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M. Beatriz S. Lopes

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M. Beatriz S. Lopes

The majority of patients with acromegaly harbor a functioning growth hormone (GH) pituitary adenoma. Growth hormone–secreting adenomas correspond to about 20% of all pituitary adenomas. From the histopathological point of view, a variety of adenomas may present with clinical signs and symptoms of GH hypersecretion including pure GH cell adenomas (densely and sparsely granulated GH adenomas), mixed GH and prolactin cell adenomas, and monomorphous adenomas with primitive cells able to secrete GH and prolactin including the acidophilic stem cell adenoma and the mammosomatotroph cell adenoma. In this article, the author reviews the main pathological features of the GH-secreting adenomas and some of the molecular genetics mechanisms involved in their pathogenesis.

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Melike Mut, M. Beatriz S. Lopes and Mark Shaffrey

Dr. Lucien Rubinstein is best remembered for his significant contributions to the field of neuropathology, particularly in the classification of nervous system tumors. His accomplishments in basic neuro-oncology and in the formulation of diagnostic principles reflected a unique talent for synthesizing fundamental clinicopathological concepts based on skillful diagnostic investigation and a thorough understanding of neurobiology. Dr. Rubinstein was the leader in the establishment of cell cultures from central nervous system (CNS) tumors. He meticulously analyzed both light and electron microscopic features of CNS tumors, recorded his findings, and patiently drew sketches to be shared generously with his colleagues and students. As a pioneer in neuropathology, in his work Dr. Rubinstein set the foundation for many enduring concepts in neurosurgery, neuro-oncology, neurology, and basic tumor biology.

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Arnaldo Neves Da Silva, Maria Beatriz Lopes and David Schiff

✓ Primary central nervous system lymphoma (PCNSL) is a rare form of primary brain neoplasm, accounting for less than 3% of all primary brain tumors. Ninety percent of cases involve a large B-cell lymphoma that presents as a homogeneously enhancing lesion or lesions, typically deep-seated in the brain parenchyma. The authors describe unusual pathological forms of PCNSLs, including low-grade, T-cell, and Burkitt types, and also rare presentations such as neurolymphomatosis and pituitary lymphomas.

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M. Beatriz S. Lopes and Edward R. Laws Jr.

Low-grade tumors of the central nervous system constitute 15 to 35% of primary brain tumors. Although this category of tumors encompasses a number of different well-characterized entities, low-grade tumors constitute every tumor not obviously malignant at initial diagnosis. In this brief review, the authors discuss the pathological classification, diagnostic procedures, treatment, and possible pathogenic mechanisms of these tumors. Emphasis is given in the neu-roradiological and pathological features of the several entities.

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Tim E. Darsaut, Giuseppe Lanzino, M. Beatriz Lopes and Steven Newman

The term “orbital tumors” comprises a wide variety of lesions that often share the same cardinal clinical finding (exophthalmos) and clinical history. Age at presentation, associated ophthalmological findings, and radiological features, however, provide invaluable information as to the possible histological type of tumor. The present article serves as an introductory overview regarding the pathological characteristics, clinical features, radiological characteristics, and principles of treatment of orbital tumors.

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M. Beatriz S. Lopes

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Mark E. Shaffrey, Elana Farace, David Schiff, James M. Larner, Melike Mut and M. Beatriz S. Lopes

Object. This study was conducted to determine whether proliferative tumor activity, as assessed using the Ki-67 immunohistochemical labeling index (LI), has prognostic utility for patients with Grade II oligoastrocytomas.

Methods. The study period spans the years 1988 to 2000. In a retrospective analysis, the authors selected cases with biopsy-proven diagnoses of Grade II oligoastrocytomas on initial presentation. The authors added new patients to this group and followed all patients prospectively at the University of Virginia Neuro-Oncology Center.

Twenty-three adult patients were followed for at least 1 year (median 40.3 months). Eleven patients with Grade II tumors and initial Ki-67 LIs less than 10% had a significantly longer median time to tumor progression (TTP, 51.8 months compared with 9.9 months) and a longer median survival (93.1 months compared with 16.1 months) than 12 patients with initial Ki-67 LIs of 10% or greater. Twelve patients with Grade III oligoastrocytomas had a mean TTP that was similar to the TTP of patients with Grade II tumors and high Ki-67 LIs (mean 4 months compared with 9.9 months) and duration of survival (13.3 months compared with 16.1 months).

Conclusions. Patients with a Grade II oligoastrocytoma and a Ki-67 LI of 10% or greater have a much shorter TTP and potentially a poorer disease prognosis than expected—more similar to patients with a Grade III oligoastrocytoma. These results indicate that in the future a measure of proliferative activity should be taken into consideration along with the World Health Organization grading criteria for oligoastrocytomas.

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Relevance of high Ki-67 in pituitary adenomas

Case report and review of the literature

Daniel M. Prevedello, Jay Jagannathan, John A. Jane Jr., M. Beatriz S. Lopes and Edward R. Laws Jr.

Pituitary adenomas are heterogeneous in growth rate, invasiveness, and recurrence. To understand the biological behavior of the individual adenoma more fully, cell proliferation markers such as monoclonal antibodies targeted against the Ki-67 antigen have been applied. The Ki-67 antigen is a protein related to cell proliferation and is expressed in cell nuclei throughout the entire cell cycle. The authors report the case of an extremely rapidly growing pituitary adenoma with cavernous sinus invasion. The lesion, which displayed a high Ki-67 labeling index (LI; 22%), was found in a 54-year-old woman who presented with diplopia and headaches. The patient underwent three transsphenoidal operations in less than 6 months and, ultimately, was treated with fractionated intensity-modulated radiation therapy. The relationships between high Ki-67 LIs and tumor recurrence, invasiveness, and growth velocity in pituitary adenomas are reviewed.

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Jason P. Sheehan, Jonas M. Sheehan, M. Beatriz Lopes and John A. Jane Sr.

✓ Diastematomyelia is a rare entity in which some portion of the spinal cord is split into two by a midline septum. Most cases occur in childhood, but some develop in adulthood. A variety of concurrent spinal anomalies may be found in patients with diastematomyelia.

The authors describe a 38-year-old right-handed woman who presented with a 7-month history of lower-extremity pain and weakness on the right side. She denied recent trauma or illness. Sensorimotor deficits, hyperreflexia, and a positive Babinski reflex in the right lower extremity were demonstrated on examination.

Neuroimaging revealed diastematomyelia extending from T-1 to T-3, an expanded right hemicord from T-2 to T-4, and a C6–7 syrinx. The patient underwent T1–3 total laminectomies, resection of the septum, untethering of the cord, and excision of the hemicord lesion. The hemicord mass was determined to be an intramedullary epidermoid cyst; on microscopic evaluation the diastematomyelia cleft was shown to contain fibroadipose connective tissue with nerve twigs and ganglion cells. Postoperatively, the right lower-extremity pain, weakness, and sensory deficits improved.

Diastematomyelia can present after a long, relatively asymptomatic period and should be kept in the differential diagnosis for radiculopathy, myelopathy, tethered cord syndrome, or cauda equina syndrome. Numerous spinal lesions can be found in conjunction with diastematomyelia. To the authors' knowledge, this is the first case in which a thoracic epidermoid cyst and cervical syrinx occurred concurrently with an upper thoracic diastematomyelia. Thorough neuraxis radiographic evaluation and surgical treatment are usually indicated.