Original Scientific Report

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

Hogan Wang

orcid.org/0000-0002-0494-4768

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

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Alexander J. Papachristos,

Corresponding Author

Alexander J. Papachristos

[email protected]

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

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

[email protected]Search for more papers by this author

Anthony J. Gill,

Anthony J. Gill

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

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

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

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Roderick Clifton-Bligh,

Roderick Clifton-Bligh

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

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

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Ahmad M. Aniss,

Ahmad M. Aniss

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

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Anthony Glover,

Anthony Glover

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

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

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Mark Sywak,

Mark Sywak

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

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

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Stan B. Sidhu,

Stan B. Sidhu

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

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

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Hogan Wang,

Hogan Wang

orcid.org/0000-0002-0494-4768

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

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Alexander J. Papachristos,

Corresponding Author

Alexander J. Papachristos

[email protected]

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

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

[email protected]Search for more papers by this author

Anthony J. Gill,

Anthony J. Gill

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

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

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

Search for more papers by this author

Roderick Clifton-Bligh,

Roderick Clifton-Bligh

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

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

Search for more papers by this author

Ahmad M. Aniss,

Ahmad M. Aniss

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

Search for more papers by this author

Anthony Glover,

Anthony Glover

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

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

Search for more papers by this author

Mark Sywak,

Mark Sywak

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

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

Search for more papers by this author

Stan B. Sidhu,

Stan B. Sidhu

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

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

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First published: 22 December 2022

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

Citations: 8

Copyright comment: Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

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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.

Graphical abstract

References

1Mete O, Asa SL, Gill AJ et al. Overview of the 2022 WHO classification of paragangliomas and pheochromocytomas. Endocr Pathol (2022) 33: 90–11410.1007/s12022-022-09704-6
10.1007/s12022-022-09704-6
CAS PubMed Web of Science® Google Scholar
2Dahia PLM Pheochromocytoma and paraganglioma pathogenesis: learning from genetic heterogeneity. Nat Rev Cancer (2014) 14: 108–11910.1038/nrc3648
10.1038/nrc3648
CAS PubMed Web of Science® Google Scholar
3Neumann HPH, Young WF, Eng C Pheochromocytoma and paraganglioma. NEJM (2019) 381: 552–56510.1056/NEJMra1806651
10.1056/NEJMra1806651
CAS PubMed Web of Science® Google Scholar
4Lenders JWM, Duh Q-Y, Eisenhofer G et al. Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. J Clin Endocr (2014) 99: 1915–194210.1210/jc.2014-1498
10.1210/jc.2014-1498
CAS PubMed Web of Science® Google Scholar
5Favier J, Amar L, Gimenez-Roqueplo AP Paraganglioma and phaeochromocytoma: from genetics to personalized medicine. Nat Rev Endocrinol (2015) 11: 101–11110.1038/nrendo.2014.188
10.1038/nrendo.2014.188
CAS PubMed Web of Science® Google Scholar
6Kim JH, Kim MJ, Kong SH et al. Characteristics of germline mutations in Korean patients with pheochromocytoma/paraganglioma. J Med Genet (2022) 59: 56–6410.1136/jmedgenet-2020-107102
10.1136/jmedgenet-2020-107102
CAS PubMed Web of Science® Google Scholar
7Liu Z, Ma J, Jimenez C et al. Pheochromocytoma: a clinicopathologic and molecular study of 390 cases from a single center. Am J Surg Pathol (2021) 45: 1155–116510.1097/PAS.0000000000001768
10.1097/PAS.0000000000001768
PubMed Web of Science® Google Scholar
8Fishbein L, Del Rivero J, Else T et al. The North American neuroendocrine tumor society consensus guidelines for surveillance and management of metastatic and/or unresectable pheochromocytoma and paraganglioma. Pancreas (2021) 50: 469–49310.1097/MPA.0000000000001792
10.1097/MPA.0000000000001792
PubMed Web of Science® Google Scholar
9Plouin PF, Amar L, Dekkers OM et al. 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 (2016) 174: G1–G1010.1530/EJE-16-0033
10.1530/EJE-16-0033
CAS PubMed Web of Science® Google Scholar
10Amar L, Bertherat J, Baudin E et al. Genetic testing in pheochromocytoma or functional paraganglioma. J Clin Oncol (2005) 23: 8812–881810.1200/JCO.2005.03.1484
10.1200/JCO.2005.03.1484
CAS PubMed Web of Science® Google Scholar
11Press D, Akyuz M, Dural C et al. Predictors of recurrence in pheochromocytoma. Surgery (2014) 156: 1523–152710.1016/j.surg.2014.08.044
10.1016/j.surg.2014.08.044
PubMed Web of Science® Google Scholar
12Amar L, Servais A, Gimenez-Roqueplo A-P et al. Year of diagnosis, features at presentation, and risk of recurrence in Patients with pheochromocytoma or secreting paraganglioma. J Clin Endocr (2005) 90: 2110–211610.1210/jc.2004-1398
10.1210/jc.2004-1398
CAS PubMed Web of Science® Google Scholar
13Gomella PT, Sanford TH, Pinto PA et al. Long-term Functional and oncologic outcomes of partial adrenalectomy for pheochromocytoma. Urology (2020) 140: 85–9010.1016/j.urology.2020.02.015
10.1016/j.urology.2020.02.015
PubMed Web of Science® Google Scholar
14Dhir M, Li W, Hogg ME et al. Clinical predictors of malignancy in patients with pheochromocytoma and paraganglioma. Ann Surg Oncol (2017) 24: 3624–363010.1245/s10434-017-6074-1
10.1245/s10434-017-6074-1
PubMed Web of Science® Google Scholar
15Amar L, Baudin E, Burnichon N et al. Succinate dehydrogenase B gene mutations predict survival in patients with malignant pheochromocytomas or paragangliomas. J Clin Endocr (2007) 92: 3822–382810.1210/jc.2007-0709
10.1210/jc.2007-0709
CAS PubMed Web of Science® Google Scholar
16Assadipour Y, Sadowski SM, Alimchandani M et al. SDHB mutation status and tumor size but not tumor grade are important predictors of clinical outcome in pheochromocytoma and abdominal paraganglioma. Surgery (2017) 161: 230–23910.1016/j.surg.2016.05.050
10.1016/j.surg.2016.05.050
PubMed Web of Science® Google Scholar
17Parasiliti-Caprino M, Lucatello B, Lopez C et al. Predictors of recurrence of pheochromocytoma and paraganglioma: a multicenter study in Piedmont, Italy. Hypertens Res (2020) 43: 500–51010.1038/s41440-019-0339-y
10.1038/s41440-019-0339-y
CAS PubMed Web of Science® Google Scholar
18Thompson LDR 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 (2002) 26: 551–56610.1097/00000478-200205000-00002
10.1097/00000478-200205000-00002
PubMed Web of Science® Google Scholar
19Wu D, Tischler AS, Lloyd RV et al. Observer variation in the application of the pheochromocytoma of the adrenal gland scaled score. Am J Surg Pathol (2009) 33: 599–60810.1097/PAS.0b013e318190d12e
10.1097/PAS.0b013e318190d12e
PubMed Web of Science® Google Scholar

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Volume47, Issue3

March 2023

Pages 690-698