. The finding of peripherin expression in some extraskeletal myxoid chondrosarcomas may suggest the ability of some tumors to demonstrate both neural and chondroid differentiation.
Journal of Cutaneous Pathology 04/2000; 27(3):141-6. · 1.56 Impact Factor
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ABSTRACT: A 16 year female with a history of developmental delay and shunted hydrocephalus presented with two months of progressive headaches, lethargy and visual disturbances. An MRI of the brain revealed a sellar and suprasellar cystic mass which was absent on a previous MRI six years earlier. The pre-operative clinical diagnosis was pituitary adenoma vs. craniopharyngioma. Histologically, the fibrous wall of the ciliated epithelial-lined cyst was thickened by non-caseating granulomatous inflammation, hemorrhage, hemosiderin, and cholesterol clefts, consistent with cyst rupture. Rathke's cleft cysts are uncommon symptomatic lesions in young people, and must be distinguished from craniopharyngioma.
Brain Pathology 05/1999; 9(2):425-6. · 3.99 Impact Factor
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ABSTRACT: A 4-year-old African American male was referred to the Pediatric Neurosurgery Service for evaluation of new onset seizures and worsening mental status. An MRI of the brain revealed a pineal region mass with diffuse leptomeningeal enhancement and compression of the basilar cisterns. A biopsy of the brain revealed histologic and immunophenotypic findings characteristic of ALK-1+ anaplastic large cell lymphoma (ALCL). ALCL rarely occurs in the central nervous system and poses a significant diagnostic challenge often leading to a delay in the initiation of appropriate treatment. We describe a case of a rapidly deteriorating clinical course in a child with central nervous system ALCL and review the current literature on ALCL occurring in the central nervous system.
Pediatric Neurosurgery 08/1970; 43(6):516-521. · 0.70 Impact Factor
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ABSTRACT: We describe the case of a 7-year-old girl who was clinically diagnosed as having a pontine glioma based on magnetic resonance imaging studies. Neoplastic cells were identified upon cytologic examination of cerebrospinal fluid. Autopsy studies revealed an anaplastic astrocytoma (WHO grade III) diffusely infiltrating the cerebral hemispheres, brain stem, cerebellum, leptomeninges, and spinal cord to the level of the conus medullaris. The Ki-67 labeling index focally approached 30%. Although many of the neoplastic cells displayed elongated twisted nuclei reminiscent of microglia, these cells stained intensely for glial fibrillary acidic protein, supporting an astrocytic origin. Unusual features of this case of gliomatosis cerebri include involvement of the entire central neuraxis, correlation with pre-mortem lumbar puncture cytology, and a markedly elevated Ki-67 labeling index.
Clinical neuropathology 18(4):190-7. · 1.04 Impact Factor
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ABSTRACT: To ascertain if a carcinoma-like component within a fibroblastic meningioma represented a metastatic carcinoma to a meningioma or malignant progression, we employed traditional immunohistochemical methods as well as comparative genomic hybridization (CGH) which compares chromosomal alterations. Vimentin and epithelial membrane antigen were strongly immunoreactive in both the fibroblastic and carcinoma-like components. The CGH profile in both components had similar chromosomal alterations, including losses of 1p, 14, 16p13-->p10 and 22. However, the CGH profiles from the fibroblastic component showed losses of 4p, 10q23-->q24 and 18, along with gains of 1q, 6q25-->qter and 13q32-->qter. The profile of the carcinoma-like component showed losses of chromosome 4, in addition to gains of 3p12-->q13.11, 5q14.3-->q23.2, 6pter-->p23, and 13q14.2-->qter. CGH analysis of a biphasic malignant meningioma confirmed that the disparate histologic components were genetically related and likely derivative from a common precursor, demonstrating genetic instability and clonal expansion. Furthermore, CGH showed that the histologically appearing low-grade fibroblastic component had not solely the characteristic alterations of a benign meningioma but had already progressed to an atypical meningioma.
Clinical neuropathology 21(6):258-64. · 1.04 Impact Factor
