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Journal of the Endocrine Society May 2024
PubMed: 38799768
DOI: 10.1210/jendso/bvae092 -
Journal of the Endocrine Society May 2024Paragangliomas (PGLs) are rare tumors in adrenal and extra-adrenal locations. Metastasis are found in approximately 5% to 35% of PGLs, and there are no reliable...
CONTEXT
Paragangliomas (PGLs) are rare tumors in adrenal and extra-adrenal locations. Metastasis are found in approximately 5% to 35% of PGLs, and there are no reliable predictors of metastatic disease.
OBJECTIVE
This work aimed to develop a prognostic score of metastatic potential in PGLs.
METHODS
A retrospective analysis was conducted of clinical data from a cohort with PGLs and tumor histological assessment. Patients were divided into metastatic PGL (presence of metastasis) and nonmetastatic PGL (absence of metastasis ≥96 months of follow-up) groups. Univariate and multivariable analysis were performed to identify predictors of metastatic potential. A prognostic score was developed based on coefficients of multivariable analysis. Kaplan-Meier curves were generated to estimate disease-specific survival (DSS).
RESULTS
Out of 263 patients, 35 patients had metastatic PGL and 110 patients had nonmetastatic PGL. In multivariable analysis, 4 features were independently related to metastatic disease and composed the Prognostic Score of Paragangliomas (PSPGL): presence of central or confluent necrosis (33 points), more than 3 mitosis/10 high-power field (HPF) (28 points), extension into adipose tissue (20 points), and extra-adrenal location (19 points). A PSPGL of 24 or greater showed similar sensitivity with higher specificity than the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and Grading System for Adrenal Pheochromocytoma and Paraganglioma (GAPP). PSPGL less than or equal to 20 was associated with a risk of metastasis of approximately 10%, whereas a PSPGL of 40 or greater was associated with approximately 80%. The presence of metastasis and Ki-67 of 3% or greater were related to lower DSS.
CONCLUSION
The PSPGL, composed of 4 easy-to-assess parameters, demonstrated good performance in predicting metastatic potential and good ability in estimating metastasis risk.
PubMed: 38799767
DOI: 10.1210/jendso/bvae093 -
AACE Clinical Case Reports 2024Exclusively dopamine-secreting paragangliomas (PGLs) are rare, and the majority of head and neck PGLs are nonsecretory. Here, we describe a patient with succinate...
BACKGROUND/OBJECTIVE
Exclusively dopamine-secreting paragangliomas (PGLs) are rare, and the majority of head and neck PGLs are nonsecretory. Here, we describe a patient with succinate dehydrogenase subunit B (SDHB) mutation and a dopamine-secreting carotid body PGL to highlight the potential importance of screening for dopamine excess in patients with suspected PGL.
CASE REPORT
We report a 34-year-old patient who presented with cranial nerve palsy and was found to have a cerebellopontine PGL. Biochemical testing demonstrated increased circulating dopamine levels with normal levels of other catecholamines. Dopamine excess improved with resection of the PGL, and subsequent genetic testing revealed an SDHB mutation.
DISCUSSION
Secretory head and neck PGLs and exclusively dopamine-secreting PGLs are both uncommon and rarely present together, although PGLs in patients with SDHB mutations often do produce dopamine. Although current guidelines do not recommend routine evaluation of the dopamine levels in patients at risk for PGL, dopamine-secreting PGLs are frequently locally invasive or metastatic.
CONCLUSION
Screening for dopamine excess in patients with a predisposition to PGL or with suspected PGL may aid in diagnosis and as a marker of successful treatment.
PubMed: 38799041
DOI: 10.1016/j.aace.2024.03.003 -
Asian Journal of Surgery May 2024
PubMed: 38797593
DOI: 10.1016/j.asjsur.2024.05.083 -
Archives of Pathology & Laboratory... May 2024Salivary gland (SG) neoplasms (SGNs) display considerable immunophenotypic diversity. A significant proportion of SG carcinomas develop metastases with increased...
CONTEXT.—
Salivary gland (SG) neoplasms (SGNs) display considerable immunophenotypic diversity. A significant proportion of SG carcinomas develop metastases with increased diagnostic difficulty at metastatic sites. Transcriptional repressor GATA binding 1 (TRPS1), a novel immunohistochemical marker for breast cancer, has been found to stain certain SGNs.
OBJECTIVE.—
To investigate TRPS1 and SRY-related HMG-box 10 (SOX10) immunoexpression in various SGNs and non-SG carcinomas, head and neck paragangliomas, and head and neck mucosal melanomas.
DESIGN.—
TRPS1 immunoreactivity score (IRS) was determined as negative or low, intermediate, or high positive; SOX10 was reported as negative or positive.
RESULTS.—
One hundred forty-eight SGNs, 5 breast carcinomas, 105 nonbreast-non-SG carcinomas, including 33 head and neck squamous cell carcinomas (HNSCCs), 6 head and neck paragangliomas, and 6 head and neck mucosal melanomas, were assessed for TRPS1. All 23 benign SGNs showed TRPS1 positivity, with the majority having high-positive IRS (17 of 23 cases; 74%). Among 125 SG carcinomas, 115 of 125 (92%) were TRPS1 positive, with high-positive IRS in 94 of 125 (75%), intermediate positive in 15 of 125 (12%), and low positive in 6 of 125 (5%). Among nonbreast-non-SG carcinomas, HNSCC, lung, thyroid, kidney, and ovarian carcinomas showed frequent TRPS1 staining. Nearly half of HNSCCs had high (11 of 18; 33%) or intermediate (4 of 18; 12%) positive IRS. Mean IRS in SG carcinomas was significantly higher than that in nonbreast-non-SG carcinomas (P < .001). None of the TRPS1-positive nonbreast-non-SG carcinomas expressed SOX10.
CONCLUSIONS.—
TRPS1 is positive in most benign and malignant SGNs. Its expression in several nonbreast-non-SG carcinomas indicates that it lacks specificity for breast and SG carcinomas, even if considering only high-positive IRS. Addition of SOX10 can increase discriminatory utility of TRPS1.
PubMed: 38797518
DOI: 10.5858/arpa.2023-0444-OA -
Impact of pheochromocytoma or paraganglioma on bone metabolism: A systemic review and meta-analysis.Journal of Clinical Densitometry : the... May 2024Preclinical and animal studies have suggested that excess catecholamines can lead to bone mineral loss. However, to date, no systematic review is available that has...
INTRODUCTION
Preclinical and animal studies have suggested that excess catecholamines can lead to bone mineral loss. However, to date, no systematic review is available that has analyzed the impact of catecholamine excess in the context of pheochromocytoma/paraganglioma (PPGL) on bone metabolism. We conducted this meta-analysis to address this knowledge gap.
METHODS
Electronic databases were searched for studies evaluating bone metabolism, including assessments of bone mineral density (BMD), quantitative computed tomography (qCT), trabecular bone score (TBS), or bone turnover markers in patients with PPGL. These markers included those of bone resorption, such as tartrate-resistant acid phosphatase 5b (TRACP-5b) and cross-linked C-telopeptide of type I collagen (CTx), as well as markers of bone formation, such as bone-specific alkaline phosphatase (BS ALP).
RESULTS
Out of the initially screened 1614 articles, data from six studies published in four different patient cohorts with PPGL that met all criteria were analysed. Individuals with PPGL had significantly lower TBS [Mean Difference (MD) -0.04 (95% CI: -0.05--0.03); p < 0.00001; I2 = 0%], higher serum CTx [MD 0.13 ng/ml (95% CI: 0.08-0.17); p < 0.00001; I2 = 0%], and higher BS-ALP [MD 1.47 U/L (95% CI: 0.30-2.64); p = 0.01; I2 = 1%]. TBS at 4-7 months post-surgery was significantly higher compared to baseline [MD 0.05 (95% CI: 0.02-0.07); p < 0.0001]. A decrease in CTx has been documented post-surgery.
CONCLUSION
Bone health deterioration is a major concern in patients with PPGL. In addition to providing a definitive cure for catecholamine excess, monitoring and treating osteoporosis is essential for individuals with secondary osteoporosis due to PPGL. Long-term studies on bone health outcomes in PPGL are warranted.
PubMed: 38796986
DOI: 10.1016/j.jocd.2024.101501 -
Problemy Endokrinologii Sep 2023We presented the clinical case of neurofibromatosis type 1 (NF-1) associated with pheochromocytoma (PHEO) in a man under 40 years old without family history. The... (Review)
Review
We presented the clinical case of neurofibromatosis type 1 (NF-1) associated with pheochromocytoma (PHEO) in a man under 40 years old without family history. The diagnosis of NF-1 was established based on 4 signs of the disease (multiple café au lait macules, scoliotic changes in posture, the presence of multiple neurofibromas, Lisch nodules). The diagnosis of PHEO was determined by a significant increase of free metanephrin/normethanephrin levels in daily urine, a malignant CT phenotype of the right adrenal tumor, and confirmed by pathomorphological study. Genetic tests revealed a new mutation in one of the alleles of NF1 gene, a deletion of a 566 bp gene fragment, including exon 19 with a size of 73 bp. This mutation leads to splicing of exons 18 and 20, frameshift, and termination of protein synthesis. A study of the level of transcription of the genes associated with PHEO (RET, TMEM127, MAX, FGFR, MET, MERTK, BRAF, NGFR, Pi3, AKT, MTOR, KRAS, MAPK) was conducted, a statistically significant decrease in the level of transcription of the KRAS and BRAF genes and increase in the level of transcription of the TMEM127 gene in comparison with control samples have been detected. This case demonstrates the need for timely recognition of NF-1 for further appropriate patient's follow up and show the effectiveness of a multidisciplinary approach to the diagnosis and treatment of NF-1-associated catecholamine-secreting tumors.
Topics: Humans; Pheochromocytoma; Neurofibromatosis 1; Male; Adrenal Gland Neoplasms; Adult; Neurofibromin 1; Mutation
PubMed: 38796761
DOI: 10.14341/probl13345 -
Problemy Endokrinologii Oct 2023Pheochromocytoma (PHEO) is a tumor from the chromaffin tissue of the adrenal medulla, capable of hyperproduction of catecholamines. The increased production of hormones... (Comparative Study)
Comparative Study
BACKGROUND
Pheochromocytoma (PHEO) is a tumor from the chromaffin tissue of the adrenal medulla, capable of hyperproduction of catecholamines. The increased production of hormones by the tumor leads to catecholamine crises, which have a pathological effect on all organs and systems. In the primary diagnosis of pheochromocytomas, it is important to determine the level of the metabolite of catecholamines - metanephrines. Currently, in clinical practice, various methods are used to determine the level of this metabolite: in blood plasma or in urine, total or only free form, fractionated analysis or unfractionated.
AIM
Comparison of the effectiveness of various methods for determining the level of metanephrines for the diagnosis of pheochromocytomas.
MATERIALS AND METHODS
A retrospective single-center cohort study was conducted on a sample of patients who were initially operated on for adrenal neoplasm at the Pirogov St. Petersburg State University High Medical Technology Clinic from November 2007 to December 2022 and who passed analysis to determine the level of blood or urine metanephrins before surgical treatment. The results of tests for metanephrine and tumor size were evaluated.
RESULTS
1088 patients with adrenal neoplasms who underwent surgical treatment were examined, of which 348 had histologically confirmed the presence of pheochromocytoma. Four types of metanephrine assays were compared: free fractionated plasma metanephrines (232 patients), unfractionated daily urine metanephrines (431 patients), fractionated total daily urine metanephrines (427 patients) and fractionated free daily urine metanephrines (178 patients). The greatest sensitivity was demonstrated by the analysis of free fractionated plasma methanephrines (95.4%). Unlike others, the sensitivity of this analysis did not decrease in the group of patients with small pheochromocytomas (3 cm or less). The greatest specificity was demonstrated by the analysis of unfractionated metanephrines in daily urine (97.8%), with the lowest sensitivity among all tests (67.6%). The study of fractionated total daily urine metanephrins showed good results of sensitivity and specificity, only slightly inferior to the best indicators, and the analysis of free daily urine metanephrins demonstrated unexpectedly low efficiency. There is a positive correlation between the level of metanephrine in the blood and the size of the tumor.
CONCLUSION
Based on the data obtained, the preferred assays for the primary diagnosis of pheochromocytoma can be considered the determination of fractionated free plasma metanephrines and fractionated total daily urine metanephrines, which is consistent with relevant clinical recommendations. It was found that the size of the tumor correlates with the severity of an increase in the level of metanephrins determined by any of the described methods.
Topics: Pheochromocytoma; Humans; Metanephrine; Adrenal Gland Neoplasms; Female; Retrospective Studies; Male; Middle Aged; Adult; Aged
PubMed: 38796760
DOI: 10.14341/probl13309 -
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 -
Annales de Cardiologie Et D'angeiologie Jun 2024Pheochromocytoma is a rare neuroendocrine tumor characterized by overproduction of catecholamines. The overproduction of catecholamines leads to cardiac remodeling which...
Pheochromocytoma is a rare neuroendocrine tumor characterized by overproduction of catecholamines. The overproduction of catecholamines leads to cardiac remodeling which manifests in several forms ranging from Takotsubo to dilated cardiomyopathy. Studies suggest that pheochromocytoma-induced cardiomyopathy can take various forms depending on the duration of catecholamine exposure. Myocarditis is a fairly rare presentation of cardiac manifestations of pheochromocytoma which are mainly dominated by Takotsubo and dilated cardiomyopathies. We report a rare case of recurrent myocarditis in a young 37-year-old patient revealing the diagnosis of adrenal pheochromocytoma. Through this case and through a review of the literature we will take stock of the epidemiology of cardiac involvement in pheochromocytoma, mainly cardiomyopathies, and we will take stock of the value of diagnosis and early management in improving the prognosis of patients.
Topics: Humans; Pheochromocytoma; Myocarditis; Adrenal Gland Neoplasms; Adult; Recurrence; Male; Female
PubMed: 38788259
DOI: 10.1016/j.ancard.2024.101768