Biomedical subjects

E T Hedley-Whyte

Publications and source records attributed to E T Hedley-Whyte.

At least 55 records · Page 3Linked to original sources

PubMed1995

Prognostic role of urokinase-type plasminogen activator in human gliomas.

Urokinase-type plasminogen activator (u-PA) is a 54-kd enzyme shown to participate in tissue degradation under certain normal and pathological conditions, including cancer invasion and metastasis. Increased u-PA expression has been found in cancers of the breast, lung, colon, and prostate, and correlated with worse outcome in patients with lung and breast cancer. We examined the correlation between u-PA expression in gliomas and patient survival. Seventy-seven gliomas from 41 men and 36 women (ages 2 to 73) were immunostained for u-PA using monoclonal antibody 394 directed against human urokinase. The tumors included 32 grade 4, 16 grade 3, and 20 grade 2 astrocytomas (Daumas-Duport scale), and 9 pilocytic astrocytomas. Strong cytoplasmic staining was found in tumor cells of all grade 4, most of the grade 3, and a few of the lower grade tumors. Adjacent normal brain tissue showed faint staining associated with subpial cell processes and white matter fibers. The fiber staining was stronger in brain tissue infiltrated by tumor cells. Cytoplasmic u-PA staining in tumor cells was scored from 0 (no staining) to 6 (strong and widespread staining). The mean u-PA scores were 5.08 +/- 0.19 (mean +/- SEM) for grade 4, 3.97 +/- 0.46 for grade 3, 1.65 +/- 0.39 for grade 2, and 1.22 +/- 0.60 for pilocytic astrocytomas. The statistical analysis was based on cytoplasmic staining only. Analysis of variance revealed significant differences between the mean u-PA scores of different grades (P < 0.02 between grades 4 and 3, and P = 0.0001 between grades 4 or 3 and 2, and between grades 4 or 3 and pilocytic), except between grade 2 and pilocytic astrocytomas. Univariate analysis indicated that u-PA score > or = 4 (P = 0.0001), tumor grade 4 (P = 0.01), and age > 50 (P < 0.001) were all significant predictors for shorter disease survival. A three-way interaction model by multivariate analysis indicated that u-PA score > or = 4, tumor grade 4, and age > 50, taken together, were significant factors for shorter patient survival (P < 0.02). We conclude that u-PA may be used as a prognostic tool in conjunction with tumor grade and patients' age in predicting survival for patients with gliomas.

Adolescent↗

PubMed1994

The role of family history in risk of childhood brain tumors.

BACKGROUND: Although brain tumors are the second most frequent malignancy in children, relatively little is known about the role of family history in risk of these tumors. METHODS: Children under the age of 18 years (n = 361) in whom primary brain tumors were diagnosed were identified from eight United States population-based Surveillance, Epidemiology, and End Results registries and compared to matched controls (n = 1083) identified by random-digit dialing. Information regarding family history of birth defects or tumors was obtained, along with data on other potential risk factors, from interviews with the mothers and fathers of the index children. RESULTS: No significant differences were found in family history of epilepsy. However, moderate elevations in risk were observed for a history of birth defects in maternal relatives, particularly for female propositi. Significantly more mothers (odds ratio [OR] = 1.63, 95% confidence limits [CL] = 1.03, 2.57) and maternal female relatives (OR = 2.15, 95% CL = 1.14, 4.06) of cases than of controls were reported to have had birth defects. History of birth defects in maternal relatives was particularly associated with childhood brain tumors of "other" (not astrocytoma or medulloblastoma) histologic type (OR = 2.37, 95% CL = 1.25, 4.53) and infratentorial tumors (OR = 1.76, 95% CL = 1.06, 2.93). Slight excesses of tumors were observed in paternal relatives of children with astrocytomas (OR = 1.43, 95% CL 0.93, 2.20) or with infratentorial tumors (OR = 1.46, 95% CL 0.97, 2.20). Risk of childhood brain tumors did not increase with the number of relatives affected with brain tumors, breast cancer, leukemia or lymphoma, soft tissue sarcomas, or all of these tumor types combined (the Li-Fraumeni syndrome). CONCLUSIONS: These findings suggest a modest increase in risk of childhood brain tumors associated with maternal family history of birth defects. Family history of tumors does not appear to contribute appreciably to an increased risk of brain tumors in children.

Adolescent↗

PubMed1994

Prognostic significance of proliferative indices in meningiomas.

The prognostic value of tumor proliferative indices in meningiomas was assessed by mitotic counts and by immunocytochemistry using a monoclonal antibody against the proliferating cell nuclear antigen (PCNA) (clone 19A2), a 36-kd nuclear protein involved in DNA synthesis. Sixty-three intracranial meningiomas were classified as benign (26), with atypical features (24) or as malignant (13). The patients included 24 men and 39 women, mean age 54.2 +/- 1.7 (mean +/- SEM) (range 15-78) at initial presentation. Twenty-four of the 63 primary tumors recurred locally, including 23.1% (6/26) of the benign, 37.5% (9/24) of the atypical, and 69.2% (9/13) of the malignant meningiomas. Among tumors that recurred, 1/9 (11%) of the atypical and 5/9 (55.5%) of the malignant tumors had had macroscopical total excision at the initial surgery. The mean interval to recurrence was 52 +/- 11.8 months. The mean progression-free follow-up period for patients without tumor recurrence was 82 +/- 8.5 months. Analysis of variance revealed that significant differences existed between tumor grades for both PCNA indices (1.16 +/- 0.29% for benign; 14.14 +/- 2.07% for atypical and 21.37 +/- 5.47% for malignant) and mitotic indices (total counts per ten high power fields) (0.08 +/- 0.05 for benign, 4.75 +/- 0.91 for atypical and 19.00 +/- 4.07 for malignant). Multivariate regression analysis indicated that mitotic index > 6 was the single most important factor (p < 0.05) for shorter disease-free interval. Age, sex and total surgical excision were not significant factors. PCNA index was a significant factor in the univariate model, but not in the multivariate model.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1994

Histologic feature reliability in childhood neural tumors. Childhood Brain Tumor Consortium.

We studied intraobserver reproducibility in recognizing the presence or absence of 57 histologic feature or patterns in a random subset of tumors (822) from the Childhood Brain Tumor Consortium database. The study protocol maximized consistency of the observer. We found that only six histologic features had high (> or = 0.75) reliability estimates while a large number had intermediate estimates of 0.50-0.74. Supratentorial or infratentorial tumor location sometimes altered reliability. Reliability estimates were unacceptable for certain histologic features often used as diagnostic criteria, descriptors of tumor characteristics, or markers of anaplasia. We hypothesize that low reliability reflects, in part, the need for more specific operational definitions, particularly those with subjective boundaries (e.g. granular bodies) may also contribute to low reliability. We also show that the kappa statistic, a commonly used measure of reliability, is inappropriate for very common or uncommon histologic features (e.g. features at the extremes of prevalence in the study cases) and we offer a simple empiric method for determining when an alternative measure, the Jaccard statistic, is appropriate.

Brain Neoplasms↗

PubMed1994

ras mutations in human prolactinomas and pituitary carcinomas.

Pituitary adenomas have been shown to be clonal in origin, indicating that one or more somatic mutations underlie tumor pathogenesis. Mutated oncogenic forms of ras protein have been identified in a number of human neoplasms, including thyroid adenomas and carcinomas. However, the potential role of activated ras in the development of specific human pituitary tumor phenotypes has not been determined. Although ras mutations were not found in glycoprotein hormone-secreting or somatotroph adenomas, we recently identified a mutation in the H-ras gene (Gly-Val) at codon 12 in a highly invasive prolactinoma. These data raise the possibility that ras mutations might play a role in the pathogenesis of PRL-secreting pituitary tumors and/or may be a marker for tumor invasiveness and malignant transformation. Therefore, we investigated 78 pituitary tumors (59 prolactinomas, 13 invasive prolactinomas, and 6 pituitary carcinomas) for activating point mutation in the three ras genes using oligonucleotide-specific hybridization. In contrast to the relatively high frequency of ras mutations in many different tumor types, no ras mutations were identified in either prolactinomas or pituitary carcinomas. Our data indicate that ras mutations are rare in prolactinomas and pituitary carcinomas.

Adolescent↗

PubMed1993

Lateral geniculate nucleus in glaucoma.

To assess glaucomatous damage to the lateral geniculate nucleus of the thalamus, as well as to its magnocellular and parvocellular layers, we examined the autopsy sections of the lateral geniculate nucleus of individuals with and without glaucoma. Five patients with a documented history of glaucoma and five controls with no ophthalmic or chronic central nervous system disease were included in this study. Neurons were counted in autopsy sections of the lateral geniculate nucleus. Cells were counted in 40 random microscopic fields of the magnocellular and parvocellular layers respectively. The mean magnocellular cell density for the glaucoma group of 2.72 +/- 0.13 cells per square millimeter (mean +/- SEM) was significantly less than that for the control group of 3.76 +/- 0.13 cells per square millimeter (P < .001). There was no statistical difference in the parvocellular layer. These data suggest that glaucoma leads to greater loss of magnocellular tissue at the level of the lateral geniculate.

Aged↗

PubMed1993

Parental smoking and risk of childhood brain tumors.

Data from a large, population-based, case-control study were analyzed to assess the role of parental smoking in childhood brain tumors. Parents of 361 cases, newly diagnosed between January 1, 1977 and December 31, 1981 and ascertained from eight Surveillance, Epidemiology, and End Results (SEER) program registries, and 1,083 controls had been interviewed. No significant differences in risks were found to be associated with maternal or paternal smoking at any time (odds ratio (OR) = 0.92 for mothers and 1.06 for fathers), during the year of birth of the child (which included both the prenatal and postnatal periods) (ORs = 0.84 for < 1 pack/day and 1.0 for > or = 1 pack/day for mothers, and 0.68 for < 1 pack/day and 1.07 for > or = 1 pack/day for fathers), or 2 years before the child was born, i.e., the pre-conception period (ORs = 0.75 for < 1 pack/day and 1.01 for > or = 1 pack/day for mothers, and 0.90 for < 1 pack/day and 1.15 for > or = 1 pack/day for fathers). Mothers were also specifically asked if they smoked during the pregnancy, and no association was found compared with never smokers (OR = 1.08, 95% confidence interval (CI) 0.80-1.45) or for ever-smokers who continued to smoke during pregnancy compared with those who stopped smoking during pregnancy (OR = 1.15, 95% CI 0.75-1.78). Finally, no significant increase in risk of brain tumors was found for the child's passive exposure to parental smoking during the period from birth to diagnosis of the brain tumor in the case. The lack of an effect of parental smoking was observed for both the major histologic types and locations of brain tumors. These findings and those from earlier studies provide no support for the hypothesis that parental cigarette smoking influences the risk of brain tumors in children.

Adult↗

PubMed1993

Nucleolar organizer regions in optic gliomas.

The biological nature of optic gliomas is controversial, with some considering them benign hamartomatous lesions, and others believing them to be true neoplasms. We evaluated the use of colloid silver impregnation of nucleolar organizer region-associated proteins (AgNORs) in making this distinction. Thirty-one optic gliomas, 14 optic nerve meningiomas, and a single case of giant cell glioblastoma multiforme (monstrocellular glioma) of the optic chiasm were stained for AgNORs and counted in a masked fashion. The optic gliomas contained 2.01 +/- 0.09 AgNORs per nucleus, similar to that of optic nerve meningiomas (2.15 +/- 0.15) and our previously reported counts for diffuse fibrillary astrocytoma (2.22 +/- 0.10), and significantly more than that of reactive astrocytosis (1.18 +/- 0.02). Six of the seven optic gliomas examined had compound AgNORs, a feature associated with malignancy in other tumour types. AgNOR counts did not correlate with clinical features, including those seen during the post-operation course. These data suggest that optic gliomas may be true neoplasms, and not benign hamartomas.

Adolescent↗

PubMed1993

Primary T-cell lymphoma of the brainstem.

Most primary CNS lymphomas are non-Hodgkin's lymphomas of B-cell lineage. We report a case of a small lymphocytic-type T-cell lymphoma localized primarily to the brainstem and compare the characteristics of primary CNS T-cell lymphomas with those of primary CNS B-cell lymphomas.

Brain Neoplasms↗

PubMed1993

Significance of proliferating cell nuclear antigen index in predicting pituitary adenoma recurrence.

The recurrence rate of pituitary adenomas has been reported to be as high as 10% to 35% despite their generally benign nature. A monoclonal antibody directed against proliferating cell nuclear antigen (PCNA) was used to investigate whether the proliferative index might help to predict adenoma recurrence. This antigen is a nuclear protein identified as the auxiliary protein of deoxyribonucleic acid polymerase delta, and its gene expression correlates with cell proliferation. The authors studied 30 patients with recurrent pituitary adenomas, 32 with nonrecurrent adenomas, and seven normal pituitary tissue samples. The mean interval to recurrence ( +/- standard error of the mean) was 5.3 +/- 0.7 years. The age- and sex-matched nonrecurrent group had a mean follow-up period of 6.6 +/- 0.3 years without clinical recurrence. Mean percentages of PCNA-positive tumor nuclei in both the initial and the second surgical specimens of the recurrent adenomas (13.45% +/- 3.02% and 19.56% +/- 3.66%, respectively) were significantly higher than that of the nonrecurrent group (2.49% +/- 1.21%). In addition, recurrent tumors had a higher PCNA index than the initial tumors in the same patients. Normal anterior pituitary gland tissue had a significantly lower mean PCNA index (0.12% +/- 0.11%) than either patient group. Stepwise multivariate regression analysis indicated that factors which collectively correlated significantly with recurrence were: high PCNA index, large tumor size, extrasellar extension, and incomplete surgical excision. The PCNA nuclear count was not associated with age, sex, or hormone hypersecretion, but was higher in macro- than in microadenomas, in tumors with extrasellar extension, and in those incompletely excised. A higher PCNA index also correlated with a shorter disease-free interval. The authors conclude that evaluation of the PCNA index assists in predicting the likelihood of pituitary adenoma recurrence.

Adenoma↗

PubMed1992

Childhood brain tumors that occupy more than one compartment at presentation. Multiple compartment tumors.

Children whose brain tumor involves two or more compartments at presentation differ clinically and pathologically from children whose brain tumor is confined to one compartment. In this study of 3,291 children with a brain tumor, at least 10% had a tumor that occupied two or three compartments at first hospitalization. Infratentorial tumors occupying multiple compartments were 1.7 times more likely to involve the cervicomedullary junction than the mesodiencephalic junction. Younger children (1-3 years) were more likely to have had multiple compartment tumors than older children. Children whose tumor was limited to the infratentorial compartment had a longer survival than children whose tumor also occupied other compartments. Ependymoma, anaplastic ependymoma, and astrocytoma (nos) were over represented among infratentorial multiple compartment tumors. Pilocytic astrocytoma, primitive neuroectodermal tumor (medulloblastoma), and desmoplastic medulloblastoma were less likely to have occupied multiple compartments at the time of the first surgical exploration. The distributions of histologic features in tumors at the cervicomedullary junction differed from those in tumors limited to the posterior fossa or to the spinal canal. Seizures were more likely if the tumor was confined to the supratentorial compartment, whereas nausea or vomiting and headache were more likely if the tumor was confined to the infratentorial compartment. Children whose tumor was confined to the spinal canal were significantly more likely to have bladder symptoms and back and/or abdominal pain than those whose tumor also involved compartments above the foramen magnum. We conclude that brain tumors apparently confined to one compartment at presentation are biologically and structurally different from tumors evident in two or more compartments.

Adolescent↗

PubMed1992

Epidemiology of seizures in children with brain tumors. The Childhood Brain Tumor Consortium.

We examined potential clinical and pathologic correlates of seizures among the 3,291 children in the Childhood Brain Tumor Consortium database. Fourteen percent had seizures prior to their hospitalization for a brain tumor. Among children who had a supratentorial tumor, seizures occurred in 22% of those less than 14 years of age. The prevalence of seizures increased to 68% of older teenagers. Among children with an infratentorial tumor, the prevalence of seizures was relatively constant at 6% over all age groups. The onset of seizures began more than one year prior to surgical tumor removal in over half of the children aged five or more with supratentorial tumors, significantly longer than for those of the same age with infratentorial tumors. Almost all children (98.9%) with an infratentorial tumor and seizures had at least one other symptom and more than three-fourths of them had at least three. Eighty-nine percent of children with a supratentorial tumor and seizures had at least one other symptom and more than one-half had at least three symptoms. Regardless of whether the tumor was above or below the tentorium, confusion or stupor and coma were more common in children with seizures than in children without seizures. Among children with supratentorial tumors, symptoms of a declining academic performance or an abnormality of personality, speech, walking, or sensation were significantly more frequent in children with seizures, while visual symptoms (other than visual loss or diplopia) and nausea or vomiting were less frequent. Among children with supratentorial tumors, those who had seizures were more likely to have paralysis of an arm, hand, or face, confusion or stupor, or coma and less likely to exhibit irritability, papilledema, optic atrophy, decreased visual acuity, pupillary abnormalities, or abducens paresis. Among children with infratentorial tumors, those with seizures were significantly less likely to have truncal ataxia, but more likely to experience confusion, stupor, or coma. In the supratentorial compartment, astrocytoma (nos), protoplasmic astrocytoma, anaplastic astrocytoma, and ependymoma were more frequently associated with seizures than was craniopharyngioma. No infratentorial tumor type was more or less likely to be associated with seizures. All common tumor types that were represented in both the supratentorial and the infratentorial compartment except astrocytoma (nos) were associated with significantly greater rates of seizures when located in the supratentorial compartment. The tumor location with the highest incidence of seizures was, as expected, the superficial cerebrum. More than 40% of the children with such tumors had seizures.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

PubMed1992

Temporal trends among childhood brain tumor biopsies. The Childhood Brain Tumor Consortium.

We sought temporal trends in the demographic, clinical, histologic feature, diagnostic class, and quality of life data over the interval 1930-1979 in the Childhood Brain Tumor Consortium database. The proportion of children younger than eight years old declined from 72% to 55% and the proportion of those older than ten more than doubled from 12% to 27%. The relative frequency of tumors in the supratentorial compartment increased significantly, while infratentorial tumors decreased. We found significant declines in supratentorial ependymomas and pilocytic astrocytomas. Similarly, some infratentorial tumors, especially ependymomas, decreased and brain stem tumors increased. Infratentorial medulloblastoma (primitive neuroectodermal tumor) increased significantly. Some individual histologic features which are markers of anaplasia increased in frequency in both supratentorial and infratentorial tumors. There was a significant increase in biopsies that contained nonneoplastic neural tissue in addition to tumor for both compartments and among supratentorial tumors there was a marked increase in the proportion of cases containing an indistinct neural tissue boundary. The probability of postoperative death declined, but the probability of survival five or ten years after surgery did not improve significantly for children who had tumors in either compartment. Among children who survived five years after the initial craniotomy, the proportion who had significant long term deficits increased. Most of this increase occurred in the last decade (1970-79). In this decade, the proportion of children for whom no deficits were reported five years following operation was 4% if they had a supratentorial tumor and 27% if they had an infratentorial tumor. The proportions of children alive five years following first surgery who had arachnoidal metastases increased significantly for infratentorial tumors.

Adolescent↗

PubMed1992

Use of the silver nucleolar organizer region (AgNOR) technique in the differential diagnosis of central nervous system neoplasia.

Because the distinction between gliosis and low-grade astrocytoma may prove difficult by routine light microscopy, we evaluated the silver nucleolar organizer region (AgNOR) technique in making this distinction. The AgNOR impregnation was performed on formalin-fixed, paraffin-embedded tissue from 49 central nervous system (CNS) biopsies: eight normal brain, 14 gliosis, 14 grade 2 astrocytoma (Daumas-Duport scale), two grade 4 astrocytoma, nine medulloblastoma, one metastatic carcinoma, and one choroid plexus papilloma. Quantitative and qualitative differences were found between gliosis and low-grade astrocytomas. In gliosis, AgNOR counts averaged 1.18 +/- 0.11 (SD) AgNOR/nucleus, while in low-grade astrocytomas AgNOR counts averaged 2.22 +/- 0.39 (p less than 0.001). Compound AgNOR were frequent in 9/14 grade 2 astrocytomas and in both grade 4 astrocytomas, whereas compound AgNOR were extremely rare in cases of gliosis. Quantitative and qualitative differences were also found between normal cerebellar internal granular cells and medulloblastoma cells. Cerebellar granular cells averaged 0.90 +/- 0.10 AgNOR/nucleus whereas medulloblastoma cells had an average of 4.52 +/- 0.95 (p less than 0.001). Compound AgNOR were seen in all medulloblastomas but not in internal granular cells. These findings suggest that the AgNOR technique may be a useful adjunct in the diagnosis of CNS neoplasia.

Astrocytoma↗

PubMed1992

Ras mutations in human pituitary tumors.

The cellular basis for pituitary neoplasia is poorly understood. Mutations that activate the ras protooncogenes have been identified in a number of different types of human cancers and potentially represent one of the genetic alterations that occur in pituitary tumors. In this study we examined 19 pituitary tumors for the occurrence of ras mutations. The tumor types included 11 nonfunctioning adenomas, 6 somatotroph adenomas, and 2 prolactinomas. Each of the three ras genes (K-ras, N-ras, and H-ras) was amplified from pituitary tumor DNA using the polymerase chain reaction. Oligonucleotide-specific hybridization was used to screen for mutations that inhibit GTPase activity and cause activation of the ras oncogene. No ras mutations were observed in 18 of the pituitary adenomas. However, a mutation was identified in codon 12 of the H-ras gene (Gly to Val) in a recurrent prolactinoma that was highly invasive and ultimately proved to be fatal. We conclude that ras mutations are uncommon in pituitary adenomas, but may provide a marker for highly invasive tumors.

Adenoma↗

PubMed1992

Glycoprotein hormone alpha-subunit production in somatotroph adenomas with and without Gs alpha mutations.

Activating mutations of the Gs alpha subunit have been identified in a subset of somatotroph adenomas. The mutant form of the Gs alpha subunit causes persistent activation of adenylyl cyclase and consequently results in high intracellular levels of cAMP. Because cAMP is known to stimulate the synthesis of the glycoprotein hormone (GPH) alpha-subunit as well as GH, we examined somatotroph tumors with and without Gs alpha mutations for GPH alpha-subunit production. GPH alpha-subunit production was assessed in vivo by measuring serum hormone levels and in vitro by analyzing hormone secretion by cultured pituitary tumor cells. DNA was extracted from the pituitary tumors of 26 acromegalic patients. The Gs alpha gene was amplified by the polymerase chain reaction and screened for mutations at codons 201 and 227 using oligonucleotide specific hybridization. Nine of the 26 tumors (35%) had point mutations at Arg 201. Seven of these tumors contained a CGT to TGT mutation (Arg to Cys) and 2 contained a CGT to CAT mutation (Arg to His). No mutations were detected at codon 227. There were no significant differences in age, sex distribution, tumor size, or serum levels of GH or insulin-like growth factor-1 between the groups of patients with or was Gs alpha mutations. The mean serum level of the free GPH alpha-subunit was 1.9-fold higher in the group with Gs alpha mutations (0.48 +/- 0.37 micrograms/L) than in patients without mutations (0.25 +/- 0.17) (P less than 0.05). In pituitary tumor cell culture, 75% of somatotroph tumors with Gs alpha mutations secreted free GPH alpha-subunit into the media compared with 45% of tumors without Gs alpha mutations. The amount of GPH alpha-subunit secretion was 12-fold greater in the group of tumors containing the Gs alpha mutation (P less than 0.05). Immunocytochemical detection of the free GPH alpha-subunit was similar in the two groups of patients with 75% positive for the GPH alpha-subunit in tumors with Gs alpha mutations and 67% positive in tumors without mutations (P = 0.69). We conclude that GPH alpha-subunit production occurs in somatotroph tumors with and without Gs alpha mutations. The increased levels of GPH alpha-subunit secretion in vivo and in vitro suggest that the Gs alpha mutation may increase the amount of preexisting GPH alpha-subunit biosynthesis in the tumors, perhaps via activation of the cAMP pathway.

Adenoma↗

PubMed1992

Clonal origins of adrenocorticotropin-secreting pituitary tissue in Cushing's disease.

It is unclear whether Cushing's disease results from a primary pituitary disorder or arises in response to abnormal hypothalamic control of the pituitary gland. Clonal analysis can provide information as to whether neoplastic tissue is derived from a monoclonal proliferation of a genetically altered cell or from a polyclonal expansion of a group of cells affected by a common stimulus. We used X-linked restriction fragment length polymorphisms at the phosphoglycerate kinase, hypoxanthine phosphoribosyltransferase, and DXS255 loci in 11 women with biochemically and pathologically confirmed Cushing's disease to determine the clonal origins of corticotroph adenomas and corticotroph hyperplasia. Tumor tissue from all 10 women with morphologically and immunohistochemically confirmed ACTH-secreting pituitary microadenomas demonstrated a monoclonal pattern. Pathologically confirmed corticotroph hyperplasia in a patient with a CRH-secreting bronchial carcinoid was found to be polyclonal. We conclude that corticotroph microadenomas in Cushing's disease are monoclonal, supporting the theory that a spontaneous somatic mutation is the primary pathogenetic mechanism in this disorder. In addition, the demonstration of polyclonality in corticotroph hyperplasia implies that excess of hypothalamic hormones is an etiologic mechanism in cases of Cushing's syndrome associated with ectopic CRH-secreting tumors.

Adrenocorticotropic Hormone↗

PubMed1992

Olfactory dysgenesis or hypoplasia: a variant in the arhinencephaly spectrum?

Postmortem examination of a 65-year-old anosmic woman revealed rudimentary olfactory bulbs, an imperforate cribriform plate, and sulcal abnormalities of the orbitofrontal surface of the brain. The remainder of the brain, skull, and body was normal. This abnormality most likely resulted from a local insult to the area of the cribriform plate during early fetal life, occurring after the induction of olfactory bulb differentiation, but before migration and complete differentiation of the olfactory bulbs. Such a lesion can be dated to approximately 11 to 12 weeks gestational age. The malformation may represent another variant in the arhinencephaly spectrum, but is termed "olfactory dysgenesis" or "olfactory hypoplasia" to separate it from true olfactory aplasia and arhinencephaly.

Aged↗