Pituitary neuroendocrine tumor: A neuropsychological comparison with intra-axial tumor.

OBJECTIVE: Despite pituitary neuroendocrine tumor (PitNET) being extra-axial tumors without direct damage to brain tissue, patients with PitNET exhibit neuropsychological impairments. However, it remains unclear whether there are neuropsychological differences between PitNET and intra-axial tumors that directly destroy the brain parenchyma. This prospective study aims to clarify this distinction to inform decision-making for intracranial tumors of diverse origins. METHODS: A total of 146 patients with PitNET, 74 patients with glioma representing intra-axial tumors, and 52 age-, sex-, and education-matched healthy controls were recruited. All patients received standard treatment and postoperative rehabilitation. Clinical data were meticulously collected, and neuropsychological tests were administered to all participants both before and 3 months after surgery. RESULTS: Both PitNET and glioma patients experience the dual burden of cognitive and affective deficits. However, the feature of these deficits differs substantially. In PitNET patients, the deficits are relatively mild and focal, whereas in glioma patients, they are severe and extensive. Specifically, PitNET patients exhibit deficits in memory, anxiety, and negative affect. In contrast, glioma patients display deficits in executive function, attention, anxiety, positive/negative affect, and empathy. Notably, except for persistent memory deficits, the majority of neuropsychological scores declines in PitNET patients are restorable and can reach improvement within a short period after standard surgical therapy and perioperative management. Conversely, glioma patients not only fail to show improvements but also demonstrate worsening in terms of general cognition and memory postoperatively. INTERPRETATION: As an extra-axial tumor, PitNET may exhibit distinctive cognitive and affective functioning compared to intra-axial tumors, highlighting the need for specific treatment approaches for PitNET patients.

Clinical and Pathological Features of Pit1/SF1 Multilineage Pituitary Neuroendocrine Tumor.

BACKGROUND AND OBJECTIVES: Lineage-based classification has critical clinical implications in pituitary neuroendocrine tumor (PitNET). As the most prevalent subtype of multilineage PitNET, PitNET originating from both pituitary-specific positive transcription factor 1 (Pit1) and steroidogenic factor-1 (SF1) lineages (Pit1/SF1-adenoma) is expected to exhibit rich and varied clinical behaviors. A comprehensive understanding of the clinical and pathological characteristics of Pit1/SF1-adenoma will provide mechanistic insight and influence the prognosis and treatment of PitNET. METHODS: A retrospective study was conducted by reviewing 57 cases of Pit1/SF1-adenoma between 2018 and 2022. We also included 88 cases of PitNET arising from Pit1 cell lineage (Pit1-adenoma) and 70 cases of PitNET arising from SF1 cell lineage (SF1-adenoma) as controls. Comprehensive data, including demographic, symptom, endocrinal, radiological, surgical, pathological, and prognostic information, were systematically collected. All specimens were immunostained for pituitary transcription factors (PTFs) and pituitary hormones. RESULTS: The detection rate was 8.0% for Pit1/SF1-adenoma within PitNET surgical specimens. Pit1/SF1-adenoma displayed a male predominance, with the mean diagnosis age falling between Pit1-adenoma and SF1-adenoma. The endocrine activity of Pit1/SF1-adenoma was lower than Pit1-adenoma but higher than SF1-adenoma. Pit1/SF1-adenoma had a higher incidence of cavernous sinus invasion (56.1%) than both Pit1-adenoma (38.6%, P = .039) and SF1-adenoma (27.1%, P = .001). Furthermore, Pit1/SF1-adenoma showed more postoperative complications than Pit1-adenoma (29.8% vs 8.0%, P = .001). Nonfunctional Pit1/SF1-adenoma had a higher radiological tumor recurrence rate than nonfunctional SF1-adenoma (34.8% vs 10.9%, P = .021). Notably, the immunostaining pattern was diverse in Pit1/SF1-adenoma, with various combinations of staining intensity for PTFs and 15 combinations for 6 pituitary hormones. Intriguingly, various PTFs combinations had no different impact on the outcome of Pit1/SF1-adenoma. CONCLUSION: Pit1/SF1-adenoma represents a unique pathological subtype of PitNET, characterized by distinctive clinical behaviors. Identifying Pit1/SF1-adenoma can facilitate more precise management of PitNET by the practical use of Pit1/SF1 immunostaining.

Characteristics of Perioperative Cognitive and Affective Function in Patients with Somatotroph Adenoma.

OBJECTIVE: In the present study, we evaluate the characteristics of cognitive and affective function in patients with somatotroph adenomas (SAs) that secrete excess growth hormone and the effects of surgical intervention. METHODS: We conducted a prospective longitudinal study, recruiting 27 patients with SAs, 29 patients with nonfunctional pituitary adenomas (NFPAs) as the lesion control group, and 24 healthy participants as the healthy controls (HCs). These three groups were matched for sex, age, and years of education. We performed multidimensional cognitive function and neuropsychological assessments 1-2 days before endoscopic endonasal transsphenoidal surgery and at 3 months postoperatively. The Mini-mental state examination, Montreal cognitive assessment, Frontal assessment battery, Trail making test, and Digit span test were used to assess multidimensional cognitive function, including general intelligence, frontal lobe function, executive function, and memory. The Hamilton anxiety scale, Beck depression inventory, and Positive and Negative Affect Schedule scale were used for the neuropsychological assessment, including anxiety, depressed mood, and positive and negative emotions. RESULTS: Compared with the HCs, the patients with SAs showed poor performance in the memory (P = 0.009) and anxiety (P = 0.013) assessments. However, no statistically significant difference was observed between patients with SAs and NFPAs for either cognitive function or effective performance. Moreover, patients with SAs did not show significant changes in cognition and affective behavior after surgery. In contrast, patients with NFPAs displayed significant improvements in memory (P = 0.015), executive function (P < 0.001), and anxiety mood (P = 0.001) performance postoperatively. CONCLUSIONS: Patients with SAs showed specific cognitive deficits and abnormal moods, which might be attributed to the overproduction of growth hormone. However, surgical intervention had a limited effect on improving the impaired cognitive function and abnormal moods in patients with SAs at short-term follow-up.

The characteristics of brain structural remodeling in patients with unilateral vestibular schwannoma.

PURPOSE: Brain structural remodeling alters related brain function. However, few studies have assessed morphological alterations of unilateral vestibular schwannoma (VS) patients. Therefore, this study examined the characteristics of brain structural remodeling in unilateral VS patients. METHODS: We recruited 39 patients with unilateral VS (19 left, 20 right) and 24 matched normal controls (NCs). We obtained brain structural imaging data using 3T T1-weighted anatomical and diffusion tensor imaging scans. Then, we evaluated both gray and white matter (WM) changes using FreeSurfer software and tract-based spatial statistics, respectively. Furthermore, we constructed a structural covariance network to assess brain structural network properties and the connectivity strength between brain regions. RESULTS: Compared with NCs, VS patients showed cortical thickening in non-auditory areas (e.g., the left precuneus), especially left VS patients, along with reduced cortical thickness in the right superior temporal gyrus (auditory areas). VS patients also showed increased fractional anisotropy in extensive non-auditory-related WM (e.g., the superior longitudinal fasciculus), especially right VS patients. Both left and right VS patients showed increased small-worldness (more efficient information transfer). Left VS patients had a single reduced-connectivity subnetwork in contralateral temporal regions (right-side auditory areas), but increased connectivity between some non-auditory regions (e.g., left precuneus and left temporal pole). CONCLUSION: VS patients exhibited greater morphological alterations in non-auditory than auditory areas, with structural reductions seen in related auditory areas and a compensatory increase in non-auditory areas. Left and right VS patients show differential patterns of brain structural remodeling. These findings provide a new perspective on the treatment and postoperative rehabilitation of VS.

Pituitary adenomas with multiple cell lineage combinations: clinicopathological features and short-term prognosis.

OBJECTIVE: There are few published data concerning pituitary adenomas (PAs) derived from multiple lineages. In this study the authors aimed to determine the clinicopathological characteristics and prognostic profiles of PAs with multiple cell lineage combinations (PAwMCs). METHODS: The authors reviewed data on 723 patients with PAs who had undergone surgery between 2018 and 2021 and identified 93 cases (12.9%) of PAwMC. They collected detailed data on these cases, including clinical information, pathological features, and prognosis. From among 589 cases of PAs with only one cell lineage (PAwOCs), they randomly selected 100 cases to investigate differences between the two tumors. To enable investigation of the characteristics of different subgroups, they further subclassified PAwMCs into 4 groups according to the following specified combinations of pituitary-associated transcription factors: group A, immunopositive for pituitary-specific positive transcription factor 1 (Pit1) and steroidogenic factor 1 (SF1); group B, immunopositive for Pit1 and T-box transcription factor (Tpit); group C, immunopositive for SF1 and Tpit; and group D, immunopositive for Pit1, SF1, and Tpit. RESULTS: Compared with PAwOC, PAwMC was more often associated with hormone hypersecretion (31.0% vs 50.0%, p = 0.037) and had worse short-term prognoses with lower complete response rates (58.7% vs 30.0%, p = 0.026) and more postoperative complications (19.4% vs 35.9%, p = 0.041). Each of the 4 PAwMC subgroups had its own clinical features. Overall, PAwMCs displayed more neurological manifestations than evidence of hypersecretion, which may be attributable to a disparity between pituitary-associated transcription factors and endocrine-related manifestations. Moreover, multiple cell lineages, tumor size (p = 0.011), and Knosp grade (p = 0.013) were all found to be critical predictors of the prognosis of PAwMC. CONCLUSIONS: The authors described a special subtype of PAs, which derived from multiple lineages. They found a unique effect of the combination of distinct cell lineages on PAs and present detailed clinicopathological and prognostic profiles of these special PAs. These data will contribute to a more comprehensive view of PAs and assist in the selection of treatment.

Posterior fossa ependymoma with preoperative cerebrospinal metastases: a case report with literature review.

BACKGROUND: Adult posterior fossa ependymomas (PF-EPN) with preoperative cerebrospinal metastases are extremely rare. Only 3 cases have been reported in previous literature. CASE PRESENTATION: A case of a 32-year-old male patient complained of headaches for three months. Pure tone audiometry showed a slight decrease in bilateral hearing. Auditory evoked potential indicated that the hearing on the left was slightly weaker than that on the right. Magnetic resonance imaging (MRI) revealed a primary tumor arising within the fourth ventricle and metastasizing to bilateral cerebellopontine angle (CPA), the third ventricle, the left lateral ventricle, T1, L1-2 and L5. A gross total resection (GTR) was performed on the lesion located in the left CPA. The histological examination showed a papillary ependymoma (WHO grade II). Immunohistochemical staining for H3K27me3 showed that nuclear positivity in more than 80% of cells. No NF2 mutation was observed. No progression was found during a 24-month follow-up. CONCLUSIONS: Our data indicate that preoperative multiple metastases in adult PF-EPN are extremely rare. This kind of disease usually has a low WHO grade and a favorable prognosis. GTR should be achieved when feasible and patients need a long-term follow-up with MRI.

Qu-Du-San-Jie decoction induces growth inhibition and vascular normalization in NF2-associated vestibular schwannoma.

Background: Neurofibromatosis type 2 (NF2) is a rare genetic syndrome that predisposes individuals to develop bilateral vestibular schwannomas (VSs) causing a high risk of life-threatening neurological complications. Traditional treatment options for NF2-associated VS usually cause neurological damage, and to date, there are no FDA-approved pharmacotherapies for NF2. The aim of this study was to evaluate the antitumor efficacy of Qu-Du-San-Jie (QDSJ) decoction, a traditional Chinese medicine formula, on NF2-associated VS and to investigate the potential underlying mechanisms. Methods: Ultra high-performance liquid chromatography-mass spectroscopy (UHPLC-MS) analysis was performed to identify the components of QDSJ and their targets. To determine the relationships between the putative targets of QDSJ and the differential genes of NF2-associated VS, the drug-disease crossover genes were screened using the UHPLC-MS data combined with our previous gene expression profiling data. The differentially expressed genes were imported into the STRING database to generate a PPI network. Differentially expressed gene targets and pathways were identified using GO and KEGG pathway enrichment analyses. The in vitro and in vivo drug efficacy of QDSJ decoction was tested using a patient-derived schwannoma cell line and a patient-derived xenograft mouse model, respectively. H&E staining, immunochemistry, and immunofluorescence staining were used to evaluate the cell proliferation and tumor vessels. Results: A total of 133 compounds were identified in QDSJ decoction using UHPLC-MS analysis. Network pharmacology showed that the regulation of necroptosis, apoptosis, cell cycle, angiogenesis, adherens junction, and neuroactive ligand-receptor interaction could be associated with the efficacy of QDSJ in treating NF2-associated VS. Treatment with QDSJ induced necrotic cell death and apoptosis of schwannoma cells in vitro and suppressed the tumor growth in vivo. Histopathological analysis revealed areas of cell necrosis and enlarged tumor blood vessels in the QDSJ-treated tumors. The numbers of cells positive for Cyclin D1 and Ki-67 were significantly reduced in QDSJ-treated tumors compared to control tumors. Immunofluorescence staining of CD31 and αSMA showed a decreased number and density of tumor vessels and normalized vessel structure in QDSJ-treated tumors. Conclusion: Our study demonstrates that QDSJ decoction shows significant antitumor activity against NF2-associated schwannoma and is a possible candidate for future clinical trials.

Visuospatial but Not Verbal Working Memory Deficits in Adult Patients With Neurofibromatosis Type 1.

Background: Cognitive dysfunction is one of the main symptoms of neurofibromatosis type 1 (NF1). As an important cognitive function, working memory (WM) has rarely been systematically analyzed in NF1 by isolating the particular domain of WM, and existing data involving WM in adult patients with NF1 are insufficient. This study aimed to investigate the characteristics of different types of WM in NF1 from the perspective of the adult population. Method: We comprehensively analyzed WM in both verbal and visuospatial WM domains by using the N-back task (including the verbal N-back task and the visuospatial N-back task) in 31 adults with NF1 and 34 healthy controls matched for age, gender, education levels, and general cognitive status. The accuracy and reaction times (RTs) in the N-back task were entered into mixed-design ANOVA. Results: Compared with healthy controls, adults with NF1 presented significantly lower mean accuracy and longer RTs in the visuospatial N-back task. However, no significant difference was found between the NF1 group and healthy controls in the verbal N-back task. Conclusions: The present study suggested that adults with NF1 might have deficits in visuospatial WM. We did not find evidence for verbal WM deficits in adult patients with NF1. Our findings supplement and refine the existing data on WM in the context of NF1.

Establishment of nomograms for the prediction of useful hearing loss in patients with neurofibromatosis type 2.

INTRODUCTION: Treatment for vestibular schwannoma (VS) in patients with neurofibromatosis type 2 (NF2) is extremely challenging due to the high risk of hearing loss. The aim of this study was to develop nomograms for the prediction of useful hearing loss in patients with NF2. METHODS: The nomogram was based on a retrospective study of 111 NF2 patients who underwent resection of large VS (> 2 cm) at Beijing Tiantan Hospital between 2011 and 2018. The utility of the proposed nomogram models was evaluated by receiver operating characteristic (ROC) curve, area under ROC curve (AUC), and calibration curve. The results were validated using a prospective cohort study on 33 patients consecutively enrolled at the same institution from 2019 to 2021. RESULTS: On multivariate analysis of the primary cohort, large tumour size (> 3 cm) and long duration of symptoms (> 24 months) were independent risk factors for preoperative useful hearing loss (AAO-HNS Class D) (P = 0.001 and P = 0.011, respectively), while large tumour size (> 3 cm), poor hearing (Class C), and lobular growth were significantly related to postoperative useful hearing loss (P < 0.001, P = 0.031 and P = 0.033, respectively). Factors derived from multivariable analysis were all assembled into the nomogram. The calibration curve for probability of hearing loss showed good agreement between predictions by nomogram models and actual observation. The ROC curves showed good predictive accuracy of the nomogram models in both cohorts (AUC: 0.708 to 0.951). CONCLUSION: The proposed nomograms resulted in accurate predictions of hearing outcomes for patients with NF2.

Selective impairment of the executive attentional network in adult patients with neurofibromatosis type 1.

Cognitive dysfunction accompanied by neurofibromatosis type 1 is one of the significant characteristics of this neurocutaneous disorder and has a serious impact on patients' quality of life. Although studies on cognitive function in children with neurofibromatosis type 1 have revealed that attentional impairment is a key deficit in these patients, few studies have examined their neuropsychological profile, especially whether the attentional function is also abnormal and specific in adult patients with neurofibromatosis type 1. In this study, we used the revised attention network test to examine the function of three attentional networks-alerting, orienting and executive control-in 20 adult patients with neurofibromatosis type 1 in comparison to 20 normal controls. Adult patients with neurofibromatosis type 1 showed significant greater conflict effect for the executive control network, but no significant differences were found for alerting and orienting network relative to normal controls. These results provide evidence that there is an attentional deficit which is specifically associated with the executive control network in adult patients with neurofibromatosis type 1.