RESUMO
Pituitary neuroendocrine tumors (PitNETs) exhibiting aggressive, treatment-refractory behavior are the rare subset that progress after surgery, conventional medical therapies, and an initial course of radiation and are characterized by unrelenting growth and/or metastatic dissemination. Two groups of patients with PitNETs were sequenced: a prospective group of patients (n = 66) who consented to sequencing prior to surgery and a retrospective group (n = 26) comprised of aggressive/higher risk PitNETs. A higher mutational burden and fraction of loss of heterozygosity (LOH) was found in the aggressive, treatment-refractory PitNETs compared to the benign tumors (p = 1.3 × 10-10 and p = 8.5 × 10-9, respectively). Within the corticotroph lineage, a characteristic pattern of recurrent chromosomal LOH in 12 specific chromosomes was associated with treatment-refractoriness (occurring in 11 of 14 treatment-refractory versus 1 of 14 benign corticotroph PitNETs, p = 1.7 × 10-4). Across the cohort, a higher fraction of LOH was identified in tumors with TP53 mutations (p = 3.3 × 10-8). A machine learning approach identified loss of heterozygosity as the most predictive variable for aggressive, treatment-refractory behavior, outperforming the most common gene-level alteration, TP53, with an accuracy of 0.88 (95% CI: 0.70-0.96). Aggressive, treatment-refractory PitNETs are characterized by significant aneuploidy due to widespread chromosomal LOH, most prominently in the corticotroph tumors. This LOH predicts treatment-refractoriness with high accuracy and represents a novel biomarker for this poorly defined PitNET category.
Assuntos
Perda de Heterozigosidade , Tumores Neuroendócrinos , Neoplasias Hipofisárias , Humanos , Perda de Heterozigosidade/genética , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/patologia , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/terapia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Estudos Retrospectivos , Mutação/genética , Estudos ProspectivosRESUMO
PURPOSE: This study was undertaken to assess the unmet needs within the endogenous Cushing's syndrome (CS) care paradigm from the endocrinologist's perspective, including data abstracted from patient charts. The study evaluated endocrinologists' perceptions on burden of illness and treatment rationale along with the long-term clinical burden of CS, tolerability of CS treatments, and healthcare resource utilization for CS. METHODS: Retrospective medical chart data from treated patients with a confirmed diagnosis of CS was abstracted using a cross-sectional survey to collect data from qualified endocrinologists. The survey included a case report form to capture patient medical chart data and a web-enabled questionnaire to capture practitioner-level data pertaining to endocrinologists' perceptions of disease burden, CS treatments, and treatment attributes. RESULTS: Sixty-nine endocrinologists abstracted data from 273 unique medical charts of patients with CS. Mean patient age was 46.5 ± 13.4 years, with a 60:40 (female:male) gender split. The mean duration of endogenous CS amongst patients was 4.1 years. Chart data indicated that patients experienced a high burden of comorbidities and symptoms, including fatigue, weight gain, and muscle weakness despite multi-modal treatment. When evaluating treatments for CS, endocrinologists rated improvement in health-related quality of life (HRQoL) as the most important treatment attribute (mean score = 7.8; on a scale of 1 = Not at all important to 9 = Extremely important). Surgical intervention was the modality endocrinologists were most satisfied with, but they agreed that there was a significant unmet treatment need for patients with CS. CONCLUSION: Endocrinologists recognized that patients with CS suffered from a debilitating condition with a high symptomatic and HRQoL burden and reported that improvement in HRQoL was the key treatment attribute influencing their treatment choices. This study highlights unmet needs for patients with CS. Patients with CS have a high rate of morbidity and comorbidity, even after treatment.
Assuntos
Síndrome de Cushing , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Síndrome de Cushing/terapia , Síndrome de Cushing/diagnóstico , Endocrinologistas , Qualidade de Vida , Estudos Retrospectivos , Estudos TransversaisRESUMO
PURPOSE: To study the long-term effect of transsphenoidal surgery (TSS) on headache in patients with non-functioning pituitary adenoma (NFPA) and identify factors predicting headache relief following TSS. METHODS: We evaluated headache in 101 consecutive patients with NFPA who underwent TSS from September 2015 to December 2021, preoperatively and 12-months post-surgery, by using the Migraine Disability Assessment (MIDAS) questionnaire. Health-related quality of life (QoL) was assessed using the EQ-5D visual analogue scale (EQ-VAS). RESULTS: Of 101 patients, 27 (27%) experienced disabling preoperative headache. Among these, the median total MIDAS score improved from 60 (interquartile range (IQR): 19-140) to 10 (IQR: 0-49) (P = 0.004). Additionally, headache frequency over a 90-day period decreased from 45 (IQR: 25-83) to 6 (IQR: 3-36) days (P = 0.002), and headache intensity decreased from 5 (IQR: 4-7) to 4 (IQR: 2-7) (P = 0.016) at 12-months post-surgery. At 12 months post-surgery, 18 (67%) of 27 patients with preoperatively disabling headache showed clinically relevant improvement of their headache, 4 (15%) showed deterioration, and 5 (19%) remained unchanged. In patients with clinically relevant improvement of their headache, the EQ-VAS score improved from 50 (IQR: 30 - 7) to 80 (IQR: 65-86) (P < 0.001). Of the 74 patients with no preoperative headache, 11 (15%) developed postoperative headache. We identified no clinical factors predicting postoperative headache relief. CONCLUSION: The study supports that clinically significant and long-lasting improvements of disabling headache and QoL can be achieved with TSS in a substantial number of patients with NFPA.
RESUMO
INTRODUCTION: Silent corticotroph tumors (siACTH) represent a rare entity of pituitary tumors (PT), usually more aggressive than other PT. Few predictor factors of recurrence in the post-operative period have been proposed until now. This study aimed (1) to evaluate the clinical outcome of siACTH after surgery according to a five-tiered clinicopathological classification (2) to compare siACTH characteristics to ACTH-secreting macroadenomas (macroCD), and silent gonadotropinomas (siLH/FSH). PATIENTS AND METHODS: Between 2008 and 2022, 29 siACTH out of 865 PT cases operated in one tertiary center were included. Clinical, paraclinical, histological, and surgical data were collected and compared to 25 macroCD and 143 siLH/FSH cases, respectively. The tumor grading was established according to both invasion (no = 1; yes = 2) and proliferation (no = a; yes = b). Progression-free survival was estimated using Kaplan-Meier method and log-rank test. RESULTS: We identified 15 (51.7%) grade 1a, 11 (37.9%) grade 2a and 3 (10.3%) grade 2b siACTH with a trend for a 7-fold-time higher risk of progression/recurrence in grade 2b as compared to 1a (p = 0.06). The repartition of tumor grades was similar between the three subgroups, however a 5.7-fold-higher risk of progression was observed in grade 1a siACTH than in grade 1a siLH/FSH (p = 0.02). Compared to siLH/FSH, higher ACTH levels may help to preoperatively identify siACTH. CONCLUSION: The five-tiered clinicopathological classification contribute to predict the risk of recurrence of operated siACTH tumors. Noteworthy, non-invasive and non-proliferative siACTH exhibit a less favorable outcomes than their siLH/FSH counterparts, which should prompt for a personalized follow up.
RESUMO
PURPOSE: Pasireotide is a novel therapeutic option for patients with acromegaly resistant to first-generation somatostatin receptor ligands. To date, real-life data are still scant, therefore, the aim of the current study is to evaluate the impact of long-term pasireotide therapy on disease control, pituitary tumor size, gluco-insulinemic and lipid profile in a real-life setting. METHODS: Retrospective study of data prospectively collected, evaluating hormonal, tumoral, and metabolic data of 28 patients with acromegaly administered with pasireotide in a pituitary tertiary referral center. RESULTS: Within the first 12 months of treatment, 70.4% of patients achieved normal IGF-I levels, which was maintained at 36-month evaluation in these responders patients. Patients who started with pasireotide 60 mg monthly exhibited significantly lower IGF-I levels after 36 months (p = 0.05) as compared to patients administered first with pasireotide 20 or 40 mg monthly. The maximal tumoral diameter was significantly decreased after 12 months of pasireotide (p < 0.001) and a further reduction was registered throughout the following months, with 41.2% of patients achieving a significant reduction (> 25% of baseline measurement) after 36 months of treatment. Fasting glucose significantly increased during the first 6 months (p < 0.001) with a gradual rise in diabetes prevalence during the following months, resulting diabetes prevalence after 36 months of pasireotide significantly increased compared to baseline (p = 0.003), although with glycated hemoglobin levels within the normal range. Diabetes was managed using oral glucose-lowering drugs or glucagon-like peptide 1 agonists, with no patient requiring insulin therapy. Pasireotide improved lipid profile, mainly during the first 12 months of treatment, by increasing HDL and decreasing triglycerides levels. CONCLUSION: Pasireotide is effective and safe in the long-term. Hyperglycemia is a common event and is manageable even without insulin treatment.
Assuntos
Acromegalia , Somatostatina , Humanos , Somatostatina/análogos & derivados , Somatostatina/administração & dosagem , Somatostatina/uso terapêutico , Masculino , Feminino , Acromegalia/tratamento farmacológico , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Idoso , Seguimentos , Resultado do Tratamento , Encaminhamento e Consulta , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like I/metabolismo , Glicemia/análiseRESUMO
TDP2 gene encodes tyrosyl DNA phosphodiesterase 2, an enzyme required for effective repair of the DNA double-strand breaks (DSBs). Spinocerebellar ataxia autosomal recessive 23 (SCAR23) is a rare disease caused by the pathogenic mutation of TDP2 gene and characterized by intellectual disability, progressive ataxia and refractory epilepsy. Thus far, merely nine patients harboring five different variants (c.425 + 1G > A; c.413_414delinsAA, p. Ser138*; c.400C > T, p. Arg134*; c.636 + 3_ 636 + 6 del; c.4G > T, p. Glu2*) in TDP2 gene have been reported. Here, we describe the tenth patient with a novel variant (c.650del, p. Gly217GlufsTer7) and new phenotype (pituitary tumor and hyperhidrosis).
Assuntos
Hiperidrose , Diester Fosfórico Hidrolases , Neoplasias Hipofisárias , Feminino , Humanos , Proteínas de Ligação a DNA/genética , Hiperidrose/genética , Mutação , Diester Fosfórico Hidrolases/genética , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/complicações , Ataxias Espinocerebelares/genética , Ataxias Espinocerebelares/complicações , Adolescente , LactenteRESUMO
BACKGROUND: Delayed epistaxis after endoscopic transnasal pituitary tumor resection (ETPTR) is a critical complication, tending to cause aspiration or hemorrhagic shock. This study assessed clinical characteristics, risk factors, and provide treatment and prevention advice of this complication. METHODS: This was a retrospective monocentric analysis of 862 patients who underwent ETPTR. Statistical analyses of clinical data revealed the incidence, sources and onset time of delayed epistaxis. Univariate analysis and binary logistic regression were used to identify risk factors. RESULTS: The incidence of delayed epistaxis was 2.78% (24/862), with an average onset time of 20.71 ± 7.39 days. The bleeding sources were: posterior nasal septal artery branch of sphenopalatine artery (12/24), multiple inflammatory mucosae (8/24), sphenopalatine artery trunk (3/24) and sphenoid sinus bone (1/24). Univariate analysis and binary logistic regression analysis confirmed that hypertension, nasal septum deviation, chronic rhinosinusitis and growth hormone pituitary tumor subtype were independent risk factors for delayed epistaxis. Sex, age, history of diabetes, tumor size, tumor invasion and operation time were not associated with delayed epistaxis. All patients with delayed epistaxis were successfully managed through endoscopic transnasal hemostasis without recurrence. CONCLUSIONS: Delayed epistaxis after ETPTR tends to have specific onset periods and risk factors. Prevention of these characteristics may reduce the occurrence of delayed epistaxis. Endoscopic transnasal hemostasis is recommended as the preferred treatment for delayed epistaxis.
Assuntos
Epistaxe , Neoplasias Hipofisárias , Humanos , Epistaxe/etiologia , Epistaxe/prevenção & controle , Epistaxe/epidemiologia , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Neoplasias Hipofisárias/cirurgia , Fatores de Risco , Adulto , Idoso , Seguimentos , Prognóstico , Incidência , Endoscopia/métodos , Endoscopia/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Adulto Jovem , Fatores de Tempo , Adolescente , Cirurgia Endoscópica por Orifício Natural/efeitos adversos , Cirurgia Endoscópica por Orifício Natural/métodosRESUMO
Over 20 years ago, Hanahan and Weinberg published a seminal review that addressed the biological processes that underly malignant transformation. This classical review, along with two revisions published in 2011 and 2022, has remain a classic of the oncology literature. Since many of the addressed biological processes may apply to non-malignant tumorigenesis, we evaluated to what extent these hallmarks pertain to the development of pituitary adenomas.Some of the biological processes analyzed in this review include genome instability generated by somatic USP8 and GNAS mutations in Cushing's diseases and acromegaly respectively; non-mutational epigenetic reprograming through changes in methylation; induction of angiogenesis through alterations of VEGF gene expression; promotion of proliferative signals mediated by EGFR; evasion of growth suppression by disrupting cyclin dependent kinase inhibitors; avoidance of immune destruction; and the promotion of inflammation mediated by alteration of gene expression of immune check points. We also elaborate further on the existence of oncogene induced senescence in pituitary tumors. We conclude that a better understanding of these processes can help us dilucidated why pituitary tumors are so resistant to malignant transformation and can potentially contribute to the development of novel anticancer treatments.
Assuntos
Acromegalia , Adenoma , Neoplasias Hipofisárias , Humanos , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/patologia , Adenoma/patologia , MutaçãoRESUMO
INTRODUCTION: Macroautophagy is a lysosome-mediated degradation process that controls the quality of cytoplasmic components and organelles, with its regulation depending on autophagy-related proteins (Atg) and with Beclin1/Atg6 and microtubule-associated protein light chain 3 (LC3/Atg8) being key players in the mammalian autophagy. As reports on this mechanism in the field of pituitary neuropathology and neuroendocrinology are scarce, our study analyzed the ultrastructural signs of macroautophagy and the expression of Beclin1 and LC3 proteins in human functioning PitNETs and in experimental pituitary tumors. METHODS: A group of humans functioning PitNETs and an experimental lactotroph model in rats of the F344 strain stimulated with estradiol benzoate (BE) were used. Ultrastructural and molecular evidence of the macroautophagic process was evaluated using different techniques. RESULTS: In functioning PitNETs cohort, 60% exhibited evidence of macroautophagy, with a significant difference found for Beclin1 and LC3 between macro- and micro-PitNETs (p < 0.05). In the experimental model, the expression of both Beclin1 and LC3 proteins was immunopositive in normal and tumoral glands when analyzed by immunofluorescence, Western blot, and immunohistochemistry. In the experimental model, protein expression was associated with increased glandular size and weight. CONCLUSIONS: Our study revealed evidence of macroautophagy at the pituitary level and the important role of Beclin1 and LC3 in the progression of functioning PitNETs, implying that this mechanism participate in regulating pituitary cell growth.
Assuntos
Macroautofagia , Neoplasias Hipofisárias , Humanos , Ratos , Animais , Proteína Beclina-1 , Ratos Endogâmicos F344 , Autofagia , Proteínas Associadas aos Microtúbulos/metabolismo , Mamíferos/metabolismoRESUMO
OBJECTIVES: Pituitary adenomas can exhibit aggressive behavior, characterized by rapid growth, resistance to conventional treatment, and early recurrence. This study aims to evaluate the clinical value of shape-related features combined with textural features based on conventional MRI in evaluating the aggressiveness of pituitary adenomas and develop the best diagnostic model. METHODS: Two hundred forty-six pituitary adenoma patients (84 aggressive, 162 non-aggressive) who underwent preoperative MRI were retrospectively reviewed. The patients were divided into training (n = 193) and testing (n = 53) sets. Clinical information, shape-related, and textural features extracted from the tumor volume on contrast-enhanced T1-weighted images (CE-T1WI), were compared between aggressive and non-aggressive groups. Variables with significant differences were enrolled into Pearson's correlation analysis to weaken multicollinearity. Logistic regression models based on the selected features were constructed to predict tumor aggressiveness under fivefold cross-validation. RESULTS: Sixty-five imaging features, including five shape-related and sixty textural features, were extracted from volumetric CE-T1WI. Forty-seven features were significantly different between aggressive and non-aggressive groups (all p values < 0.05). After feature selection, four features (SHAPE_Sphericity, SHAPE_Compacity, DISCRETIZED_Q3, and DISCRETIZED_Kurtosis) were put into logistic regression analysis. Based on the combination of these features and Knosp grade, the model yielded an area under the curve value of 0.935, with a sensitivity of 94.4% and a specificity of 82.9%, to discriminate between aggressive and non-aggressive pituitary adenomas in the testing set. CONCLUSION: The radiomic model based on tumor shape and textural features study from CE-T1WI might potentially assist in the preoperative aggressiveness diagnosis of pituitary adenomas. KEY POINTS: ⢠Pituitary adenomas with aggressive behavior exhibit rapid growth, resistance to conventional treatment, and early recurrence despite gross resection and may require multiline treatments. ⢠Shape-related features and texture features based on CE-T1WI were significantly correlated with the Ki-67 labeling index, mitotic count, and p53 expression, and the proposed model achieved a favorable prediction of the aggressiveness of PAs with an AUC value of 0.935. ⢠The prediction model might provide valuable guidance for individualized treatment in patients with PAs.
Assuntos
Adenoma , Neoplasias Hipofisárias , Humanos , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/patologia , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Adenoma/diagnóstico por imagem , Adenoma/cirurgia , Adenoma/patologiaRESUMO
BACKGROUND: Ectopic pituitary adenoma (EPA) is defined as a special type of pituitary adenoma that originates outside of the sellar region, is extra- or intra-cranially located, and without connection to normal pituitary tissue. EPA is extremely rare, with most cases presented as case reports or small case series. Due to nonspecific symptoms and laboratory indicators, the preoperative diagnosis, treatment and management for EPA remain challenging. CASE PRESENTATION: Here, we report the imaging phenotype and pathological findings of a case of invasive EPA in a 47-year-old woman. A preoperative non-contrast CT scan revealed a 5.8 × 3.6 × 3.7 cm soft tissue mass located in the sphenoid sinus and clivus. MRI showed an ill-defined solid mass with heterogeneous signals on T1-weighted and T2-weighted images. The mass displayed infiltrative growth pattern, destroying bone of the skull base, invading adjacent muscles and encasing vessels. The patient underwent partial tumor resection via transsphenoidal endoscopic surgery. Pathological examination led to diagnosis of ectopic ACTH-secreting pituitary adenoma. Post-surgery, the patient received external beam radiotherapy. CONCLUSION: EPA with invasive growth pattern has rarely been reported. The imaging phenotype displays its relationship to the pituitary tissue and surrounding structures. Immunohistochemical examination acts as a crucial role in differentiating EPA from other skull base tumors. This case report adds to the literature on EPA by summarizing its characteristics alongside a review of the literature.
Assuntos
Adenoma Hipofisário Secretor de ACT , Adenoma , Cordoma , Neoplasias Hipofisárias , Humanos , Adenoma Hipofisário Secretor de ACT/diagnóstico , Adenoma Hipofisário Secretor de ACT/patologia , Adenoma Hipofisário Secretor de ACT/cirurgia , Neoplasias Hipofisárias/cirurgia , Adenoma/cirurgia , Hipófise/cirurgia , Imageamento por Ressonância MagnéticaRESUMO
PURPOSE: A clinicopathological classification has been designed to predict recurrence/progression in patients with pituitary adenomas (PAs). We aimed to study its usefulness in predicting PAs that will have a challenging disease course and may require more often complex multimodal and multiple therapeutic approaches. METHODS: Retrospective analysis of 129 patients with PAs operated in our institution between 2001 and 2020 (84 non-clinically functioning PAs, 32 acromegaly, 9 Cushing's disease, 2 prolactinomas and 2 thyrotropinomas). Grading was based on invasion and proliferation: 1a (non-invasive, non-proliferative; n = 59), 1b (non-invasive, proliferative; n = 17), 2a (invasive, non-proliferative; n = 38), and 2b (invasive, proliferative; n = 15). RESULTS: Of the 129 patients, 68 (52.7%) were females, and the mean age at diagnosis was 53.7 ± 15.4 years. The mean follow-up duration was 93.1 ± 61.8 months. Grade 2b PAs when compared to other grades (2b-2a-1b-1a) had significantly higher rates of persistent tumor remnant within 1-year after operation (93-78-18-30%; p < 0.001), active disease at last follow-up (40-27-12-10%; p = 0.004), re-operation (27-16-0-5%; p = 0.023), irradiation (53-38-12-7%; p < 0.001), multimodal treatment (67-49-18-25%; p = 0.003), multiple treatment (33-27-6-9%; p = 0.017). Patients with grade 2b PAs also required a higher mean number of treatments (2.6-2.1-1.2-1.4; p < 0.001). CONCLUSIONS: This clinicopathological classification appears to be a useful grading system to identify PAs that may be more refractory and more often require complex multimodal and multiple therapeutic approaches. Invasive PAs, especially grade 2b tumors, may be more likely to need complex treatment approach, including radiotherapy, and may display higher rates of active disease at last follow-up, despite receiving higher number of treatments.
Assuntos
Adenoma , Neoplasias Hipofisárias , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Masculino , Neoplasias Hipofisárias/patologia , Estudos Retrospectivos , Portugal , Hipófise/patologia , Adenoma/patologiaRESUMO
INTRODUCTION: Refractory pituitary adenomas are those that have progressed following standard of care treatments. Medical therapy options for these challenging tumors are limited. PURPOSE: To review the landscape of tumor directed medical therapies and off-label investigational approaches for refractory pituitary adenomas. METHODS: Literature on medical therapies for refractory adenomas was reviewed. RESULTS: The established first-line medical therapy for refractory adenomas is temozolomide, which importantly may increase survival, but clinical trial data are still needed to clearly establish its efficacy, identify biomarkers of response, and clarify eligibility and outcome criteria. Other therapies for refractory tumors have only been described in case reports and small case series. CONCLUSION: There are currently no approved non-endocrine medical therapies for refractory pituitary tumors. There is an urgent need for identifying effective medical therapies and studying them in multi-center clinical trials.
Assuntos
Adenoma , Neoplasias Hipofisárias , Humanos , Neoplasias Hipofisárias/patologia , Dacarbazina/uso terapêutico , Antineoplásicos Alquilantes/uso terapêutico , Adenoma/patologia , Temozolomida/uso terapêuticoRESUMO
Only a limited number of studies have focused on the results of the Endoscopic Endonasal Approach (EEA) for treatment of prolactinomas. We sought to assess the effectiveness of EEA for prolactinoma surgery, identify factors for disease remission, and present our approach for the management of persistent disease. Forty-seven prolactinomas operated over 10 years, with a mean follow-up of 59.9 months, were included. The primary endpoints were early disease remission and remission at last follow-up. Resistance/intolerance to DA were surgical indications in 76.7%. Disease remission was achieved in 80% of microprolactinomas and 100% of microprolactinomas enclosed by the pituitary. Early disease remission was correlated with female gender (p=0.03), lower preoperative PRL levels (p=0.014), microadenoma (p=0.001), lack of radiological hemorrhage (p=0.001), absence of cavernous sinus (CS) invasion (p<0.001), and extent of resection (EOR) (p<0.001). Persistent disease was reported in 48.9% of patients, with 47% of them achieving remission at last follow-up with DA therapy alone. Repeat EEA and/or radiotherapy were utilized in 6 patients, with 66.7% achieving remission. Last follow-up remission was achieved in 76.6%, with symptomatic improvement in 95.8%. Factors predicting last follow-up remission were no previous operation (p=0.001), absence of CS invasion (p=0.01), and EOR (p<0.001). Surgery is effective for disease control in microprolactinomas. In giant and invasive tumors, it may significantly reduce the tumor volume. A multidisciplinary approach may lead to long-term disease control in three-quarters of patients, with symptomatic improvement in an even greater proportion.
Assuntos
Neoplasias Hipofisárias , Prolactinoma , Humanos , Feminino , Prolactinoma/cirurgia , Prolactinoma/patologia , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/patologia , Prognóstico , Resultado do Tratamento , Estudos RetrospectivosRESUMO
Optical coherence tomography (OCT) is a useful tool for predicting visual recovery after the removal of pituitary tumors. However, the utility of OCT in patients with pituitary tumors and a normal visual field is unclear. We aimed to analyze OCT features in pituitary tumors without visual field defects. Pituitary tumors without visual field defects were selected. A total of 138 eyes from 69 patients, assessed by the Humphrey visual field test and OCT, were enrolled in this study. Using preoperative coronal sections of MR images, patients were divided into chiasmal compression (CC) and non-chiasmal compression (non-CC) groups, and OCT characteristics were examined. The CC and non-CC groups consisted of 40 and 29 patients, respectively. There were no differences in age, sex, tumor type, or degree of visual field testing, but the tumor size was different between the two groups. On OCT, macular thickness ganglion cell complex (mGCC) was significantly thinner in the CC group than that in the non-CC group (112.5 vs 117.4 um, P < 0.05). Based on a database of healthy participants, 24% and 2% of eyes in the CC and non-CC groups had abnormal mGCC thickness (P < 0.01), respectively. In a sub-analysis of the CC group, patients with an abnormal mGCC thickness were older than a normal one (58.2 vs 41.1 years, p < 0.01). OCT can detect early optic nerve damage due to optic CC by pituitary tumors, even in normal visual fields. The degree of mGCC thinning may provide an appropriate surgical timing for pituitary tumors that compress the optic chiasm.
Assuntos
Traumatismos do Nervo Óptico , Neoplasias Hipofisárias , Humanos , Testes de Campo Visual , Campos Visuais , Tomografia de Coerência Óptica/métodos , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/cirurgia , Células Ganglionares da Retina/patologia , Transtornos da Visão/etiologia , Quiasma Óptico/diagnóstico por imagemRESUMO
Breast cancer is a malignant type with morbidity ranking the first of women globally. As widely acknowledged, there exist close links between ncRNA-mRNA axis and breast cancer. In this study, we first overviewed expression and prognostic values of pituitary tumor transforming gene (PTTGs) in breast cancer. Next, two binding miRNAs (miR-186-5p and miR-655-3p) of PTTG1 in breast cancer were identified. Subsequently, several potential upstream ncRNAs of PTTG1-miR-186-5p/miR-655-3p axis in breast cancer were successively screened out, consisting of 11 lncRNAs, 17 circRNAs and 12 pseudogene-derived RNAs. Enrichment analysis for downstream target genes of PTTG1-miR-186-5p/miR-655-3p axis revealed that this axis is associated with TGF-beta signaling and MAPK signaling pathways. Further investigation demonstrated AURKA was one of the most key hub genes. Collectively, we established a potential PTTG1-related ncRNA-mRNA regulatory network in breast cancer.
Assuntos
Neoplasias da Mama , MicroRNAs , RNA Longo não Codificante , Humanos , Feminino , Neoplasias da Mama/genética , MicroRNAs/metabolismo , RNA não Traduzido/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genéticaRESUMO
Sellar melanocytomas represent a small subgroup of primary melanocytic tumors arising from leptomeningeal melanocytes. They are benign, slow-growing tumors with a high risk of recurrence. We report two cases of sellar melanocytoma treated at the same institute. A 35-year-old woman presented with amenorrhea and an intrasellar mass with suprasellar extension simulating a hemorrhagic pituitary adenoma. The second case is a 51-year-old man with progressive visual loss and a recurrence of primary sellar and suprasellar melanocytoma. The first patient underwent gross total resection and the second patient underwent subtotal resection. Neither of them was treated with postoperative adjuvant therapies. The second patient had tumor regrowth 75 months after surgery; he therefore underwent gamma knife radiosurgery. Both patients are alive and well at the last follow-up (140 and 93 months, respectively).
Assuntos
Adenoma , Neoplasias Hipofisárias , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adenoma/cirurgia , Terapia Combinada , Imageamento por Ressonância Magnética , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/cirurgia , CrânioRESUMO
Pituitary tumors (PT) are mostly benign, although occasionally they demonstrate aggressive behavior, invasion of surrounding tissues, rapid growth, resistance to conventional treatments, and multiple recurrences. The pathogenesis of PT is still not fully understood, and the factors responsible for its invasiveness, aggressiveness, and potential for metastasis are unknown. RAF/MEK/ERK and mTOR signaling are significant pathways in the regulation of cell growth, proliferation, and survival, its importance in tumorigenesis has been highlighted. The aim of our review is to determine the role of the activation of PI3K/AKT/mTOR and RAF/MEK/ERK pathways in the pathogenesis of pituitary tumors. Additionally, we evaluate their potential in a new therapeutic approach to provide alternative therapies and improved outcomes for patients with aggressive pituitary tumors that do not respond to standard treatment. We perform a systematic literature search using the PubMed, Embase, and Scopus databases (search date was 2012-2023). Out of the 529 screened studies, 13 met the inclusion criteria, 7 related to the PI3K/AKT/mTOR pathway, and 7 to the RAF/MEK/ERK pathway (one study was used in both analyses). Understanding the specific factors involved in PT tumorigenesis provides opportunities for targeted therapies. We also review the possible new targeted therapies and the use of mTOR inhibitors and TKI in PT management. Although the RAF/MEK/ERK and PI3K/AKT/mTOR pathways play a pivotal role in the complex signaling network along with many interactions, further research is urgently needed to clarify the exact functions and the underlying mechanisms of these signaling pathways in the pathogenesis of pituitary adenomas and their role in its invasiveness and aggressive clinical outcome.
Assuntos
Sistema de Sinalização das MAP Quinases , Neoplasias Hipofisárias , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias Hipofisárias/tratamento farmacológico , Fosfatidilinositol 3-Quinases/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , CarcinogêneseRESUMO
PURPOSE: Cushing's disease (CD) is often explained by a single somatic sequence change. Germline defects, however, often go unrecognized. We aimed to determine the frequency and associated phenotypes of genetic drivers of CD in a large cohort. METHODS: We studied 245 unrelated patients with CD (139 female, 56.7%), including 230 (93.9%) pediatric and 15 (6.1%) adult patients. Germline exome sequencing was performed in 184 patients; tumor exome sequencing was also done in 27 of them. A total of 43 germline samples and 92 tumor samples underwent Sanger sequencing of specific genes. Rare variants of uncertain significance, likely pathogenic (LP), or pathogenic variants in CD-associated genes, were identified. RESULTS: Germline variants (13 variants of uncertain significance, 8 LP, and 11 pathogenic) were found in 8 of 19 patients (42.1%) with positive family history and in 23 of 226 sporadic patients (10.2%). Somatic variants (1 LP and 7 pathogenic) were found in 20 of 119 tested individuals (16.8%); one of them had a coexistent germline defect. Altogether, variants of interest were identified at the germline level in 12.2% of patients, at the somatic level in 7.8%, and coexisting germline and somatic variants in 0.4%, accounting for one-fifth of the cohort. CONCLUSION: We report an estimate of the contribution of multiple germline and somatic genetic defects underlying CD in a single cohort.
Assuntos
Neoplasias , Hipersecreção Hipofisária de ACTH , Feminino , Humanos , Sequenciamento do Exoma , Predisposição Genética para Doença , Mutação em Linhagem Germinativa/genética , Neoplasias/genética , Fenótipo , Hipersecreção Hipofisária de ACTH/epidemiologia , Hipersecreção Hipofisária de ACTH/genéticaRESUMO
PURPOSE: To examine the contemporary epidemiology of adult pituitary tumors with a particular focus on uncommon tumor types, using the 2017 WHO Classification of pituitary tumors. METHODS: Adult patients presenting with a pituitary or sellar tumor between 2004 and 2017 were identified from the U.S. National Cancer Database, with tumor type categorized according to the 2017 WHO classification. Descriptive epidemiological statistics were evaluated and reported for all pituitary tumor types and subtypes. RESULTS: 113,349 adults with pituitary tumors were identified, 53.0% of whom were female. The majority of pituitary tumors were pituitary adenomas (94.0%), followed by craniopharyngiomas (3.8%). Among pituitary adenomas, whereas 71.6% of microadenomas presented in females, only 46.7% of macroadenomas and 41.3% of giant adenomas did (p < 0.001). For craniopharyngiomas, 71.2% were adamantinomatous and 28.8% were papillary, with adamantinomatous tumors associated with Black non-Hispanic race/ethnicity (ORadj = 2.44 vs. White non-Hispanic, 99.9 %CI = 1.25-4.75, p < 0.001) in multivariable analysis. The remaining 0.7% (n = 676) of pathology-confirmed pituitary tumor types were composed of: 21% tumors of the posterior pituitary, 16% chordomas, 11% pituitary carcinomas (i.e. adenohypophyseal histology with metastasis; herein most frequently to bone), 10% meningiomas, 8% germ cell tumors, 7% hematolymphoid (largely DLBCLs), and 4% neuronal/paraneuronal (largely gangliogliomas). Pituitary carcinomas and posterior pituitary tumors demonstrated a male predilection (62.2% and 56.0%, respectively), whereas sellar meningiomas predominated in females (84.1%). Age, race/ethnicity, tumor size, and overall survival further varied across uncommon pituitary tumor types. CONCLUSIONS: Our findings provide a detailed contemporary dissection of the epidemiology of common and uncommon adult pituitary tumors in the context of WHO2017.