Expression of c-myc and c-fos and binding sites for estradiol and progesterone in human pituitary tumors

Abstract

We studied the concentration ofmRNA from the oncogenes c-myc and c-fos in human pituitary adenomas by Northern blot hybridization (35 somatotrophinomas, 9 prolactinomas, 21 nonsecreting and 3 adrenocorticotrophinomas). The concentration of estrogens and progesterone rec~ptors was also investigated. The levels of c-myc and c-fos mRNA was higher in nonsecreting tumors which were generally the largest.and had a higher percentage of recurrence after surgery than the other groups. High concentration of estrogen receptors was observed in tumors derived from cells which are normally the target of this hormone, mainly prolactinomas. They were also present in somatotrophic and nonsecreting adenomas, related to the presence of prolactin or gonadotrophin cells in these tumors. The presence of estrogen receptors indicates that the tumor cells maintain their differentiation and a good prognosis as is the case for prolactinomas. We did not find any relationship between estrogen receptors and the concentration ofc-myc and c-fos oncogenes. Larger adenomas (mainly nonsecreting) had higher levels ofc-myc and c-fos mRNA than the other tumors and they-had an important percentage of recurrence after surgery. It is clear that tumor size is related to the outcome after surgery and that nonsecreting adenomas are usually large because of the late diagnosis. However two large somatotrophinomas with extrasellar expansion also had overexpression of both oncogenes and both relapsed after surgery. [Neural Res 1998; 20: 709-712]     

Pediatric pituitary adenoma: a series of 42 patients.

Pituitary adenomas are uncommon in childhood. This report describes the presentation, endocrinological profile, management and outcome of 42 children with pituitary adenomas. The majority of the tumors were functioning adenomas (40/42, 95.2%). Only two patients (4.8%) had non-functioning tumors. Amongst the functioning tumors, there were 20 patients (47.6%) with prolactinomas, 11 patients (26.2%) with Cushing's disease and nine patients (21.4%) with growth hormone (GH)-secreting adenomas. The most common presenting features were endocrinopathy and visual disturbances. The majority of tumors were macroadenomas, with only eight patients (all with Cushing's disease) having a microadenoma. Transsphenoidal tumor decompression was performed in most cases (71.4%). Complications following transcranial surgery were more frequent when compared to transsphenoidal surgery. There was one death following surgery. Response to radiotherapy was satisfactory. Overall, 67.6% of patients achieved endocrinological remission. Of these, 89% of the children with GH-secreting tumors and 100% of the children with Cushing's disease achieved remission. We conclude that the transsphenoidal approach is effective and safe in surgery for pituitary adenomas in children and is the procedure of choice if there is no contraindication. The combination of surgery and radiotherapy, as well as medical therapy with bromocriptine, achieves good results in the management of these uncommon tumors.     

内镜下经鼻蝶入路垂体腺瘤切除术

目的探讨内镜下经鼻蝶入路切除垂体腺瘤的方法、疗效和并发症。方法回顾性分析2002年6月至2005年8月,在我院神经外科接受内镜下经鼻蝶入路切除术的66例垂体腺瘤的临床资料。男性32例,女性34例,年龄在18岁到73岁,平均44岁。其中微腺瘤11例,大腺瘤55例;无功能腺瘤46例,泌乳素腺瘤13例,生长激素腺瘤7例。结果全切除49例,近全切除12例,大部切除5例。微腺瘤全切除10例,近全切除1例;鞍内大腺瘤全切除23例,近全切除4例;鞍内和鞍上大腺瘤全切除16例,近全切除4例,大部切除3例;侵及海绵窦的5例大腺瘤3例近全切除,2例大部切除。所有病例中,术后有28例尿崩症,5例垂体前叶功能低下,1例颅内感染和1例鼻窦炎。结论内镜下切除垂体腺瘤是一种安全、有效和并发症少的治疗方法,尤其适合治疗微小腺瘤和局限于鞍内和蝶窦的垂体腺瘤。     

Pituitary tumors in children: clinical analysis of 21 cases

Objective The aim of this study is to review the results of surgery for pituitary adenomas in children less than 18 years old. Materials and methods A retrospective review was done of pituitary adenoma patients with the age of less than 18 years who were treated in the period 1979–2003 at Dr. Shariati Hospital. Conclusions Twenty-one patients (12 girls and 9 boys) were identified. The age range (mean) in girls and boys was 9–18 (15.8) and 9–17 (14.8) years, respectively. The duration of follow-up was 1–23 (13.4) years. Eight patients (38.1%) had adrenocorticotropic hormone-secreting tumors, 33.3% had prolactin-secreting tumors, 19% had growth hormone-secreting tumors, and 9.53% had nonfunctioning adenomas. Multidisciplinary management included surgery and, if necessary, reoperation with/without radiotherapy and pharmacotherapy. Eleven patients, mostly with prolactinomas, acromegaly, and nonfunctioning adenomas, needed reoperation and radiotherapy. There were two deaths, one of which was because of apoplexy. The biological behavior of pediatric pituitary adenomas seems more aggressive than adults’ adenomas. The chance of pituitary apoplexy in pediatric invasive pituitary adenoma is high.     

Pituitary tumours in adolescence: clinical behaviour and neuroimaging features of seven cases.

The clinicopathologic features of seven paediatric patients with pituitary adenomas (2 male, 5 female; mean age 14.3 years) were reviewed. There were three non-functioning adenomas, three prolactinomas, and one growth hormone producing adenoma. Five patients presented with visual field deficits, and six patients had endocrine symptoms, which included menstrual irregularities in all female patients, pubertal delay in two females, and growth delay and gigantism in one case each. On neuroimaging studies, five adenomas showed parasellar extension, while the remaining two prolactinomas were intrasellar microadenomas. While two patients with prolactinomas received good results with bromocriptine treatment alone, the remaining five patients underwent either craniotomy or transsphenoidal surgery. Postoperatively, visual disturbances improved markedly in all patients. Two patients also received replacement hormonal therapy. While six patients have been stable for 3.6 years on average, one non-functioning tumour recurred 2 years after the initial transcranial subtotal resection of the tumour. Although there are still many unknowns concerning the biology and optimal treatments for paediatric pituitary adenomas, many of them are assumed to be relatively rapidly growing tumours, while others merely have an earlier tumour genesis than in adults.     

Non-surgical management of hormone-secreting pituitary tumors

Hormone-secreting pituitary tumors account for about 30% of all pituitary tumors. Successful long-term management of patients with these tumors frequently requires a multimodality team approach. Given that the role and efficacy of neurosurgical resection of hormone-secreting pituitary tumors is well described, we focus this review on the other important treatment modalities that are becoming increasingly crucial in the management of acromegaly, Cushing’s disease and prolactinomas. Medical management with standard and novel drugs as well as the role and effectiveness of radiation therapy and radiosurgery are discussed in detail.     

Significance of leptin expression in invasive potential of pituitary adenomas

We immunohistochemically examined the expression of leptin in pituitary adenomas to investigate the correlation between the invasiveness of tumours and leptin expression. The subjects consisted of 79 patients with pituitary adenoma and were classified into the following groups: (1) non-functioning adenomas; (2) GH-secreting adenomas; (3) prolactinomas; (4) ACTH-secreting adenomas; (5) others (LH, FSH or TSH-secreting adenomas). Thereafter all cases were subdivided according to the size of tumour and the presence of invasion to the surrounding tissue. Among non-functioning adenomas, there was no significant difference between invasive and non-invasive non-functioning adenoma. In functioning adenomas, a significant difference in leptin expression was noted in intrasellar non-invasive adenomas compared to other adenomas. There was also a significant difference in leptin expression between non-invasive and invasive adenomas regardless of size. These results suggest that leptin has a role in the invasive potential of functioning adenomas.     

Preservation of hormonal function by identifying pituitary gland at endoscopic surgery

ObjectiveThe endonasal endoscopic approach has been established for perisellar tumor surgery with a higher resection rate and reduced complications. We analyzed the potential to identify the pituitary gland under endoscopic view, at surgery and see its relation to postoperative hormonal insufficiency in endonasal endoscopic procedures.MethodsBetween January 2011 and January 2014, 70 cases of pituitary adenomas with preoperative intact pituitary function underwent endoscopic endonasal transsphenoidal procedures for intrasellar pathologies. Endocrinologists and neurosurgeons followed these patients prospectively. Special attention was paid to intraoperative identification of gland tissue, surgical complications, degree of resection and postoperative hormonal insufficiency.ResultsThe pituitary gland was identified in 57 out of 70 procedures (81.4%). Eleven percent (8 of 70 patients) had persistent pituitary insufficiency. Two of these 8 patients belonged to the group with pituitary gland identification (2 out of 57); thus, when the pituitary gland was identified during the procedure postoperative hormonal insufficiency was seen in 3.5% of cases. Failure of pituitary gland identification presented with hormonal insufficiency of 46.2%. In analysis with Fisher’s exact test, there was a high significant correlation between the identification of the pituitary gland intraoperatively and normal pituitary function postoperatively (p < 0.005). On follow up radical tumor resection was seen in 88% (62 of 70 patients).ConclusionsThis study indicates that identification and preservation of pituitary gland tissue and function is possible in endoscopic transsphenoidal surgery. This preservation of gland tissue is a positive predictor of postoperative normal pituitary function.     

nm23基因表达与垂体腺瘤侵袭性和预后的关系研究

目的探讨nm23基因表达与垂体腺瘤侵袭性和预后的关系。方法以免疫组化S-P法检测nm23基因在手术切除的45例垂体腺瘤标本中的表达。随访术后5年患者的复发情况、激素恢复水平以及症状改善情况,进行综合评分,并将其与nm23基因表达作相关性分析。结果侵袭性垂体腺瘤21例,nm23中度以上表达( / )8例(38.1%);非侵袭性垂体腺瘤24例,nm23中度以上表达20例(83.3%)。nm23基因在侵袭性垂体腺瘤中的表达比在非侵袭性垂体腺瘤中明显降低(P<0.01)。在nm23中、高表达( / )组病例中预后优17例,良6例,差5例;在nm23低表达( /-)组病例中预后优1例,良9例,差7例。nm23无、低表达病例组的预后明显比中、高表达组的预后差(P<0.01)。结论nm23基因表达的差异可能作为判断垂体腺瘤侵袭性以及初步判断垂体腺瘤患者预后的指标。     

Transsphenoidal adenomectomy for GH-, PRL- and ACTH-secreting pituitary tumours: outcome analysis in a series of 125 patients

Abstract Transsphenoidal surgery (TSS) is a well recognised treatment for secreting pituitary adenomas, however a very wide variation of clinical outcomes and recurrence rates has been reported, depending on the different criteria used to define the cure. We reported the clinical outcome of a large series of patients operated on for a secreting pituitary adenoma according to the most recent stringent criteria of biochemical remission nowadays accepted. One hundred and twenty-five consecutive patients with a secreting pituitary adenoma (42 PRL-, 67 GH- and 16 ACTH-secreting adenomas) who were operated on by the two same neurosurgeons were considered for the study. Biochemical remission of disease was achieved in 56% of patients; 78% for patients with microadenoma and 47% for patients with macroadenomas, respectively. No cases of mortality or major immediate postoperative complications were observed. Tumour size, high hormone levels and dural invasion were significantly correlated to a poor surgical outcome. The recurrence rates ranged between 0 and 24%, being higher for PRL-secreting tumours. In conclusion, TSS is safe and effective in secreting pituitary tumours. It is still the first treatment for GH- and ACTH-secreting adenomas, whereas in patients with prolactinomas, surgery should be reserved for cases of resistance or intolerance to dopamine agonists.     

The first 100 transsphenoidally operated pituitary adenomas in a non-specialised centre: surgical results and tumour-recurrence

From 118 transsphenoidally operated patients, 100 had a pituitary adenoma; 33 prolactinomas, 20 HGH-producing, 2 ACTH-producing and 45 inactive adenomas. The first transsphenoidal operation did not cause any mortality; after reoperation for suspected recurrence on follow-up, 2 patients died; thus, the global management mortality was 1.8%. As surgical complications, diabetes insipidus occurred in 5%, hypopituitarism in 4%. Age at operation was significantly higher in female patients with micro– than with m aero prolactin o m as, and also markedly higher in men than in women with prolactinomas. Preoperative serum prolactin levels were related to tumour size and age and demonstrated an important prognostic factor of postoperative cure. The prognosis of preoperative visual field defects was dependent on preoperative duration.

During a follow-up period of 1-6.3 years, 7 patients were reoperated for recurrence of their tumour after intervals of 2-4.5 years; 6 of these patients had had inactive macroadenomas, 1 an ACTH-producing macroadenoma. In 3 of these patients, radiation therapy had been performed. The highest recurrence-rate (19%) among 100 patients was found in patients with inactive macroadenomas with a follow-up of more than 2 years.     

Craneofaringiomas: experiencia y resultados

IntroductionCraniopharyngiomas are a big challenge in the neurosurgical field. Because these lesions involve important systems, surgeons must weigh the risks of aggressive resection against the long-term challenges of recurrence. We present the outcomes of our patients based on clinical results, degree of resection, recurrence and disease-free survival.Materials and methodsWe reviewed medical records in all patients who had undergone surgical resection for craniopharyngioma at (Hospital Italiano de Buenos Aires) between 2007 and 2019. We considered ophthalmological examinations, imaging studies, endocrinological studies and surgical complications. Radical resections were planned in all of the patients. To help choose the correct surgical approach, craniopharyngiomas were classified based on tumor location.ResultsThirty cases of craniopharyngioma were analysed. 12.5% were classified as intrasellar, 12.5% as prechiasmatic, 43.75% as retrochiasmatic, and 31.25% as intraventricular. Overall, 38 cases involved a transcranial surgery (15 orbitozygomatic approach; 19 pterional approach and 4 transcallosal approach), seven involved a transsphenoidal approach, two microscopic transnasal approach and one ventricular endoscopy for emptying the craniopharyngioma cyst. Gross-total resection was achieved in 43.7% and near-total resection (more than 90%) in 25%. The mean follow-up period after resection was 4.7 years. Tumor recurrence occurred in 48%, with an average of 42.7 disease-free months.ConclusionTotal tumor resection is the best treatment for craniopharyngioma. Due to its high morbidity and mortality, a multidisciplinary team is necessary for the management of these tumors.     

Harvey Cushing��s early experience with pediatric gliomas

Purpose

Diagnosing and operating pediatric patients with intracranial lesions posed a greater diagnostic challenge for physicians during the early twentieth century. At the time, an intracranial neoplasm was indistinctively diagnosed as a glioma, encompassing a broad category of brain tumor pathologies. The treatment and surgical interventions followed for children diagnosed with gliomas is not well-described in the literature from this time.

Methods

Following IRB approval, and through the courtesy of the Alan Mason Chesney Archives, we reviewed the Johns Hopkins Hospital surgical files from 1896?C1912. Patients 18?years or younger, who underwent surgical intervention by Cushing for suspected intracranial tumors, were selected.

Results

Of the eight pediatric cases diagnosed with gliomas by Cushing, four cases were later diagnosed as medulloblastomas by Dr. Cushing in 1925. Of the remaining four pediatric cases, one was diagnosed as a brainstem glioma and another as a ventricular glioma. We describe the remaining two cases.

Conclusion

These examples illustrate Cushing??s approach to treating brain tumors diagnosed as gliomas in pediatric patients, focusing on an initial decompression and followed by a thorough surgical exploration for tumor. Furthermore, these cases demonstrate Cushing??s early attempts to manage such lesions in children and highlight the challenges faced in diagnosing and localizing intracranial lesions within this group of patients.     

复发性库欣病的MRI特点和再次经蝶手术疗效分析

目的探讨复发性库欣病的MRI特点和再次经蝶手术疗效。方法回顾性分析28例复发性库欣病的MRI特点、术前诊断、手术技巧、并发症和疗效。结果28例库欣病复发时间距第一次手术6-72个月，平均33.5个月。蝶鞍冠状位增强MRI显示微腺瘤15例，未见明确肿瘤13例。术中明确肿瘤并经病理证实为垂体腺瘤24例，术中及病理均未见肿瘤4例。近期（术后6个月内）疗效：治愈20例（71.4％），改善5例（17.9％），无效3例（10.7％）。术后随访10个月～8年，再次复发3例，行双侧肾上腺切除和垂体放疗，2例出现Nelson综合征。结论复发性库欣病MRI检查肿瘤发现率较低，再次经蝶手术是治疗复发性库欣病有效的方法。     

Arachnoid Remodeling by Clipping Technique Facilitates Surgical Maneuverability during Transsphenoidal Surgery for Pituitary Macroadenoma

ObjectivePituitary adenomas frequently extend into the suprasellar space. After a suprasellar tumor is removed, the superiorly extended arachnoid becomes redundant and sinks down into the intrasellar space which often hiders visualization and accessibility to the hidden space behind the evaginated arachnoid. We introduced arachnoid remodeling by clipping technique, and evaluated its usefulness and safety during TSS. MethodsTotal 223 patients who underwent arachnoid remodeling with our new clipping technique were included. Redundant arachnoid was clipped along the dural edge with multiple 2.6-mm titanium clips until the redundant arachnoid membrane no longer blocked the surgical route. To check for possible deterioration of hormonal function by this technique, we assessed anterior pituitary function of 166 patients who underwent arachnoid remodeling by clipping and compared this with those of other 429 control patients. ResultsOur technique greatly enhanced the accessibility and visualization of intrasellar and parasellar spaces, both of which are generally hindered by redundant arachnoid during transsphenoidal surgery (TSS). We found no difference in anterior pituitary function between a clip-assisted arachnoid remodeling group and the control group, implying that this technique does not result in hypopituitarism. ConclusionDuring TSS for pituitary adenomas with suprasellar extension, arachnoid remodeling by clipping technique is very useful and convenient for the management of the redundant arachnoid membrane to enhance visualization and surgical accessibility.     

Identification of proliferating human anterior pituitary adenoma cells in vitro

Abstract

A method to determine whether dispersed human anterior pituitary adenoma cells proliferate in mixed culture was developed. Fifteen pituitary adenomas were dispersed enzymatically to single cells, following which twelve were double immunostained after eight days. Proliferating cells were identified immunologically following one hour of bromo-deoxyuridine incorporation. Adenoma cells were subsequently identified with an anti-neuron-specific enolase antibody system. A time course of bromo-deoxyuridine labelling was performed on three nonfunctional adenomas over a four day period, with bromo-deoxyuridine being added to cultures at one hour, 24 hours and four days prior to immunostaining. Double immunolabelled cells were unambiguously identified by a dark brown nucleus surrounded by red cytoplasm. Eight out of 12 pituitary adenomas (two prolactinomas,. three nonfunctional, three growth hormone secreting) showed an increased bromo-deoxyuridine labelling index (range 0.1%-1.4%). Bromo-deoxyuridine incorporation over four days showed an increase in bromo-deoxyuridine from 0.02%, 0.03% and 3.3% at one hour to 10.1 %,. 1.3% and 5.0% at four days, respectively,. but evidence of mitosis was scant. This study shows that pituitary adenomas may proliferate in vitro and that this double immunostaining method may be used as an in vitro proliferation assay in a mixed cell population. [Neural Res 1997; 19: 420-425]     

单鼻孔经蝶入路显微手术治疗垂体微腺瘤

目的探讨垂体微腺瘤的诊断和手术方法。方法回顾性分析经单鼻孔蝶窦入路显微手术切除的48例垂体微腺瘤患者的临床资料。此48例垂体微腺瘤中,PRL腺瘤18例,GH腺瘤9例,ACTH腺瘤6例,无分泌功能腺瘤15例。结果肿瘤全切45例,次全切3例;33例分泌腺瘤中,术后激素水平降至正常22例,下降大于50%的6例,5例变化不明显。结论垂体微腺瘤的诊断应结合临床症状、内分泌检测和MR检查结果考虑,经单鼻孔蝶窦入路显微手术是其治疗的理想方法。     

Gangliocitoma selar asociado a adenoma hipofisario productor de hormona de crecimiento. Caso clínico

IntroductionIntrasellar gangliocytomas are uncommon entities which, unusually, may be found in association with hormone-releasing pituitary adenomas.Case reportThe patient was a 49-year-old female who presented a sellar lesion with associated acromegaly. A trans-sphenoidal tumour was removed, with no medical improvement. Histopathological analysis revealed a gangliocytoma with an associated somatotroph adenoma.DiscussionWe found 85 cases of intrasellar gangliocytomas with associated hormone-releasing pituitary adenomas reported in the literature, with the following distribution: 50 growth hormone-releasing (GH) cases (59%), 15 mixed (GH and prolactin-releasing) cases (17%), 11 prolactin-releasing cases (13%), 7 adrenocorticotropic hormone-releasing (ACTH) cases (8%) and 2 corticotropin hormone-releasing (CRH) cases (2%).ConclusionsMixed gangliocytomas-adenomas are uncommon entities. Association with growth hormone-releasing cases is more frequent and the most common presentation is among middle-aged females. Diagnosis is histopathological. Identification of this entity is important because it may lead to a limitation in therapeutic response in incomplete resections.     

Significance of immunohistochemical expression of Rab3B and SNAP-25 in growth hormone-producing pituitary adenomas

Exocytosis proteins play an important role in the secretory activities of anterior pituitary cells and adenoma cells. An immunohistochemical study was conducted to elucidate the functional significance of these proteins in growth hormone (GH)-producing adenomas. We studied 40 GH-producing adenomas, 10 prolactinomas, and 10 clinically nonfunctioning (NF) adenomas immunohistochemically with antibodies specific for Rab3B and SNAP-25, both of which are considered essential in secretory activities of the pituitary, and keratin 8 (clone CAM5.2). The tumor volume (TV) was estimated with high-resolution magnetic resonance imaging. Immunoreactivity for Rab3B, which was granular in the cytoplasm, varied in GH adenomas, but was negative in prolactinomas and NF adenomas. Reactivity for SNAP-25, which was linear on the plasma membrane, varied in GH adenomas, and was intensely positive in prolactinomas, and negative in NF adenomas. In GH adenomas, an increased percentage of adenoma cells with dot-like immunoreactivity for keratin 8 was associated with decreased reactivities for Rab3B (R=0.739, P<0.0001) and SNAP-25 (R=0.840, P<0.0001). Increased reactivity for SNAP-25 correlated positively with plasma GH level per unit TV (R=0.685, P<0.0001). The immunoreactivities for Rab3B and SNAP-25 may reflect the number of secretory granules and exocytosis activity, respectively, in pituitary adenomas, including GH adenomas.