Pituitary Gland Carcinoma

4 pts received TT at recurrence, within clinical trials: one with grade 3 meningioma and ALK rearrangement treated with alectinib, one with PTCH1 mutant medulloblastoma treated with vismodegib, and two with high TMB treated with nivolumab/ipilumumab. The incidence of targettable molecular alterations in adult CNS tumor patients was lower than in GBM. Nevertheless, in a few selected cases TT have the potential to increase treatment options at recurrence and improve outcomes.

Although further research is needed to firmly establish a possible association, this case also highlights the necessity of exploring genetic backgrounds when patients present with clinical manifestations not readily explained by a single endocrine disorder. Investigating potential genetic associations is crucial since a positive genetic test allows for the testing of relatives, genetic counseling, and proper surveillance of individuals at risk.

GNAS mutations are prevalent among Chinese acromegaly patients, correlating with reduced pituitary tumor sizes and enhanced GH secretion functions. Our findings underscore the influence of gender on the clinical manifestations of GNAS mutations. Accordingly, we recommend that future clinical and foundational researches on acromegaly give heightened consideration to gender-specific differences.

Pasireotide long-acting release (PAS-LAR) is a second-generation somatostatin receptor ligand (SRL) approved for acromegaly treatment. These findings suggest that PAS-LAR is an effective option for acromegaly patients resistant to fgSRL, but careful monitoring of glucose levels is essential. The high heterogeneity observed across studies emphasizes the need for identifying PAS-LAR response biomarkers to set-up individualized treatment approaches for optimizing patient outcomes.

Our findings point to a pivotal role of PANX1 in promoting PA invasion, which indicated a potential therapeutic target for invasive PA.

TRIM21 may represent a therapeutic target for tumors, and inhibiting TRIM21 could be a potential strategy for tumor treatment.

P=N/A, N=500, Not yet recruiting, Beijing Tiantan Hospital, Capital Medical University; Beijing Tiantan Hospital, Capital Medical University

P4, N=290, Not yet recruiting, Beijing Tian Tan Hospital, Capital Medical University; Beijing Tian Tan Hospital, Capital Medical University

P4, N=882, Not yet recruiting, Beijing Tiantan Hospital

sPitNETs fall into three relevant cytogenetic groups: highly aneuploid tumors characterized by known prognostically favorable features and low aneuploidy tumors including specific subtype with chromosome 11 loss.

Importantly, B2R-D2R complexes were detected in human prolactinomas and nonfunctioning pituitary adenomas (NFPA), but not in mixed (prolactin + growth hormone) secreting adenomas. These results suggest that overexpression of B2R in resistant prolactinomas may promote the formation of B2R-D2R complexes, with B2R precluding D2R signaling, thus generating resistance to D2R agonists.

Microscopic trans-sphenoidal resection is associated with a lower risk of under-treatment. Postoperative outcomes and clinical benefits of curative surgeries are based on the complete type of surgical removal and size of the pituitary adenomas mass (Level of Evidence: 3; Technical Efficacy Stage: 4).

In this specific setting, treatment with somatostatin receptor ligands seems to have a protective role on fracture risk. Based on this evidence, a comprehensive osteometabolic evaluation should be performed in all patients with TSHoma, including assessment of BTM, measurement of BMD, and morphometric evaluation of VFs, both at diagnosis and then during follow-up, particularly in patients at high risk for fragility fractures.

Urinary free cortisol measurement was 21-fold the upper limit of the reference range (3,614.0 nmol/24 h), and cortisol concentration did not decrease after 1mg-dexamethasone suppression test (1,812 nmol/L for an expected value <50 nmol/L), confirming the ACTH-dependent CS...Hypercortisolism symptoms were effectively managed with an adrenal enzyme inhibitor (ketoconazole) in combination with somatostatin analogs...This redifferentiation phenomenon in neuroendocrine tumors should be further investigated as patients might be, under certain conditions, eligible for PRRT. Therefore, we suggest that newly occurring paraneoplastic syndromes in patients with NEC should always be evaluated using 68Ga-DOTATATE PET/CT.

Although many different scoring systems for SST2 immunohistochemistry showing correlation with SRL response have been reported, among which the immunoreactivity score (IRS) has been the most consistently used, a universally validated immunohistochemical technique and scoring scheme is lacking. Efforts should be made on collaborative multicenter studies aiming at validating homogeneous immunostaining protocols and a scoring system for SST2 and SST5 expression, to help clinicians to define the optimal therapeutic strategy for the patients with somatotroph tumors.

P=N/A, N=200, Active, not recruiting, Huashan Hospital

P=N/A, N=600, Completed, Huashan Hospital | Recruiting --> Completed

PTTG1 shows potential as a cancer diagnostic, prognostic, and chemosensitivity marker. Increased PTTG1 expression is linked to resistance to cancer treatment. The mechanism could be linked to PTTG1's role in promoting cytotoxic T lymphocyte dysfunction and mediating T cell exhaustion. It is feasible to consider PTTG1, which is expressed on Treg and Tprolif cells, as a new therapeutic target for overcoming immunotherapy resistance.

Co-expression of multiple transcription factors is an important factor associated with clinical behavior and endocrine outcomes in patients with GHPA.

In contrast, overexpression of VDAC2 in regrowing PAs suggests an antiapoptotic role for this gene. In summary, the genes evaluated might be involved in the biopathology of PAs.

TMZ demonstrates promising efficacy in eliciting tumor responses in patients with PRA. MGMT and MSH6 have emerged as potential biomarkers for predicting treatment response. Furthermore, radiation with concurrent TMZ may significantly improve outcomes in patients with RPA.

Finally, we analyzed PTEN/PI3K activation in a collection of human pituitary tumors. Overall, our study delineates the intricate interplay between the PTEN and ERK signaling pathways, providing insights into sex-specific mechanisms of pituitary tumorigenesis and potential therapeutic strategies for prolactinomas.

We conclude that metastatic PitNET is not the only high-grade form of pituitary NEN. If further confirmed, these histopathologic and/or molecular features could provide advanced warning of biological aggressiveness and be applied towards a future grading scheme.

Our work reveals MAX as a broad suppressor of neuroendocrine tumorigenesis through its ability to maintain a balance of genomic occupancies among the diverse transcription factors in the MYC network. MAX inactivation deregulates multiple transcription factors to induce neuroendocrine cancers.

Both, AdFITC(E2)-CAR T-cell tumor infiltration and biocidal activity were Octo-Fluo concentration-dependent, with high doses of Octo-Fluo, saturating both the CAR and the SSTR2 antigen independently, leading to the loss of tumor infiltration and biocidal activity due to the loss of bridge formation. Our findings demonstrate the potential of using AdFITC(E2)-CAR T-cells with Octo-Fluo as a versatile, on-off tunable bispecific adaptor for targeted CAR T-cell immunotherapy against SSTR2-positive NETs.

Paediatric PA present multiple peculiarities that may challenge their adequate management. They are overall proportionally larger and more aggressive than in adults, with potential mass effects including hypopituitarism. Hormonal hypersecretion is frequent, resulting in clinical syndromes affecting normal growth and pubertal development. Prolactinomas represent the most frequent subtype of PA found during childhood, followed by adrenocorticotropin (ACTH) and growth hormone (GH)-secreting adenomas, while clinically non-functioning adenomas are exceptionally diagnosed before the age of 16. The occurrence of a pituitary tumour in a young individual should also prompt genetic testing in each case, searching for either germline mutations in one of the known genes that may drive inherited/familial PA (such as the multiple endocrine neoplasia type 1 or MEN1 gene, or the aryl hydrocarbon receptor Interacting protein or AIP gene), or for a mosaic activating mutation of GNAS as found in the McCune-Albright syndrome.

Silencing Cdk5 or Mcm2 suppressed cell proliferation and colony formation in the 293T cell lines. Therefore, our findings provide a new mouse model of intermediate lobe-originated pituitary adenoma induced by p25/Cdk5 and unveil a previously unappreciated role of Cdk5 and Mcm2 in pituitary adenoma tumorigenesis.

Our study introduces a novel molecular classification for pituitary adenomas, independent of traditional histological methods. Each subtype features distinct genetic, molecular, and immunological profiles. We have isolated pituitary adenoma stem-like cells (PASCs), pairing them with tumor tissues for detailed transcriptomic analysis. These PASCs exhibit diverse molecular traits consistent with the new classification.

Spliceosome machinery provide novel insights into the pathogenesis of GH-secreting pituitary tumor and highlight the potential role of TCERG1 as a biomarker for tumor aggressiveness.

Mechanistically, AR promotes cell proliferation and PRL secretion and confers drug resistance by transcriptionally regulating NRF2 expression to maintain redox homeostasis in PA cells. Finally, combining AR targeting agents with BRC shows promise as a therapeutic strategy for treating PRL adenomas.

Pituitary spindle cell oncocytoma is a rare entity among pituitary tumors. This case report highlights the clinical, radiological, histopathological, and immunohistochemical features of PSCO. Surgeons and pathologists should consider this rare diagnosis in patients with sellar and suprasellar masses, as early recognition and complete surgical resection can lead to favorable outcomes.

The heterozygous missense mutation in the AR gene found in this family with familial idiopathic hyperprolactinemia is not yet explained. Hence, further research is warranted to elucidate the functional implications of this mutation on AR and its role in the pathogenesis of hyperprolactinemia.

If meningiomas, craniopharyngiomas, and germ cell tumors are excluded, the remaining lesions include a broad spectrum of uncommon, benign, and aggressive, often diagnostically challenging lesions. This review aims to summarize the essential clinicopathological features of tumors of the posterior pituitary gland, infundibulum spectrum expressing thyroid transcription factor 1, and primary sellar atypical rhabdoid teratoid tumor, and provide the criteria for their diagnosis and management.

P=N/A, N=10, Recruiting, The First Affiliated Hospital of Xiamen University | Not yet recruiting --> Recruiting

This study elucidates the biological basis of psoriasis. At the same time, it was discovered that PTTG1 derived from exhausted T cells serves as a diagnostic biomarker for psoriasis. Leptomycin B could be a potential drug for targeted treatment of psoriasis on PTTG1.

Younger patients with macroadenoma and hyperprolactinemia are more likely to have preoperative hypogonadism. Neurosurgical treatment can normalize LH, FSH, and total testosterone in approximately 30% of these patients.

This case emphasizes the need for comprehensive assessment in patients with acromegaly to address coexisting diabetic complications. Surgical and radiotherapeutic management of acromegaly can lead to significant metabolic improvements, highlighting the importance of interdisciplinary care in managing these complex cases.

Taken together, EGFR and STAT3-related lncRNAs may be involved in the pathogenesis of NFPA.

There was no glomerular or proximal tubular damage at the time of the study, as proven by the normal levels of the biomarkers nephrin and KIM-1. Studies including more patients with uncontrolled disease are needed to clarify the utility of nephrin and KIM-1 for the detection of early kidney involvement in acromegalic patients.

Overall, SNS can significantly treat HPRL liver depression at both animal and cellular levels, and effectively alleviate the related symptoms by regulating lipid metabolism. AKT1, TNF and IL6 may be key targets.

AVM showed vasculitis, endarteritis, endothelial damage, leukocyte plug, and damage to the vessel wall with fragmentation of the collagen and actin filaments. The sellar mass showed a non-functioning pituitary adenoma with hemorrhagic foci and necrosis as well as a proteinaceous vs. lipid material deposition with minimal vascular changes such as endothelial hyperplasia with minimal vasculitis and hyperplasia of reticular stellate cells, with positive glial fibrillary acidic protein (GFAP), which expressed low expression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), IL6, IL10, IL17, tumor necrosis factor-alpha (TNFa), HIF1a, factor VIII (FVIII), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and VEGF receptor 2 (VEGFR2). The patient's polymerase chain reaction COVID-19 test was positive, and she died three days after the surgery procedure. In our knowledge of COVID-19 brain lesions and in the literature review, this was a rare case of a double pathology associated with COVID-19 infection characterized by rupture of the AVM with hemorrhages and brain infarcts associated with endarteritis, vessel wall injuries, and pituitary apoplexy.

The patient underwent left adrenal surgery; somatostatin analogue lanreotide was started for the pancreatic lesions; the pituitary adenoma, being small and non-secreting, was not treated. A genetic test was performed to confirm the diagnosis of MEN1 syndrome, finding an association with a recently discovered mutation: the (NM_130799.2):c.758delC (p.Ser253Cysfs*28) in exon 4.