Clinicopathological Correlates of PIT1 and SF1-Multilineage Pituitary Neuroendocrine Tumors and the Diagnostic Utility of NKX2.2 Immunohistochemistry in Pituitary Pathology.

CONTEXT.­: PIT1 and SF1-multilineage pituitary neuroendocrine tumors (PitNETs) have been defined since the classification of adenohypophysial tumors based on the PIT1, SF1, and TPIT transcription factors. OBJECTIVE.­: To describe the clinicopathologic features of PIT1 and SF1-multilineage PitNETs and to contribute to the pituitary pathology practice by questioning the expression of NKX2.2 in PitNETs. DESIGN.­: We reviewed 345 PitNETs and described the clinicopathologic features of 8 PIT1 and SF1-multilineage tumors. NKX2.2 positivity and staining pattern were compared to those of 45 PitNETs from the control group. RESULTS.­: PIT1 and SF1-multilineage PitNET patients had a mean age of 41.13 (range, 14-58 years) and a mean diameter of 14.0 mm (range, 8-20 mm). The most common clinical presentation was acromegaly (6 of 8), and postoperative remission was achieved in all patients. On histomorphologic examination, a pseudopapillary pattern was seen in 5 of the tumors, either focally or diffusely. In addition to PIT1 and SF1, there was a diffuse staining with growth hormone and a predominantly perinuclear staining with cytokeratin 18. With NKX2.2, all multilineage tumors were positive, of which 5 were diffuse and 3 were focal. In the control group, 8 tumors (8 of 45) were positive, of which only 1 was diffuse and 7 were focal. CONCLUSIONS.­: In conclusion, NKX2.2 is a transcription factor that can be used as an additional tool in pituitary pathology, and PIT1 and SF1-multilineage PitNETs are specific tumors that usually present with acromegaly, show signs of a nonaggressive clinical course, have a pseudopapillary histomorphology, and express NKX2.2.

Medium and Long-Term Data from a Series of 96 Endoscopic Transsphenoidal Surgeries for Cushing Disease.

OBJECTIVE: Postoperative data on Cushing's disease (CD) are equivocal in the literature. These discrepancies may be attributed to different series with different criteria for remission and variable follow-up durations. Additional data from experienced centers may address these discrepancies. In this study, we present the results obtained from 96 endoscopic transsphenoidal surgeries (ETSSs) for CD conducted in a well-experienced center. METHODS: Pre- and postoperative data of 96 ETSS in 87 patients with CD were included. All cases were handled by the same neurosurgical team between 2014 and 2022. We obtained data on remission status 3-6 months postoperatively (medium-term) and during the latest follow-up (long-term). Additionally, magnetic resonance imaging (MRI) and pathology results were obtained for each case. RESULTS: The mean follow-up duration was 39.5±3.2 months. Medium and long-term remission rates were 77% and 82%, respectively. When only first-time operations were considered, the medium- and long-term remission rates were 78% and 82%, respectively. The recurrence rate in this series was 2.5%. Patients who showed remission between 3-6 months had higher longterm remission rates than did those without initial remission. Tumors >2 cm and extended tumor invasion of the cavernous sinus (Knosp 4) were associated with lower postoperative remission rates. CONCLUSION: Adenoma size and the presence/absence of cavernous sinus invasion on preopera-tive MRI may predict long-term postoperative remission. A tumor size of 2 cm may be a supporting criterion for predicting remission in Knosp 4 tumors. Further studies with larger patient populations are necessary to support this finding.

Ventral amygdalofugal pathway as an integrated surgically important network: microsurgical anatomy and segmentation based on fiber dissection.

OBJECTIVE: The ventral amygdalofugal pathway (VAFP) provides afferent and efferent connections to the amygdala and spans along some of the frequently traversed intra-axial surgical corridors as a dominant fiber bundle. This study aimed to reveal the frequently overlooked VAFP fibers by examining their courses and connections to the basal forebrain, septal region, hypothalamus, thalamus, tegmentum, and brainstem. METHODS: Ten postmortem human brains were used to display the characteristics of the VAFP, and fiber dissection results were compared with those of tractography. RESULTS: From anterior to posterior, the VAFP was separated into 5 different portions: 1) amygdala-substantia innominata; 2) amygdaloseptal (diagonal band of Broca); 3) amygdalo-thalamic; 4) amygdalo-hypothalamic, intermingling with the medial forebrain bundle and extending to the bed nucleus of stria terminalis; and 5) amygdalotegmental. The results of fiber dissections were confirmed with findings obtained from diffusion tensor tractography. CONCLUSIONS: This study supports the concept that interconnected forebrain, diencephalic, mesencephalic, and brainstem connections of the VAFP form an integrated surgically important network. The fiber dissection findings also provide the neuroanatomical basis for VAFP segmentation, which may help neurosurgeons better appreciate the complex microsurgical anatomy of the amygdalar connections. Amygdala-substantia innominata and amygdalotegmental connections are demonstrated for the first time and clarified within the structure of the VAFP.

Effect of Resection and Surgical Experience on Survival in Patients with Craniopharyngiomas: Endoscopic Transsphenoidal Surgery in Series of 31 Cases.

AIM: To share the surgical outcomes of 31 patients who underwent endoscopic endonasal transsphenoidal surgery (EETS) at a single center. MATERIAL AND METHODS: This retrospective analysis of 31 craniopharyngioma cases (2013-2022) with a minimum 6-month follow-up included demographic data, preoperative findings, postoperative resection volumes, recurrence rates, pathological diagnoses, and complications. RESULTS: Herein, 34 EETS surgeries were performed on 31 patients (12 males, 19 females). The presenting symptoms included visual loss (58%), hypopituitarism (54.8%), and diabetes insipidus (25.8%). Gross total resection was achieved in 87% of the patients, with 64.5% total and 22.5% near-total resection. Total resection prevented recurrences, contrasting with 75% recurrence in the subtotal resection patients (p=0.000). The primary patients showed 73.1% total resection, while only 20% of the recurrent patients achieved it (p=0.049). When comparing the first 16 cases with the last 15 cases in terms of surgical experience, the rates of resection (p=0.040) and recurrence-free survival (p=0.020) in the last 15 cases were statistically significant. Patients with preoperative visual loss demonstrated 94.4% improvement or stability postoperatively. Postoperative complications included hypopituitarism (71.4%), permanent diabetes insipidus (60.8%), worsening vision (6.5%), cerebrospinal fluid leakage (9.7%), meningitis (6.5%), and a 3.2% perioperative mortality rate. CONCLUSION: This study underscores the role of surgical resection in craniopharyngiomas, emphasizing the impact of surgical experience on recurrence-free survival. Primary surgery, with minimal complications and maximal resection, is crucial in managing recurrence challenges. Endoscopic endonasal transsphenoidal surgery, particularly in experienced centers, offers advantages such as panoramic vision and access to the third ventricle base, facilitating total and near-total resection and extending recurrence-free survival.

A rare tumor in the sellar region: ganglioglioma, a case report and a general overview.

BACKGROUND: Gangliogliomas are rare mixed neuronal-glial tumors of the central nervous system, accounting for less than 2% of intracranial tumors. CASE DESCRIPTION: This report presents a rare case of ganglioglioma in the sellar region of a 3-year-old and 5-month-old pediatric patient. The patient underwent surgical intervention initially through a transnasal transsphenoidal approach and subsequently through a transcranial pterional craniotomy approach. Subsequently, radiotherapy and chemotherapy were administered for residual tumor tissue. The purpose of this report is to highlight the presence of ganglioglioma as a distinct diagnosis in sellar region tumors, discuss the surgical, radiotherapy, and/or chemotherapy treatment options for sellar region gangliogliomas based on the literature, and contribute the patient's follow-up and treatment outcomes to the existing literature. CONCLUSION: Complete tumor resection may not be feasible in sellar region gangliogliomas, especially in pediatric cases, due to endocrinological and vision-related complications. In cases where complete resection is not possible, radiotherapy and/or chemotherapy may be considered. However, the optimal treatment approach has not yet been established, and further research is needed.

Results of Intraoperative Sodium Fluorescein Video Angiography and Its Repeated Use in a Series of Brain Aneurysm Surgeries.

AIM: To present the properities of intraoperative sodium fluorescein video angiography (NaF-V) use in intracranial aneurysm surgery and to discuss the limitations of repeated NaF-V administration. MATERIAL AND METHODS: The clinical findings and imaging results during and after surgery for patients with aneurysm who underwent surgery between September 2020 and June 2022 were examined. NaF-V and micro-doppler imaging were used to control the flow of the parent and perforating arteries and obliteration of the aneurysm dome. The dose of sodium fluorescein administered via the central venous route was 5 mg/kg. RESULTS: Overall, 102 aneurysms were treated during 95 operations in 92 patients. NaF-V was applied at least once in all operations, twice in 17, and thrice in 3 operations. The period between repeated doses of NaF-V ranged from 4 to 50 min. The method allowed for the desired imaging of the parent and perforating arteries in all cases but failed to provide satisfactory results regarding the complete obliteration of the aneurysm dome in three cases. No NaF-V-related complications were encountered in any case. CONCLUSION: Sodium fluorescein is safe, with a high minimum toxic dosage, and provides benefits, even in repeated use, in the evaluation of perforating and parent arteries. NaF-V is effective when used alternatively or in combination with various methods.

Ubiquitin-specific Protease 8 Gene Expression in Sporadic Pituitary Adenomas.

OBJECTIVES: In sporadic pituitary adenomas, the role of Ubiquitin-specific protease 8 (USP8) is not clearly defined. Mutations in USP8 gene are known to influence formation of the corticotroph adenomas. However, it has not been clarified whether changes in expression of USP8 have an impact on other pituitary adenomas or not. In this study we addressed the changes in USP8 gene expression levels in pituitary adenomas (PA) relative to non-adenomatous brain tissue. MATERIAL AND METHODS: USP8 gene expression analysis was performed on a total of 43 tissue samples from human pituitary adenomas and on 16 tissue samples from non-pituitary brain tissues (control group). Adenomatous tissues and control tissues were assessed for quantification of RNA expression of USP8.The levels of USP8 gene expression were determined relative to those in control group. RESULTS: Overall, the USP8 gene expression levels in PA were 3.7 times higher than the control brain tissues (CBT) (p=0.002). However, after stratification, only the USP8 in the secretory PA were higher than CBT(p=0.002). CONCLUSIONS: Present findings support that USP8 gene expression levels may contribute to pitutary tumorigenesis and hormonogenesis..

Results of Endoscopic Surgery in Patients with Pituitary Adenomas : Association of Tumor Classification Grades with Resection, Remission, and Complication Rates.

OBJECTIVE: The endoscopic endonasal transsphenoidal approach is a widely-used method for the surgical treatment of pituitary adenomas. We aimed to evaluate the results of endoscopic surgery by comparing preoperative classification methods and investigating their relationship with postoperative resection and remission rates and complications. METHODS: We retrospectively reviewed the medical records of 236 patients (118 males) who underwent surgery for pituitary adenomas. Preoperative Knosp classification, tumor size (TS), suprasellar extension (SSE), postoperative resection and remission rates, and complications were evaluated. RESULTS: The follow-up period was 3 months to 6 years. The patients' ages ranged between 16 and 84 years. Endocrinologically, 114 patients (48.3%) had functional adenoma (FA), and 122 patients (51.7%) had non-functional adenoma (NFA). Among the FA group, 92 (80.7%) showed remission. A statistically significant difference was found between patients with and without remission in terms of the Knosp, TS, and SSE classifications (p<0.01). Knosp, TS, and SSE classification grades were found to be correlated with the resection rates (p<0.01). Meningitis was seen in seven patients (3.0%), diabetes insipidus in 16 (6.9%; permanently in two [0.9%]), and rhinorrhea in 19 (8.1%). Thirty-six patients (15.3%) developed pituitary insufficiency and received hormone replacement therapy. CONCLUSION: The resection categories and remission rates of FAs were directly proportional to the adenoma sizes and Knosp grades, while the degree of suprasellar growth further complicated resection and remission rates. Adenoma sizes less than 2 cm and SSEs less than 1 cm are associated with favorable remission and resection rates.

Multi-Level Anterior Cervical Decompression in Multi-Level Cervical Spondylotic Myelopathy without Extending the Corpus Resection: A Cadaveric Study of a Novel Surgical Technique.

AIM: To perform three-level decompression with a single-level corpectomy by modifying the fusion with anterior cervical corpectomy (ACC-F) method on a cadaver. MATERIAL AND METHODS: The anterior cervical region of four whole-head cadavers was dissected. The corpectomy was performed under a surgical microscope with a MT4-20+ ultrasonic bone dissector (UBD) tip. Superior and inferior decompression were conducted and viewed with a 70° neuroendoscope using two types (vertically and horizontally oriented) of specially designed 23 mm-long, 90°-angled UBD tips. RESULTS: After neck dissection and the removal of the thyroid and cricoid cartilages, C5 corpectomy and adjacent-level discectomies were performed. Following discectomy and corpectomy, superior and inferior decompression were conducted with specially designed UBD tips and viewed with a 70° neuroendoscope. A three-level anterior cervical decompression was provided with a single-level corpectomy. CONCLUSION: This study demonstrated that two more level decompression is possible with a single-level corpectomy in the cervical region using the new technique.

Robotic Surgical Approach to the Mesial Temporal Region: A Preliminary Three-Dimensional Cadaveric Study of Technical Feasibility.

OBJECTIVE: Robotic surgical systems are used worldwide in various fields. In this study, we present the advantages and disadvantages of the most common robotic surgical system, the da Vinci Xi system, in the supracerebellar transtentorial approach to the mesial temporal region and discuss options for its integration into neurosurgery. METHODS: Our study was conducted at the Advanced Simulation and Applied Endoscopic Surgery Training and Research Center and Anatomy Laboratory. Four formalin-fixed human cadaveric head specimens with red silicone dye injected into their arterial structures and blue silicone dye injected into their venous structures were used in the study. Dissections were performed in microscopic and robotic stages. All phases were photographed using a three-dimensional photographic technique. RESULTS: The mesial temporal lobe could be accessed via the supracerebellar transtentorial route with the use of the robotic system. We show that the robotic system can be used in difficult approaches and narrow regions with a wider exposure and superior image quality than with the microscopic approach, improving the ergonomics for the surgeon. The shortcomings of robotic systems are examined and innovative solutions are offered. CONCLUSIONS: This study shows the advantages and disadvantages of the robotic surgical approach to the mesial temporal region via the supracerebellar transtentorial route. Robotic surgical systems can play a major role in neurosurgical practices with the tools designed and the innovative solutions determined in this study. Nevertheless, further research and development of these systems and related instruments are necessary to ensure their wider implementation in neurosurgery.

Mammillothalamic and Mammillotegmental Tracts as New Targets for Dementia and Epilepsy Treatment.

BACKGROUND: Recently, neuromodulation through deep brain stimulation (DBS) has appeared as a new surgical procedure in the treatment of some types of dementia and epilepsy. The mammillothalamic and mammillotegmental tracts are involved among the new targets. To our knowledge, a review article focused specifically on these mammillary body efferents is lacking in the medical literature. Their contribution to memory is, regrettably, often overlooked. METHODS: A review of the relevant literature was conducted. RESULTS: There is evidence that mammillary bodies can contribute to memory independently from hippocampal formation, but the mechanism is not yet known. Recent studies in animals have provided evidence for the specific roles of these mammillary body efferents in regulating memory independently. In animal studies, it has been shown that the disruption of the mammillothalamic tract inhibits seizures and that electrical stimulation of the mammillary body or mammillothalamic tract raises the seizure threshold. In humans, DBS targeting the mammillary body through the mammillothalamic tract or the stimulation of the anterior thalamic nucleus, especially in the areas closely related to the mammillothalamic tract, has been found effective in patients with medically refractory epilepsy. Nonetheless, little knowledge exists on the functional anatomy of the mammillary body efferents, and their role in the exact mechanism of epileptogenic activity and in the memory function of the human brain. CONCLUSIONS: A comprehensive knowledge of the white matter anatomy of the mammillothalamic and mammillotegmental tracts is crucial since they have emerged as new DBS targets in the treatment of various disorders including dementia and epilepsy.