The vast majority of pituitary neuroendocrine tumors (PitNETs) are benign and slow growing with a low relapse rate over many years after surgical resection. However, about 40% are locally invasive and may not be surgically cured, and about one percentage demonstrate an aggressive clinical behavior. Exceptionally, these aggressive tumors may metastasize outside the sellar region to the central nervous system and/or systemically. The 2017 (4th Edition) WHO Classification of Pituitary Tumors abandoned the terminology \"atypical adenoma\" for tumors previously considered to have potential for a more aggressive behavior since its prognostic value was not established. The 2022 (5th Edition) WHO Classification of the Pituitary Tumors emphasizes the concept that morphological features distinguish indolent tumors from locally aggressive ones, however, the proposed histological subtypes are not consistent with the real life clinical characteristics of patients with aggressive tumors/carcinomas. So far, no single clinical, radiological or histological parameter can determine the risk of growth or malignant progression. Novel promising molecular prognostic markers, such as mutations in ATRX, TP53, SF3B1, and epigenetic DNA modifications, will need to be verified in larger tumor cohorts. In this review, we provide a critical analysis of the WHO guidelines for prognostic stratification and diagnosis of aggressive and metastatic PitNETs. In addition, we discuss the new WHO recommendations for changing ICD-O and ICD-11 codes for PitNET tumor behavior from a neoplasm either \"benign\" or \"unspecified, borderline, or uncertain behavior\" to \"malignant\" neoplasm regardless of the clinical presentation, histopathological subtype, and tumor location. We encourage multidisciplinary initiatives for integrated clinical, histological and molecular classification, which would enable early recognition of these challenging tumors and initiation of more appropriate and aggressive treatments, ultimately improving the outcome.

UNASSIGNED: Endoscopic transsphenoidal surgery can be performed by two surgeons, including an endoscopist (PE/2S), and by a single surgeon with an endoscope-holder system (PE/1S + H). We analyzed the surgical outcome, and outcome predictors in acromegaly patients in endoscopic transsphenoidal surgery using floor standing pneumatic endoscope-holder system.
UNASSIGNED: Endoscopic transsphenoidal surgery was performed with PE/1S+H (n = 51) and PE/2S (n = 20). Postoperative remission was evaluated by the 2010 consensus criteria for acromegaly. We compared the surgical results of PE/2S style and PE/1S+H style, and investigated the factors associated with favorable surgical outcomes.
UNASSIGNED: There was no difference in clinical background between the PE/2S and the PE/1S + H groups. The remission rates for PE/2S and PE/1S+H were 65.0% and 82.4%, respectively, with no significant difference (p = 0.128). In consecutive 71 cases, statistically useful predictors of remission were low preoperative growth hormone (GH) level (<12 ng/mL), low Knosp grade (0-2), and low revised Knosp grade (0-3A). In the conventional Knosp grade 0-2 and 3/4, the sensitivity was 0.76 and the specificity was 0.81. In the revised Knosp grade 0-3A and 3B/4, the sensitivity was 0.96 and the specificity was 0.44.
UNASSIGNED: The outcome of GH-producing pituitary neuroendocrine tumors surgically removed by PE/1S+H could be almost equivalent to that by PE/2S. Preoperative low GH level and Knosp grades, including revised Knosp grades, are useful preoperative predictors for surgical remission of acromegaly.

OBJECTIVE: Nonfunctional pituitary neuroendocrine tumors (PitNETs) exhibit wide variability in growth pattern based on subtype. Silent corticotroph adenomas (SCAs) demonstrate aggressive growth compared to other nonfunctional adenomas (NFPAs), especially into the cavernous sinus. In this study, we sought to characterize other growth patterns of SCAs in comparison to NFPAs.
METHODS: We performed a retrospective analysis of all patients with nonfunctional PitNETs treated with surgical resection via endoscopic endonasal approach (EEA) at a single institution from August 1, 2018, to May 11, 2024. Preoperative computed tomography (CT) and magnetic resonance imaging (MRI) were reviewed to determine extension into the suprasellar space, sphenoid sinus, cavernous sinus, and clivus.
RESULTS: Ninety-one patients were included, including 20 SCAs and 71 NFPAs. SCAs demonstrated significantly greater rates of growth into the sphenoid sinus (55.0% vs. 23.94%, p=0.013), clivus (65.0% vs. 16.9%, p<0.0001), and cavernous sinus (defined as Knosp grade 3 or 4; 55.0% vs. 23.35%, p=0.016). Other NFPAs were more likely to grow into the suprasellar space (92.96% vs. 75.0%, p=0.038). Tumor volume was similar between groups (11.93 cm3 vs. 9.06 cm3, p=0.2).
CONCLUSIONS: Silent corticotroph PitNETs demonstrate predilection for invasion of bony structures, with higher rates of growing through the sellar floor into the sphenoid sinus, growing posteroinferiorly into the clivus, and laterally into the cavernous sinuses. Other nonfunctional PitNETs tended to follow the path of least resistance, growing superiorly into the suprasellar space. These differences in growth patterns may account for some of the clinical challenges of treating silent corticotroph PitNETs.

Pituitary neuroendocrine tumor is the third most common primary intracranial tumor. Its main clinical manifestations include abnormal hormone secretion symptoms, symptoms caused by tumor compression of the surrounding pituitary tissue, pituitary stroke, and other anterior pituitary dysfunction. Its pathogenesis is yet to be fully understood. Surgical treatment is still the main treatment. Despite complete resection, 10%-20% of tumors may recur. While dopamine agonists are effective in over 90% of prolactinomas, prolonged use and individual variations can lead to increased drug resistance and a gradual decline in efficacy, which ultimately requires surgical intervention. Nonsteroidal anti-inflammatory drugs reduce the production of inflammatory mediator prostaglandins by inhibiting the activity of cyclooxygenase and exert antipyretic, analgesic, antiplatelet, and anti-inflammatory effects. In recent years, many in-depth studies have confirmed the potential of nonsteroidal anti-inflammatory drugs as a preventive and antitumor agent. It has been extensively utilized in the prevention and treatment of various types of cancer. However, their specific mechanisms of action still need to be fully elucidated. This article summarizes recent research progress on the expression of cyclooxygenase in pituitary neuroendocrine tumors and the treatment of nonsteroidal anti-inflammatory drugs. It provides a feasible theoretical basis for further research on pituitary neuroendocrine tumors and explores potential therapeutic targets.

BACKGROUND: The locations of pituitary neuroendocrine tumor (PitNET) and anterior clinoid meningioma (ACM) appear to be very close but essentially different, as the former is inside the sella turcica while the latter is in the intradural space. A collision tumor thus requires a specific treatment strategy but has been rarely reported.
METHODS: A 77-year-old woman presented with progressive visual impairment due to significant compression of the optic apparatus by a collision of PitNET and ACM. With a minimally invasive two-stage therapeutic strategy, the ACM was first resected using an endoscopic mini-pterional approach, then the PitNET was removed with an endoscopic transnasal approach 8 weeks later, leading to significant improvement in visual function. The authors\' literature search identified only 2 documented cases of a similar collision.
CONCLUSIONS: This case underscores the complexity of the decision-making process in the management of collision tumors and suggests the potential benefit of staged minimally invasive surgical interventions in preserving visual function. Further accumulation of cases is warranted for refining the treatment strategy. https://thejns.org/doi/10.3171/CASE24240.

OBJECTIVE: Pseudocapsular resection is a well-recognized, useful approach to achieve endocrinological remission in functioning pituitary neuroendocrine tumors (PitNETs). However, its advantage in nonfunctioning PitNETs (NF-PitNETs) has not been established. This study aimed to clarify the contribution of pseudocapsular resection to the prevention of NF-PitNET recurrence in long-term follow-up.
METHODS: This retrospective study included 132 patients who underwent total tumor removal and were followed for more than 5 years after surgery. The patients were categorized into those who underwent total pseudocapsular resection (n = 67) and those who did not (n = 65). The nonpseudocapsule (nonpseudocap) resection group included patients who underwent partial pseudocapsular resection and those in whom the pseudocapsule was not resected, did not exist, or could not be identified during surgery. The main outcome measures were the tumor recurrence rate and site of recurrence.
RESULTS: In the nonpseudocap resection group, 2 patients (3.1%) had tumor recurrence in the cavernous sinus and 5 (7.7%) had tumor recurrence in the pituitary fossa. In the pseudocapsule (pseudocap) resection group, only 2 patients (3.0%) had tumor recurrence in the cavernous sinus and 0 patients had tumor recurrence in the pituitary fossa. Tumor recurrence in the pituitary fossa was more likely to occur in the nonpseudocap resection group than in the pseudocap resection group (p = 0.0267). Multivariate regression analysis revealed that pseudocapsular resection was a significant factor for reducing the tumor recurrence rate in the pituitary fossa (p = 0.0107).
CONCLUSIONS: Pseudocapsular resection may reduce the rate of tumor recurrence and improve the management of NF-PitNETs in long-term follow-up.

BACKGROUND: Mounting evidence underscores the significance of cellular diversity within the endocrine system and the intricate interplay between different cell types and tissues, essential for preserving physiological balance and influencing disease trajectories. The pituitary gland, a central player in the endocrine orchestra, exemplifies this complexity with its assortment of hormone-secreting and nonsecreting cells.
CONCLUSIONS: The pituitary gland houses several types of cells responsible for hormone production, alongside nonsecretory cells like fibroblasts and endothelial cells, each playing a crucial role in the gland\'s function and regulatory mechanisms. Despite the acknowledged importance of these cellular interactions, the detailed mechanisms by which they contribute to pituitary gland physiology and pathology remain largely uncharted. The last decade has seen the emergence of groundbreaking technologies such as single-cell RNA sequencing, offering unprecedented insights into cellular heterogeneity and interactions. However, the application of this advanced tool in exploring the pituitary gland\'s complexities has been scant. This review provides an overview of this methodology, highlighting its strengths and limitations, and discusses future possibilities for employing it to deepen our understanding of the pituitary gland and its dysfunction in disease states.
CONCLUSIONS: Single-cell RNA sequencing technology offers an unprecedented means to study the heterogeneity and interactions of pituitary cells, though its application has been limited thus far. Further utilization of this tool will help uncover the complex physiological and pathological mechanisms of the pituitary, advancing research and treatment of pituitary diseases.

Unlike somatotroph tumors, the data on correlates of tumor granulation patterns in functional TPIT lineage pituitary neuroendocrine tumors (corticotroph tumors) have been less uniformly documented in most clinical series. This study evaluated characteristics of 41 well-characterized functional corticotroph tumors consisting of 28 densely granulated corticotroph tumors (DGCTs) and 13 sparsely granulated corticotroph tumors (SGCTs) with respect to preoperative clinical and radiological findings, tumor proliferative activity (including mitotic count and Ki-67 labeling index), and postoperative early biochemical remission rates. The median (interquartile range (IQR)) tumor size was significantly larger in the SGCT group [16.00 (16.00) mm in SGCT vs 8.5 (9.75) mm in DGCT, p = 0.049]. T2-weighted signal intensity and T2 intensity (quantitative) did not yield statistical significance based on tumor granulation; however, the T2 intensity-to-white matter ratio was significantly higher in SGCTs (p = 0.049). The median (IQR) Ki-67 labeling index was 2.00% (IQR 1.00%) in the DGCT group and 4.00% (IQR 7.00%) in the SGCT group (p = 0.043). The mitotic count per 2 mm2 was higher in the SGCT group (p = 0.001). In the multivariate analysis, the sparse granulation pattern (SGCT) remained an independent predictor of a lower probability of early biochemical remission irrespective of the tumor size and proliferative activity (p = 0.012). The current study further supports the impact of tumor granulation pattern as a biologic variable and warrants the detailed histological subtyping of functional corticotroph tumors as indicated in the WHO classification of pituitary neuroendocrine tumors. More importantly, the assessment of the quantitative T2 intensity-to-white matter ratio may serve as a preoperative radiological harbinger of SGCTs.

Aggressive pituitary neuroendocrine tumors (PitNETs) present significant morbidity, and multimodal therapies including surgery, radiotherapy, and medications are frequently required. Chemotherapy, particularly temozolomide, is often pursued for tumors that progress despite these treatments. Although peptide receptor radionuclide therapy (PRRT) using radiolabeled somatostatin analogs is approved for the treatment of well-differentiated gastrointestinal neuroendocrine tumors, its use in aggressive PitNETs is limited. We describe the case of a 65-year-old man who presented with vision changes and hypopituitarism at age 33 secondary to a nonfunctioning gonadotroph PitNET. His initial treatment included a craniotomy followed by radiation therapy. With tumor regrowth, he required transsphenoidal surgeries at age 44 and age 52. At age 56, further tumor regrowth and a positive octreotide scan prompted treatment with long-acting octreotide for 1 year. Given absent tumor response, 12 cycles (4 treatment cycles and 8 maintenance cycles) of PRRT with 177Lutetium-DOTATATE were pursued. This resulted in partial response with significant tumor shrinkage. Notably, there was no tumor regrowth 40 months after treatment discontinuation. This is only the second report on the effectiveness of PRRT in patients with aggressive gonadotroph PitNETs. We also provide an overview of PRRT for PitNETs and describe clinical outcomes previously reported in the literature.

Mixed pituitary adenoma/PitNET-gangliocytomas (PA/PitNET-GC) have been reported in small series over the past 20 years; some had limited immunohistochemistry (IHC) data. We interrogated our experience over 20 years, focusing on patterns of the GC component and IHC results for anterior pituitary hormones, transcription factors, NFP, and CAM5.2. A search of cases from 2002 to 2023 yielded 20 cases: 7M:13F, ages 20-71 years; 17 macroadenomas, 1 microadenoma, 2 ectopic. GC was co-associated with 4 corticotroph, 2 densely granulated lactotroph, 5 mixed lactotroph-somatotroph, 1 immature PIT1-lineage tumor, and 8 sparsely granulated GH; the latter all had a minor lactotroph component. Patterns were: discrete nodular foci of GC (9/20), extensive GC differentiation often overshadowing the PA/PitNET (7/20), and intimate admixture of smaller bands of neuropil and individual metaplastic ganglion cells within PA/PitNET (4/20). NFP highlighted small cohesive regions of neuropil and identified greater axonal content, including individual axons within \"pure\" PA/PitNET areas, than appreciated on H&E. CAM5.2 IHC often revealed cells with neuronal morphologies to a greater extent than NFP and in different areas within the same tumor. These data suggest that the combined use of NFP and CAM5.2 IHC best reveals transition from PA to GC phenotype, with CAM5.2 positivity reflecting earlier stages of transformation.