Imaging brain tumors -- beyond three dimensions.
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Aged↗
Biomedical subjects
E R Laws
Publications and source records attributed to E R Laws.
Proliferative activity and invasiveness among pituitary adenomas and carcinomas: an analysis using the MIB-1 antibody.
Although histologically benign, one-third of all pituitary tumors will be invasive of surrounding structures. In this study, the relationship between the proliferative activity in pituitary adenomas and their invasiveness was investigated. Invasion was defined as gross, operatively or radiologically apparent infiltration of dura or bone. Using the recently developed MIB-1 monoclonal antibody, which recognizes the Ki-67 cell cycle-specific nuclear antigen, the growth fractions of 37 noninvasive adenomas, 33 invasive adenomas, and 7 primary pituitary carcinomas were determined. All tumors were fully classified by histology, immunohistochemistry, and electron microscopy. The mean Ki-67 -derived growth fractions for noninvasive adenomas, invasive adenomas, and pituitary carcinomas were 1.37 +/- 0.15%, 4.66 +/- 0.57%, and 11.91 +/- 3.41%, respectively (mean +/- standard error of the mean). An analysis of variance and then individual pairwise comparisons confirmed significant differences in the mean Ki-67 labeling index between each of the three tumor groups (P < 0.01). The mean growth fraction of hormonally active pituitary adenomas (3.25 +/- 0.26%) was significantly higher than that for nonfunctioning adenomas (2.06 +/- 0.23%) (P = 0.03). Establishing a threshold labeling index of 3% served to distinguish invasive from noninvasive adenomas with 97% specificity and 73% sensitivity and was associated with positive and negative predictive values of 96 and 80%, respectively. Although invasive pituitary tumors exhibited significantly higher growth fractions than did noninvasive tumors, there were individual exceptions, indicating that in a subpopulation of invasive pituitary tumors, factors other than proliferative activity determine invasive potential.
Adult↗
Tumor-specific expression and alternate splicing of messenger ribonucleic acid encoding activin/transforming growth factor-beta receptors in human pituitary adenomas.
Activin, a member of the transforming growth factor-beta (TGF beta) cytokine family, acts as a pituitary cell mitogen via a novel family of receptor-linked serine/threonine (Ser/Thr) kinases. Pituitary tumors synthesize activin subunits, and the autocrine action of these growth factors may modulate tumor proliferation. We, therefore, investigated the expression of activin/TGF beta type I receptor messenger ribonucleic acids (mRNAs), designated ALK1 through ALK5 (ALK = activin receptor-like kinase), and type II receptor mRNAs using RT-PCR in 34 human pituitary adenomas of all phenotypes and normal pituitary tissue. ALK2 and ALK5, specific mediators of activin and TGF beta signals, respectively, were found to be expressed only in tumor and not in normal pituitary cells, and ALK2 expression was found only in tumors of a mammosomatotroph cell lineage. ALK1, ALK3, and ALK4 mRNAs were found in both normal and neoplastic pituitary cells. The alternatively spliced cytoplasmic domain of ALK4 consists of 11 kinase subdomains, that are critical for modulating receptor function and intracellular signaling. Truncated forms of the ALK4 cytoplasmic domain lacking these subdomains may attenuate activin signal transduction and affect both tumor phenotype and proliferation via the formation of inactive type I/type II complexes. Three truncated ALK4 receptor mRNAs generated by alternate splicing of the cytoplasmic Ser/Thr kinase domain were found to be tumor specific. One of these truncated receptor mRNAs, ALK4-5, is a novel splice variant that has not been previously described. Expression of the ActRII and T beta RII type II receptor mRNAs, which specifically bind activin and TGF beta, respectively, was highly prevalent among all tumor subtypes and normal pituitary tissue. However, ActRIIB, an activin-specific type II receptor that displays a 3- to 4-fold higher affinity for ligand than ActRII, was expressed in 94% of tumors, but was not prevalent in normal tissue. These data are the first to demonstrate tumor-specific expression of Ser/Thr kinase receptors mRNAs and their splice variants in human pituitary adenomas.
Activin Receptors↗
Symptomatic intrasellar hemangioblastoma in a child treated with subtotal resection and adjuvant radiosurgery. Case report.
The first documented case of a symptomatic intrasellar hemangioblastoma is described, occurring in an 11-year-old girl with stigmata of von Hippel-Lindau disease who presented with headaches, progressive bitemporal hemianopsia, and adenohypophysial dysfunction. A subtotal resection of the lesion was achieved with two separate surgical procedures: a transsphenoidal approach and a subfrontal craniotomy. Subsequent growth of residual tumor was treated with combined conventional radiotherapy and stereotactic radiosurgery. Two years following completion of these adjuvant therapies, no residual tumor was evident on magnetic resonance imaging. Previous experience with hemangioblastoma in this region, as well as the rationale for radiotherapy in the treatment of incompletely resected lesions, is reviewed.
Brain Neoplasms↗
p53 expression in pituitary adenomas and carcinomas: correlation with invasiveness and tumor growth fractions.
Although most pituitary tumors are well differentiated, histologically benign neoplasms, their clinical behavior is known to vary greatly. These lesions are relentlessly aggressive in some instances yet biologically indolent in others, but these prognostically relevant differences in behavior are not reflected in their histopathological appearance. As a means of identifying intrinsically aggressive pituitary tumors, we evaluated 70 pituitary adenomas and 7 primary pituitary carcinomas for their expression of the p53 gene product, a nuclear phosphoprotein whose immunohistochemical accumulation has served as an unfavorable prognostic factor for a wide range of human neoplasms. All tumors were fully classified by immunohistochemistry and electron microscopy; adenomas were further stratified on the basis of their invasion status, the latter being defined as gross operatively or radiologically apparent infiltration of dura or bone. Conclusive nuclear immunopositivity for p53 was identified in a total of 12 tumors, all being either invasive adenomas or primary pituitary carcinomas. A clear and highly significant association was evident between p53 expression and tumor behavior, as the proportion of p53-positive cases among noninvasive adenomas, invasive adenomas, and pituitary carcinomas was 0, 15.2, and 100%, respectively (chi 2 = 44.72; degrees of freedom, 2; P << 0.001). A comparison of previously reported growth fraction data with p53 expression indicated that the mean Ki-67-derived growth fraction of p53-positive tumors was significantly higher than that of p53-negative tumors (10.41 +/- 2.20 versus 2.51 +/- 0.28%) (+/- standard error of the mean, two-sample t test for independent samples, P = 0.004). There was no apparent relationship between the functional status of the tumor and p53 expression; positivity was observed among somatotroph, lactotroph, corticotroph, and clinically nonfunctioning pituitary tumors. These data indicate that p53 expression, when conclusively present in pituitary tumors, may be of some diagnostic usefulness as a marker of biologically aggressive behavior.
Adenoma↗
The classification and molecular biology of pituitary adenomas.
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Adenoma↗
Surgical management of pituitary adenomas.
Surgical management of pituitary adenomas continues to be a safe and effective method, suitable for a large number of patients suffering from the effects of these lesions. Frequently surgery is just part of an overall programme that includes medical management and radiation therapy as well. It is important for the physicians and the patients to understand that surgery alone may not be totally successful, but that with careful follow-up and appropriate adjunctive management, patients with pituitary tumours may live normal lives, and may enjoy reversal of the endocrine and visual problems that had been caused by their tumours. Careful study of surgically managed patients has contributed to some of the advances that have occurred in the overall management of pituitary adenomas and in our understanding of their biology, pathophysiology and pathogenesis.
Adenoma↗
Long term follow-up of transsphenoidal surgery for the treatment of Cushing's disease in childhood.
Transsphenoidal removal of pituitary adenomas has become the accepted treatment for Cushing's disease. As Cushing's disease is rare in childhood, few reports describe extended follow-up after transsphenoidal surgery for this disease in children. Twenty-two patients less than 19 yr of age were diagnosed with Cushing's disease by standard testing. All patients underwent transsphenoidal surgery (TSS) as primary treatment at Mayo Clinic between 1975 and 1990. Follow-up was available in all patients and averaged 6.7 yr. Adenomas were identified pathologically in 19 patients and visualized by the surgeon in the remainder. There was 1 macroadenoma. Ten patients are considered cured with a mean follow-up of 5.5 yr. Five patients had evidence of persistent disease within 6 months of TSS and required further treatment. Seven patients had remission lasting greater than 6 months with subsequent relapse (mean time to recurrence, 7.0 yr). In children treated with TSS for Cushing's disease, the rate of cure with extended follow-up is only approximately 50%. This rate is much lower than that in adults and may indicate that Cushing's disease is more aggressive in childhood. As TSS is associated with low morbidity, we feel it is still the treatment of choice for Cushing's disease in children.
Adenoma↗
Acute presentation of an intracranial mass.
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Acute Disease↗
Tumoral calcium pyrophosphate dihydrate deposition disease mimicking a cervical spine neoplasm: case report.
A case of tumoral calcium pyrophosphate dihydrate crystal deposition disease involving the upper cervical spine is reported. It presented clinically, radiographically, and by preliminary intraoperative pathological evaluation as a possible malignant soft tissue tumor. An aggressive resection of the lesion was performed. This case differs from previous reports of calcium pyrophosphate dihydrate crystal deposition disease of the cervical spine by the size, location, and radiographic appearance of the lesion. We suggest that radical surgical procedures should not be performed without consideration of this diagnosis in lesions with similar presentations. A brief review of spinal and tumoral calcium pyrophosphate dihydrate crystal deposition is presented.
Adult↗
Delayed hyponatremia after transsphenoidal surgery for pituitary adenoma. Report of nine cases.
Hyponatremia, usually attributed to the syndrome of inappropriate secretion of antidiuretic hormone, typically occurs in a delayed fashion following transsphenoidal removal of a pituitary adenoma. In a series of 99 consecutive patients who underwent transsphenoidal surgery for pituitary adenoma, nine patients developed delayed hyponatremia, seven of whom were symptomatic. Of these seven patients, four had been discharged from the hospital and required readmission on postoperative Day 7 to 9. In the nine patients who developed hyponatremia, on the average, serum sodium levels began to fall on Day 4 and reached a nadir on Day 7 (mean serum sodium nadir 123 mmol/L). The development of delayed hyponatremia was associated with the presence of a macroadenoma in eight of the nine patients. Seven of the nine patients had serum sodium levels less than 130 mmol/L and required treatment. One patient was treated with fluid restriction alone and six were treated with both fluid restriction and intravenous urea therapy. Twenty-four and 48 hours after urea administration, serum sodium levels rose by an average of 6 and 10 mmol/L, respectively, and at discharge, levels averaged 136 mmol/L. Intravenous administration of urea provides a rapid yet safe means of correcting symptomatic hyponatremia when fluid restriction alone is inadequate. In this article, the authors discuss the pathogenesis of delayed hyponatremia.
Adenoma↗
Radical resection for the treatment of glioma.
The surgical management of gliomas of the brain continues to be an area for investigation and of some controversy. Many of the questions can be answered by careful clinical investigation, using modern techniques of epidemiology and carefully controlled prospective studies. Until these studies are available, a strong case can be made for the treatment of many gliomas of the brain with radical surgical resection. In some cases this strategy can provide cures or long-term remissions, and in others it can provide disease control when combined with adjunctive measures, such as radiation therapy.
Brain Neoplasms↗
Migration of fresh human malignant astrocytoma cells into hydrated gel wafers in vitro.
Individual astrocytoma cells expressing a cytoplasmic form of p185c-neu migrated along basement membrane lined surfaces after xenografing fresh low or high grade human malignant astrocytomas into host rat brain. We now study the migratory capacity of fresh human malignant astrocytoma cells seeded on hydrated gel wafers composed of artificial basement membrane or collagen I, a normal and lesion-related CNS extracellular matrix component. Approximately 10(7) mechanically disrupted cells (with small clumps) of 3 fresh low grade and 6 fresh high grade astrocytomas were seeded on the surface of artificial basement membrane and collagen I wafers (11 x 16 mm). The wafers were then prepared for scanning electron microscopy and immunohistochemistry at 1, 3, 5, and 7 days after seeding. Regardless of tumor grade, a morphologically similar class of cells was observed to migrate through collagen I gels in 24 hours and 0.5-1.5 mm into artificial basement membrane gels in 7 days. Immunohistochemistry revealed that the migrated cells from low and high grade astrocytomas were positive for glial fibrillary acidic protein (GFAP)) and expressed cytoplasmic human-specific p185c-neu. These data indicate that fresh human malignant astrocytoma cells that contain GFAP and express cytoplasmic p185c-neu have a high degree of migratory capacity and could be the cell in the tumor involved in intraparenchymal metastasis and poor patient survival in high grade astrocytomas of the human brain.
Astrocytoma↗
Transsphenoidal removal of craniopharyngioma.
Transsphenoidal microsurgical removal is appropriate therapy for a significant number of craniopharyngiomas. Favorable factors for the transsphenoidal approach are enlargement of the sella, cystic lesion and preoperative hypopituitarism. A series of 76 operative cases is presented. Long-term follow-up revealed successful results in 81% of patients.
Adolescent↗
Estrogen receptor expression in human pituitary: correlation with immunohistochemistry in normal tissue, and immunohistochemistry and morphology in macroadenomas.
Forty-one human pituitary adenoma specimens were examined for the presence of estrogen receptor (ER) messenger ribonucleic acid and protein using a combination of ribonuclease protection assay, [3H] estradiol ([3H]E2) binding, and ER immunohistochemistry. ER messenger ribonucleic acid prevalence was high in PRL-immunoreactive tumors (2 of 2), moderate in GH/PRL tumors (2 of 5), and low or absent (0 of 4) in GH tumors. In the GH/PRL-immunostaining tumors, the presence of the ER was uniformly associated with elevated serum PRL levels. Among the gonadotropin-immunostaining tumors, 10 of 17 were ER positive; within this group, those with gonadotroph adenoma characteristics were ER positive, whereas those with null cell/oncocytic characteristics were ER negative. Of the tumors that did not immunostain for any known anterior pituitary hormones, 3 of 11 were ER positive. ER immunohistochemistry in 14 tumors revealed a 100% correlation with ribonuclease protection assay results, whereas [3H]E2 binding, determined in 9 tumors, showed an 87% correlation. In summary, it appears that PRL and a specific class of gonadotropin-immunostaining tumors (identifiable by specific characteristics on electron microscope) contain ER, whereas GH-immunostaining tumors are ER negative. ER expression in normal pituitary paralleled that in macroadenomas (GH, 2.3%; PRL, 50%; FSH, 70%; LH, 83%; TSH, 4%; ACTH, 1%). The ER-positive tumors represent a subset whose growth and secretory profiles may be influenced by the gonadal steroidal milieu or by pharmacological agents that affect E2 levels or ER function.
Adenoma↗
Pituitary adenomas in childhood and adolescence.
A clinicopathological study of 56 pediatric patients with non-ACTH-secreting pituitary adenomas removed by a transsphenoidal neurosurgical approach was undertaken to better define the clinical presentation, to assess demographic factors, to determine the immunohistochemical staining characteristics of the tumors, and to evaluate the outcome of transsphenoidal surgical treatment and other adjuvant therapies. A separate analysis of prolactinoma patients was performed. All tumors were confirmed histologically and immunophenotyped for pituitary hormones. Forty-one patients had tumors that stained for PRL alone, eight patients had tumors that stained for PRL and GH, six patients had plurihormonal adenomas, and one patient had a tumor that stained for glycoprotein hormones. No tumors contained GH alone. Macroadenomas exceeded microadenomas (1.4:1). There were no male patients with microadenomas of any type. Females outnumbered males (3.3:1). Patients presented most frequently with headache, menstrual dysfunction (in females), galactorrhea, and hypopituitarism. All but one of the patients with hypopituitarism at presentation had macroadenomas. Tumor staining characteristics did not always correlate well with clinical status, especially with regard to GH-containing tumors. Pediatric pituitary tumors did not appear to be more invasive or more aggressive than adult pituitary tumors, contrary to some previous reports. The patients with microadenomas had a 70% operative cure rate and a 65% long term cure rate; the recurrence rate for microadenoma patients was 25%. Macroadenoma patients had a 33% operative cure rate, a 55% long term cure rate, and a recurrence rate of 33%. Thus, microadenoma and macroadenoma patients had similar long term cure rates, but macroadenoma patients required more aggressive adjuvant therapy (second surgery, radiation, or bromocriptine) and had higher rates of hypopituitarism (52% of macroadenoma patients vs. 0% of microadenoma patients required long term hormone replacement).
Adenoma↗
Magnetic resonance imaging measurements of pituitary stalk compression and deviation in patients with nonprolactin-secreting intrasellar and parasellar tumors: lack of correlation with serum prolactin levels.
Prolactin (PRL) Levels are frequently elevated in patients with non-PRL-secreting adenomas or other intrasellar and parasellar diseases ("pseudoprolactinomas"). This phenomenon is believed to result from a loss of dopaminergic inhibition on pituitary lactotrophs and is known as the "stalk-section effect." Using magnetic resonance imaging scans and a high-magnification sella technique, we measured a number of parameters indicative of the disruption of normal sellar structures. The investigator was blind to the patient's diagnosis and PRL level while collecting the data. Parameters measured were the tumor size, the angular deviation of the pituitary stalk, and the degree of compression of the pituitary stalk. Measurements were obtained from 44 patients with pathologically confirmed tumors that had no immunohistochemical reactivity to PRL. PRL levels were often higher than expected. Four patients (9%) had a PRL level of more than 150 ng/ml, and three patients (7%) had a PRL level of 200 ng/ml or more. One patient with a plasmacytoma eroding the sella floor had a PRL level as high as 504 ng/ml. There was no significant correlation of PRL level and the degree of pituitary stalk compression, stalk deviation, or tumor size. PRL levels were found to be markedly elevated in some patients with a tumor causing little distortion of the pituitary stalk. Conversely, PRL levels were often normal despite evidence of massive distortion of the stalk. Therefore, magnetic resonance imaging evidence of pituitary stalk distortion cannot be used to determine the diagnosis of prolactinoma versus pseudoprolactinoma in most cases.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenoma↗
Novel features of tumors that secrete both growth hormone and prolactin in acromegaly.
The most prominent previously reported clinical features of growth hormone (GH) and prolactin (PRL)-secreting pituitary adenomas associated with acromegaly have included the high incidence of galactorrhea in women and a generally more favorable response to dopamine agonist therapy. The authors analyzed a consecutive series of 62 acromegalic patients treated with transsphenoidal microsurgery. GH-PRL tumors were found in 30% of the patients. There was a significant difference in sex distribution between acromegalics with the GH-PRL tumor subtype and all other acromegalics. Women represented 73% of the GH-PRL immunostain subtype, as compared with the overall sex distribution of 33 women (53%) and 29 men (47%) for the entire series of acromegalic patients. Individuals with the GH-PRL subtype had significantly higher postoperative GH levels than those with the GH subtype, and significantly higher postoperative GH levels when compared with all other acromegalics with a variety of immunostain subtypes. Linear regression analysis of the pre- and postoperative GH data revealed that the increased postoperative GH levels in the GH-PRL immunostain subtype were independent of the invasiveness of the tumor and of sex of the subject. When the same linear regression technique was used, lower preoperative levels of thyroxine and thyroid-stimulating hormone were observed in the GH-PRL subtype. These data suggest inherent differences characteristic of tumors that secrete both growth hormone and prolactin.
Acromegaly↗