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11:00
12:30
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Paraganglioma
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Akiyo TanabeJapan
Speaker
Update in Management of Pheochromocytoma and ParagangliomaPheochromocytoma and paraganglioma (PPGL) are rare endocrine neoplasms. Because it is difficult to predict the future development of metastasis based on biochemical testing or pathological findings, all PPGLs were reclassified as malignant tumors with metastatic potential in the revised 2017 WHO Classification of Endocrine Tumors. In Japan, the clinical practice guidelines for PPGL were revised in 2025. The diagnosis of PPGL requires the presence of tumors with characteristic findings. A definitive diagnosis is made based on elevated serum and urinary metanephrine fractions, positive tumor 123I-MIBG scintigraphy, and pathological findings in surgical cases. Measurement of plasma or urinary catecholamine fractions is no longer recommended because of its limited diagnostic accuracy; instead, measurement of plasma or urinary metanephrine fractions, which are metabolites of catecholamines, is currently recommended. Imaging modalities include computed tomography (CT), magnetic resonance imaging (MRI), and 123I-MIBG scintigraphy; however, 68Ga-DOTATATE positron emission tomography, which offers higher specificity and superior spatial resolution, is increasingly being used as an alternative to 123I-MIBG scintigraphy. The first-line treatment is tumor resection, regardless of whether metastasis is present or not. In patients at high surgical risk, catecholamine synthesis inhibitors (metyrosine) may be administered preoperatively in combination with α-adrenergic blockers. Because there is no clearly established effective therapy for metastatic disease, multidisciplinary management is required, combining debulking surgery to control catecholamine excess, systemic therapies such as CVD chemotherapy, 131I-MIBG therapy, and somatostatin receptor radionuclide therapy, as well as local treatments including external beam radiotherapy and transarterial embolization. Although tyrosine kinase inhibitors and immune checkpoint inhibitors have been investigated, their therapeutic efficacy remains limited. Even in patients with metastatic disease, active surveillance without immediate treatment —so-called watch and wait— may be a reasonable option for those with slow tumor growth, well-controlled catecholamine-related symptoms, and a low risk of local organ damage, with active treatment initiated upon evidence of disease progression. Pathogenic variants in PPGL-associated genes are identified in approximately 20–40% of patients, and variant-specific diagnostic and therapeutic algorithms are increasingly being proposed.
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Roderick Clifton-BlighAustralia
Speaker
What's New in the Adrenal Medulla?Phaeochromocytomas (PCs) are adrenal chromaffin cell tumours; paragangliomas (PGLs) are derived either from parasympathetic paraganglia of the skull base and neck (HNPGLs: glomus caroticum, jugulare, tympanicum and vagale) and anterior/middle mediastinum, or from sympathetic-associated chromaffin paraganglia in the abdomen, pelvis and (rarely) the posterior mediastinum. PCs and PGLs (collectively, PPGLs) present in myriad ways, often dependent upon their specific genetic alteration (either germline or somatic).
This talk will highlight many recent advances in diagnosis and treatment of PPGLs, including an update on biochemical assessment, structural and functional imaging, histology, genetics and treatment. Since there is no known prevention, early detection of tumors and surgical resection remains the only chance of cure. It follows that appropriate surveillance of patients with genetic PPGL predisposition is the most effective means to reduce morbidity and mortality in these syndromes, albeit with many potential challenges including cost, parental concern about testing children, burden of a lifetime surveillance program, and concerns about accessing insurance.
Treatment of metastatic PPGL remains challenging, albeit with recent trials showing modest efficacy of multikinase inhibitors (e.g. sunitinib and cabozantinib) or HIF2-targeted therapy (belzutifan). Radionuclide therapy with either MIBG or Lutate may be appropriate for patients with slowly progressive disease. Machine-learning algorithms can now identify patients with high risk of developing metastatic disease, opening the potential for clinical trials to test efficacy of adjuvant therapies.
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Wan-Chen WuTaiwan
Speaker
Genetics of Paragangliomas (Pheochromocytomas)Background: Pheochromocytomas and paragangliomas (PPGLs) represent the most heritable human neoplasms, with nearly 80% of cases now attributable to either germline or somatic driver mutations. As we move into 2026, the paradigm of PPGL management has shifted from symptomatic treatment to genotype-driven precision care. This presentation integrates global molecular advancements with a specific focus on the unique genetic signatures identified within the Asia-Oceania region, particularly highlighting recent discoveries from the Taiwan research team.
Molecular Classification and Pathway Signatures: Advanced multi-omics profiling has refined the classification of PPGLs into at least eight distinct molecular subtypes, primarily converging on three key signaling clusters: Pseudohypoxia (e.g., SDHx, VHL, FH), Kinase Signaling (e.g., RET, NF1, HRAS), and Wnt-Altered pathways (e.g., MAML3 fusions, CSDE1). Each cluster is characterized by a unique "molecular-clinical-biochemical-imaging" quadruple phenotype, which dictates tumor location, secretory profile, metastatic potential, and responsiveness to specific functional imaging modalities.
The Asia-Oceania Perspective and the Taiwan Experience: Emerging data suggest significant ethnic variations in the genetic architecture of PPGLs. While Sino-Caucasian comparative studies have identified a higher prevalence of HRAS and FGFR1 mutations in Chinese cohorts, pioneering research from the National Taiwan University Hospital (NTUH) team has unveiled critical local nuances. A defining feature of the Taiwanese genetic landscape is the identification of a notable founder effect in the SDHD gene, which distinguishes local patients from other East Asian populations. These findings, alongside multicenter data from Korea, underscore the necessity of population-specific diagnostic algorithms in the Asia-Pacific region.
Clinical Translation and Precision Management: The high prevalence of pathogenic variants -even in "apparently sporadic" or "incidental" presentations - mandates universal genetic testing for all PPGL patients. For those with initial negative results, longitudinal multigene panel retesting is essential as the list of susceptibility genes expands. Genotype-informed care now guides every facet of clinical practice, from personalized surveillance and the selection of functioning scan (such as 68Ga-DOTATATE PET/CT) to the application of targeted therapies (such as HIF-2α inhibitors).
Conclusion: By bridging global molecular frameworks with localized research, such as the SDHD founder effect observed in Taiwan, we can achieve a higher standard of precision medicine. As we convene for AOCE 2026 in Taipei, these insights emphasize the importance of regional collaboration and the implementation of specific screening strategies to optimize the long-term outcomes for PPGL patients across Asia and beyond.
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