Challenges in Paragangliomas and Pheochromocytomas: from Histology to Molecular Immunohistochemistry

Juhlin, C. Christofer

doi:10.1007/s12022-021-09675-0

Cited by 36 publications

(54 citation statements)

References 117 publications

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“…Though both genes are highly associated with PCCs and PGLs, the pathogenicity of these variants remains uncertain in this case. However, it has been reported that SDHB, C, or D mutated cases display SDHB immunonegativity [ 23 , 24 ], and the SDHB immunostaining in PGL of this case was positive, so it has been suggested that the pathogenicity of the SDHD variant in this case is low. Meanwhile, 28 gene mutations, including 8 germline mutations, have been reported in follicular lymphoma [ 25 ], but no candidate mutations were detected among those genes.…”

Section: Discussionmentioning

confidence: 77%

Retroperitoneal Paraganglioma With Asymptomatic Follicular Lymphoma: A Case Report

Kakizawa

Yamashita

Nakashima

et al. 2021

Journal of the Endocrine Society

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Paraganglioma (PGL) is a rare tumor originating from extra-adrenal paraganglionic chromaffin tissues, and most sympathetic PGLs have excessive catecholamine secretion. However, nonfunctional PGLs are sometimes found. Although malignant PGL is defined by metastasis to nonchromaffin tissues, it is difficult to predict malignancies due to the lack of reliable markers of potential malignancies. We report the case of a 69-year-old Japanese woman with an incidental retroperitoneal tumor and multiple enlarged mesenteric lymph nodes simultaneously. The patient had no subjective symptoms and there were no laboratory findings suggesting catecholamine hypersecretion. Both the retroperitoneal tumor and the enlarged mesenteric lymph nodes showed high accumulation of fluorodeoxyglucose (FDG), whereas metaiodobenzylguanidine (MIBG) was accumulated only at the retroperitoneal tumor. Although a retroperitoneal tumor was diagnosed as nonfunctional PGL by examination including MIBG scintigraphy, the cause of enlarged mesenteric lymph nodes could not be diagnosed by imaging and biochemical tests. As a result of retroperitoneal tumor resection and mesenteric lymph nodes sampling, histopathological examination revealed that a retroperitoneal tumor was PGL and enlarged mesenteric lymph nodes were follicular lymphoma. To reveal an underlying genetic factor, we performed whole exome sequencing of genomic DNA, and we identified 2 possible candidate variants in SDHD and DLST, but the pathogenicity of these variants remains uncertain in the present case. This rare case reinforces the importance of histopathological diagnosis of nonchromaffin tissue lesions in patients with PGL for the appropriate treatment strategy.

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Section: Discussionmentioning

confidence: 77%

Retroperitoneal Paraganglioma With Asymptomatic Follicular Lymphoma: A Case Report

Kakizawa

Yamashita

Nakashima

et al. 2021

Journal of the Endocrine Society

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“…Tumor cells exhibit a granular and slightly basophilic cytoplasm, and nuclei can vary in size and appearance, with either mono- or pleomorphic features [ 13 , 73 ]. Immunoreactivity to classic neuroendocrine markers such as CgA and synaptophysin is almost always present, and second-generation neuroendocrine markers ISL LIM Homeobox 1 (ISL1) and INSM1 have also been found as reliable markers of an adrenal medullary origin in pheochromocytoma [ 74 , 75 , 76 ] ( Figure 3 ).…”

Section: Resultsmentioning

confidence: 99%

Pheochromocytomas and Abdominal Paragangliomas: A Practical Guidance

Calissendorff

Juhlin

Bancos

et al. 2022

Cancers

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Pheochromocytomas and abdominal paragangliomas (PPGLs) are rare tumors arising from the adrenal medulla or the sympathetic nervous system. This review presents a practical guidance for clinicians dealing with PPGLs. The incidence of PPGLs has risen. Most cases are detected via imaging and less present with symptoms of catecholamine excess. Most PPGLs secrete catecholamines, with diffuse symptoms. Diagnosis is made by imaging and tests of catecholamines. Localized disease can be cured by surgery. PPGLs are the most heritable of all human tumors, and germline variants are found in approximately 30–50% of cases. Such variants can give information regarding the risk of developing recurrence or metastases as well as the risk of developing other tumors and may identify relatives at risk for disease. All PPGLs harbor malignant potential, and current histological and immunohistochemical algorithms can aid in the identification of indolent vs. aggressive tumors. While most patients with metastatic PPGL have slowly progressive disease, a proportion of patients present with an aggressive course, highlighting the need for more effective therapies in these cases. We conclude that PPGLs are rare but increasing in incidence and management should be guided by a multidisciplinary team.

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“…Genetic studies are playing a growing role in the clinical investigation and management of various cancers in the developed world. This is true for endocrine neoplasias like PPGL, where a large number of new target genes have been identified recently (17). In the developing world, technological and budgetary constraints conspire to limit greatly the availability and use of clinical genetics, thereby hindering optimal management.…”

Section: Discussionmentioning

confidence: 99%

Dutch founder SDHB exon 3 deletion in patients with pheochromocytoma-paraganglioma in South Africa

Gordon

Beckers

Castermans

et al. 2022

Endocrine Connections

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Objective: Screening studies have established genetic risk profiles for diseases such as multiple endocrine neoplasia type 1 (MEN1) and pheochromocytoma-paraganglioma (PPGL). Founder effects play an important role in regional/national epidemiology of endocrine cancers, particularly PPGL. Founder effects in the Netherlands have been described for various diseases, some of which established themselves in South Africa due to Dutch emigration. The role of Dutch founder effects in South Africa have not been explored in PPGL. Design: We performed a single-center study in South Africa of the germline genetic causes of isolated/syndromic neuroendocrine tumors. Methods: Next-generation panel and multiplex ligand-dependent probe amplification for endocrine neoplasia risk genes. Results: From a group of 13 patients we identified six with PPGL, four with sporadic or familial isolated pituitary adenomas (FIPA), and three with clinical MEN1; genetic variants were identified in 9/13 cases. We identified the Dutch founder exon 3 deletion in SDHB in two apparently-unrelated individuals with distinct ethnic backgrounds that had metastatic PPGL. Asymptomatic carriers with this Dutch founder SDHB exon 3 deletion were also identified. Other PPGL patients had variants in SDHB, SDHD and three MEN1 variants were identified among MEN1 and young-onset pituitary adenoma patients. Conclusions: This is the first identification of a Dutch founder effect for PPGL in South Africa. Awareness of the presence of this exon 3 SDHB deletion could promote targeted screening at a local level. Insights into PPGL genetics in South Africa could be achieved by studying existing patient databases for Dutch founder mutations in SDHx genes.

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Challenges in Paragangliomas and Pheochromocytomas: from Histology to Molecular Immunohistochemistry

Cited by 36 publications

References 117 publications

Retroperitoneal Paraganglioma With Asymptomatic Follicular Lymphoma: A Case Report

Retroperitoneal Paraganglioma With Asymptomatic Follicular Lymphoma: A Case Report

Pheochromocytomas and Abdominal Paragangliomas: A Practical Guidance

Dutch founder SDHB exon 3 deletion in patients with pheochromocytoma-paraganglioma in South Africa

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