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Chapter 33: Pheochromocytoma

Karel Pacak; Tito Fojo

INTRODUCTION

Epidemiology

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Epidemiology
Incidence✫: 3–8 cases per one million population
Median age: 42 years
Male to female ratio: 1:1

✫The annual incidence of pheochromocytoma in the United States is not precisely known, but the high prevalence (0.05%) of pheochromocytomas found in autopsy series indicates that the tumor is underdiagnosed and that the annual incidence is likely to be higher than indicated

 

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Pathology

  • Approximately 80–85% of pheochromocytomas are located in the adrenal gland. The remaining 15–20% are located along the paraaortic sympathetic chain, aortic bifurcation, and urinary bladder

  • Bilateral tumors occur in ~10% of patients and are much more common in familial pheochromocytomas

  • 5–36% of pheochromocytomas are metastatic, but no widely accepted pathologic criteria or biomarkers exist for differentiating between benign and metastatic pheochromocytoma

  • A diagnosis of malignancy requires evidence of metastases at nonchromaffin sites (only bones or lymph nodes) distant from that of the primary tumor

  • Although most cases of pheochromocytomas are sporadic, a significant proportion occur secondary to several hereditary syndromes. Hereditary contribution is approximately 30%. The propensity of malignancy in hereditary pheochromocytoma syndromes is highly variable

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Pheochromocytoma in Common Hereditary Syndromes
Hereditary Syndrome Gene Frequency✫ Predisposition to Malignancy Adrenal Disease Extraadrenal Disease
Von Hippel-Lindau disease (VHL) VHL 6–20% 3–5% ++ –/+
Multiple endocrine neoplasia types IIA and IIB (MEN IIA, MEN IIB) RET 30–50% <3% ++ –
Neurofibromatosis type 1 (NF1) NF 1–5% <3% ++ –
Familial paraganglioma and/or pheochromocytoma caused by mutation of succinate dehydrogenase gene family members SDHB 20–50% 50–80% + ++
SDHD 15–43% 5–15% + ++
SDHC <1% 10–20% – + (Head and neck)
SDHA <1% 15–20 + +
SDHAF2 Extremely rare Not described – + (Head and neck)
None described TMEM127 3% Not described + –/+
MAX 1% 10% + +

++, very common; +, common; –, rare (there are various reports and data are presented as the best estimate)

✫Frequency in sporadic tumors

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