Asunto(s)
Adenoma , Imagen por Resonancia Magnética , Neoplasias Hipofisarias , Humanos , Neoplasias Hipofisarias/diagnóstico por imagen , Neoplasias Hipofisarias/diagnóstico , Neoplasias Hipofisarias/patología , Adenoma/patología , Adenoma/diagnóstico por imagen , Femenino , Síndrome , Adulto , Persona de Mediana Edad , MasculinoRESUMEN
PURPOSE: Craniopharyngioma is a tumor derived from the squamous epithelium of Rathke's pouch. Despite successful excision, recurrence is common, typically occurring at the original tumor site. More rarely, recurrences can manifest at distant locations. This article reports on three distinct types of ectopic recurrence and reviews the existing literature. METHODS: We reviewed clinical records and neuroimaging data of craniopharyngioma patients at our institution, identifying three cases of ectopic recurrence. Additionally, we conducted a literature review of similar cases published between 1975 and 2023, focusing on historical background, pathophysiology, clinical and radiological features, and treatment options. RESULTS: We identified nineteen articles detailing ectopic recurrence of craniopharyngiomas in pediatric patients. The right frontal lobe was the most frequently reported site of recurrence. The shortest interval to recurrence was 11 months, while the longest was 14 years. Most cases were managed with surgical resection, yielding positive outcomes. In our cases, the recurrence sites were temporal intraparenchymal, intraosseous orbital, and occipital intraventricular. All were successfully treated with surgery, with no subsequent recurrences. CONCLUSION: Although craniopharyngiomas are histologically benign, they can recur locally and, more rarely, at distant sites. Surgical intervention is generally well-tolerated. Further research into tumor cell dissemination mechanisms is essential to develop strategies for preventing ectopic recurrence.
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Craneofaringioma , Recurrencia Local de Neoplasia , Neoplasias Hipofisarias , Humanos , Craneofaringioma/cirugía , Craneofaringioma/diagnóstico por imagen , Craneofaringioma/patología , Neoplasias Hipofisarias/cirugía , Neoplasias Hipofisarias/patología , Neoplasias Hipofisarias/diagnóstico por imagen , Recurrencia Local de Neoplasia/cirugía , Niño , Masculino , Femenino , Adolescente , PreescolarRESUMEN
PURPOSE: To evaluate clinical, laboratory, radiological, therapeutic, and prognostic characteristics of patients with acromegaly according to the size of the growth hormone (GH)-secreting pituitary adenoma at diagnosis. METHODS: Observational, retrospective, single-center study of patients with acromegaly followed at a tertiary center. Data were collected regarding clinical presentation, characteristics of the adenoma in the magnetic resonance imaging, GH and IGF-1 levels, and disease control after surgery or adjuvant treatment (normal IGF-1 levels). Patients were divided according to the adenoma size at diagnosis in: group I < 10 mm; II 10-19 mm; III 20-29 mm; IV 30-39 mm; and V ≥ 40 mm. Comparisons were made between the groups, and correlations of tumor size with disease parameters, ROC curves, and logistic regression analyses were performed to investigate tumor size and confounding factors that could impact the outcomes. RESULTS: 117 patients were studied [59 women, age at diagnosis 43 ± 13 years; group I = 11 patients (9%); group II 54 (46%); group III 34 (29%); group IV 10 (9%); group V 8 (7%)]. Hypopituitarism, cavernous sinus invasion, GH levels, and use of somatostatin receptor ligands had their prevalence increased according to the adenoma size. Age showed a negative correlation with tumor size. A tumor diameter around 20 mm was the best predictor for the presence of hypopituitarism, invasiveness, need of adjuvant therapies, and poorer disease control. CONCLUSION: Adenomas < 20 mm showed lower morbidity and better therapeutic response in acromegaly, while those ≥ 20 mm had similar clinical, therapeutic, and prognostic behavior.
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Acromegalia , Humanos , Acromegalia/patología , Femenino , Masculino , Adulto , Persona de Mediana Edad , Estudios Retrospectivos , Pronóstico , Hormona de Crecimiento Humana/metabolismo , Imagen por Resonancia Magnética , Factor I del Crecimiento Similar a la Insulina/metabolismo , Adenoma/patología , Adenoma/terapia , Adenoma Hipofisario Secretor de Hormona del Crecimiento/patología , Adenoma Hipofisario Secretor de Hormona del Crecimiento/terapia , Neoplasias Hipofisarias/patología , Neoplasias Hipofisarias/terapiaRESUMEN
INTRODUCTION: AMPK (AMP-activated protein kinase) is an enzyme that acts as a metabolic sensor and regulates multiple pathways via phosphorylating proteins in metabolic and proliferative pathways. The aim of this work was to study the activated cellular AMPK (phosphorylated-AMPK at Thr172, pAMPK) levels in pituitary tumor samples from patients with sporadic and familial acromegaly, as well as in samples from normal human pituitary gland. METHODS: We studied pituitary adenoma tissue from patients with sporadic somatotroph adenomas, familial acromegaly with heterozygote germline variants in the aryl hydrocarbon receptor interacting protein (AIP) gene (p.Q164*, p.R304* and p.F269_H275dup) and autopsy from normal pituitary glands without structural alterations. RESULTS: Cellular levels of pAMPK were significantly higher in patients with sporadic acromegaly compared to normal pituitary glands (p < 0.0001). Tissues samples from patients with germline AIP mutations also showed higher cellular levels of pAMPK compared to normal pituitary glands. We did not observe a significant difference in cellular levels of pAMPK according to the cytokeratin (CAM5.2) pattern (sparsely or densely granulated) for tumor samples of sporadic acromegaly. CONCLUSION: Our data show, for the first time in human cells, an increase of cellular levels of pAMPK in sporadic somatotropinomas, regardless of cytokeratin pattern, as well as in GH-secreting adenomas from patients with germline AIP mutations.
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Proteínas Quinasas Activadas por AMP , Adenoma , Adenoma Hipofisario Secretor de Hormona del Crecimiento , Humanos , Proteínas Quinasas Activadas por AMP/metabolismo , Proteínas Quinasas Activadas por AMP/genética , Masculino , Adenoma Hipofisario Secretor de Hormona del Crecimiento/genética , Adenoma Hipofisario Secretor de Hormona del Crecimiento/metabolismo , Adenoma Hipofisario Secretor de Hormona del Crecimiento/patología , Femenino , Persona de Mediana Edad , Adulto , Adenoma/genética , Adenoma/patología , Adenoma/metabolismo , Adenoma/enzimología , Acromegalia/genética , Acromegalia/patología , Acromegalia/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Anciano , Neoplasias Hipofisarias/genética , Neoplasias Hipofisarias/patología , Neoplasias Hipofisarias/metabolismo , Neoplasias Hipofisarias/enzimología , Fosforilación , Hipófisis/metabolismo , Hipófisis/patología , Regulación Neoplásica de la Expresión GénicaRESUMEN
INTRODUCTION: Sellar metastases (SM) are rare manifestations of malignancy. Breast and lung cancer are the most common primary tumors. Most cases are diagnosed in patients with advanced malignant disease; however, symptoms of pituitary involvement can precede the diagnosis of the primary tumor. METHODS: Retrospective analysis of symptoms at presentation, hormonal, radiological and histological findings, management, and outcome of patients with SM from 2009 to 2020. RESULTS: Eighteen patients'cases were included, 11 with histological confirmation. Median (m) age was 53 years (range 35-75), 53% male. Primary malignant tumors: 8 lungs, 6 breast, 1 follicular thyroid carcinoma, 1 Hodgkin lymphoma, and 2 clear cell renal carcinomas. The m time between the diagnosis of the primary neoplasm and the occurrence of the SM was 108 months (range: 11-180). In 8 patients the diagnosis of the primary neoplasm was made after the finding of the symptomatic sellar mass. Insipidus diabetes, adenohypophysis deficit, visual disorders, headache, and cranial nerve deficits were evident in 78, 77, 61, 39 and 39% of the cases, respectively. Fifteen patients harbored supra / parasellar masses, in three a lesion was limited to the pituitary gland, and stalk. Eleven out of 18 (61.1%) of the patients were operated on by the trans-sphenoidal approach, for diagnostic and / or decompressive purposes. Eighteen died, with a median survival time of 6 months (1-36). DISCUSSION: In the presence of a pituitary lesion with diffuse gadolinium uptake, associated with insipidus diabetes and / or visual disorder SM should be suspected even in patients without a history of oncological disease.
Introducción: La región selar es un sitio infrecuente de metástasis, encontrándose en el 1% de las cirugías hipofisarias. Los tumores primarios más habituales son mama y pulmón. En general son diagnosticadas en pacientes con enfermedad avanzada, aunque pueden ser el debut de la enfermedad oncológica. Métodos: Análisis retrospectivo de las características clínicas, bioquímicas, radiológicas de pacientes con metástasis selares o hipofisarias (MS) durante el periodo 2009-2020. Resultados: Se reportaron 18 casos de pacientes, 11 de ellos con confirmación histológica. La mediana de edad fue 53 años (rango: 35-75), 53% hombres. La localización del tumor primario fue: 8 pulmón, 6 mama, 1 carcinoma folicular de tiroides, 1 linfoma Hodgkin y 2 carcinomas renales de células claras. La media de tiempo entre el diagnóstico del tumor primario y la aparición de la MS -en los casos de presentación metacrónica- fue 108 meses (rango: 11-180). En 8 pacientes (44.4%), el diagnóstico de la neoplasia primaria se hizo a partir del hallazgo de la masa selar. Diabetes insípida, hipopituitarismo, trastornos visuales, oftalmoplejía y cefalea se presentaron en el 78, 77, 61, 39 y 39%, respectivamente. Quince pacientes presentaron masas con extensión supra/paraselar; y 3 lesión limitada a la hipófisis y tallo. Fueron operados 11/18 por vía transesfenoidal, para diagnóstico y/o descompresión. Fallecieron 17, con una mediana de sobrevida de 6 meses (1- 36). Discusión: La sospecha de MS debe estar presente ante una masa selar y supraselar con captación difusa del gadolinio, diabetes insípida, hipopituitarismo y/o disfunción visual, aun en pacientes sin antecedentes oncológicos.
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Neoplasias Hipofisarias , Humanos , Persona de Mediana Edad , Masculino , Femenino , Anciano , Adulto , Estudios Retrospectivos , Neoplasias Hipofisarias/secundario , Neoplasias Hipofisarias/diagnóstico , Neoplasias Hipofisarias/patología , Neoplasias Hipofisarias/terapia , Imagen por Resonancia MagnéticaRESUMEN
Pituitary neuroendocrine tumors (PitNET) are known to be variably infiltrated by different immune cells. Nonetheless, their role in pituitary oncogenesis has only begun to be unveiled. The immune microenvironment could determine the biological and clinical behavior of a neoplasm and may have prognostic implications. To evaluate the expression of immune-related genes and to correlate such expression with the presence of infiltrating immune cells in forty-two PitNETs of different lineages, we performed whole transcriptome analysis and RT-qPCR. Deconvolution analysis was carried out to infer the immune cell types present in each tumor and the presence of immune cells was confirmed by immunofluorescence. We found characteristic expression profiles of immune-related genes including those encoding interleukins and chemokines for each tumor lineage. Genes such as IL4-I1, IL-36A, TIRAP, IL-17REL, and CCL5 were upregulated in all PitNETS, whereas IL34, IL20RA, and IL-2RB characterize the NR5A1-, TBX19-, and POU1F1-derived tumors, respectively. Transcriptome deconvolution analysis showed that M2 macrophages, CD4+ T cells, CD8+ T cells, NK cells, and neutrophils can potentially infiltrate PitNET. Furthermore, CD4+ and CD8+ T cells and NK cells infiltration was validated by immunofluorescence. Expression of CCL18, IL-5RA, and HLA-B as well as macrophage tumor infiltration could identify patients who can potentially benefit from treatment with immune checkpoint inhibitors.
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Tumores Neuroendocrinos , Neoplasias Hipofisarias , Transcriptoma , Microambiente Tumoral , Humanos , Neoplasias Hipofisarias/genética , Neoplasias Hipofisarias/inmunología , Neoplasias Hipofisarias/patología , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Tumores Neuroendocrinos/genética , Tumores Neuroendocrinos/inmunología , Tumores Neuroendocrinos/patología , Regulación Neoplásica de la Expresión Génica , Perfilación de la Expresión Génica/métodos , Masculino , Femenino , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Persona de Mediana Edad , AdultoRESUMEN
GH-secreting tumors represent 15 % to 20 % of all pituitary neuroendocrine tumors (pitNETs), of which 95 % occur in a sporadic context, without an identifiable inherited cause. Recent multi-omic approaches have characterized the epigenomic, genomic, transcriptomic, proteomic and kynomic landscape of pituitary tumors. Transcriptomic analysis has allowed us to discover specific transcription factors driving the differentiation of pituitary tumors and gene expression patterns. GH-secreting, along with PRL- and TSH-secreting pitNETs are driven by POU1F1; ACTH-secreting tumors are determined by TBX19; and non-functioning tumors, which are predominantly of gonadotrope differentiation are conditioned by NR5A1. Upregulation of certain miRNAs, such as miR-107, is associated with tumor progression, while downregulation of others, like miR-15a and miR-16-1, correlates with tumor size reduction. Additionally, miRNA expression profiles are linked to treatment resistance and clinical outcomes, providing insights into potential therapeutic targets. Specific somatic mutations in GNAS, PTTG1, GIPR, HGMA2, MAST and somatic variants associated with cAMP, calcium signaling, and ATP pathways have also been associated with the development of acromegaly. This review focuses on the oncogenic mechanisms by which sporadic acromegaly can develop, covering a complex series of molecular alterations that ultimately alter the balance between proliferation and apoptosis, and dysregulated hormonal secretion.
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Acromegalia , Neoplasias Hipofisarias , Humanos , Acromegalia/genética , Neoplasias Hipofisarias/genética , Neoplasias Hipofisarias/metabolismo , Neoplasias Hipofisarias/patología , Tumores Neuroendocrinos/genética , Tumores Neuroendocrinos/patología , MicroARNs/genéticaRESUMEN
CONTEXT: The tumor microenvironment (TME) includes diverse cellular components such as mesenchymal stem cells (MSCs) and immune cells, among others. MSC have been isolated from different tumors and they favor tumor cell growth; however, their role in pituitary tumors (PTs) remains unknown. OBJECTIVE: Herein we report the presence of MSCs in 2 adrenocorticotropin (ACTH)-secreting PTs causing Cushing disease (MCU), 2 nonfunctioning adenomas of gonadotrope differentiation (MNF), and 2 nontumoral pituitary glands (MS). METHODS: We have analyzed the transcriptomic profiles by RNA sequencing and compared MSCs in terms of their immunosuppressive effects against lymphoid T-cell and macrophage populations by means of cocultures and flow cytometry. RESULTS: Our transcriptomic analysis revealed molecular differences between MSCs derived from nontumoral pituitaries and MSCs derived from PTs. Two distinct subpopulations of MSC emerged: one displaying immunosuppressive properties and the other with increased proproliferative capabilities, regardless of their origin. MSCs derived from ACTH- and nonfunctioning PTs, but not those derived from nontumoral glands, significantly inhibited the proliferation of activated T cells, favored the generation of regulatory T cells, and promoted M2 macrophage polarization. Such immunosuppressive effects were correlated with an upregulation of programmed death ligand 1 and intracellular expression of macrophage colony-stimulating factor (M-CSF) and interleukin-10. Importantly, MSC derived from ACTH-PTs showed a higher immunosuppressive potential than MSC isolated from nonfunctioning tumors. CONCLUSION: This study demonstrates the presence of at least 2 MSC subpopulations in the pituitary gland and suggests that immunosuppressive effects of MSCs may have important implications in PT growth.
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Células Madre Mesenquimatosas , Neoplasias Hipofisarias , Microambiente Tumoral , Humanos , Células Madre Mesenquimatosas/inmunología , Células Madre Mesenquimatosas/metabolismo , Microambiente Tumoral/inmunología , Neoplasias Hipofisarias/inmunología , Neoplasias Hipofisarias/patología , Femenino , Masculino , Persona de Mediana Edad , Adulto , Adenoma/patología , Adenoma/inmunología , Adenoma/metabolismo , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/patología , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/inmunología , Hipófisis/inmunología , Hipófisis/metabolismo , Macrófagos/inmunología , Macrófagos/metabolismoRESUMEN
BACKGROUND: Pituitary adenomas (PA) are neoplasms of pituitary adenohypophyseal cell lineage, which are the third most common cause of brain tumors among adults. Due to hormone secretion, PAs are closely related to metabolic syndrome (MetS). However, the relationship between these two entities has been scarcely studied to date. PURPOSE: This paper aims to evaluate changes in the metabolic status of patients with PA before and after surgical treatment and to look for differences in metabolic outcomes among patients according to the adenoma type and the surgery success rate. METHODS: We assessed patients with PA who went through transsphenoidal surgery for its treatment, documenting metabolic parameters before and after surgery, analyzed whole sample changes, and then stratified them according to adenoma type (nonfunctioning, somatotroph, lactotroph, and corticotroph), and surgery success (total resection, near-total resection, partial resection, subtotal resection). RESULTS: A total of 214 patients were enrolled for this study. The prevalence of MetS with AACE criteria went from 51.52% before surgery to 28.99% after surgery (P < 0.001). Hyperglycemia (HG) was the most beneficial component; it went from 56% pre-surgery to 40.51% post-surgery (P = 0.03). The total resection group had the best improvement, with a significant decrease of prevalence in MetS from 83 to 16% (P < 0.001), and every component, except hypoalphalipoproteinemia (HA): obesity went from 96 to 67% (P < 0.001), arterial hypertension (AH) 59 to 24% (P < 0.001), HG 74 to 23% (P < 0.001), and hypertriglyceridemia (HTG) from 81 to 54% (P < 0.001). According to MetS prevalence, there was no difference in the improvement according to PA type. CONCLUSION: Surgical treatment in patients with PA is associated with MetS improvement.
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Adenoma , Síndrome Metabólico , Neoplasias Hipofisarias , Adulto , Humanos , Neoplasias Hipofisarias/cirugía , Neoplasias Hipofisarias/patología , Síndrome Metabólico/cirugía , Síndrome Metabólico/etiología , Procedimientos Neuroquirúrgicos/efectos adversos , Adenoma/cirugía , Adenoma/patología , Seno Esfenoidal/cirugía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
PURPOSE: To prospectively evaluate the usefulness of T1-weighted imaging (T1WI) and diffusion-weighted imaging (DWI) sequences in predicting the consistency of macroadenomas. In addition, to determine their values ââas prognostic factors of surgical outcomes. METHODS: Patients with pituitary macroadenoma and surgical indication were included. All patients underwent pre-surgical magnetic resonance imaging (MRI) that included the sequences T1WI before and after contrast administration and DWI with the apparent diffusion coefficient (ADC) map. Post-surgical MRI was performed at least 3 months after surgery. The consistency of the macroadenomas was evaluated at surgery, and they were grouped into soft and intermediate/hard adenomas. Mean ADC values, signal on T1WI and the ratio of tumor ADC values ââto pons (ADCR) were compared with tumor consistency and grade of surgical resection. RESULTS: A total of 80 patients were included. A softened consistency was found at surgery in 53 patients and hardened in 27 patients. The median ADC in the soft consistency group was 0.532 × 10-3 mm2/sec (0.306 - 1.096 × 10-3 mm2/sec), and in the intermediate/hard consistency group was 0.509 × 10-3 mm2/sec (0.308 - 0.818 × 10-3 mm2/sec). There was no significant difference between the median values ââof ADC, ADCR and signal on T1W between the soft and hard tumor groups, or between patients with and without tumor residue. CONCLUSION: Our results did not show usefulness of the DWI and T1WI for assessing the consistency of pituitary macroadenomas, nor as a predictor of the degree of surgical resection.
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Adenoma , Neoplasias Hipofisarias , Humanos , Neoplasias Hipofisarias/diagnóstico por imagen , Neoplasias Hipofisarias/cirugía , Neoplasias Hipofisarias/patología , Imagen de Difusión por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/métodos , Adenoma/diagnóstico por imagen , Adenoma/cirugía , Adenoma/patología , Estudios RetrospectivosRESUMEN
IMPORTANCE: Prolactinomas occurring during the reproductive period exhibit a characteristic behavior. There are, however, gaps in the literature regarding the behavior of these tumors after menopause. OBJECTIVE: This study aimed to review and characterize the influence of menopause on prolactinoma behavior. EVIDENCE REVIEW: A systematic review of observational prospective or retrospective studies and clinical trials on prolactinomas was conducted in two situations: tumors diagnosed in the reproductive period (before menopause), with follow-up in the postmenopausal period, or prolactinomas diagnosed in the postmenopausal period, without language or date restrictions. Data extracted from the articles included patient and tumor characteristics (prolactinoma type, previous treatment, symptoms, and serum prolactin [PRL] levels). FINDINGS: This study included five studies comprising 180 participants. Prolactinomas diagnosed in women of reproductive age are treated with dopaminergic agonists (DAs), with indications of treatment withdrawal after menopause, exhibited stable tumor behavior and PRL levels. Considering the diagnosis during the postmenopausal period, macroprolactinomas were more prevalent and showed tumor shrinkage when DAs were used. Cabergoline, the most commonly used drug, lowers PRL levels and reduces symptoms associated with adenoma. CONCLUSIONS AND RELEVANCE: Microadenomas diagnosed before menopause can be followed up without treatment. Prolactinomas diagnosed after menopause are typically macroadenomas. Cabergoline remains the treatment of choice in the presence of clinical or compressive symptoms. We recommend at least one annual follow-up for such patients.
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Neoplasias Hipofisarias , Prolactinoma , Humanos , Femenino , Prolactinoma/tratamiento farmacológico , Prolactinoma/patología , Cabergolina/uso terapéutico , Posmenopausia , Neoplasias Hipofisarias/tratamiento farmacológico , Neoplasias Hipofisarias/patología , Agonistas de Dopamina/uso terapéutico , Estudios Retrospectivos , Estudios Prospectivos , Prolactina/uso terapéuticoRESUMEN
INTRODUCTION: Studies addressing the methylation pattern in adamantinomatous craniopharyngioma (ACP) are lacking. OBJECTIVE: To identify methylation signatures in ACPs regarding clinical presentation and outcome. METHODS: Clinical and pathology data were collected from 35 patients with ACP (54% male; 18.1 years [2-68]). CTNNB1 mutations and methylation profile (MethylationEPIC/Array-Illumina) were analyzed in tumoral DNA. Unsupervised machine learning analysis of this comprehensive methylome sample was achieved using hierarchical clustering and multidimensional scaling. Statistical associations between clusters and clinical features were achieved using the Fisher test and global biological process interpretations were aided by Gene Ontology enrichment analyses. RESULTS: Two clusters were revealed consistently by all unsupervised methods (ACP-1: n = 18; ACP-2: n = 17) with strong bootstrap statistical support. ACP-2 was enriched by CTNNB1 mutations (100% vs 56%, P = .0006), hypomethylated in CpG island, non-CpG Island sites, and globally (P < .001), and associated with greater tumor size (24.1 vs 9.5 cm3, P = .04). Enrichment analysis highlighted pathways on signaling transduction, transmembrane receptor, development of anatomical structures, cell adhesion, cytoskeleton organization, and cytokine binding, and cell type-specific biological processes as regulation of oligodendrocytes, keratinocyte, and epithelial cells differentiation. CONCLUSION: Two clusters of patients with ACP were consistently revealed by unsupervised machine learning methods, with one of them significantly hypomethylated, enriched by CTNNB1 mutated ACPs, and associated with increased tumor size. Enrichment analysis reinforced pathways involved in tumor proliferation and in cell-specific tumoral microenvironment.
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Craneofaringioma , Metilación de ADN , Epigénesis Genética , Neoplasias Hipofisarias , beta Catenina , Humanos , Craneofaringioma/genética , Craneofaringioma/patología , Masculino , Femenino , Neoplasias Hipofisarias/genética , Neoplasias Hipofisarias/patología , Adolescente , Adulto , Niño , Persona de Mediana Edad , Adulto Joven , beta Catenina/genética , beta Catenina/metabolismo , Preescolar , Anciano , Mutación , Islas de CpG/genética , Regulación Neoplásica de la Expresión GénicaRESUMEN
Pituitary tumors (PT) are highly heterogeneous neoplasms, comprising functioning and nonfunctioning lesions. Functioning PT include prolactinomas, causing amenorrhea-galactorrhea in women and sexual dysfunction in men; GH-secreting adenomas causing acromegaly-gigantism; ACTH-secreting corticotrophinomas causing Cushing disease (CD); and the rare TSH-secreting thyrotrophinomas that result in central hyperthyroidism. Nonfunctioning PT do not result in a hormonal hypersecretion syndrome and most of them are of gonadotrope differentiation; other non-functioning PT include null cell adenomas and silent ACTH-, GH- and PRL-adenomas. Less than 5% of PT occur in a familial or syndromic context whereby germline mutations of specific genes account for their molecular pathogenesis. In contrast, the more common sporadic PT do not result from a single molecular abnormality but rather emerge from several oncogenic events that culminate in an increased proliferation of pituitary cells, and in the case of functioning tumors, in a non-regulated hormonal hypersecretion. In recent years, important advances in the understanding of the molecular pathogenesis of PT have been made, including the genomic, transcriptomic, epigenetic, and proteomic characterization of these neoplasms. In this review, we summarize the available molecular information pertaining the oncogenesis of PT.
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Adenoma , Neoplasias Hipofisarias , Masculino , Embarazo , Humanos , Femenino , Neoplasias Hipofisarias/genética , Neoplasias Hipofisarias/patología , Proteómica , Adenoma/genética , Adenoma/patología , Genómica , Hormona Adrenocorticotrópica/genética , Hormona Adrenocorticotrópica/metabolismo , Perfilación de la Expresión Génica , Epigénesis GenéticaRESUMEN
Adamantinomatous craniopharyngioma (ACP) is a rare sellar region tumor seen in 0.5-2 cases per million persons each year,1 presenting a bimodal distribution that peaks at 5-15 years in children and 45-60 years in adults.2 Arising from embryonic remnants of the Rathke pouch epithelium, ACPs are associated with calcifications in 90% of cases and grow cranially toward the floor of the diencephalon.1 Craniopharyngiomas are benign but locally aggressive tumors, with microsurgery being the best chance of cure.3 The natural history is to compress the optic apparatus and hypothalamic-pituitary axis as they expand, with a propensity to encase the carotids. Endoscopic transbasal approaches have gained wide acceptance in the management of these tumors.4-6 However, open microsurgical approaches via pterional and orbitozygomatic craniotomies afford wider visualization of different corridors that help mitigate the surgical risks.7-9 The orbitozygomatic craniotomy allows lesions that extend above the optic chiasm to be safely approached from an inferior-to-superior corridor.9 The wide exposure of the basal arachnoid cisterns allows protection of the lenticulostriate perforators during resection.8-11 We demonstrate a step-by-step orbitozygomatic approach with dissection of the sylvian, carotid, carotid-oculomotor, chiasmatic, and lamina terminalis cisterns that allowed safe resection of a third ventricular ACP. The patient was a male in his 70s, who presented with progressive headaches and visual impairment. Magnetic resonance imaging showed a multicystic suprasellar lesion extending through the third ventricle. The surgery was performed with no complication (Video 1). Postoperative vision stabilized, and magnetic resonance imaging showed complete resection.
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Craneofaringioma , Neoplasias Hipofisarias , Neoplasias de la Base del Cráneo , Adulto , Niño , Humanos , Masculino , Craneofaringioma/diagnóstico por imagen , Craneofaringioma/cirugía , Craneofaringioma/patología , Neoplasias Hipofisarias/diagnóstico por imagen , Neoplasias Hipofisarias/cirugía , Neoplasias Hipofisarias/patología , Craneotomía/métodos , Neoplasias de la Base del Cráneo/cirugía , MicrocirugiaRESUMEN
INTRODUCTION: Pituitary adenomas, benign tumors, can lower quality of life. Pituitary adenomas that invade the medial wall and cavernous sinus (CS) indicate tumor recurrence and partial surgical excision. Despite the cavernous sinus's complexity and risks, new research has improved the surgical procedure and made excision safer. This comprehensive review and single-arm meta-analysis evaluates endocrinological remission and resection rates in pituitary adenomas to determine the benefits and risks of MWCS resection. METHODS: Databases were systematically searched for studies documenting the resection of the medial wall of the cavernous sinus. The primary outcome was endocrinological remission in patients who underwent resection of the MWCS. RESULTS: Eight studies were included in the final analysis. The pooled proportion of endocrinological remission (ER) was 63.3%. The excision of MWCS pooled a gross total resection (GTR) proportion of 72.9%. Finally, ICA injury attained a pooled ratio of 0.5%, indicating minimal morbidity in the procedure. CONCLUSION: The cavernous sinus was ruled out, proving the MWCS excision is safe. Limiting population selection to Knosp 3A or lower enhanced GTR frequencies and lowered recurrence, according to subgroup analyses. This meta-analysis shows that MWCS resection can be a beneficial treatment option for pituitary tumors, when there is no macroscopic medial wall invasion and careful patient selection is done, especially for GH- and ACTH-producing tumors that can cause life-threatening metabolic changes.
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Adenoma , Seno Cavernoso , Neoplasias Hipofisarias , Humanos , Neoplasias Hipofisarias/cirugía , Neoplasias Hipofisarias/patología , Seno Cavernoso/cirugía , Seno Cavernoso/patología , Calidad de Vida , Recurrencia Local de Neoplasia/patología , Adenoma/cirugía , Adenoma/patología , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
Pituitary apoplexy refers to a rare clinical syndrome consisting of signs and symptoms that occur due to rapid expansion of the contents of the sella turcica. It can occur spontaneously or associated with pituitary tumors. It can have a broad clinical spectrum, but usually presents with severe headache, visual impairment and hypopituitarism. Sudden onset of symptoms associated to imagiologic confirmation makes the diagnosis. Surgical treatment is advised when there is important compression of the optic tract. We present a case report and a review of the literature on pituitary apoplexy in pregnancy. The cases were reviewed to obtain information on maternal characteristics, clinical presentation, diagnostic studies, therapeutic modalities and maternal and fetal outcomes. Our review found 36 cases of pituitary apoplexy in pregnancy. Most of the cases occurred in the second trimester of pregnancy and headache was the most frequent symptom at presentation. Surgical therapy was required in more than half of the patients. In what respect maternal and fetal outcomes, there were 3 cases of preterm delivery and one case of maternal death. Our clinical case and literature review reinforces the importance of an early diagnosis to avoid potential adverse consequences.
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Muerte Materna , Apoplejia Hipofisaria , Neoplasias Hipofisarias , Embarazo , Femenino , Recién Nacido , Humanos , Apoplejia Hipofisaria/diagnóstico , Apoplejia Hipofisaria/terapia , Apoplejia Hipofisaria/complicaciones , Neoplasias Hipofisarias/complicaciones , Neoplasias Hipofisarias/patología , Neoplasias Hipofisarias/cirugía , Atención Prenatal , Cefalea/complicaciones , Cefalea/terapiaRESUMEN
Third nerve palsy is a rare complication of transsphenoidal surgery and has been merely mentioned in different studies, but there is not any rigorous analysis focusing on this particular complication. The purpose of this study is to analyze this complication after transsphenoidal surgery for a pituitary adenoma to better understand its pathophysiology and outcome. The authors retrospectively analyzed 3 cases of third nerve palsy selected from the 377 patients operated via a transsphenoidal route between 2012 and 2021 at FLENI, a private tertiary neurology and neurosurgical medical center located in Buenos Aires, Argentina. The three patients who presented this complication were operated on via an endoscopic approach. It was observed that an extension into the cavernous sinus (Knosp grade 4) and to the oculomotor cistern was present in the three patients. The deficit was apparent immediately after surgery in two patients. For these two patients, the supposed mechanism of ophthalmoplegia was an intraoperative nerve lesion. The other patient became symptomatic in the 48 h following the surgery. The mechanism implied in this case was intracavernous hemorrhagic suffusion. The latter patient completely recovered the third nerve deficit in the 3 months that followed, while the other two recovered after 6 months postoperative. Oculomotor nerve palsy after transsphenoidal surgery is a very rare complication and appears to be transient in most cases. The invasion of both the cavernous sinus and the oculomotor cistern seems to be a major factor in its physiopathology and should be preoperatively analyzed on magnetic resonance imaging (MRI); recognizing such extension should play an important role in the surgeon's operative considerations.
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Adenoma , Cirugía Endoscópica por Orificios Naturales , Enfermedades del Nervio Oculomotor , Neoplasias Hipofisarias , Humanos , Neoplasias Hipofisarias/cirugía , Neoplasias Hipofisarias/patología , Estudios Retrospectivos , Enfermedades del Nervio Oculomotor/etiología , Procedimientos Neuroquirúrgicos/métodos , Cirugía Endoscópica por Orificios Naturales/efectos adversos , Cirugía Endoscópica por Orificios Naturales/métodos , Adenoma/cirugía , Adenoma/patología , Resultado del TratamientoRESUMEN
Introducción: desde el punto de vista anatómico, los adenomas hipofisarios (AH) se observan en el 10% de la población. Son en su mayoría pequeños y no funcionantes. La mayoría de los incidentalomas descubiertos en estudios de imágenes con alta resolución pedidos en situaciones clínicas frecuentes, como el traumatismo craneoencefálico, el accidente cerebrovascular y las demencias, corresponden a AH indolentes. Nos preguntamos cuál es la relevancia clínica de los adenomas hipofisarios. Desarrollo: los AH clínicamente relevantes son tumores en su mayoría benignos que conllevan, en diferentes proporciones, aumento en la morbilidad y/o mortalidad de los pacientes por mecanismos relacionados con la hipersecreción hormonal, la insuficiencia hormonal y/o los efectos de masa ocupante. La prevalencia de los AH clínicamente relevantes es mayor de la que se suponía hace 20 años. Afecta aproximadamente a 1/1000 habitantes. Los más prevalentes son los prolactinomas y los adenomas no funcionantes. La acromegalia, la enfermedad de Cushing y los tumores agresivos se traducen en pacientes complejos con mayor morbimortalidad. El diagnóstico temprano y el tratamiento multimodal proveen una razonable mejoría de la sobrevida. El estudio epidemiológico de los AH clínicamente relevantes es importante para la estimación del impacto en los sistemas de salud. Conclusiones: los estudios por imágenes de mejor resolución continuarán señalando incidentalomas hipofisarios. Una evaluación cuidadosa de los pacientes podrá identificar aquellos AH clínicamente relevantes. (AU)
Introduction: from the anatomical point of view, pituitary adenomas (HA) are observed in 10% of the population. They are mostly small and non-functioning. Most incidentalomas discovered in high-resolution imaging studies ordered in frequent clinical situations, such as head trauma, stroke and dementia, correspond to indolent HA. We wonder what is the clinical relevance of pituitary adenomas. Development: clinically relevant HAs are mostly benign tumors that lead, in different degrees, to an increased morbidity and/or mortality in patients by mechanisms related to hormone hypersecretion, hormone insufficiency and/or occupying mass effects. The prevalence of clinically relevant HA is higher from what was assumed 20 years ago. It affects approximately 1/1000 of the population. The most prevalent are prolactinomas and non-functioning adenomas. Acromegaly, Cushing's disease and aggressive tumors make for complex patients with increased morbidity and mortality. Early diagnosis and multimodal treatment provide a reasonable improvement in survival. Epidemiological study of clinically relevant HAs is important for estimating the impact on health systems. Conclusions: Higher-resolution imaging studies will continue to highlight pituitary incidentalomas. Careful evaluation of patients will identify clinically relevant HAs. (AU)
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Humanos , Masculino , Femenino , Adulto , Adulto Joven , Neoplasias Hipofisarias/epidemiología , Acromegalia/epidemiología , Prolactinoma/epidemiología , Adenoma/epidemiología , Hallazgos Incidentales , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/epidemiología , Neoplasias Hipofisarias/patología , Neoplasias Hipofisarias/diagnóstico por imagen , Adenoma/patología , Adenoma/diagnóstico por imagen , Relevancia ClínicaRESUMEN
PURPOSE: The ellipsoid equation came in an attempt to facilitate the estimation of tumor volume, by measuring the height, width, and anteroposterior length of the lesion. The estimated tumor volume can sometimes be different between methods, thus, it is of extreme interest to evaluate if the methods are significantly different, as well as to discuss the main limitations of each one. METHODS: This is an observational, analytical, cross-sectional study. A systematic review of the literature was also performed in order to discuss the results observed in the present study. RESULTS: A total of 82 patients (43 males and 39 females) ranging in age from 15 to 78 years (mean 47.95 ± 14.76) were included in the study. Seven patients were classified as Knosp grade 0 (8.5%), 36 Knosp grade 1 (44%), 14 Knosp grade 2 (17%), 20 Knosp grade 3 (24.4%), 5 Knosp grade 4 (6.1%). The tumor volume estimated by 3D planimetric assessment, non-simplified ellipsoid equation, and simplified ellipsoid formula averaged 10.68 cm³, 10.36 cm³, and 9.9 cm³ respectively. CONCLUSION: A simplified form of the ellipsoid equation increases the divergence between the measurement obtained in planimetry, and should be discouraged, in view of the new automated methods of performing quick calculations using periodic digits. The non-simplified form underestimated the tumor volume by 2.9% on average but did so regularly. In clinical practice, measurement should be accompanied by an evaluation of tumor morphology.
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Neoplasias Hipofisarias , Masculino , Femenino , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Neoplasias Hipofisarias/patología , Carga Tumoral , Estudios Transversales , Tamaño de los Órganos , Estudios Observacionales como AsuntoRESUMEN
PURPOSE: Dopamine agonists (DA) are the gold-standard for prolactinoma and hyperprolactinemia treatment. Intolerance to DA leading to drug drop out occurs in 3 to 12% of cases. We provide here a review of published data about DA intolerance and present a case report concerning the use of intravaginal cabergoline. METHODS: We review the literature on the definition, the pathogenesis, frequency and management of DA intolerance. In addition, the review provides strategies to enhance tolerability and avoid precocious clinical treatment withdrawal. RESULTS: Cabergoline is often cited as the most tolerable DA and its side effects tend to ameliorate within days to weeks. Restarting the same drug at a lower dose or switching to another DA can be used in cases of intolerance. The vaginal route can be tried specifically if there are gastrointestinal side effects in the oral administration. Symptomatic treatment could be attempted, although mainly based on a strategy used in other diseases. CONCLUSIONS: Due to limited data, no guidelines have been developed for the management of intolerance in DA treatment. The most frequent management is to perform transsphenoidal surgery. Nevertheless, this manuscript provides data derived from published literature and expert opinion, suggesting new approaches to this clinical issue.