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Veterinary Pathology May 2019Pheochromocytoma is frequent in dogs and carries a guarded prognosis. Current histological criteria may not predict malignant behavior in dogs, similar to humans. In...
Pheochromocytoma is frequent in dogs and carries a guarded prognosis. Current histological criteria may not predict malignant behavior in dogs, similar to humans. In humans, characterization of tumors has been refined using the pheochromocytoma of the adrenal gland scaled score (PASS) and by immunohistochemistry. The study aim was to investigate PASS and immunohistochemical markers used in humans in 24 dogs with pheochromocytoma that underwent adrenalectomy. Dogs with pheochromocytomas were reviewed and tumors collected. Histological sections were evaluated to apply the PASS and were single-labeled for chromogranin A, Ki-67, COX-2, p53, BCL-2, c-erbB-2, vascular endothelial growth factor, and S100. Survival, age, and vascular and capsular invasion were compared for PASS and immunohistochemical markers; results of PASS were also compared for each marker. Associations between markers were tested. PASS and immunohistochemical markers did not differ for survival, age, and vascular and capsular invasion. Tumors showing BCL-2 expression in >50% cells had lower PASS than those with lower expression (PASS: 7 ± 2 vs 9 ± 2; P = .011). Tumors positive for S100 had higher PASS than those that were negative (PASS: 10 ± 2 vs 7 ± 2; P = .001). Results of the different markers were not associated. In conclusion, in the context of canine pheochromocytoma, PASS and the selected immunohistochemical markers are not associated with survival, age, or vascular or capsular invasion. The higher PASS in S100-positive tumors may indicate that pheochromocytomas developing morphologic changes acquire S100 expression. The significance of lower PASS in tumors with elevated BCL-2 expression is uncertain. Overall, the use of PASS and the present immunohistochemical markers may not be useful in dogs with pheochromocytoma.
Topics: Adrenal Gland Neoplasms; Adrenal Glands; Adrenalectomy; Animals; Biomarkers, Tumor; Dog Diseases; Dogs; Female; Male; Pheochromocytoma; Prognosis
PubMed: 30595108
DOI: 10.1177/0300985818819174 -
Cell and Tissue Research May 2018Pheochromocytomas and their extra-adrenal counterpart paragangliomas (PGLs; together called PPGLs), belong to the family of neural crest-derived tumors. Given the... (Review)
Review
Pheochromocytomas and their extra-adrenal counterpart paragangliomas (PGLs; together called PPGLs), belong to the family of neural crest-derived tumors. Given the overexpression of a wide variety of specific targets in PPGLs, it seems that these tumors are optimally suited to be imaged by specific radiopharmaceuticals. Thus, theranostics approaches with somatostatin agonists and antagonists are rapidly evolving in the setting of these tumors and may be considered as the next step in the therapeutic arsenal of metastatic PPGLs.
Topics: Adrenal Gland Neoplasms; Humans; Molecular Imaging; Paraganglioma; Pheochromocytoma; Radiopharmaceuticals; Theranostic Nanomedicine
PubMed: 29450723
DOI: 10.1007/s00441-018-2791-4 -
Endocrine Reviews Dec 2017A molecular biology-based taxonomy has been proposed for pheochromocytoma and paraganglioma (PPGL). Data from the Cancer Genome Atlas revealed clinically relevant... (Review)
Review
A molecular biology-based taxonomy has been proposed for pheochromocytoma and paraganglioma (PPGL). Data from the Cancer Genome Atlas revealed clinically relevant prognostic and predictive biomarkers and stratified PPGLs into three main clusters. Each subgroup has a distinct molecular-biochemical-imaging signature. Concurrently, new methods for biochemical analysis, functional imaging, and medical therapies have also become available. The research community now strives to match the cluster biomarkers with the best intervention. The concept of precision medicine has been long awaited and holds great promise for improved care. Here, we review the current and future PPGL classifications, with a focus on hereditary syndromes. We discuss the current strengths and shortcomings of precision medicine and suggest a condensed manual for diagnosis and treatment of both adult and pediatric patients with PPGL. Finally, we consider the future direction of this field, with a particular focus on how advanced molecular characterization of PPGL can improve a patient's outcome, including cures and, ultimately, disease prevention.
Topics: Adrenal Gland Neoplasms; Biomarkers, Tumor; Genetic Predisposition to Disease; Humans; Molecular Diagnostic Techniques; Mutation; Paraganglioma; Pheochromocytoma; Precision Medicine
PubMed: 28938417
DOI: 10.1210/er.2017-00062 -
Journal of the National Cancer Institute Jan 2022
Topics: Adrenal Gland Neoplasms; Electron Transport; Humans; Paraganglioma; Pheochromocytoma
PubMed: 34415349
DOI: 10.1093/jnci/djab160 -
Journal of the American Veterinary... Aug 2019
Topics: Adrenal Gland Neoplasms; Animals; Cat Diseases; Cats; Female; Pheochromocytoma
PubMed: 31355720
DOI: 10.2460/javma.255.4.433 -
Frontiers in Endocrinology 2022Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors with heterogeneous clinical presentations and potential lethal outcomes. The diagnosis is...
Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors with heterogeneous clinical presentations and potential lethal outcomes. The diagnosis is based on clinical suspicion, biochemical testing, imaging and histopathological confirmation. Increasingly widespread use of imaging studies and surveillance of patients at risk of PPGL due to a hereditary background or a previous tumor is leading to the diagnosis of these tumors at an early stage. This has resulted in an increasing use of the term "silent" PPGL. This term and other variants are now commonly found in the literature without any clear or unified definition. Among the various terms, "clinically silent" is often used to describe the lack of signs and symptoms associated with catecholamine excess. Confusion arises when these and other terms are used to define the tumors according to their ability to synthesize and/or release catecholamines in relation to biochemical test results. In such cases the term "silent" and other variants are often inappropriately and misleadingly used. In the present analysis we provide an overview of the literature and propose standardized terminology in an attempt at harmonization to facilitate scientific communication.
Topics: Humans; Pheochromocytoma; Paraganglioma; Adrenal Gland Neoplasms; Catecholamines
PubMed: 36325453
DOI: 10.3389/fendo.2022.1021420 -
Medicine Dec 2015Pheochromocytoma and paraganglioma (PPG) are rare and late-diagnosed catecholamine secreting tumors, which may be associated with unrecognized and/or severe... (Review)
Review
Pheochromocytoma and paraganglioma (PPG) are rare and late-diagnosed catecholamine secreting tumors, which may be associated with unrecognized and/or severe cardiomyopathies. We performed a computer-assisted systematic search of the electronic Medline databases using the MESH terms "myocarditis," "myocardial infarction," "Takotsubo," "stress cardiomyopathy," "cardiogenic shock", or "dilated cardiomyopathy," and "pheochromocytoma" or "paraganglioma" from 1961 to August 2012. All detailed case reports of cardiomyopathy due to a PPG, without coronary stenosis, and revealed by acute symptoms were included and analyzed. A total of 145 cases reports were collected (49 Takotsubo Cardiomyopathies [TTC] and 96 other Catecholamine Cardiomyopathies [CC]). At initial presentation, prevalence of high blood pressure (87.7%), chest pain (49.0%), headaches (47.6%), palpitations (46.9%), sweating (39.3%), and shock (51.0%) were comparable between CC and TTC. Acute pulmonary edema (58.3% vs 38.8%, P = 0.03) was more frequent in CC. There was no difference in proportion of patients with severe left ventricular systolic dysfunction (LV Ejection Fraction [LVEF] < 30%) at initial presentation between both groups (P = 0.15). LVEF recovery before (64.9% vs 40.8%, P = 0.005) and after surgical resection (97.7% vs 73.3%, P = 0.001) was higher in the TTC group. Death occurred in 11 cases (7.6%). In multivariate analysis, only TTC was associated with a better LV recovery (0.15 [0.03-0.67], P = 0.03). Pheochromocytoma and paraganglioma can lead to different cardiomyopathies with the same brutal and life-threatening initial clinical presentation but with a different recovery rate. Diagnosis of unexplained dilated cardiomyopathy or TTC should lead clinicians to a specific search for PPG.
Topics: Acute Disease; Adrenal Gland Neoplasms; Cardiomyopathies; Chronic Disease; Humans; Pheochromocytoma; Prognosis
PubMed: 26683930
DOI: 10.1097/MD.0000000000002198 -
Archives of Pathology & Laboratory... Feb 2015von Hippel-Lindau (VHL) disease is an autosomal dominant disorder caused by heterozygous mutations in the VHL tumor suppressor gene that is characterized by the... (Review)
Review
von Hippel-Lindau (VHL) disease is an autosomal dominant disorder caused by heterozygous mutations in the VHL tumor suppressor gene that is characterized by the occurrence of multiple endocrine and nonendocrine lesions. This review focuses on the endocrine manifestations of VHL disease. Pancreatic neuroendocrine proliferations (ductuloinsular complexes, islet dysplasia, endocrine microadenoma, and neuroendocrine tumors), pheochromocytomas, and extra-adrenal paragangliomas are important endocrine manifestations of VHL disease. They frequently display characteristic clinical, biochemical, and histopathologic features that, although not pathognomonic, can be helpful in suggesting VHL disease as the underlying etiology and distinguishing these tumors from sporadic cases. Recent improvements in treatment and outcomes of renal cell carcinomas have allowed pancreatic neuroendocrine tumors to emerge as a significant source of metastatic disease, making the accurate recognition and classification of these neoplasms by the pathologist of utmost importance to determine prognosis, treatment, and follow-up strategies for affected patients.
Topics: Adrenal Gland Neoplasms; Carcinoma, Renal Cell; Cell Proliferation; Diagnosis, Differential; Humans; Kidney Neoplasms; Mutation; Neuroendocrine Tumors; Pancreas; Pancreatic Neoplasms; Paraganglioma; Pheochromocytoma; Von Hippel-Lindau Tumor Suppressor Protein; von Hippel-Lindau Disease
PubMed: 25611110
DOI: 10.5858/arpa.2013-0520-RS -
Archives of Endocrinology and Metabolism Oct 2017Phaeochromocytoma and paraganglioma are rare catecholamine-producing tumours, recognised to have one of the richest hereditary backgrounds of all neoplasms, with... (Review)
Review
Phaeochromocytoma and paraganglioma are rare catecholamine-producing tumours, recognised to have one of the richest hereditary backgrounds of all neoplasms, with germline mutations seen in approximately 30% of patients. They can be a part of genetic syndromes such as MEN 2 or Neurofibromatosis type 1, or can be found as apparently sporadic tumours. Germline mutations are almost always found in syndromic patients. Nonetheless, apparently sporadic phaeochromocytoma too show high germline mutation rates. Early detection of a genetic mutation can lead to early diagnosis of further tumours via surveillance, early treatment and better prognosis. Apart from this, the genetic profile has important relevance for tumour location and biochemical profile, and can be a useful predictor of future tumour behaviour. It also enables family screening and surveillance. Moreover, recent studies have demonstrated significant driver somatic mutations in up to 75% of all tumours. Arch Endocrinol Metab. 2017;61(5):490-500.
Topics: Adrenal Gland Neoplasms; Germ-Line Mutation; Humans; Paraganglioma; Pheochromocytoma
PubMed: 29166454
DOI: 10.1590/2359-3997000000299 -
Physiological Research Sep 2017This work discusses the clinical performance of chromogranin A, free metanephrine and normetanephrine determination in plasma using a radioimmunoanalytical methods for...
This work discusses the clinical performance of chromogranin A, free metanephrine and normetanephrine determination in plasma using a radioimmunoanalytical methods for the diagnosis of pheochromocytoma and paraganglioma. Blood samples were collected from 55 patients (46 pheochromocytomas, 9 paragangliomas). A sampling of biological materials was performed preoperatively and about one week, six months and one year after adrenal gland surgery. The comparative group without a diagnosis of pheochromocytoma/paraganglioma consisted of 36 pheochromocytoma/paraganglioma patients more than 4 months after adrenal gland surgery, and of 87 patients, 16 of them with multiple endocrine neoplasia, 9 with medullary and 5 with parafolicullar carcinoma of the thyroid gland. The rest were patients with various adrenal gland disorders. Chromogranin A, metanephrine and normetanephrine were determined in the EDTA-plasma using a radioimmunoassay kits Cisbio Bioassays, France and IBL International GmbH, Germany. Clinical sensitivity was 96 % for the combination of metanephrine and normetanephrine, and 93 % for chromogranin A. Clinical specificity was 100 % for the combination metanephrine and normetanephrine, and 96 % for chromogranin A. Falsely elevated levels of chromogranin A were observed in 1 patient with chronic renal insufficiency and 9 analyses were influenced by the administration of proton pump inhibitors. These results were excluded of CGA specificity. Both the combination of plasma free metanephrine, normetanephrine and chromogranin A as determined by radioimmunoassays, which are simple without the necessity of special laboratory material, are effective markers of pheochromocytoma or paraganglioma. Chromogranin A exerts association to malignity and all markers are associated with tumor mass.
Topics: Adolescent; Adrenal Gland Neoplasms; Adult; Aged; Biomarkers, Tumor; Chromogranin A; Female; Humans; Male; Metanephrine; Middle Aged; Normetanephrine; Pheochromocytoma; Radioimmunoassay; Young Adult
PubMed: 28948824
DOI: 10.33549/physiolres.933719