-
The Journal of Clinical Endocrinology... Jun 2023Aggressive pituitary tumors (APTs) and pituitary carcinomas (PCs) are heterogeneous with regard to clinical presentation, proliferative markers, clinical course, and...
Aggressive pituitary tumors (APTs) and pituitary carcinomas (PCs) are heterogeneous with regard to clinical presentation, proliferative markers, clinical course, and response to therapy. Half of them show an aggressive course only many years after the first apparently benign presentation. APTs and PCs share several properties, but a Ki67 index greater than or equal to 10% and extensive p53 expression are more prevalent in PCs. Mutations in TP53 and ATRX are the most common genetic alterations; their detection might be of value for early identification of aggressiveness. Treatment requires a multimodal approach including surgery, radiotherapy, and drugs. Temozolomide is the recommended first-line chemotherapy, with response rates of about 40%. Immune checkpoint inhibitors have emerged as second-line treatment in PCs, with currently no evidence for a superior effect of dual therapy compared to monotherapy with PD-1 blockers. Bevacizumab has resulted in partial response (PR) in few patients; tyrosine kinase inhibitors and everolimus have generally not been useful. The effect of peptide receptor radionuclide therapy is limited as well. Management of APT/PC is challenging and should be discussed within an expert team with consideration of clinical and pathological findings, age, and general condition of the patient. Considering that APT/PCs are rare, new therapies should preferably be evaluated in shared standardized protocols. Prognostic and predictive markers to guide treatment decisions are needed and are the scope of ongoing research.
Topics: Humans; Pituitary Neoplasms; Temozolomide; Bevacizumab
PubMed: 36856733
DOI: 10.1210/clinem/dgad098 -
Journal of Neurosurgery Jan 2007
Topics: Activities of Daily Living; Adolescent; Child; Child, Preschool; Craniopharyngioma; Follow-Up Studies; Glasgow Outcome Scale; Humans; Male; Neoplasm Recurrence, Local; Pituitary Neoplasms; Postoperative Complications; Quality of Life; Reoperation; Retrospective Studies
PubMed: 17233304
DOI: 10.3171/ped.2007.106.1.1 -
Neuroendocrinology 2020The pituitary fossa is an uncommon site for metastatic tumor spread. Metastatic lesions to the sellar area derived mostly from breast, lung, renal, prostate, and colon... (Review)
Review
The pituitary fossa is an uncommon site for metastatic tumor spread. Metastatic lesions to the sellar area derived mostly from breast, lung, renal, prostate, and colon cancers, and rarely from other solid and hematologic malignancies. Almost every cancer has been reported as a source of pituitary metastasis. Pituitary metastasis can involve both the anterior and posterior lobes, but the neuro-hypophysis is mainly involved. Clinical manifestations include diabetes insipidus, hypopituitarism, headache, visual disturbances, ophthalmoplegia, and also compression of adjacent structures by aggressive tumor masses. Metastatic spread to the pituitary from a distant primary malignancy is commonly associated with metastases to other tissues and poor prognosis, unless efficient systemic targeted medical treatment is available for the primary cancer (melanoma, lymphoma).
Topics: Humans; Pituitary Neoplasms
PubMed: 32101869
DOI: 10.1159/000506810 -
Reviews in Endocrine & Metabolic... Jun 2020Surgery of aggressive pituitary adenomas and pituitary carcinomas is part of the interdisciplinary management of these difficult to treat tumors. Invasion, giant size... (Review)
Review
Surgery of aggressive pituitary adenomas and pituitary carcinomas is part of the interdisciplinary management of these difficult to treat tumors. Invasion, giant size and unusual, asymmetric extent of these tumors frequently require modifications or extensions of the standard approaches for transsphenoidal and transcranial surgery. Frequently, only debulking procedures can be performed. In aggressive and hormone secreting adenomas, the remission rates achieved by surgery alone are relatively poor and adjuvant medical treatments or irradiation are needed. Safe resection of as much tumor as possible and symptomatic control is aimed at, rather than remission. Many procedures are required for rapid progression of lesions or recurrences, in order to extend the survival of the patients. Metastases of pituitary carcinomas within the cranial cavity or spine can be attacked. Since they can occur anywhere in the brain or spinal canal they require the entire battery of neurosurgical approaches. Unfortunately, in this group of pituitary tumors, the complication rates are higher than in primary operations of enclosed adenomas. The respective techniques with their facilities and limitations are reviewed in this article.
Topics: Adenoma; Carcinoma; Humans; Neoplasm Invasiveness; Pituitary Neoplasms
PubMed: 32500483
DOI: 10.1007/s11154-020-09563-8 -
Clinical Medicine (London, England) Mar 2023Pituitary incidentalomas are common findings with increasing use of modern neuroradiological imaging undertaken for symptoms unrelated to pituitary disease. The...
Pituitary incidentalomas are common findings with increasing use of modern neuroradiological imaging undertaken for symptoms unrelated to pituitary disease. The prevalence of these lesions is ∼10% in autopsy studies and the incidence varies from 10% to 38% on magnetic resonance imaging in the published literature. They are almost always benign in nature and most are non-functioning (non-secreting) adenomas. Although many individuals are asymptomatic at diagnosis, some with functioning (secreting) pituitary adenomas or larger non-functioning adenomas have symptoms. All identified cases should have a thorough clinical and endocrinological evaluation to help with precise management, which depends on the size of the lesion, hormonal status (functioning versus non-functioning adenoma) and the presence of visual deficits resulting from optic nerve compression by the pituitary adenoma. Here, we provide an overview of the initial assessment and management of pituitary incidentalomas for clinicians not routinely involved in the management of pituitary disease.
Topics: Humans; Incidental Findings; Pituitary Neoplasms; Pituitary Diseases; Adenoma; Magnetic Resonance Imaging
PubMed: 36958836
DOI: 10.7861/clinmed.2023-0020 -
Endocrine Reviews Dec 2020Substantial advances have been made recently in the pathobiology of pituitary tumors. Similar to many other endocrine tumors, over the last few years we have recognized... (Review)
Review
Substantial advances have been made recently in the pathobiology of pituitary tumors. Similar to many other endocrine tumors, over the last few years we have recognized the role of germline and somatic mutations in a number of syndromic or nonsyndromic conditions with pituitary tumor predisposition. These include the identification of novel germline variants in patients with familial or simplex pituitary tumors and establishment of novel somatic variants identified through next generation sequencing. Advanced techniques have allowed the exploration of epigenetic mechanisms mediated through DNA methylation, histone modifications and noncoding RNAs, such as microRNA, long noncoding RNAs and circular RNAs. These mechanisms can influence tumor formation, growth, and invasion. While genetic and epigenetic mechanisms often disrupt similar pathways, such as cell cycle regulation, in pituitary tumors there is little overlap between genes altered by germline, somatic, and epigenetic mechanisms. The interplay between these complex mechanisms driving tumorigenesis are best studied in the emerging multiomics studies. Here, we summarize insights from the recent developments in the regulation of pituitary tumorigenesis.
Topics: Carcinogenesis; Epigenesis, Genetic; Humans; Pituitary Neoplasms
PubMed: 32201880
DOI: 10.1210/endrev/bnaa006 -
Neuroendocrinology 2022Dopamine agonists (DAs) are preferred for the treatment of prolactinomas and are usually very effective. Nonetheless, 20-30% of bromocriptine- and approximately 10% of... (Review)
Review
Dopamine agonists (DAs) are preferred for the treatment of prolactinomas and are usually very effective. Nonetheless, 20-30% of bromocriptine- and approximately 10% of cabergoline-treated individuals exhibit resistance to DAs. In addition, the mechanism underlying this phenomenon remains elusive. In this study, we summarize the major findings regarding the role of microRNAs (miRNAs) in the pathogenesis of DA-resistant prolactinoma (DARP). Currently available evidence suggests that miRNAs are usually dysregulated in DARP and that, although controversial, the dysregulated miRNAs target the transforming growth factor (TGF)-β, dopamine 2 receptor (D2R), or estradiol (E2)/estrogen receptor (ER) signaling pathways to mediate the therapeutic effect of DAs. These findings provide new incentives for research on innovative strategies for predicting patients' responsiveness to dopamine therapies and for developing treatment approaches. Unfortunately, recent studies tended to focus exclusively on the differential miRNA expression profiles between DARP and dopamine-sensitive prolactinoma, and no definitive consensus has been reached regarding the role of these miRNAs in the modulation mechanism. Therefore, current and future efforts should be directed toward the exploration of the mechanism underlying the dysregulation of miRNAs as well as of the target proteins that are affected by the dysregulated miRNAs. Furthermore, the modulation of the expression of dysregulated miRNAs, which target the D2R, TGF-β, or E2/ER signaling pathways, might be a promising alternative to treat patients with DARP and improve their prognosis.
Topics: Dopamine; Dopamine Agonists; Drug Resistance, Neoplasm; Humans; MicroRNAs; Pituitary Neoplasms; Prolactinoma
PubMed: 34034260
DOI: 10.1159/000517356 -
Reviews in Endocrine & Metabolic... Jun 2020Pituitary tumors are not rare if prevalence rates from autopsy or radiological series are considered; approximately 0.5% of all pituitary adenomas will come to medical... (Review)
Review
Pituitary tumors are not rare if prevalence rates from autopsy or radiological series are considered; approximately 0.5% of all pituitary adenomas will come to medical attention. Less than 0.1% of these pituitary adenomas will become malignant, and probably around 0.5% of all detected adenomas will display an aggressive course. However, the exact incidence of both aggressive pituitary adenomas and pituitary carcinomas is unknown, as most data come from series with selected patients, such as surgically treated patients, which is likely not a reflection of all patients with a pituitary adenoma. An aggressive pituitary adenoma is not well-defined; even though an overarching definition, capturing both immunohistochemical and clinical characteristics is probably not waterproof, adoption of a widely accepted definition will be very helpful to harmonize research and establish more reliable epidemiological data.
Topics: Adenoma; Humans; Neoplasm Invasiveness; Pituitary Neoplasms
PubMed: 32361816
DOI: 10.1007/s11154-020-09556-7 -
Neurologia Medico-chirurgica 2014Atypical pituitary adenomas (APAs) are aggressive tumors, harboring a Ki-67 (MIB-1) staining index of 3% or more, and positive immunohistochemical staining for p53... (Review)
Review
Atypical pituitary adenomas (APAs) are aggressive tumors, harboring a Ki-67 (MIB-1) staining index of 3% or more, and positive immunohistochemical staining for p53 protein, according to the World Health Organization (WHO) classification in 2004. Pituitary carcinomas (PC) usually develop from progressive APAs and predominantly consist of hormone-generating tumors, defined by the presence of disseminations in the cerebrospinal system or systemic metastases. Most of the cases with these malignant pituitary adenomas underwent surgeries, irradiations and adjuvant medical treatments, nevertheless, the therapies are mainly palliative. Recently, the efficacy of temozolomide (TMZ), an orally administered alkylating agent, has been reported as an alternative medical treatment. However, some recent studies have demonstrated a significant recurrence rate after effective response to TMZ. Further clinical and pathological researches of malignant pituitary adenomas will be required to improve the outcome of patients with these tumors.
Topics: Adenoma; Administration, Oral; Antineoplastic Agents, Alkylating; Cell Transformation, Neoplastic; Combined Modality Therapy; Dacarbazine; Disease Progression; Humans; Magnetic Resonance Imaging; Neoplasm Recurrence, Local; Pituitary Gland; Pituitary Hormones; Pituitary Neoplasms; Temozolomide
PubMed: 25446382
DOI: 10.2176/nmc.ra.2014-0178 -
Frontiers in Endocrinology 2020Pituitary adenomas, accounting for 15% of diagnosed intracranial neoplasms, are usually benign and pharmacologically and surgically treatable; however, the critical... (Review)
Review
Pituitary adenomas, accounting for 15% of diagnosed intracranial neoplasms, are usually benign and pharmacologically and surgically treatable; however, the critical location, mass effects and hormone hypersecretion sustain their significant morbidity. Approximately 35% of pituitary tumors show a less benign course since they are highly proliferative and invasive, poorly resectable, and likely recurring. The latest WHO classification of pituitary tumors includes pituitary transcription factor assessment to determine adenohypophysis cell lineages and accurate designation of adenomas, nevertheless little is known about molecular and cellular pathways which contribute to pituitary tumorigenesis. In malignant tumors the identification of cancer stem cells radically changed the concepts of both tumorigenesis and pharmacological approaches. Cancer stem cells are defined as a subset of undifferentiated transformed cells from which the bulk of cancer cells populating a tumor mass is generated. These cells are able to self-renew, promoting tumor progression and recurrence of malignant tumors, also conferring cytotoxic drug resistance. On the other hand, the existence of stem cells within benign tumors is still debated. The presence of adult stem cells in human and murine pituitaries where they sustain the high plasticity of hormone-producing cells, allowed the hypothesis that putative tumor stem cells might exist in pituitary adenomas, reinforcing the concept that the cancer stem cell model could also be applied to pituitary tumorigenesis. In the last few years, the isolation and phenotypic characterization of putative pituitary adenoma stem-like cells was performed using a wide and heterogeneous variety of experimental models and techniques, although the role of these cells in adenoma initiation and progression is still not completely definite. The assessment of possible pituitary adenoma-initiating cell population would be of extreme relevance to better understand pituitary tumor biology and to identify novel potential diagnostic markers and pharmacological targets. In this review, we summarize the most updated studies focused on the definition of pituitary adenoma stem cell phenotype and functional features, highlighting the biological processes and intracellular pathways potentially involved in driving tumor growth, relapse, and therapy resistance.
Topics: Adenoma; Animals; Cell Transformation, Neoplastic; Drug Resistance, Neoplasm; Humans; Neoplasm Recurrence, Local; Neoplastic Stem Cells; Pituitary Neoplasms
PubMed: 32153500
DOI: 10.3389/fendo.2020.00054