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Anthony T Yachnis

Publications and source records attributed to Anthony T Yachnis.

18 recordsLinked to original sources
PubMed2006

Radiotherapy after subtotally resected or recurrent ganglioglioma.

PURPOSE: Gangliogliomas can recur after subtotal resection (STR). The role of postoperative radiation therapy (RT) is undefined. METHODS AND MATERIALS: Eight consecutive patients with low-grade gangliogliomas (n = 7) or anaplastic gangliogliomas (n = 1) were treated with RT between 1987 and 2004. Median age was 17 years. Five patients received adjuvant RT after STR at a median time of 6 weeks after surgery. Three patients received salvage RT at a median time of 17 months after surgery. The median dose of RT was 54 Gy. Control was defined as no progressive disease on serial imaging. Median follow-up was 8.8 years. RESULTS: Of the 7 patients with low-grade gangliogliomas, 3 were controlled after RT and 4 recurred locally. Recurrences were controlled with further surgery (n = 2), chemotherapy (n = 1), or re-irradiation (n = 1) (median follow-up, 9 years after salvage therapy). Patients who received adjuvant RT after STR of their low-grade gangliogliomas had an overall local control rate of 75%. All 3 patients who were treated with salvage RT had recurrences in the treated area alone (n = 2) or in the treated area with leptomeningeal spread (n = 1). The patient with an anaplastic ganglioglioma was treated with adjuvant RT, and had recurrence in the radiation field after 4 months, then died 1 month later. CONCLUSIONS: Adjuvant RT may be indicated to treat select patients with subtotally resected gangliogliomas. Salvage RT for recurrence is probably less effective for long-term control; however, patients who recur may still be candidates for effective salvage therapies in the absence of malignant transformation.

Adolescent↗
PubMed2006

Pontine atypical neurocytoma: case report.

OBJECTIVE AND IMPORTANCE: Neurocytomas are typically located within the supratentorial ventricular system. Extraventricular neurocytomas are very rare, and this is only the second reported case of a pontine neurocytoma. We discuss the clinical presentation, histology, and treatment of these rare tumors. CLINICAL PRESENTATION: A 58-year-old man presented with a 4-month history of headache and unilateral facial and distal extremity paresthesia. Magnetic resonance imaging (MRI) scans demonstrated a 2.6 x 2.2-cm ring-enhancing cystic mass in the right pons. INTERVENTION: MRI-guided stereotactic biopsy yielded a diagnosis of atypical neurocytoma. Because of the location and malignant histological features of the tumor, the patient was initially treated with external beam radiation therapy. Several months later, MRI scans demonstrated tumor progression. The patient then underwent three rounds of temozolomide chemotherapy, during and after which his symptoms worsened. Aggressive subtotal resection of the tumor was achieved via a right suboccipital craniectomy. CONCLUSION: Twenty-eight months postoperatively, the patient is symptom free, and MRI scans demonstrate no evidence of residual or recurrent tumor.

Brain Stem Neoplasms↗
PubMed2006

Brainstem stereotactic biopsy sampling in children.

OBJECT: Although it is widely accepted that biopsy sampling is not indicated for the diagnosis and empiric treatment of diffuse pontine glioma, it is common to encounter patients with brainstem lesions that cannot be diagnosed on the basis of imaging studies alone. In cases not amenable to resection, a tissue diagnosis may still be necessary to make appropriate treatment recommendations. The authors retrospectively reviewed their institutional experience with stereotactic biopsy procedures in pediatric patients during a 4-year period. METHODS: A three-dimensional graphics workstation was used for trajectory planning to obtain biopsy samples of brainstem lesions in 10 patients. One patient experienced mild diplopia postoperatively. No other morbidity was noted; no patient died as a result of the procedure. The biopsy procedure yielded a pathological diagnosis in all cases. A later resection in one patient resulted in a change in diagnosis. Overall, the pathological findings were varied, and in some cases the tissue diagnosis altered the treatment recommendations. CONCLUSIONS: The findings in this small series suggest that brainstem stereotactic biopsy sampling in children is a safe procedure with a high diagnostic yield. In patients in whom radiographic findings are not consistent with diffuse pontine glioma and resection is not appropriate, stereotactic biopsy sampling should be considered.

Adolescent↗
PubMed2005

Clinicopathologic and genetic profile of intracranial marginal zone lymphoma: a primary low-grade CNS lymphoma that mimics meningioma.

PURPOSE: Although rare overall, marginal zone B-cell lymphoma (MZBCL) is the most common primary low-grade CNS lymphoma reported in the literature. The aim of this study is to elucidate the biology and genetic features of this unusual tumor. PATIENTS AND METHODS: Fifteen CNS MZBCLs were studied clinically, pathologically, and genetically, including fluorescent in situ hybridization analyses with commercially available MALT1 and IgH break-apart and centromere 3, 7, 12, and 18 probes. RESULTS: CNS MZBCLs preferentially affect middle-aged women (female-to-male ratio, 4:1), with 93% presenting as dural-based masses mimicking meningioma. Ten patients with 1 to 7.6 years of follow-up after diagnosis showed no evidence of disease after radiation and/or chemotherapy. Like MZBCLs outside of the CNS, they consisted of CD20+, CD3- small B lymphocytes with varying degrees of plasmacytic differentiation and predominantly kappa light-chain restriction (78%). Lymphoid follicles with follicular colonization were seen in three patients and deposition of amyloid was noted in samples from two patients, one of which was tumefactive. Neither Bcl-6 protein nor Epstein-Barr virus-encoded RNA was expressed. Trisomy 3 was detected in six of 12 patients, with no rearrangements of MALT1 or IgH and no trisomies of 7, 12, or 18 detected. CONCLUSION: Our data suggest that intracranial MZBCL is an indolent primary CNS lymphoma that typically presents as a meningioma-like dural-based mass. Trisomy 3, but not MALT1 or IgH translocation, is a common genetic abnormality that may contribute to the pathogenesis of this CNS lymphoma.

Adult↗
PubMed2005

Paraneoplastic chorea with leukoencephalopathy presenting with obsessive-compulsive and behavioral disorder.

Chorea is a rare manifestation of paraneoplastic disease and is associated with CV2/CRMP-5 antibodies. Obsessive-compulsive disorder and large-scale white matter abnormalities on MRI have not been previously reported in association with these antibodies. We report on a case of CV2 paraneoplastic syndrome with obsessive-compulsive behavior preceding the motor manifestations of chorea with associated leukoencephalopathy on MRI. The literature on paraneoplastic chorea is reviewed.

Aged↗
PubMed2005

Lhermitte-Duclos disease: a report of 31 cases with immunohistochemical analysis of the PTEN/AKT/mTOR pathway.

Lhermitte-Duclos disease (LDD) is a rare cerebellar tumor associated with Cowden disease (CD) and germline mutations in the PTEN gene. To further define these relationships, we reviewed clinical and pathologic findings in 31 LDD cases and analyzed the status of the PTEN pathway in 11 of them. We hypothesized that the granule cell hypertrophy in LDD is secondary to activation of mammalian target of rapamycin (mTOR), a downstream effector in the PTEN/AKT pathway and a major regulator of cell growth. Histopathologically, in addition to the classical findings of LDD, we observed prominent vascular proliferation and vacuolization of the white matter in many of the lesions. Four patients met diagnostic criteria for CD, and many of the remaining patients had some clinical features of CD. Immunohistochemical analysis showed high levels of phospho-AKT and phospho-S6 in the large ganglionic cells forming the lesions, indicating activation of the PTEN/AKT/mTOR pathway and suggesting a central role for mTOR in the pathogenesis of LDD. These data support recommendations for genetic testing and screening for CD in patients with LDD and suggest a novel therapy for LDD through pharmacologic inhibition of mTOR.

Adolescent↗
PubMed2005

INI1 protein expression distinguishes atypical teratoid/rhabdoid tumor from choroid plexus carcinoma.

Central nervous system atypical teratoid/rhabdoid tumor (AT/RT) and choroid plexus carcinoma (CPC) are rare, highly malignant tumors that predominantly arise in infants and young children. Overlapping clinical, histologic, ultrastructural, or immunophenotypic features may obscure the diagnosis in some cases. AT/RT is characterized by deletions and/or mutations of the INI1 tumor-suppressor gene on chromosome band 22q11.2. We have recently developed an INI1 immunohistochemical staining assay. Negative staining of tumor cells resulting from inactivation of the INI1 gene is a consistent feature of AT/RT. Mutations of INI1 in some CPCs have been reported. The purpose of the present study was to determine if immunohistochemical staining with an INI1 antibody would provide a sensitive means of distinguishing between CPC and AT/RT. We examined 28 tumors with a submitted diagnosis of CPC. Twenty-one CPCs showed retained expression of INI1 and seven tumors showed loss of INI1 expression. Cytogenetic, FISH, and/or INI1 mutation results were also available for 13 tumors. In three of the seven cases, monosomy 22 was the only cytogenetic abnormality, suggestive of AT/RT. However, monosomy 22 was also identified in 3 tumors with complex karyotypes that retained INI1 expression. The 7 tumors that were immunonegative for INI1 had features that were consistent with AT/RT. Immunostaining for INI1 protein is retained in the majority of CPC and is lost in AT/RT. This expression pattern seems to better define the 2 groups of tumors than does light or electron microscopy, routine immunohistochemistry, or cytogenetic analysis alone.

Adolescent↗
PubMed2005

Pushing the limits of radiotherapy for atypical and malignant meningioma.

PURPOSE: The purpose of this study was to report the outcome of an extremely aggressive radiotherapy program in patients with atypical and malignant meningioma (60 Gy at 1.5 Gy per fraction twice daily +/- radiosurgery boost). METHODS AND MATERIALS: Thirty-six patients received radiotherapy with curative intent between 1984 and 1999 for atypical (27 patients) or malignant (9 patients) meningioma. All patients had a minimum of 2 years follow up. RESULTS: The overall 5-year local control, cause-specific survival, and absolute survival rates were 45%, 39%, and 36%, respectively. Accelerated hyperfractionated radiotherapy resulted in a local control rate of 45% compared with 50% for patients treated with less aggressive schedules (P = 0.99). A radiosurgery boost did not improve tumor control. The complication rate for those treated with accelerated hyperfractionated radiotherapy was dramatically higher (grade 3-5: 55% vs. 0%, grade 4-5: 27% vs. 0%. both P <0.05). CONCLUSION: Our data suggests that 50 to 60 Gy delivered with conventional, once-daily fractionation is probably the optimal schedule for atypical and malignant meningioma. More aggressive radiotherapy fractionation schedules and radiosurgery are unlikely to improve outcome.

Adult↗
PubMed2005

Neonatal hypothalamic hamartoma: a differentiating nonlethal hamartoblastoma.

The authors report on a patient with a large hypothalamic hamartoma with a cleft lip and palate and seizures. Neuroimaging revealed a large extraaxial, intradural mass in the prepontine and interpeduncular cisterns with significant distortion of the brainstem. A stereotactic transfontanel needle biopsy revealed a cellular lesion that contained immature-appearing neuroepithelial cells consistent with prior descriptions of hypothalamic hamartoblastoma. While having a low level of proliferation by Ki67 (MIB-1) labeling, the lesion also contained evidence of neuronal maturation, with many cells expressing neuronal nuclear antigen as observed during immunohistochemical analysis. Further clinical evaluation revealed no other significant congenital abnormalities, and the patient was discharged home. Outpatient follow up has continued for 2 years and the patient has been doing well, requiring no further treatment. This case illustrates that, despite its immature and proliferative histological appearance, this rare neonatal mass can be regarded as a "differentiating" hypothalamic hamartoma and can have a favorable prognosis.

Abnormalities, Multiple↗
PubMed2004

Bone marrow transdifferentiation in brain after transplantation: a retrospective study.

BACKGROUND: End-organ repair by adult haemopoietic stem cells is under great scrutiny with investigators challenging the notion of these cells' plasticity. Some investigations of animals and short-term human bone marrow transplants suggest that bone marrow can repair brain. We looked for evidence of clinically relevant marrow-derived restorative neurogenesis: long-term, multilineage, neural engraftment that is not the result of cell-fusion events. METHODS: We examined autopsy brain specimens from three sex-mismatched female bone-marrow-transplantation patients, a female control, and a male control. We did immunohistochemistry, fluorescence in-situ hybridisation, and tissue analysis to look for multilineage, donor-derived neurogenesis. FINDINGS: Hippocampal cells containing a Y chromosome were present up to 6 years post-transplant in all three patients. Transgender neurons accounted for 1% of all neurons; there was no evidence of fusion events since only one X chromosome was present. Moreover, transgender astrocytes and microglia made up 1-2% of all glial cells. INTERPRETATION: Postnatal human neuropoiesis happens, and human haemopoietic cells can transdifferentiate into neurons, astrocytes, and microglia in a long-term setting without fusing. Transplantable human haemopoietic cells could serve as a therapeutic source for long-term regenerative neuropoiesis.

Adult↗
PubMed2004

Pituicytoma: report of two cases and clues regarding histogenesis.

OBJECTIVE AND IMPORTANCE: The pituicytoma is a rare primary tumor of the neurohypophysis. Although histologically benign, the location and vascular nature of these tumors can make surgical resection difficult. We present a report of two patients with pituicytomas and review the literature regarding treatment and prognosis for this unusual lesion. Possible histogenetic relationships of this tumor with other pituitary neoplasms are presented. CLINICAL PRESENTATION: Patient 1 was a 45-year-old man who presented with a 5-year history of decreased libido. He was found to have a 2-cm suprasellar mass on a magnetic resonance imaging scan. Patient 2 was a 48-year-old man who presented with multiple endocrine complaints. He was found to have an intrasellar mass on magnetic resonance imaging. INTERVENTION: Patient 1 underwent a right frontal craniotomy, with a subtotal resection of the suprasellar mass through the lamina terminalis. The residual tumor was treated with fractionated stereotactic radiotherapy. The intrasellar mass in Patient 2 was resected via a transsphenoidal approach. On surveillance magnetic resonance imaging, the tumor was found to have recurred and expanded into the suprasellar space. The patient underwent a right frontal craniotomy for decompression and a subtotal resection of the tumor. The patient experienced a second recurrence 7 years after the initial procedure and was subsequently treated with fractionated stereotactic radiotherapy. CONCLUSION: Pituicytomas are a distinct form of pituitary gland neoplasia that may recur if subtotally resected. These neurohypophysial tumors may contain a small subpopulation of previously unrecognized bcl-2-immunoreactive cells, whose role in the histogenesis of pituicytoma deserves further study.

Adenoma↗
PubMed2003

Giant cell glioblastoma and pleomorphic xanthoastrocytoma show different immunohistochemical profiles for neuronal antigens and p53 but share reactivity for class III beta-tubulin.

CONTEXT: Giant cell glioblastoma multiforme (GCGBM) and pleomorphic xanthoastrocytoma (PXA) are clinically, radiographically, and histologically distinct tumors of the central nervous system. However, they share features of gross circumscription, reticulin deposition, lymphocytic infiltrates, and prominent populations of tumor giant cells. Neuronal antigens have been detected in the neoplastic cells of PXAs, but to our knowledge have not been studied previously in GCGBMs. While TP53 is mutated in most GCGBMs, a feature usually paralleled by strong immunostaining of the protein, the expression pattern of PXAs has not been extensively studied. OBJECTIVES: To compare the immunoprofiles of GCGBM and PXA with regard to neuronal antigens and p53 and to evaluate the potential diagnostic utility of such a panel. DESIGN: Archival paraffin sections of 9 GCGBMs and 9 PXAs were immunostained for class III beta-tubulin, neuronal nuclear antigen, neurofilament protein, synaptophysin, glial fibrillary acidic protein, and p53. RESULTS: Giant cell glioblastomas were strongly immunoreactive for class III beta-tubulin and glial fibrillary acidic protein, but showed only rare staining for the other neuronal polypeptides. In contrast, PXAs usually showed at least focal staining of individual tumor cells for most of the neuronal antigens tested. Tubulin was strongly positive in tumor giant cells and in smaller neoplastic cells of both tumor types. Double-immunolabeling revealed distinct populations of tumor cells that expressed either glial fibrillary acidic protein or tubulin and dual-labeling of individual cells in GCGBM and PXA. Strong p53 staining was observed in many tumor cells in 5 of 8 GCGBMs tested, while staining for this antigen was negative or focally positive in 6 of 8 PXAs examined. CONCLUSIONS: Giant cell glioblastoma multiforme and PXA show distinct patterns of immunoreactivity for neuronal antigens and p53 that may be useful diagnostically in difficult cases or in limited samples. These results provide further evidence of neuronal antigen expression by PXA.

Adolescent↗
PubMed2002

Cortical dysgenesis and epilepsy.

Cortical dysgenesis (CD) describes a wide spectrum of brain anomalies that involve abnormal development of the cerebral cortex. There is a strong association between CD and epilepsy, and it comprises a significant proportion of children and adults whose epilepsy cannot be controlled with medications. There has been intense effort to define the relationship between CD and epilepsy so that more effective therapies can be devised. These efforts have ranged from detailed study of people with CD and epilepsy from a clinical standpoint to single-cell analysis of mRNA expression and postsynaptic receptor function. Animal models have also been developed to mimic certain aspects of CD in a situation when quantitative, controlled, and interventional experiments can be performed that would not be possible in a clinical setting. This review will give an overview of human CD syndromes and their causes, when possible, and describe some specific abnormalities in dysplastic cortex that may underlie its epileptogenic potential. It will also review several animal models of CD that have been studied mechanistically from the standpoint of epileptogenesis. In conclusion, some general trends will be proposed based on human and animal studies to encapsulate our current understanding of CD and how it causes epilepsy.

Animals↗
PubMed2002

Intraoperative consultation for nervous system lesions.

The pathologist responsible for nervous system intraoperative consultations must know basics of the clinical history, details of the location and imaging characteristics of the lesion, and must be familiar with known clinicopathologic entities. Although cytologic and frozen section techniques have not changed significantly in the past 15 years, significant advancements in neuroimaging have greatly improved the ability to generate an accurate preoperative differential diagnosis. Such information can greatly aid the pathologist during intraoperative consultation. This review concerns the intraoperative cytologic and frozen section findings of the major clinicopathologic entities encountered in surgical neuropathology. While neoplastic processes of the central nervous system will be emphasized, important non-neoplastic conditions that mimic brain tumors will also be covered. A basic clinicopathologic approach to successful neurosurgical intra-operative consultation is provided.

Adult↗
PubMed2002

Ex vivo high-resolution magnetic resonance imaging of the brain in Joubert's syndrome.

This study employs ex vivo high-resolution magnetic resonance imaging (MRI) to examine anatomic structures in an intact brain of a child with Joubert's syndrome. Several of the specific hindbrain malformations associated with Joubert's syndrome are well resolved with ex vivo MRI, including the "molar tooth sign," which arises from enlarged and maloriented superior cerebellar peduncles, hypoplastic vermis, and deepening of the interpeduncular fossa. Superior resolution was achieved compared with that of in vivo MRI and included visualization of the inferior olives. One high-resolution study also showed that the decreased width of the brainstem isthmus is probably caused by failure of superior cerebellar peduncles to cross the midline at that level. The results of this study suggest that high-resolution MRI may be useful in screening the brainstem for malformations that can be studied histologically in a much more targeted fashion.

Child, Preschool↗
PubMed2001

Rhombencephalosynapsis with massive hydrocephalus: case report and pathogenetic considerations.

Rhombencephalosynapsis (RS) is a rare cerebellar malformation characterized by vermian agenesis or hypogenesis, fusion of the hemispheres, and closely apposed or fused dentate nuclei. This report concerns a 29-year-old Caucasian female with a history of profound retardation and chronic hydrocephalus. Multiple shunts had been placed and there had been several admissions for shunt infections. Autopsy confirmed massive hydrocephalus and revealed marked aqueductal stenosis. The cerebellum was small with vermian aplasia, closely apposed dentate nuclei, fusion of the middle cerebellar peduncles, and a small fourth ventricle. Associated defects included fusion of the inferior colliculi and absence of dorsal olivary nuclei. This spectrum of anomalies is consistent with RS and could be explained by an embryological defect of dorsal pattering that affects the "isthmic organizer" at the mesencephalic-metencephalic border. Molecular analysis of dorsalizing genes, such as Lmx1a, which regulate early developmental events at the pontomesencephalic junction, may reveal a mutation or mutations unique to RS.

Adult↗