Identification of core genes of craniopharyngioma angiogenesis based on single-cell nuclear transcriptome sequencing.

This study aimed to explore the core genes of craniopharyngioma angiogenesis for targeted vascular therapy based on single-cell nuclear transcriptome sequencing. For single-cell nuclear transcriptome sequencing, we collected six samples from the tumor center and adjacent hypothalamic tumor tissues from three patients with craniopharyngioma, as well as four normal brain tissues based on Gene Expression Omnibus. We screened genes with differential up-regulation between vascular endothelial cells of craniopharyngioma and those of normal brain tissues, performed GO and KEGG analysis, constructed the protein-protein interaction network, and selected key genes verified using immunofluorescence. After data cleaning and quality control, 623 craniopharyngioma endothelial cells and 439 healthy brain endothelial cells were obtained. Compared with normal brain endothelial cells, craniopharyngioma endothelial cells were screened for 394 differentially up-expressed genes (DEGs). GO and KEGG results showed that DEGs probably modulated endothelial cells, adherens junction, focal adhesion, migration, actin cytoskeleton, and invasion via the PI3K-AKT, Rap1, Ras, Wnt, and Hippo pathways. The core genes screened were CTNNB1, PTK2, ITGB1, STAT3, FYN, HIF1A, VCL, SMAD3, PECAM1, FOS, and CDH5. This study obtained possible anti-angiogenic genes in craniopharyngioma. Our results shed novel insights into molecular mechanisms and craniopharyngioma treatment.

The "Double-Peak" Pattern of Pituitary Adenoma Intrasellar Pressure and Its Effects on the Microvascular Structure.

OBJECTIVE: The purpose of the present study was to investigate the relationship between the intrasellar pressure (ISP) and the microvascular structure of pituitary adenomas. METHODS: We retrospectively analyzed the ISP in 66 patients with pituitary adenomas. The corresponding microvascular structure was obtained using immunohistochemistry and analyzed for its correlation with the ISP. RESULTS: The average ISP was 25.89 ± 8.27 mm Hg, and the ISP was not related to the size of the adenoma (Pearson correlation coefficient, 0.103; P = 0.415). The ISPs of adenomas with different Knosp grades were significantly different (P < 0.05). From grade 0 to grade 4, at first, the ISP increased with the Knosp grade and reached the first peak at grade 2. It then decreased at grade 3 and increased again at grade 4, showing a "double-peak" pattern. The minimal diameter and perimeter of the microvessels and the vessel-covered area percentage were positively related to the ISP. When these parameters were compared among the adenomas of different Knosp grades, they also exhibited a "double-peak" pattern. CONCLUSIONS: In the present study, we found that with the increase in pituitary adenoma size and invasion of the surrounding tissues, the ISP of pituitary adenomas showed a "double-peak" pattern. The ISP and certain parameters of the microvascular structure are related, because the microvasculature adaptively changes its structure in response to the changing ISP to ensure a sufficient blood supply to the adenoma. The specific mechanism of this phenomenon requires further study.

Preoperative vascular heterogeneity and aggressiveness assessment of pituitary macroadenoma based on dynamic contrast-enhanced MRI texture analysis.

PURPOSE: To assess the vascular heterogeneity and aggressiveness of pituitary macroadenomas (PM) using texture analysis based on Dynamic Contrast-Enhanced MRI (DCE-MRI). METHOD: Fifty patients with pathologically confirmed PM, including 32 patients with aggressive PM (aggressive group) and 18 patients with non-aggressive PM (non-aggressive group), were included in this study. The preoperative DCE-MRI and clinical data were collected from all patients. The features based on Ktrans, Ve, and Kep were generated using Omni-Kinetics software. Independent-samples t-test and Mann-Whitney U test were used for comparison between two groups. Logistic regression analysis was used to determine the optimal model for distinguishing aggressive and non-aggressive PM. RESULTS: Six features related to tumor morphology, 24 features in Ktrans, 20 features in Ve, and 3 features in Kep were significantly different between the aggressive and non-aggressive groups. Volume count, gray-level non-uniformity in Ktrans, voxel value sum in Ve and run-length non-uniformity in Kep (AUC = 0.816, 0.903, 0.785, 0.813) were considered the best feature for tumor diagnosis. After modeling, the diagnosis efficiency of mean model and total model was desirable (AUC = 0.859 and 0.957), and the diagnostic efficiency of morphological, Ktrans, Ve and Kep features model was improved (AUC = 0.845, 0.951, 0.847, 0.804). CONCLUSIONS: Texture analysis based on DCE-MRI elucidates the vascular heterogeneity and aggressiveness of pituitary adenoma. The total model could be used as a new noninvasive method for predicting the aggressiveness of pituitary macroadenoma.

Assessment of microvessel perfusion of pituitary adenomas: a feasibility study using turbo spin-echo-based intravoxel incoherent motion imaging.

OBJECTIVES: To evaluate the feasibility of assessment of microvessel perfusion of pituitary adenomas with intravoxel incoherent motion (IVIM) imaging using single-shot turbo spin-echo-based diffusion-weighted imaging (SS-TSE-DWI). METHODS: We examined 51 consecutive patients with pituitary adenomas (35 non-functioning and 16 functioning) and 32 patients with normal pituitary glands using SS-TSE-DWI IVIM. The diffusion coefficient (D), the perfusion fraction (f), and the pseudo-diffusion coefficient (D*) were calculated pixel-by-pixel for each adenoma and normal pituitary gland. We also obtained the pathological microvessel area (MVA) of each adenoma. The IVIM parameters in adenomas were compared with those in normal pituitary glands using the Mann-Whitney U test. The correlation between the MVA and IVIM f of adenomas was analyzed using Spearman's rank correlation coefficient. RESULTS: The mean D (× 10-3 mm2/s) in adenomas was 0.723 ± 0.253, which was significantly lower than that in normal pituitary glands (0.862 ± 0.128; p < 0.0001). The mean f (%) in adenomas was 10.74 ± 4.51, which was significantly lower than that in normal pituitary glands (13.26 ± 4.32, p = 0.0251). No significant difference was found in the mean D*. We found a significant positive correlation between MVA and f in non-functioning adenomas (ρ = 0.634, p < 0.0001) as well as in all adenomas (ρ = 0.451, p = 0.0009). CONCLUSIONS: Assessment of microvessel perfusion of pituitary adenomas based on SS-TSE-DWI IVIM is feasible. Compared to normal pituitary glands, pituitary adenomas were characterized by lower D and f. KEY POINTS: • Assessment of microvessel perfusion of pituitary adenomas based on SS-TSE-IVIM is feasible. • SS-TSE-IVIM helps with evaluation of the vascularity of pituitary lesions. • Pituitary adenomas were characterized by lower D and f than normal pituitary glands.

Automatic image processing pipeline for tracking longitudinal vessel changes in magnetic resonance angiography.

BACKGROUND: Cerebral vessel diameter changes objectively and automatically derived from longitudinal magnetic resonance angiography (MRA) facilitate quantification of vessel changes and further modeling. PURPOSE: To characterize longitudinal changes in intracranial vessel diameter using time-of-flight (TOF) MRA. STUDY TYPE: Retrospective longitudinal study. SUBJECT POPULATION: IN all, 112 pediatric patients, aged 9.96 ± 4.59 years, with craniopharyngioma from 2006-2011 scanned annually. FIELD STRENGTH/SEQUENCE: 1.5T and 3T TOF MRA. STATISTICAL TESTS: Chi-square and Wilcoxon-Mann-Whitney tests. ASSESSMENT: Manual measurements using interventional angiography was established as a reference standard for diameter measurements. Constant and linear quantile regression with absolute difference, percentage difference, and relative difference was used for outlier detection. RESULTS: Major vessels surrounding the circle of Willis were successfully segmented except for posterior communicating arteries, mostly due to disease-related hypoplasia. Diameter measurements were calculated at 1-mm segments with a median computed vessel diameter of 1.25 mm. Diameter distortion due to registration was within 0.04 mm for 99% of vessel segments. Outlier detection using quantile regression detected less than 4.34% as being outliers. Outliers were more frequent in smaller vessels and proximity to bifurcations (P < 0.001). DATA CONCLUSION: Using the proposed method, objective changes in vessel diameter can be acquired noninvasively from routine longitudinal imaging. High-throughput analyses of imaging-derived vascular trees combined with clinical and treatment parameters will allow rigorous modeling of vessel diameter changes. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1063-1074.

Characterization of Skull Base Lesions Using Pseudo-Continuous Arterial Spin Labeling.

PURPOSE: Pseudo-continuous arterial spin labeling (pCASL) is a non-invasive magnetic resonance (MR) perfusion technique. Our study aimed at estimating the diagnostic performance of the pCASL sequence in assessing the perfusion of skull base lesions both qualitatively and quantitatively and at providing cut-off values for differentiation of specific skull base lesions. METHODS: In this study 99 patients with histopathologically confirmed skull base lesions were retrospectively enrolled. Based on a pathological analysis, the lesions were classified as hypervascular and non-hypervascular. Patients were divided into two subgroups according to the anatomical origin of each lesion. The MRI study included pCASL and 3D T1-weighted fat-saturated post-contrast sequences. Of the patients seven were excluded due to technical difficulties or patient movement. The lesions were classified by two raters, blinded to the diagnosis as either hyperperfused or non-hyperperfused, based on the pCASL sequence. The normalized tumor blood flow (nTBF) of each lesion was determined. Qualitative and quantitative characteristics of hypervascular and non-hypervascular lesions were compared. RESULTS: Visual assessment enabled correct classification of 98% of the lesions to be performed. Quantitatively, we found significant differences between the nTBF values for hypervascular and non-hypervascular lesions (p < 0.001) and provided cut-off values, allowing meningioma and schwannoma to be distinguished from meningioma and adenoma. Significant differences were also found within the hypervascular group, namely, paraganglioma was more hyperperfused than meningioma (p = 0.003) or metastases (p = 0.009). CONCLUSION: The present study demonstrates the high diagnostic performance of pCASL in characterizing skull base lesions by either visual assessment or nTBF quantification. Adding the pCASL sequence to the conventional protocol of skull base assessment can be recommended.

Pituitary apoplexy following lumbar fusion surgery in prone position: A case report.

RATIONALE: Pituitary apoplexy (PA) is a syndrome caused by acute hemorrhage or infarction of the pituitary gland, generally within a pituitary adenoma. PA following spinal surgery is a very rare complication and may be difficult to diagnose. However, early diagnosis of PA is essential for the timely treatment of pan-hypopituitarism and prevention of severe neurologic complications. PATIENT CONCERNS: A 73-year-old man had a posterior lumbar fusion surgery over a period of 8 hours on prone position. The patient complained of severe intractable headache accompanied by ophthalmalgia and ptosis on right eye 2 days after the surgery. DIAGNOSIS: Brain magnetic resonance imaging revealed a 1.3 × 2.6 × 2 cm mass in the sellar fossa and suprasellar region and the laboratory tests indicated pan-hypopituitarism. INTERVENTIONS: High-dose intravenous steroid therapy and trans-sphenoidal hypophysectomy were performed. OUTCOMES: Pathological evaluation of the surgical specimen revealed a pituitary adenoma with total necrosis, indicating that the PA occurred because of tumor infarction. The patient recovered fully after resection of the pituitary adenoma and hormonal therapy. LESSONS: Even though the incidence is low, PA has been related to blood pressure fluctuations or vasospasm during surgery. PA should be considered during differential diagnosis in cases of postoperative severe headache or ophthalmic complications.

Double pituitary adenomas associated with persistent trigeminal artery: a rare case report and the review of literature.

Multiple pituitary adenomas are rare. We present a quite unique case of double pituitary adenomas associated with persistent trigeminal artery (PTA) treated by endoscopic surgery. To the best of our knowledge, this is the first report in the literature. A 64-year-old woman was referred to our hospital for suspicion of acromegaly. Preoperative magnetic resonance imaging revealed two separate intrasellar masses with intrasellar vascular structure. Right cerebral angiography showed medial-type PTA. The patient underwent endoscopic transsphenoidal surgery and both tumors were resected completely. Postoperative immunohistopathologic examination revealed two histologic types of adenoma: the first tumor was positive for growth hormone (GH), while the second was considered nonfunctioning. Postoperatively, the patient's serum levels of GH and insulin-like growth factor-1 returned to normal. We observed an extremely rare case of double pituitary adenomas associated with PTA. Preoperative neuroimaging and modern endoscopic surgery are valuable to confirm diagnosis of double pituitary adenomas and identify anatomical localization of PTA.

Immediate ex-vivo diagnosis of pituitary adenomas using confocal reflectance microscopy: a proof-of-principle study.

OBJECTIVE The objective of this study was to evaluate the feasibility of using confocal reflectance microscopy (CRM) ex vivo to differentiate adenoma from normal pituitary gland in surgical biopsy specimens. CRM allows for rapid, label-free evaluation of biopsy specimens with cellular resolution while avoiding some limitations of frozen section analysis. METHODS Biopsy specimens from 11 patients with suspected pituitary adenomas were transported directly to the pathology department. Samples were immediately positioned and visualized with CRM using a confocal microscope located in the same area of the pathology department where frozen sections are prepared. An H & E-stained slide was subsequently prepared from imaged tissue. A neuropathologist compared the histopathological characteristics of the H & E-stained slide and the matched CRM images. A second neuropathologist reviewed images in a blinded fashion and assigned diagnoses of adenoma or normal gland. RESULTS For all specimens, CRM contrasted cellularity, tissue architecture, nuclear pleomorphism, vascularity, and stroma. Pituitary adenomas demonstrated sheets and large lobules of cells, similar to the matched H & E-stained slides. CRM images of normal tissue showed scattered small lobules of pituitary epithelial cells, consistent with matched H & E-stained images of normal gland. Blinded review by a neuropathologist confirmed the diagnosis in 15 (94%) of 16 images of adenoma versus normal gland. CONCLUSIONS CRM is a simple, reliable approach for rapidly evaluating pituitary adenoma specimens ex vivo. This technique can be used to accurately differentiate between pituitary adenoma and normal gland while preserving biopsy tissue for future permanent analysis, immunohistochemical studies, and molecular studies.

The Likelihood of Remnant Nonfunctioning Pituitary Adenomas Shrinking Is Associated with the Lesion's Blood Supply Pattern.

OBJECTIVE: Nonfunctioning pituitary adenomas (NFPA) often shrink after transsphenoidal surgery. However, little is known about the predictors of spontaneous NFPA regression. The aim of this study was to determine whether the blood supply pattern of remnant NFPA lesions was associated with the likelihood of such lesions shrinking. METHODS: A total of 37 remnant tumors in 31 patients who were treated at the Department of Neurosurgery, Yamagata University Hospital, were included in this study. All patients underwent preoperative dynamic 3.0T magnetic resonance imaging (MRI) to evaluate their tumors' arterial blood supplies, followed by endoscopic transsphenoidal surgery and intraoperative 1.5T MRI. Follow-up MRI scans were obtained at 1-2 weeks and 3-6 postoperative months. RESULTS: We detected tumor shrinkage in 15 of 37 (40.5%) remnant tumors on follow-up MRI scans obtained at 3-6 postoperative months. Remnant tumors were found in rostral and caudal locations in 21 and 16 cases, respectively. Rostral remnant tumors were significantly more likely to shrink (P < 0.0001). The tumors were classified into 3 groups according to their blood supply patterns (23 ascending, 6 descending, and 2 monophasic). The ascending blood supply pattern was found to be a positive predictor of tumor shrinkage (P = 0.002). Furthermore, no remnant tumors with rich blood supplies underwent spontaneous regression (P < 0.0001). CONCLUSIONS: Evaluations of the blood supplies of remnant NFPA via preoperative dynamic MRI and the locations of the remnant tumors could be useful for predicting postoperative tumor shrinkage.

Uneven Distribution of Regional Blood Supply Prompts the Cystic Change of Pituitary Adenoma.

BACKGROUND: Previous studies have suggested that the cystic change of pituitary adenoma might be related to the blood supply and metabolism of the tumor; however, the exact pathologic mechanism underlying the cystic change remains unknown. OBJECTIVES: We aimed to assess the features of regional blood supply of pituitary adenoma and examine its relationship with the cystic change of pituitary adenoma. METHODS: Patients (N = 79) with pituitary adenoma admitted to our hospital were divided into the parenchyma group (n = 40) or the cystic change group (n = 39). Dynamic contrast-enhanced magnetic resonance imaging of the pituitary adenoma was conducted for the parenchyma group and the steepest slopes (SSmax, reflecting regional blood supply) at different areas were calculated. The location of cystic change of the pituitary adenoma was recorded and analyzed for the cystic change group. RESULTS: The parenchyma group showed an upper SSmax of 2.52 ± 1.18, a lower SSmax of 2.89 ± 1.46, a left SSmax of 2.71 ± 1.31, and a right SSmax of 2.66 ± 1.29. The difference between the upper and lower SSmax was statistically significant (P < 0.001), with no difference between the left and right regions (P = 0.668). The location of cystic change of the pituitary adenoma was mainly in the upper region, accounting for 48.7% of cases. CONCLUSIONS: Regional blood supply is unevenly distributed in the parenchymal pituitary adenoma, with reduced blood supply in the upper than the lower region. Cystic change mainly occurs in the upper region of pituitary adenoma.

Role of a p53 polymorphism in the development of nonfunctional pituitary adenomas.

Non-functional pituitary adenomas (NFPAs) are among the commonest intracranial neoplasms. While histologically benign, NFPAs sometimes become large enough to limit therapeutic options and reduce quality of life. Investigations of the molecular etiology of NFPAs have failed to identify prevalent genetic changes and, while a role for p53 has been suggested, TP53 gene alterations have yet to be described in NFPAs. We found that the polymorphism rs1042522:C > G in codon 72 of exon 4 of the TP53 gene, whose C variant produces a proline and is more common in most ethnicities, has a G variant producing an arginine in 79.8% of NFPAs (n = 42; p < 1.411 × 10-18 vs. 1000 Genomes database), causing patients to present a decade earlier with symptomatic NFPAs. In cultured NFPA cells, transfection with the rs1042522 G variant versus the C variant reduced expression of cell arrest gene p21 and increased proliferation. These findings suggest that this TP53 polymorphism influences NFPA growth.

Quantitative analysis of anatomical relationship between cavernous segment internal carotid artery and pituitary macroadenoma.

Cavernous segment internal carotid artery (CSICA) injury during endoscopic transsphenoidal surgery for pituitary tumor is rare but fatal. The aim of this study is to investigate anatomical relationship between pituitary macroadenoma and corresponding CSICA using quantitative means with a sense to improve safety of surgery.In this retrospective study, a total of 98 patients with nonfunctioning pituitary macroadenomas undergoing endoscopic transsphenoidal surgeries were enrolled from 2005 to 2014. Intercarotid distances between bilateral CSICAs were measured in the 4 coronal levels, namely optic strut, convexity of carotid prominence, median sella turcica, and dorsum sellae. Parasellar extension was graded and recorded by Knosp-Steiner classification.Our findings indicated a linear relationship between size of pituitary macroadenoma and intercarotid distance over CSICA. The correlation was absent in pituitary macroadenoma with Knosp-Steiner grade 4 parasellar extension.Bigger pituitary macroadenoma makes more lateral deviation of CSICA. While facing larger tumor, sufficient bony graft is indicated for increasing surgical field, working area and operative safety.

Dopamine agonist resistance-related endocan promotes angiogenesis and cells viability of prolactinomas.

Dopamine agonists (DAs) are the first-line treatment of prolactinomas. They function through the dopamine 2 receptor (D2R) in the tumor cells. Endocan, also called endothelial cell-specific molecule-1 (ESM1), has been described as a marker of neoangiogenesis. However, whether ESM1 promotes the resistance of prolactinomas to DA therapy is largely unknown. In our study, 25 patients with prolactinomas were divided into resistant- and sensitive- groups according to the clinical response to bromocriptine. We found that ESM1-microvessel density of resistant prolactinomas was significantly higher than that of sensitive prolactinomas (47.9 ± 11.6, n = 8, vs 13.1 ± 2.8, n = 17, p = 0.0006), indicating that ESM1 was a DA resistance-related gene. Immunostaining showed that ESM1 was expressed in tumor vessels and sporadic tumor cells, and ESM1 was overlapped with the Smooth Muscle Actin (SMA) and von Willebrand Factor (VWF) in the tumor vessels. Silencing of ESM1 markedly suppressed the viability of GH3 and MMQ cells in vitro, and furthermore, significantly increased the sensitivity of GH3 and MMQ cells to DA treatment. Additionally, silencing of ESM1 down-regulated the angiogenesis-associated genes, such as VEGFR2, FGF2, CD34, CD31, VWF, and EGFR. Knockdown of ESM1 decreased endothelial tube formation of HUVECs, and significantly increased the sensitivity of HUVECs to Avastin treatment. Therefore, we first demonstrate that DA resistance-related ESM1 promotes the angiogenesis and tumor cells growth of prolactinomas, suggesting that ESM1 may be a novel therapeutic target for prolactinomas.

Evaluation of Fine Feeding System and Angioarchitecture of Giant Pituitary Adenoma--Implications for Establishment of Surgical Strategy.

BACKGROUND: Giant pituitary adenomas carry higher surgical risks despite recent advances in microsurgical and/or endoscopic surgery, and postoperative acute catastrophic changes without major vessel disturbance are still extremely difficult to predict, may manifest as postoperative pituitary apoplexy, and are associated with poor outcomes. METHODS: Eight males and 4 females aged 31-72 years (mean 50.7 years) with giant pituitary adenomas underwent preoperative investigation of fine angioarchitecture using C-arm cone-beam computed tomography with a flat-panel detector. Angiographical findings were used to decide the surgical routes and compared with clinical outcome. RESULTS: Feeding arteries were verified in 10 of 12 patients, whereas no feeding arteries were evident in 2 patients. The patients were divided into the faint tumor staining group and the significant staining group, which was reconfirmed by region of interest analysis. The former group had faint supply from the ipsilateral superior hypophyseal arteries and meningohypophyseal trunk, and the latter group had significant supply from the meningohypophyseal and inferolateral trunks, which passed centrifugally from the inferoposterior pole of the tumor. All patients were treated through the extended transsphenoidal approach. Intraoperative bleeding was significantly greater in the latter group (P = 0.013). All patients had improvement of neurologic deficit and were released from the intensive care unit within a few days. CONCLUSIONS: Major blood supply of giant pituitary adenomas originates from branches of the infraclinoidal portion of the internal carotid artery, different from the normal anterior pituitary gland. Surgical route should depend on not only tumor shape and extension but also feeding systems.

Primary meningeal melanocytoma of the sellar region: review of the literature and differential diagnosis with special reference to angiographical features.

PURPOSE: Primary intracranial melanocytomas are rare neoplasms, especially in the sellar region. Intracranial melanocytoma is usually a dural-based tumor, fed by dural arterial branches in a manner similar to meningioma. Primary sellar melanocytoma may be misdiagnosed as hemorrhagic pituitary macroadenoma, spindle cell oncocytoma, and intrasellar meningioma. These tumors differ in some radiological respects, but are difficult to differentiate preoperatively. METHODS: Only five cases of primary sellar/suprasellar melanocytic tumors, excluding melanomas have been reported thus far. In this paper, we report an instructive new case of a 31-year-old woman presenting with a 2-year history of amenorrhea and an intrasellar mass with suprasellar extension, suggestive of hemorrhagic pituitary adenoma. RESULTS: Transsphenoidal surgical excision was difficult due to extensive bleeding from the lesion, and at the time, the tumor could not be diagnosed histopathologically. Six years later, we operated again because of tumor regrowth. Angiography revealed a hypervascular tumor, which was fed from the dorsal sellar floor. We had difficulty resecting the tumor, but achieved total removal. Our case had typical radiographic characteristics of melanocytoma, revealed by both magnetic resonance imaging and angiography. However, it was difficult to reach a final diagnosis. Further histopathological examination, including immunohistochemical and ultrastructural studies, was helpful for diagnosis of melanocytoma. CONCLUSIONS: Primary sellar melanocytic tumors are derived from melanocytes in the meningeal lining of the sellar floor or in the diaphragm sellae, based on both embryological assumptions and the clinical findings of our case. We discuss the problems of differential diagnosis and management of primary sellar melanocytic tumors.

Pituitary image: pituicytoma.

INTRODUCTION: Pituicytoma is a rare tumor arising from the neurohypophysis or pars intermedia of the adenohypophysis. CASE REPORT: A 36 year old male came to our observation presenting polydipsia, polyuria, polyphagia, decreased libido and altered sleep-wake rhythm. The biochemical tests showed hypotonic urine, mild hyperprolactinemia, hypogonadotropic hypogonadism, central hypothyroidism. Magnetic resonance revealed an expansive lesion of the suprasellar region (slightly isointense on T1, hyperintense on T2, impregnating contrast medium), that was partially removed by trans-cranial neurosurgical approach. The histopathological diagnosis was pituicytoma. After surgery, in addition to endocrine disorders, the patient presented severe neurological sequelae and hyperthermia, likely due to damage of the hypothalamus, followed by a progressive metabolic syndrome. The residual tumor was monitored by MRI, and, due to the early gradual increase in volume, was treated by stereotactic radiosurgery. DISCUSSION/CONCLUSIONS: Pituicytomas are often difficult to distinguish from other hypothalamic or pituitary lesions. However, their identification would be preferable in a pre-operative setting in order to optimize the work-up and to initiate a proactive management of the expected complications.

Evaluation of the antiangiogenic effects of octreotide on growth hormone-producing pituitary adenoma using arterial spin-labeling perfusion imaging.

Decreased absolute tumor blood flow (TBF) measured by arterial spin labeling perfusion imaging (ASL-PI) on 3-tesla magnetic resonance imaging demonstrated the reduced size and growth hormone (GH) secretion of a large GH-producing pituitary adenoma in a 32-year-old man in response to octreotide therapy. The study shows the usefulness of ASL-PI in providing a biomarker of the antiangiogenic effect of octreotide.

Intraoperative indocyanine green videoangiography for identification of pituitary adenomas using a microscopic transsphenoidal approach.

PURPOSE: Initial successful surgical treatment of pituitary adenomas is crucial to reach long-term remission. Indocyanine green (ICG) videoangiography (VA) is well established in vascular neurosurgery nowadays and several reports described ICG application in brain tumor surgery. We designed this study to evaluate the feasibility of intravenous application of ICG and visualisation of a pituitary lesion via the fluorescence mode of the operation microscope. METHODS: 22 patients with pituitary adenomas were treated with transsphenoidal microsurgery and were included in this study. Intraoperatively 25 mg ICG was administered intravenously and visualized via the fluorescence mode of the operation microscope (Pentero/Zeiss). RESULTS: 22 patients qualified for transsphenoidal surgery presenting with different clinical symptoms (13 patients with acromegaly, 6 with M. Cushing and 3 with other symptoms like vision disorder or dizziness) and identification of a pituitary lesion (21 of 22 patients) in preoperative MR-imaging (mean diameter: 9 mm; SD 3.6; 6 macroadenomas, 15 microadenomas, 1 MR-negative). In all 22 patients ICG VA was performed during surgery. No technical failures or adverse events after drug administration occurred. Visualization was optimal approximately 2.4 min after intravenous application. In all patients the adenoma could be detected via two different types of visualization: direct visualization by fluorophore emission versus indirect detection of the adenoma by a lower ICG fluorescence compared to the surrounding tissue. CONCLUSION: Our data show that intraoperative ICG VA can be a useful and easily applicable additional diagnostic tool for visualization of pituitary lesions using the microscopic approach.

Crosstalk between tumor blood vessels heterogeneity and hormonal profile of pituitary adenomas: evidence and controversies.

AIM: Pituitary adenomas are intracranial tumors with controversial histopathology and heterogeneous clinical behaviour. Angiogenesis and tumor blood vessels' role in pathogenesis, remain one of the great pituitary tumor mysteries. No connection between tumor vessel heterogeneity, hormonal profile and biological behaviour has been reported. We aimed to study pituitary adenomas blood vessels concerning their immature, intermediate or mature phenotype and microvessel density, correlated with immunohistochemical hormonal profile and hormone values in serum and cerebrospinal fluid. MATERIALS AND METHODS: We classified pituitary adenomas according to hormone profile and we applied a double immunostaining highlighting both endothelial and perivascular cells for a more accurate assessment of blood vessel types. RESULTS: Overall microvessel density was found to be highest in growth hormone-secreting adenomas (48.51 ± 12.15) and lowest in prolactinomas (29.15 ± 18.78). When we differentially counted tumor blood vessels we observed a predominance of immature and intermediate blood vessels compared to mature ones. A significant correlation was found between immature tumor blood vessels and tissue prolactin expression, as assessed by immunhistochemistry (p=0.044). A partial correlation was found between serum (p=0.036) and cerebrospinal prolactin values (p=0.006) with immature and intermediate blood vessels. Also, a partial correlation has been reported only between mature blood vessels and cerebrospinal fluid prolactin values (p=0.008). No correlation was obtained for other types of pituitary adenomas. CONCLUSION: Our results suggest a strong involvement of prolactin with a dual role in pituitary adenomas vasculature remodelling by acting both on endothelial and perivascular cells, a finding that could partially explain discrepancies between clinical diagnosis and hormonal profile.