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Trends in Cancer Jan 2018Recent comprehensive molecular analysis allowed the identification of unique molecular signatures in pheochromocytomas (PHEOs) and paragangliomas (PGLs). Here we... (Review)
Review
Recent comprehensive molecular analysis allowed the identification of unique molecular signatures in pheochromocytomas (PHEOs) and paragangliomas (PGLs). Here we summarize the main pathway clusters activated by PHEO- and PGL-susceptibility genes: pseudohypoxic, kinase, and Wnt signaling. Molecular characterization and clustering of PHEOs and PGLs may help in the application of principles of personalized medicine and in decision making for targeted therapy of these tumors.
Topics: Adrenal Gland Neoplasms; Genomics; Humans; Molecular Targeted Therapy; Mutation; Paraganglioma; Pheochromocytoma; Precision Medicine; Signal Transduction; Wnt Proteins
PubMed: 29413423
DOI: 10.1016/j.trecan.2017.11.001 -
Problemy Endokrinologii Oct 2023Currently, all pheochromocytoma/paraganglioma (PPGLs) are considered malignant due to metastatic potential. Consequently, PPGLs are divided into «metastatic» and... (Review)
Review
Currently, all pheochromocytoma/paraganglioma (PPGLs) are considered malignant due to metastatic potential. Consequently, PPGLs are divided into «metastatic» and «non-metastatic». Metastatic PPGLs can be with synchronous metastasis (metastases appear simultaneously with the identified primary tumor) or metachronous (metastases develop after removal of the primary tumor). The term metastatic PPGLs is not used in the presence of tumor invasion into surrounding organs and tissues, without the presence of distant metastases of lymphogenic or hematogenic origin. It is generally believed that about 10% of pheochromocytomas and about 40% of sympathetic paragangliomas have metastatic potential. On average, the prevalence of PPGLs with the presence of metastases is 15-20%. Risk factors for metastatic PPGLs are widely discussed in the literature, the most significant of which are groups of clinical, morphological and genetic characteristics. The review presents a discussion of such risk factors for metastatic PPGLs as age, localization and type of hormonal secretion of the tumor, the size and growth pattern of the adrenal lesion, the presence of necrosis and invasion into the vessels, the tumor capsule surrounding adipose tissue, high cellular and mitotic activity, Ki-67 index, expression of chromogranin B and S100 protein, the presence of genetic mutations of three main clusters (pseudohypoxia, kinase signaling and Wnt signaling).Over the past two decades, a number of authors have proposed various predictor factors and scales for assessing a probability of metastatic PPGLs. The review contains detailed description and comparison of sensitivity and specificity of such predictor scales as PASS, GAPP, M-GAPP, ASES and COPPS.
Topics: Humans; Pheochromocytoma; Adrenal Gland Neoplasms; Risk Factors; Paraganglioma; Neoplasm Metastasis
PubMed: 38796759
DOI: 10.14341/probl13331 -
Cancer Medicine Jul 2023Pheochromocytomas (PCCs) are rare neuroendocrine tumors derived from the chromaffin cells of the adrenal medulla. When these tumors have an extra-adrenal location, they... (Review)
Review
Pheochromocytomas (PCCs) are rare neuroendocrine tumors derived from the chromaffin cells of the adrenal medulla. When these tumors have an extra-adrenal location, they are called paragangliomas (PGLs) and arise from sympathetic and parasympathetic ganglia, particularly of the para-aortic location. Up to 25% of PCCs/PGLs are associated with inherited genetic disorders. The majority of PCCs/PGLs exhibit indolent behavior. However, according to their affiliation to molecular clusters based on underlying genetic aberrations, their tumorigenesis, location, clinical symptomatology, and potential to metastasize are heterogenous. Thus, PCCs/PGLs are often associated with diagnostic difficulties. In recent years, extensive research revealed a broad genetic background and multiple signaling pathways leading to tumor development. Along with this, the diagnostic and therapeutic options were also expanded. In this review, we focus on the current knowledge and recent advancements in the diagnosis and treatment of PCCs/PGLs with respect to the underlying gene alterations while also discussing future perspectives in this field.
Topics: Humans; Pheochromocytoma; Paraganglioma; Carcinogenesis; Cell Transformation, Neoplastic; Adrenal Gland Neoplasms
PubMed: 37145019
DOI: 10.1002/cam4.6010 -
Reviews in Endocrine & Metabolic... Feb 2023While most adrenal tumors are identified incidentally and are non-functional, hormone-secreting tumors can cause morbidity and mortality. Hemodynamic lability and... (Review)
Review
While most adrenal tumors are identified incidentally and are non-functional, hormone-secreting tumors can cause morbidity and mortality. Hemodynamic lability and hypertension in pregnancy are associated with worse maternal and fetal outcomes. Achieving a diagnosis of hormone excess due to adrenal tumors can be clinically more difficult in the gravid patient due to normal physiologic alterations in hormones and symptoms related to pregnancy. This review focuses on some nuances of the diagnostic work-up, perioperative care, and surgical management of adrenally-mediated cortisol excess, primary aldosteronism, and pheochromocytoma and paraganglioma in the pregnant patient.
Topics: Pregnancy; Female; Humans; Adrenalectomy; Adrenal Gland Neoplasms; Pheochromocytoma; Hypertension; Hormones
PubMed: 35776233
DOI: 10.1007/s11154-022-09744-7 -
Turk Patoloji Dergisi 2015Genomic studies in the recent decades lead to the identification of new genetic mutations that have been shown to play detrimental roles in the formation of... (Review)
Review
Genomic studies in the recent decades lead to the identification of new genetic mutations that have been shown to play detrimental roles in the formation of pheochromocytoma or paraganglioma. The majority of these genetic mutations detected affect two major cellular pathways - pseudo hypoxic pathway and kinase signalling pathway. Genetic mutations also resulted in syndromes related to paraganglioma/pheochromocytoma. The classical syndromes comprise - neurofibromatosis, multiple neuroendocrine neoplasia (MEN) (II and III) syndromes and von Hippel-Lindau syndrome. Also, mutations in succinate dehydrogenase genes contribute to the understanding of hereditary paragangliomapheochromocytoma syndromes, Carney's triad and Carney- Stratakis syndrome. Lesions newly known to be associated with the genetic mutations in pheochromocytoma/ paraganglioma include gastrointestinal stromal tumour and renal cell carcinoma. Pathological features, proliferative index, genetic and biochemical parameters could help to predict the malignant potential of paraganglioma and pheochromocytoma. Different predictive systems have been proposed and with the help of immunochemical studies. Pathologist should be aware of the advances in knowledge and contribute to the validation of the pathological features and markers for prediction of malignant potential of this group of tumours.
Topics: Adrenal Gland Neoplasms; Biomarkers, Tumor; Biopsy; Genetic Predisposition to Disease; Humans; Immunohistochemistry; Molecular Diagnostic Techniques; Paraganglioma, Extra-Adrenal; Phenotype; Pheochromocytoma; Predictive Value of Tests; Prognosis
PubMed: 26177321
DOI: 10.5146/tjpath.2015.01318 -
Chirurgie (Heidelberg, Germany) Mar 2024Pheochromocytoma is a rare but severe disease of the adrenal glands. The aim of this study is to present and discuss recent developments in the diagnosis and treatment... (Review)
Review
BACKGROUND
Pheochromocytoma is a rare but severe disease of the adrenal glands. The aim of this study is to present and discuss recent developments in the diagnosis and treatment of pheochromocytoma.
MATERIAL AND METHODS
A narrative review article based on the most recent literature is presented.
RESULTS AND DISCUSSION
The proportion of pheochromocytomas as tumors of adrenal origin is about 5% of incidentally discovered adrenal tumors. The classical symptomatic triad of headaches, sweating, and palpitations occurs in only about 20% of patients, while almost all patients show at least 1 of these symptoms. To diagnose pheochromocytoma, levels of free plasma metanephrines or alternatively, fractionated metanephrines in a 24‑h urine collection is required in a first step. In the second step an imaging procedure, computed tomography (CT) or magnetic resonance imaging (MRI), is performed to localize the adrenal tumor. Functional imaging is also recommended to preoperatively detect potential metastases. Genetic testing should always be offered during the course of treatment as 30-40% of pheochromocytomas are associated with genetic mutations. The dogma of preoperative alpha blockade is increasingly being questioned and has been controversially discussed in recent years. Minimally invasive removal of the adrenal tumor is the standard surgical procedure to cure patients with pheochromocytoma. The transabdominal and retroperitoneal laparoscopic approaches are considered equivalent. The choice of the minimally invasive procedure depends on the expertise and experience of the surgeon and should be tailored accordingly. Individualized and regular follow-up care is important after surgery.
Topics: Humans; Pheochromocytoma; Precision Medicine; Adrenal Gland Neoplasms; Adrenal Glands; Metanephrine
PubMed: 37957403
DOI: 10.1007/s00104-023-01988-6 -
Current Opinion in Oncology Jan 2016Pheochromocytomas and paragangliomas (PPGLs) are rare tumours, strongly associated with inherited susceptibility gene mutations, and presenting limited therapeutic... (Review)
Review
PURPOSE OF REVIEW
Pheochromocytomas and paragangliomas (PPGLs) are rare tumours, strongly associated with inherited susceptibility gene mutations, and presenting limited therapeutic options for patients with metastatic disease. This review discusses the recent developments in the characterization of PPGL genetic heterogeneity and associated tumorigenesis pathways, together with their potential clinical relevance.
RECENT FINDINGS
The mutational landscape of PPGL is now well defined, especially with the contribution of next-generation sequencing. Up to 70% of these tumours harbour a germline or a somatic mutation in one of the numerous predisposing genes. In parallel, 'omics' analyses have identified mutation-linked subsets of tumours substantially associated with molecular signatures suggesting new therapeutic targets for patients with a malignant transformation of the disease.
SUMMARY
In the near future, extended molecular testing of PPGL could be used to determine therapeutic approaches and assess diagnosis and prognosis biomarkers. Considering the current development of next-generation sequencing-based genetic screening, this technology appears as a good option to improve both PPGL molecular diagnosis and patient management.
Topics: Adrenal Gland Neoplasms; Genetic Predisposition to Disease; High-Throughput Nucleotide Sequencing; Humans; Mutation; Paraganglioma; Pheochromocytoma; Precision Medicine
PubMed: 26599293
DOI: 10.1097/CCO.0000000000000249 -
Langenbeck's Archives of Surgery Mar 2022Composite phaeochromocytoma is a tumour containing a separate tumour of neuronal origin in addition to a chromaffin cell tumour. This study reports on two cases from a... (Review)
Review
INTRODUCTION
Composite phaeochromocytoma is a tumour containing a separate tumour of neuronal origin in addition to a chromaffin cell tumour. This study reports on two cases from a single centre's records and presents a systematic literature review of composite phaeochromocytomas.
METHODS
In addition to describing 2 case reports, a systematic search of the Medline database from inception up to April 2020 was done for human case reports on composite phaeochromocytomas. Relevant titles and/or abstracts were screened, and full texts were reviewed to identify appropriate studies. Data was extracted and a descriptive analysis of presentation, clinical features, management strategies and outcomes was performed. The quality of included studies was assessed using a critical appraisal checklist.
RESULTS
There were 62 studies included, with a total of 94 patients. Of 91 patients where data was available, the median (range) age of patients was 48 (4-86) years. Of 90 patients where information was provided, 57% were female. In at least 28% of patients, a genetic cause was identified. Common presenting features include abdominal pain, palpable mass, cardiovascular and gastrointestinal symptoms. The most common tumour component with phaeochromocytoma is ganglioneuroma; other components include ganglioneuroblastoma, neuroblastoma and malignant peripheral nerve sheath tumours. In patients with follow-up data (n=48), 85% of patients were alive and well at a median (range) follow-up time of 18 (0.5-168) months.
CONCLUSION
Composite phaeochromocytoma is a rare tumour, with a significant genetic predisposition. This review summarises available epidemiological data, which will be useful for clinicians managing this rare condition.
Topics: Adrenal Gland Neoplasms; Aged; Aged, 80 and over; Brain Neoplasms; Female; Humans; Middle Aged; Pheochromocytoma
PubMed: 33651160
DOI: 10.1007/s00423-021-02129-5 -
Current Cardiology Reports May 2021Pheochromocytoma and paraganglioma (PPGL) in pregnancy is a rare entity and management of these patients is fraught with uncertainty. Our objective is to review current... (Review)
Review
PURPOSE OF REVIEW
Pheochromocytoma and paraganglioma (PPGL) in pregnancy is a rare entity and management of these patients is fraught with uncertainty. Our objective is to review current literature and discuss diagnosis and management of these patients.
RECENT FINDINGS
Outcomes of PPGL in pregnancy have improved in recent years. The greatest risk for adverse maternal and fetal outcomes is the diagnosis of PPGL after delivery. Alpha- and beta-adrenergic blockade is well tolerated and is associated with less adverse outcomes. Antepartum surgery is not associated with improved maternal or fetal outcomes. Biochemical testing and cross-sectional imaging should be performed prior to conception for patients with a known germline variant associated with PPGL.
CONCLUSIONS
Medical therapy should be initiated when PPGL is diagnosed in pregnancy. Antepartum surgery should be reserved for special circumstances. Case detection testing in high-risk patients can identify PPGL before pregnancy.
Topics: Adrenal Gland Neoplasms; Female; Humans; Paraganglioma; Pheochromocytoma; Pregnancy
PubMed: 33961120
DOI: 10.1007/s11886-021-01485-4 -
Frontiers in Endocrinology 2020Pheochromocytoma (PCC) and paraganglioma (PGL) are rare neuroendocrine tumors associated with high cardiovascular morbidity and variable risk of malignancy. The current... (Review)
Review
Pheochromocytoma (PCC) and paraganglioma (PGL) are rare neuroendocrine tumors associated with high cardiovascular morbidity and variable risk of malignancy. The current therapy of choice is surgical resection. Nevertheless, PCCs/PGLs are associated with a lifelong risk of tumor persistence or recurrence. A high rate of germline or somatic mutations in numerous genes has been found in these tumors. For some, the tumorigenic processes are initiated during embryogenesis. Such tumors carry gene mutations leading to pseudohypoxic phenotypes and show more immature characteristics than other chromaffin cell tumors; they are also often multifocal or metastatic and occur at an early age, often during childhood. Cancer stem cells (CSCs) are cells with an inherent ability of self-renewal, de-differentiation, and capacity to initiate and maintain malignant tumor growth. Targeting CSCs to inhibit cancer progression has become an attractive anti-cancer therapeutic strategy. Despite progress for this strategy for solid tumors such as neuroblastoma, brain, breast, and colon cancers, no substantial advance has been made employing similar strategies in PCCs/PGLs. In the current review, we discuss findings related to the identification of normal chromaffin stem cells and CSCs, pathways involved in regulating the development of CSCs, and the importance of the stem cell niche in development and maintenance of CSCs in PCCs/PGLs. Additionally, we examine the development and feasibility of novel CSC-targeted therapeutic strategies aimed at eradicating especially recurrent and metastatic tumors.
Topics: Adrenal Gland Neoplasms; Animals; Humans; Neoplastic Stem Cells; Paraganglioma; Pheochromocytoma
PubMed: 32158431
DOI: 10.3389/fendo.2020.00079