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The Journal of Clinical Endocrinology... Sep 2023Pheochromocytomas and paragangliomas (PPGLs) with pathogenic mutations in the succinate dehydrogenase subunit B (SDHB) are associated with a high metastatic risk....
CONTEXT
Pheochromocytomas and paragangliomas (PPGLs) with pathogenic mutations in the succinate dehydrogenase subunit B (SDHB) are associated with a high metastatic risk. Somatostatin receptor 2 (SSTR2)-dependent imaging is the most sensitive imaging modality for SDHB-related PPGLs, suggesting that SSTR2 expression is a significant cell surface therapeutic biomarker of such tumors.
OBJECTIVE
Exploration of the relationship between SSTR2 immunoreactivity and SDHB immunoreactivity, mutational status, and clinical behavior of PPGLs. Evaluation of SSTR-based therapies in metastatic PPGLs.
METHODS
Retrospective analysis of a multicenter cohort of PPGLs at 6 specialized Endocrine Tumor Centers in Germany, The Netherlands, and Switzerland. Patients with PPGLs participating in the ENSAT registry were included. Clinical data were extracted from medical records, and immunohistochemistry (IHC) for SDHB and SSTR2 was performed in patients with available tumor tissue. Immunoreactivity of SSTR2 was investigated using Volante scores. The main outcome measure was the association of SSTR2 IHC positivity with genetic and clinical-pathological features of PPGLs.
RESULTS
Of 202 patients with PPGLs, 50% were SSTR2 positive. SSTR2 positivity was significantly associated with SDHB- and SDHx-related PPGLs, with the strongest SSTR2 staining intensity in SDHB-related PPGLs (P = .01). Moreover, SSTR2 expression was significantly associated with metastatic disease independent of SDHB/SDHx mutation status (P < .001). In metastatic PPGLs, the disease control rate with first-line SSTR-based radionuclide therapy was 67% (n = 22, n = 11 SDHx), and with first-line "cold" somatostatin analogs 100% (n = 6, n = 3 SDHx).
CONCLUSION
SSTR2 expression was independently associated with SDHB/SDHx mutations and metastatic disease. We confirm a high disease control rate of somatostatin receptor-based therapies in metastatic PPGLs.
Topics: Humans; Adrenal Gland Neoplasms; Neoplasms, Second Primary; Paraganglioma; Pheochromocytoma; Receptors, Somatostatin; Retrospective Studies; Succinate Dehydrogenase
PubMed: 36946182
DOI: 10.1210/clinem/dgad166 -
Annals of Oncology : Official Journal... Nov 2020
Topics: Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Adrenocortical Carcinoma; Follow-Up Studies; Humans; Pheochromocytoma
PubMed: 32861807
DOI: 10.1016/j.annonc.2020.08.2099 -
Endocrine Sep 2019Takotsubo syndrome (TS), also known as neurogenic stunned myocardium or broken heart syndrome, is a recognized acute cardiac syndrome. In about 70% of cases, the... (Review)
Review
Takotsubo syndrome (TS), also known as neurogenic stunned myocardium or broken heart syndrome, is a recognized acute cardiac syndrome. In about 70% of cases, the syndrome is preceded by an emotional or a physical stressor. Among the innumerable physical trigger factors that may induce TS are pheochromocytomas and paragangliomas (PPGLs). PPGL-associated cardiovascular complications as "myocarditis", "myocardial infarction", "reversible cardiomyopathies", and "transient repolarization electrocardiographic changes" have been described since more than 70 years. During the last two decades, dozens of cases of PPGL-induced TS have been reported. PPGLs display increased catecholamine levels, sometimes massively elevated, which may trigger TS, most likely through hyperactivation of sympathetic nervous system including the cardiac sympathetic nerve terminal disruption with norepinephrine seethe and spillover. PPGL-induced TS is characterized by a dramatic clinical presentation with hemodynamic compromise and high complication rates. The prevalence of global and apical sparing pattern of TS in PPGL-induced TS is significantly higher than in other TS populations. In this report, the associations of PPGL-induced cardiovascular complications are analyzed, and clinical features, complications, outcome and treatment of PPGL-induced TS are reviewed.
Topics: Adrenal Gland Neoplasms; Humans; Paraganglioma; Pheochromocytoma; Takotsubo Cardiomyopathy
PubMed: 31399912
DOI: 10.1007/s12020-019-02035-3 -
Surgical Pathology Clinics Dec 2019Pheochromocytomas and extra-adrenal paragangliomas are rare neuroendocrine neoplasms with characteristic histologic and immunohistochemical features. These tumors can... (Review)
Review
Pheochromocytomas and extra-adrenal paragangliomas are rare neuroendocrine neoplasms with characteristic histologic and immunohistochemical features. These tumors can arise in several anatomic locations, necessitating that their diagnostic recognition extends beyond the realm of endocrine disorders. A practical and reproducible risk stratification system for these tumors is still in development. In this rapidly evolving era of molecular medicine, it is essential for pathologists to equip themselves with a framework for understanding the classification of paragangliomas and pheochromocytomas and be informed of how they might advise their colleagues with regard to prognostication and appropriate follow-up.
Topics: Adrenal Gland Neoplasms; Biomarkers, Tumor; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Immunohistochemistry; Mutation; Neoplasm Grading; Paraganglioma; Pheochromocytoma; Succinate Dehydrogenase
PubMed: 31672301
DOI: 10.1016/j.path.2019.08.009 -
Frontiers in Endocrinology 2023
Topics: Humans; Child; Adrenal Gland Neoplasms; Pheochromocytoma
PubMed: 37342263
DOI: 10.3389/fendo.2023.1227835 -
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 -
Endocrine-related Cancer Oct 2023This article is a summary of the plenary lecture presented by Jared Rosenblum that was awarded the Manger Prize at the Sixth International Symposium on... (Review)
Review
This article is a summary of the plenary lecture presented by Jared Rosenblum that was awarded the Manger Prize at the Sixth International Symposium on Pheochromocytoma/Paraganglioma held on 19-22 October 2022 in Prague, Czech Republic. Herein, we review our initial identification of a new syndrome of multiple paragangliomas, somatostatinomas, and polycythemia caused by early postzygotic mosaic mutations in EPAS1, encoding hypoxia-inducible factor 2 alpha (HIF-2α), and our continued exploration of new disease phenotypes in this syndrome, including vascular malformations and neural tube defects. Continued recruitment and close monitoring of patients with this syndrome as well as the generation and study of a corresponding disease mouse model as afforded by the pheochromocytoma/paraganglioma translational program at the National Institutes of Health has provided new insights into the natural history of these developmental anomalies and the pathophysiologic role of HIF-2α. Further, these studies have highlighted the importance of the timing of genetic defects in the development of related disease phenotypes. The recent discovery and continued study of this syndrome has not only rapidly evolved our understanding of pheochromocytoma and paraganglioma but also deepened our understanding of other developmental tumor syndromes, heritable syndromes, and sporadic diseases.
Topics: Animals; Mice; Pheochromocytoma; Syndrome; Paraganglioma; Basic Helix-Loop-Helix Transcription Factors; Adrenal Gland Neoplasms
PubMed: 37450881
DOI: 10.1530/ERC-23-0050 -
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