The "chameleon" sellar lesions: a case report of unexpected sellar lesions.

Introduction: The sellar region and its boundaries represent a challenging area, harboring a variety of tissues of different linings. Therefore, a variety of diseases can arise or involve in this area (i.e., neoplastic or not). A total of three challenging cases of "chameleon" sellar lesions treated via EEA were described, and the lesions mimicked radiological features of common sellar masses such as craniopharyngiomas and/or pituitary adenomas, and we also report a literature review of similar cases. Methods: A retrospective analysis of three primary cases was conducted at the Università degli Studi di Napoli Federico II, Naples, Italy. Clinical information, radiological examinations, and pathology reports were illustrated. Results: A total of three cases of so-called "chameleon" sellar lesions comprising two men and one woman were reported. Based on the intraoperative finding and pathological examination, we noticed that case 1 had suprasellar glioblastoma, case 2 had a primary neuroendocrine tumor, and case 3 had cavernous malformation. Conclusion: Neurosurgeons should consider "unexpected" lesions of the sellar/suprasellar region in the preoperative differential diagnosis. A multidisciplinary approach with the collaboration of neurosurgeons, neuroradiologists, and pathologists plays a fundamental role. The recognition of unusual sellar lesions can help surgeons with better preoperative planning; so an endoscopic endonasal approach may represent a valid surgical technique to obtain decompression of the optic apparatus and vascular structures and finally a pathological diagnosis.

PATZ1 is a new prognostic marker of glioblastoma associated with the stem-like phenotype and enriched in the proneural subtype.

Glioblastoma (GBM), the most malignant of the brain tumors, has been classified on the basis of molecular signature into four subtypes: classical, mesenchymal, proneural and neural, among which the mesenchymal and proneural subtypes have the shortest and longest survival, respectively. Here we show that the transcription factor PATZ1 gene is upregulated in gliomas compared to normal brain and, among GBMs, is particularly enriched in the proneural subtype and co-localize with stemness markers. Accordingly, in GBM-derived glioma-initiating stem cells (GSCs) PATZ1 is overexpressed compared to differentiated tumor cells and its expression significantly correlates with the characteristic stem cell capacity to grow as neurospheres in vitro. Interestingly, survival analysis demonstrated that PATZ1 lower levels informed poor prognosis in GBM and, specifically, in the proneural subgroup, suggesting it may serve a role as diagnostic and prognostic biomarker for intra-subtype heterogeneity of proneural GBM. We also show that PATZ1 suppresses the expression of the mesenchyme-inducer CXCR4, and that PATZ1 and CXCR4 are inversely correlated in GSC and proneural GBM. Overall these findings support a central role of PATZ1 in regulating malignancy of GBM.

Cervical extradural "en-plaque" meningioma.

OBJECTIVE: Spinal meningiomas with concurrent extradural localization and "en-plaque" growth are exceptional, with only five reported cases in the literature. We report another case and discuss the peculiar diagnostic and surgical features of this very unusual pattern of growth. CASE REPORT: A 74-year-old woman was observed because of a rapidly progressive tetraparesis, more marked in the left arm. Magnetic resonance imaging depicted an inhomogeneously enhancing tumor of the cervical spine, extending from C4 to T1, with diffuse dural enhancement and extension into the left brachial plexus roots. At operation by laminotomy from C4 to C7 a firm posterior extradural tumor arising from the dura was resected; however, the diffusely infiltrated dura could not be removed. Histology was in favor of a transitional meningioma (WHO I). Postoperatively, irradiation to the operative field with 50 Gy was performed. At follow-up, 18 months after surgery, clinical improvement to moderate tetraparesis was evidenced. CONCLUSIONS: Spinal extradural "en-plaque" meningiomas have been mainly reported in women and at the cervical region, and show extension to many spinal levels as well as diffuse dural infiltration. Preoperatively, they may be differentiated from spinal metastases and lymphomas because of the presence of a "dural tail" sign and calcifications. The surgical resection is mainly limited to the posterior and lateral extradural tumor component, whereas the whole invaded dura is very difficult to resect, mainly in cases with circumferential infiltration. This results in a high rate of tumor recurrence.

Effect of treatment with depot somatostatin analogue octreotide on primary hyperparathyroidism (PHP) in multiple endocrine neoplasia type 1 (MEN1) patients.

BACKGROUND: In patients with multiple endocrine neoplasia type 1 (MEN1), expression of somatostatin receptor (SST) in parathyroid adenomas and effectiveness of therapy with somatostatin analogues on primary hyperparathyroidism (PHP) have been scarcely investigated. OBJECTIVE: To evaluate the effects of depot long acting octreotide (OCT-LAR) in patients with MEN1-related PHP. PATIENTS: Eight patients with a genetically confirmed MEN1, presenting both PHP and duodeno-pancreatic neuroendocrine tumours (NET), were enrolled. DESIGN: The initial treatment was OCT-LAR 30 mg every 4 weeks. This therapy was established to stabilize the duodeno-pancreatic NET before to perform parathyroidectomy for PHP. Before OCT-LAR therapy, a SST scintigraphy was performed in all patients. SST subtype 2A immunohistochemistry was performed on parathyroid tumour samples from three patients undergone parathyroidectomy after OCT-LAR therapy. MEASUREMENTS: Serum concentrations of PTH, calcium and phosphorus as well as the 24-h urine calcium : creatinine ratio and the renal threshold phosphate concentration were evaluated before and after OCT-LAR. RESULTS: After OCT-LAR therapy, hypercalcaemia and hypercalciuria normalized in 75% and 62.5% of patients, respectively, and serum phosphorus and renal threshold phosphate significantly increased. Serum PTH concentrations significantly decreased in all patients and normalized in two of them. SST subtype 2A immunostaining was found in all parathyroid adenomas investigated, while SST scintigraphy showed a positive parathyroid tumour uptake in three of eight patients (37.5%). CONCLUSION: Six months of OCT-LAR therapy controlled hypercalcaemia and hypercalciuria in two-thirds of patients with MEN1-related PHP. Direct OCT-LAR effects mediated by binding to SST expression on parathyroid tumour cells are likely the main mechanism to explain the activity of this compound on calcium and phosphorus abnormalities in MEN1 PHP.

Dopamine receptor expression and function in human normal adrenal gland and adrenal tumors.

Dopamine is known to play a role in the modulation of aldosterone and catecholamine secretion from the adrenal gland, where dopamine receptors (DR), in particular the DR type 2 (D(2)), have been found to be expressed. DR expression has also been demonstrated in some types of benign adrenal tumors. The aims of the current study were to evaluate DR expression and D(2) localization in the normal adrenal gland and in different types of benign and malignant adrenal tumors, as well as to evaluate the in vitro effects of the dopamine agonists bromocriptine and cabergoline on hormone secretion in nontumoral adrenal cells. Adrenal tissues from 25 patients, subjected to adrenal surgery for different diseases, were studied. These included three normal adrenals; five adrenal hyperplasias; four aldosterone-secreting, two cortisol-secreting, and two clinically nonfunctioning adrenal adenomas; two aldosterone-secreting, two cortisol-secreting, and two androgen-secreting adrenal carcinomas; and three pheochromocytomas. In all tissues, DR and D(2) isoform (D(2long) and D(2short)) expression was evaluated by RT-PCR. D(2) localization was also evaluated by immunohistochemistry using a specific polyclonal antibody, whereas D(2)-like receptor expression was evaluated by receptor-ligand binding study, using the radiolabeled D(2) analog (125)I-epidepride. The effects of bromocriptine and cabergoline on baseline and ACTH and/or angiotensin II-stimulated aldosterone, cortisol, and androstenedione secretion were evaluated in cell cultures derived from five different adrenal hyperplasia. At RT-PCR, both D(1)-like and D(2)-like receptors were expressed in all normal and hyperplastic adrenals. D(2) and D(4) were expressed in aldosterone- and cortisol-secreting adenomas, cortisol-secreting carcinomas, and clinically nonfunctioning adenomas, whereas no DR was expressed in aldosterone- and androgen-secreting carcinomas. D(2), D(4), and D(5) were expressed in pheochromocytomas. In all D(2)-positive tissues, both D(2) isoforms were expressed, with the exception of one case of aldosterone-secreting adenoma and the cortisol-secreting carcinomas, in which only the D(2long) isoform was expressed. D(2)-like receptor expression was confirmed at receptor-ligand binding study. At immunohistochemistry, D(2) was mainly localized in the zona glomerulosa and reticularis of the adrenal cortex and, to a lesser extent, in the zona fasciculata and medulla of normal and hyperplastic adrenal tissue. In the positive tumors, D(2) was localized in the tumoral cells. At the in vitro study, a significant inhibition of both baseline and ACTH-stimulated aldosterone secretion was found after high-dose cabergoline, but not bromocriptine, administration; and a significant inhibition of angiotensin-II-stimulated aldosterone secretion was found after both bromocriptine and cabergoline administration in the adrenal hyperplasias. In conclusion, the current study demonstrated that both D(1)-like and D(2)-like receptors are expressed in the normal adrenal gland and in a percentage of adrenal adenomas or carcinomas. Bromocriptine and cabergoline induce only a minor inhibition of the secretion of adrenal hormones in the nontumoral adrenal gland in vitro, not excluding, however, the possible effective use of dopamine agonists in vivo in the treatment of adrenal tumors.

Dopamine receptor expression and function in corticotroph pituitary tumors.

The role of dopamine agonist treatment in corticotroph pituitary tumors is controversial. The aim of this study was to evaluate D(2) receptor expression in 20 corticotroph pituitary tumors and to correlate it to the in vitro effect of dopamine agonists on ACTH secretion and the in vivo effect of short-term cabergoline treatment on cortisol secretion. D(2) expression was evaluated by receptor-ligand binding, immunohistochemistry, and RT-PCR. A 50% or more decrease in daily urinary cortisol levels was considered a significant clinical response. At receptor-ligand binding, specific binding of [(125)I]epidepride was found in 80% of cases. At immunohistochemistry, specific D(2) immunostaining was found in 75% of cases. D(2) expression was found in 83.3% of cases (D(2long) in 40%, D(2short) in 20%, and both in 40%) by RT-PCR. Significant in vitro inhibition of ACTH secretion was found in 100% of D(2)-positive cases, but not in 100% of D(2)-negative cases by either bromocriptine or cabergoline. A significant in vivo inhibition of cortisol secretion after 3-month cabergoline treatment was found in 60%, although a normalization of cortisol secretion was found in 40% of cases. All cabergoline-responsive cases were associated with D(2) expression, whereas all noncabergoline-responsive cases but one were not associated with D(2) expression. In conclusion, functional D(2) receptors were expressed in approximately 80% of corticotroph pituitary tumors. The effectiveness of cabergoline in normalizing cortisol secretion in 40% of cases supports its therapeutic use in the management of Cushing's disease.