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World Journal of Clinical Cases May 2024Paraganglioma (PGL) located in the retroperitoneum presents challenges in diagnosis and treatment due to its hidden location, lack of specific symptoms in the early...
BACKGROUND
Paraganglioma (PGL) located in the retroperitoneum presents challenges in diagnosis and treatment due to its hidden location, lack of specific symptoms in the early stages, and absence of distinctive manifestations on imaging.
CASE SUMMARY
A 56-year-old woman presented with a left upper abdominal mass discovered 1 wk ago during a physical examination. She did not have a history of smoking, alcohol consumption, or other harmful habits, no surgical procedures or infectious diseases, and had a 4-year history of hypertension. Upon admission, she did not exhibit fever, vomiting, or abdominal distension. Physical examination indicated mild percussion pain in the left upper abdomen, with no palpable enlargement of the liver or spleen. Laboratory tests and tumor markers showed no significant abnormalities. Enhanced computed tomography and magnetic resonance imaging of the upper abdomen revealed a cystic solid mass in the left epigastrium measuring approximately 6.5 cm × 4.5 cm, with inhomogeneous enhancement in the arterial phase, closely associated with the lesser curvature of the stomach and the pancreas. The patient underwent laparoscopic resection of the retroperitoneal mass, which was successfully removed without tumor rupture. A 12-month postoperative follow-up period showed good recovery.
CONCLUSION
This case report details the successful laparoscopic resection of a retroperitoneal subclinical PGL, resulting in a good recovery observed at the 12-month follow-up. Interestingly, the patient also experienced unexpected cure of hypertensive disease.
PubMed: 38817224
DOI: 10.12998/wjcc.v12.i15.2672 -
Annales D'endocrinologie May 2024Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors with high heritability, justifying systematic genetic screening for a germline variant in one of...
CONTEXT
Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors with high heritability, justifying systematic genetic screening for a germline variant in one of the twenty predisposing genes described to date.
PURPOSE
To describe the experience of one endocrine oncogenetic laboratory over a period of 21 years (2001-2022), from the beginning of PPGL genotyping with Sanger sequencing in 2001 to the implementation of next-generation sequencing (NGS).
METHOD
The activity database of an academic oncogenetic laboratory was searched to extract patients/relatives identified with a pathogenic variant/likely pathogenic variant (PV/LPV) over a period of 21 years. Clinical and genetic data were compared.
RESULTS
In total, 606 index cases with PPGL and 444 relatives were genotyped. Genotyping of index cases was performed by Sanger sequencing and gene deletion analysis in 327 cases and by NGS in 279. Germline PV/LPV spanning 10 genes was identified in 165 index cases (27.2%). Several recurrent PV/LPVs in SDHx were observed in non-related index cases, the most frequent being SDHD, c.170-1G>T (n=28). This subgroup showed great phenotypic variability both between and within families in terms of both tumor location and number. Four patients (1.1%) with PV/LPV in SDHx had 3PA (Pituitary Adenoma and pheochromocytoma/paraganglioma) syndrome. 258 relatives (58.1%) had inherited a PV/LPV in one driver gene. The rate of PV/LPV carriers who were symptomatic at first imaging evaluation was 32%, but varied between<20% in SDHB and SDHC and >50% in SDHD, VHL and MAX.
CONCLUSION
Our experience confirmed previously established genotype-phenotype correlations, but also highlights atypical clinical presentations, even for the same genetic variant. These data must be taken into account for optimal patient follow-up and management.
PubMed: 38815921
DOI: 10.1016/j.ando.2024.05.024 -
Cureus Apr 2024Pheochromocytomas (PCCs) and paragangliomas (PGLs) represent tumors arising from chromaffin cells of the adrenal medulla and extra-adrenal sympathetic paraganglia,...
Pheochromocytomas (PCCs) and paragangliomas (PGLs) represent tumors arising from chromaffin cells of the adrenal medulla and extra-adrenal sympathetic paraganglia, respectively. PCCs commonly produce one or more catecholamines (epinephrine, norepinephrine, and dopamine), but rarely are they biochemically silent. PGLs on the other hand, generally do not produce catecholamines. They have the highest heritability of all adrenal tumors and are known to be associated with genetic mutations. Patients with hereditary tumors typically present at a younger age and with multifocal disease when compared to sporadic disease. Specific genetic mutations have been well established with hereditary syndromes involving PCC/PGLs. Further research has aimed to identify other mutations and delineate specific phenotypes associated with these mutations. A 34-year-old woman presented for evaluation following a laparoscopic appendectomy that identified a 4-cm well-differentiated neuroendocrine tumor on final pathology. Further work-up included a repeat CT scan followed by a Dotatate PET CT scan which revealed a large (7.3 x 5.8 cm) periaortic mass related to the left adrenal gland. Functional adrenal work-up was negative and her Chromogranin A level was 679 ng/mL. She did report intermittent chest tightness and palpitations but was otherwise asymptomatic. The patient subsequently underwent an exploratory laparotomy with left adrenalectomy and adjacent tumor resection as well as completion of right hemicolectomy with ileocolonic anastomosis. Surgical pathology revealed two distinct masses consistent with multifocal PCC. No residual tumor was found in the colectomy specimen and 24 lymph nodes were negative. She had an uneventful recovery and genetic testing showed a variant of uncertain significance for the POLE and VHL genes. She has received genetic counseling and will be enrolled in an appropriate surveillance protocol.
PubMed: 38813302
DOI: 10.7759/cureus.59295 -
Scientific Reports May 2024Robotic adrenalectomy (RA) has gained significant popularity in the management of adrenal gland diseases. We report our experience at a single tertiary institution and...
Robotic adrenalectomy (RA) has gained significant popularity in the management of adrenal gland diseases. We report our experience at a single tertiary institution and evaluate the safety and surgical outcomes of RA. The data of 122 consecutive patients who underwent RA from October 2009 to December 2022 at Korea University Anam Hospital (Seoul, Korea) were reviewed. There were no perioperative complications. Clinicopathological features and surgical outcomes were retrospectively analyzed through complete chart reviews. Noteworthy findings include the influence of sex, tumor size, and body mass index on operation time, with the female and small tumor groups exhibiting shorter operation times (P = 0.018 and P = 0.009, respectively). Pheochromocytoma was identified as a significant independent risk factor for a longer operation time in the multivariate analysis [odds ratio (OR), 3.709; 95% confidence interval (CI), 1.127-12.205; P = 0.031]. A temporal analysis revealed a decreasing trend in mean operation times across consecutive groups, reflecting a learning curve associated with RA adoption. RA is a safe and effective operative technique alternative to laparoscopic adrenalectomy that has favorable surgical outcomes and enhances the convenience of the operation.
Topics: Humans; Female; Adrenalectomy; Male; Robotic Surgical Procedures; Middle Aged; Retrospective Studies; Treatment Outcome; Adult; Adrenal Gland Neoplasms; Operative Time; Aged; Pheochromocytoma; Risk Factors; Postoperative Complications; Laparoscopy
PubMed: 38806567
DOI: 10.1038/s41598-024-63105-9 -
PloS One 2024Pheochromocytoma, or paraganglioma (PPGL), is a tumor that arises from catecholamine-producing chromaffin cells of the adrenal medulla or paraganglion. Systemic therapy,...
Evaluation of pharmacokinetics, safety, and efficacy of [211At] meta-astatobenzylguanidine ([211At] MABG) in patients with pheochromocytoma or paraganglioma (PPGL): A study protocol.
BACKGROUND
Pheochromocytoma, or paraganglioma (PPGL), is a tumor that arises from catecholamine-producing chromaffin cells of the adrenal medulla or paraganglion. Systemic therapy, such as the combination of cyclophosphamide, vincristine, and dacarbazine or therapeutic radiopharmaceuticals such as [131I] meta-iodobenzylguanidine (MIBG), may be administered in cases of locally advanced tumors or distant metastases. However, the current therapies are limited in terms of efficacy and implementation. [211At] meta-astatobenzylguanidine (MABG) is an alpha-emitting radionuclide-labeled ligand that has demonstrated remarkable tumor-reducing effects in preclinical studies, and is expected to have a high therapeutic effect on pheochromocytoma cells.
METHODS
We are currently conducting an investigator-initiated first-in-human clinical trial to evaluate the pharmacokinetics, safety, and efficacy of [211At] MABG. Patients with locally unresectable or metastatic PPGL refractory to standard therapy and scintigraphically positive [123I] MIBG aggregation are being recruited, and a 3 + 3 dose escalation design was adopted. The initial dose of [211At] MABG is 0.65 MBq/kg, with a dose escalation in a 1:2:4 ratio in each cohort. Dose-limiting toxicity is observed for 6 weeks after a single bolus dose of [211At] MABG, and the patients are observed for 3 months to explore safety and efficacy profiles. The primary endpoint is dose-limiting toxicity to determine both maximum tolerated and recommended doses. The secondary endpoints include radiopharmacokinetics, urinary radioactive excretion rate, urinary catecholamine response rate, objective response rate, progression free survival, [123I] MIBG scintigraphy on reducing tumor accumulation, and quality of life.
TRIALS REGISTRATION
jRCT2021220012 registered on 17 June 2022.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Adrenal Gland Neoplasms; Guanidines; Paraganglioma; Pheochromocytoma; Radiopharmaceuticals; Treatment Outcome; Clinical Trials, Phase I as Topic
PubMed: 38805424
DOI: 10.1371/journal.pone.0303623 -
World Journal of Surgical Oncology May 2024In clinical practice, genetic testing has become standard for many cancerous diseases. While a diagnosis of a single hereditary syndrome is not uncommon, the coexistence...
BACKGROUND
In clinical practice, genetic testing has become standard for many cancerous diseases. While a diagnosis of a single hereditary syndrome is not uncommon, the coexistence of two genetic diseases, even with partially common symptoms, remains unusual. Therefore, targeted next-generation sequencing (NGS), along with genetic consultation and imaging studies, is essential for every patient with confirmed paraganglioma. In this report, we present two sisters diagnosed with multiple endocrine neoplasia type 2 (MEN2A) and familial paraganglioma syndrome type 1 (FPGL1).
CASE PRESENTATION
After presenting to the clinic with neck tumors persisting for several months, both patients underwent tumor removal procedures following imaging and laboratory studies. Pathological reports confirmed the diagnosis of paragangliomas. Subsequently, genetic testing, including NGS, revealed a mutation in the rearranged during transfection (RET) gene: the heterozygous change (c.2410G > A), (p.Val804Met), and a variant of the succinate dehydrogenase complex subunit D (SDHD) gene: (c.64 C > T), (p.Arg22Ter). Subsequently, thyroidectomy procedures were scheduled in both cases.
CONCLUSION
To the best of our knowledge, this is the first report presenting these two mutations in two related patients, resulting in distinctive genetic syndromes with similar manifestations. This underscores that although infrequent, multiple hereditary disorders may co-occur in the same individual.
Topics: Humans; Female; Multiple Endocrine Neoplasia Type 2a; Siblings; Succinate Dehydrogenase; Adult; Proto-Oncogene Proteins c-ret; Prognosis; Thyroidectomy; Mutation; Genetic Testing; Pedigree; Paraganglioma; High-Throughput Nucleotide Sequencing
PubMed: 38802890
DOI: 10.1186/s12957-024-03418-1 -
Cureus Apr 2024Paragangliomas are sympathetic and parasympathetic para-ganglia neuroendocrine tumors of the autonomic nervous system. We analyzed a bifocal paraganglioma case of a...
Paragangliomas are sympathetic and parasympathetic para-ganglia neuroendocrine tumors of the autonomic nervous system. We analyzed a bifocal paraganglioma case of a 52-year-old patient in December 2013 with hearing loss and right ear pain, headaches, episodes of vomiting, and abdominal pain ten months before her medical consultation. The diagnosis of a right tympano-jugular glomus paraganglioma was based on cerebral magnetic resonance imaging and treated with radiotherapy. In 2016, the patient presented with worsening digestive symptoms; therefore, a second mesocolic localization was suspected by abdominal computed tomography and was histologically confirmed on the resection specimen of the mass. The surgery was the only treatment. After a follow-up of 11 years, the patient remained in good condition. Paraganliomas are rare tumors, their bifocal location in our patient represents an even rarer entity. Given the nonspecific symptomatology, the diagnosis of the retroperitoneal location simultaneously with that of the head and neck was difficult. Our objective is to emphasize the staging workup for paraganglioma, although it is mostly a benign tumor with slow growth.
PubMed: 38800343
DOI: 10.7759/cureus.59048 -
Radiology Case Reports Aug 2024A paraganglioma is a neuroendocrine tumor that may secrete catecholamines and present with symptoms of sympathetic overload such as hypertension and diaphoresis. It is...
A paraganglioma is a neuroendocrine tumor that may secrete catecholamines and present with symptoms of sympathetic overload such as hypertension and diaphoresis. It is important that paragangliomas are identified, as they must often be treated by surgical excision. IgG4-related retroperitoneal fibrosis (IgG4-RPF) is a systemic inflammatory disease that results in the infiltration of IgG4-positive plasma cells in the retroperitoneum. Such fibrosis may adversely affect nearby organs and tissues. Here, we describe a case of combined paraganglioma and IgG4-RPF in a 47-year-old female patient. This case demonstrates the deleterious effect of these two conditions when they occur simultaneously.
PubMed: 38800075
DOI: 10.1016/j.radcr.2024.04.065 -
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