-
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 -
Current Treatment Options in Oncology Oct 2023Temporal bone paragangliomas (TBPs) are indolent, classically benign and highly vascular neoplasms of the temporal bone. There are two types of TBPs, tympanomastoid... (Review)
Review
Temporal bone paragangliomas (TBPs) are indolent, classically benign and highly vascular neoplasms of the temporal bone. There are two types of TBPs, tympanomastoid paragangliomas (TMPs) and tympanojugular paragangliomas (TJPs). The most common symptoms are hearing loss and pulsatile tinnitus. Diagnostic workup, besides conventional physical and laboratory examinations, includes biochemical testing of catecholamine and genetic testing of SDHx gene mutations as well as radiological examination. Although surgery is traditionally the mainstay of treatment, it is challenging due to the close proximity of tumor to critical neurovascular structures and thus the high risk of complications, especially in patients with advanced lesions. Radiotherapy and active surveillance have been increasingly recommended for selected patients. Decision on treatment should be made comprehensively. Curative effect depends on various factors. Long-term follow-up with clinical, laboratory, and radiological examinations is essential for all patients.
Topics: Humans; Paraganglioma; Temporal Bone; Mutation; Genetic Testing; Retrospective Studies; Head and Neck Neoplasms
PubMed: 37556048
DOI: 10.1007/s11864-023-01127-7 -
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 -
Hormone and Metabolic Research =... Jul 2019Since Felix Fränkel's account of pheochromocytoma in 1886, great discoveries and vast advancements in the diagnosis, genetics, anatomical and functional imaging... (Review)
Review
Since Felix Fränkel's account of pheochromocytoma in 1886, great discoveries and vast advancements in the diagnosis, genetics, anatomical and functional imaging techniques, and surgical management of pheochromcytoma and paraganglioma (P-PGL) have been made. The improved insight in the pathophysiology of P-PGL and more accurate detection methods enable physicians to tailor the treatment plan to an individual based on the genetic profile and tumor behavior. This review will cover briefly the clinical features, diagnosis, genetic mutations, and imaging modalities that are used to guide current surgical management of these rare and interesting endocrinopathies.
Topics: Adrenal Gland Neoplasms; Humans; Mutation; Pheochromocytoma; Precision Medicine
PubMed: 31307109
DOI: 10.1055/a-0926-3618 -
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 -
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 -
Endocrinology and Metabolism (Seoul,... Jun 2021Pheochromocytoma and paraganglioma (PPGL) is diagnosed through biochemical confirmation of excessive catecholamines in urine and plasma. Recent technological...
BACKGROUND
Pheochromocytoma and paraganglioma (PPGL) is diagnosed through biochemical confirmation of excessive catecholamines in urine and plasma. Recent technological developments have allowed us to measure urinary free metanephrines; however, the diagnostic accuracy of these new methods and the diagnostic cutoff values have not been evaluated.
METHODS
This is a retrospective study of 595 subjects, including 71 PPGL cases and 524 controls. PPGL was based on pathological confirmation. Subjects with no evidence of PPGL over 2 years were included in the control group.
RESULTS
Urinary free metanephrines yielded similar area under the curve (AUC) to urinary fractionated metanephrines and plasma free metanephrines. However, urinary free normetanephrine yielded a better AUC than did urinary fractionated normetanephrine. The optimal cutoff for urinary free metanephrine and normetanephrine corrected for urinary creatinine yielded 97.2% sensitivity and 98.1% specificity.
CONCLUSION
Urinary free metanephrines are a reliable method for diagnosing PPGL in Asian populations compared with existing biochemical methods.
Topics: Adrenal Gland Neoplasms; Humans; Metanephrine; Paraganglioma; Pheochromocytoma; Retrospective Studies; Sensitivity and Specificity
PubMed: 34107605
DOI: 10.3803/EnM.2020.925 -
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 -
The Lancet. Digital Health Sep 2023Pheochromocytomas and paragangliomas have up to a 20% rate of metastatic disease that cannot be reliably predicted. This study prospectively assessed whether the...
BACKGROUND
Pheochromocytomas and paragangliomas have up to a 20% rate of metastatic disease that cannot be reliably predicted. This study prospectively assessed whether the dopamine metabolite, methoxytyramine, might predict metastatic disease, whether predictions might be improved using machine learning models that incorporate other features, and how machine learning-based predictions compare with predictions made by specialists in the field.
METHODS
In this machine learning modelling study, we used cross-sectional cohort data from the PMT trial, based in Germany, Poland, and the Netherlands, to prospectively examine the utility of methoxytyramine to predict metastatic disease in 267 patients with pheochromocytoma or paraganglioma and positive biochemical test results at initial screening. Another retrospective dataset of 493 patients with these tumors enrolled under clinical protocols at National Institutes of Health (00-CH-0093) and the Netherlands (PRESCRIPT trial) was used to train and validate machine learning models according to selections of additional features. The best performing machine learning models were then externally validated using data for all patients in the PMT trial. For comparison, 12 specialists provided predictions of metastatic disease using data from the training and external validation datasets.
FINDINGS
Prospective predictions indicated that plasma methoxytyramine could identify metastatic disease at sensitivities of 52% and specificities of 85%. The best performing machine learning model was based on an ensemble tree classifier algorithm that used nine features: plasma methoxytyramine, metanephrine, normetanephrine, age, sex, previous history of pheochromocytoma or paraganglioma, location and size of primary tumours, and presence of multifocal disease. This model had an area under the receiver operating characteristic curve of 0·942 (95% CI 0·894-0·969) that was larger (p<0·0001) than that of the best performing specialist before (0·815, 0·778-0·853) and after (0·812, 0·781-0·854) provision of SDHB variant data. Sensitivity for prediction of metastatic disease in the external validation cohort reached 83% at a specificity of 92%.
INTERPRETATION
Although methoxytyramine has some utility for prediction of metastatic pheochromocytomas and paragangliomas, sensitivity is limited. Predictive value is considerably enhanced with machine learning models that incorporate our nine recommended features. Our final model provides a preoperative approach to predict metastases in patients with pheochromocytomas and paragangliomas, and thereby guide individualised patient management and follow-up.
FUNDING
Deutsche Forschungsgemeinschaft.
Topics: United States; Humans; Pheochromocytoma; Retrospective Studies; Prospective Studies; Cross-Sectional Studies; Paraganglioma; Adrenal Gland Neoplasms; Machine Learning
PubMed: 37474439
DOI: 10.1016/S2589-7500(23)00094-8 -
Journal of Nuclear Medicine : Official... Sep 2021Whereas benign pheochromocytomas and paragangliomas are often successfully cured by surgical resection, treatment of metastatic disease can be challenging in terms of...
Whereas benign pheochromocytomas and paragangliomas are often successfully cured by surgical resection, treatment of metastatic disease can be challenging in terms of both disease control and symptom control. Fortunately, several options are available, including chemotherapy, radiation therapy, and surgical debulking. Radiolabeled metaiodobenzylguanidine (MIBG) and somatostatin receptor imaging have laid the groundwork for use of these radiopharmaceuticals as theranostic agents. I-MIBG therapy of neuroendocrine tumors has a long history, and the recent approval of high-specific-activity I-MIBG for metastatic or inoperable pheochromocytoma or paraganglioma by the U.S. Food and Drug Administration has resulted in general availability of, and renewed interest in, this treatment. Although reports of peptide receptor radionuclide therapy of pheochromocytoma and paraganglioma with Y- or Lu-DOTA conjugated somatostatin analogs have appeared in the literature, the approval of Lu-DOTATATE in the United States and Europe, together with National Comprehensive Cancer Network guidelines suggesting its use in patients with metastatic or inoperable pheochromocytoma and paraganglioma, has resulted in renewed interest. These agents have shown evidence of efficacy as palliative treatments in patients with metastatic or inoperable pheochromocytoma or paraganglioma. In this continuing medical education article, we discuss the therapy of pheochromocytoma and paraganglioma with I-MIBG and Y- or Lu-DOTA-somatostatin analogs.
Topics: Paraganglioma; Pheochromocytoma; Positron-Emission Tomography; Radionuclide Imaging
PubMed: 34475242
DOI: 10.2967/jnumed.120.259697