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Genotype–Phenotype Correlations and Clinical Outcomes in 155 Cases of Pheochromocytoma and Paraganglioma

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Abstract

Background

Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumours, often associated with germline mutations that influence the disease biology and clinical course. We aimed to describe the genotypic and phenotypic characteristics of a consecutive series of PPGL patients and correlate mutation status with clinical outcomes.

Methods

We performed a retrospective cohort study of all PPGL patients who presented to a tertiary referral centre between March 2005 and February 2022. Genotypic, phenotypic and follow-up data were analysed.

Results

A total of 140 patients were included. Of these, 94 (67%) patients underwent genetic testing and a mutation was detected in 36 (38%) patients. Mutation presence was associated with younger age, smaller tumour size and bilateral adrenal tumours. Disease recurrence occurred at a median time of 5.4 (IQR 2.8–11.0) years after treatment in 21 (15%) patients, of which 14 (67%) had a mutation in a susceptibility gene. Recurrence pattern was influenced by mutation type; higher local recurrence risk for SDHA, SDHB, and MEN2B disease, and higher metastatic risk for SDHB, VHL and MEN2A disease. Recurrence occurred in three (3%) patients with mutation absence. Multivariate analysis revealed that age  ≤40 years and mutation presence were associated with increased risk of disease recurrence.

Conclusions

Genotypic characteristics strongly influence disease presentation and recurrence risk, which may occur more than 5 years after initial treatment. Routine genetic testing of PPGL patients is warranted given the high prevalence of mutations, allowing for prognostication and tailored follow-up. In the presence of germline mutations, follow-up should be life-long.

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References

  1. Mete O, Asa SL, Gill AJ et al (2022) Overview of the 2022 WHO classification of paragangliomas and pheochromocytomas. Endocr Pathol 33:90–114

    Article  CAS  Google Scholar 

  2. Dahia PLM (2014) Pheochromocytoma and paraganglioma pathogenesis: learning from genetic heterogeneity. Nat Rev Cancer 14:108–119

    Article  CAS  Google Scholar 

  3. Neumann HPH, Young WF, Eng C (2019) Pheochromocytoma and paraganglioma. NEJM 381:552–565

    Article  CAS  Google Scholar 

  4. Lenders JWM, Duh Q-Y, Eisenhofer G et al (2014) Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. J Clin Endocr 99:1915–1942

    Article  CAS  Google Scholar 

  5. Favier J, Amar L, Gimenez-Roqueplo AP (2015) Paraganglioma and phaeochromocytoma: from genetics to personalized medicine. Nat Rev Endocrinol 11:101–111

    Article  CAS  Google Scholar 

  6. Kim JH, Kim MJ, Kong SH et al (2022) Characteristics of germline mutations in Korean patients with pheochromocytoma/paraganglioma. J Med Genet 59:56–64

    Article  CAS  Google Scholar 

  7. Liu Z, Ma J, Jimenez C et al (2021) Pheochromocytoma: a clinicopathologic and molecular study of 390 cases from a single center. Am J Surg Pathol 45:1155–1165

    Article  Google Scholar 

  8. Fishbein L, Del Rivero J, Else T et al (2021) The North American neuroendocrine tumor society consensus guidelines for surveillance and management of metastatic and/or unresectable pheochromocytoma and paraganglioma. Pancreas 50:469–493

    Article  Google Scholar 

  9. Plouin PF, Amar L, Dekkers OM et al (2016) European Society of Endocrinology Clinical Practice Guideline for long-term follow-up of patients operated on for a phaeochromocytoma or a paraganglioma. Eur J Endocrinol 174:G1–G10

    Article  CAS  Google Scholar 

  10. Amar L, Bertherat J, Baudin E et al (2005) Genetic testing in pheochromocytoma or functional paraganglioma. J Clin Oncol 23:8812–8818

    Article  CAS  Google Scholar 

  11. Press D, Akyuz M, Dural C et al (2014) Predictors of recurrence in pheochromocytoma. Surgery 156:1523–1527

    Article  Google Scholar 

  12. Amar L, Servais A, Gimenez-Roqueplo A-P et al (2005) Year of diagnosis, features at presentation, and risk of recurrence in Patients with pheochromocytoma or secreting paraganglioma. J Clin Endocr 90:2110–2116

    Article  CAS  Google Scholar 

  13. Gomella PT, Sanford TH, Pinto PA et al (2020) Long-term Functional and oncologic outcomes of partial adrenalectomy for pheochromocytoma. Urology 140:85–90

    Article  Google Scholar 

  14. Dhir M, Li W, Hogg ME et al (2017) Clinical predictors of malignancy in patients with pheochromocytoma and paraganglioma. Ann Surg Oncol 24:3624–3630

    Article  Google Scholar 

  15. Amar L, Baudin E, Burnichon N et al (2007) Succinate dehydrogenase B gene mutations predict survival in patients with malignant pheochromocytomas or paragangliomas. J Clin Endocr 92:3822–3828

    Article  CAS  Google Scholar 

  16. Assadipour Y, Sadowski SM, Alimchandani M et al (2017) SDHB mutation status and tumor size but not tumor grade are important predictors of clinical outcome in pheochromocytoma and abdominal paraganglioma. Surgery 161:230–239

    Article  Google Scholar 

  17. Parasiliti-Caprino M, Lucatello B, Lopez C et al (2020) Predictors of recurrence of pheochromocytoma and paraganglioma: a multicenter study in Piedmont, Italy. Hypertens Res 43:500–510

    Article  CAS  Google Scholar 

  18. Thompson LDR (2002) Pheochromocytoma of the adrenal gland scaled score (pass) to separate benign from malignant neoplasms: a clinicopathologic and immunophenotypic study of 100 Cases. Am J Surg Pathol 26:551–566

    Article  Google Scholar 

  19. Wu D, Tischler AS, Lloyd RV et al (2009) Observer variation in the application of the pheochromocytoma of the adrenal gland scaled score. Am J Surg Pathol 33:599–608

    Article  Google Scholar 

Download references

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Authors and Affiliations

  1. Northern Clinical School, Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia

    Hogan Wang, Alexander J. Papachristos, Anthony J. Gill, Anthony Glover, Mark Sywak & Stan B. Sidhu

  2. Endocrine Surgical Unit, Royal North Shore Hospital, Northern Sydney Local Health District, Sydney, NSW, Australia

    Alexander J. Papachristos, Ahmad M. Aniss, Anthony Glover, Mark Sywak & Stan B. Sidhu

  3. NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, Northern Sydney Local Health District, Sydney, NSW, Australia

    Anthony J. Gill

  4. Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia

    Anthony J. Gill

  5. Department of Endocrinology, Royal North Shore Hospital, Northern Sydney Local Health District, Sydney, NSW, Australia

    Roderick Clifton-Bligh

  6. Cancer Genetics Laboratory, Kolling Institute of Medical Research, Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia

    Roderick Clifton-Bligh

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  1. Hogan Wang
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Correspondence to Alexander J. Papachristos.

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Wang, H., Papachristos, A.J., Gill, A.J. et al. Genotype–Phenotype Correlations and Clinical Outcomes in 155 Cases of Pheochromocytoma and Paraganglioma. World J Surg 47, 690–698 (2023). https://doi.org/10.1007/s00268-022-06862-w

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  • DOI: https://doi.org/10.1007/s00268-022-06862-w

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