Phaeochromocytoma is a rare, usually benign, malignancy of the adrenal gland that is associated with a number of familial germline mutations.
Epidemiology
Phaeochromocytoma is a neoplasm of adults, usually between 20 to 60 years of age.
Aetiology and Pathogenesis
About 75% of cases are sporadic with no known cause. The remainder are associated with germline mutations:
- Multiple Endocrine Neoplasia Type 2a/2b is due to mutation of the RET gene. A number of different mutations exist. The most important malignancy is medullary thyroid cancer which almost always occurs and patients should have thyroidectomy at a young age. Patients also develop parathyroid adenomas.
- Von-Hippel Lindau syndrome is due to germline mutation of the VHL gene which is involved in regulation of hypoxa-inducible factor 1 (HIF1). This promotes tumourogenesis and is also associated with renal cell carcinoma, haemangioblastoma and endocrine pancreatic neoplasms.
- Neurofibromatosis type 1 is associated with glioma (particularly optic nerve glioma), meningioma, neurofibroma, and malignant peripheral nerve sheath tumours.
Natural History
Most lesions behave in a benign fashion and surgical excision is curative. A small number may metastasise but this is not related to histological appearance.
Clinical Presentation
Patients may present with hypertension (90%) and the majority of these will have paroxysmal episodes with sweating, palpitations and extremely high hypertension (> 200 mmHg). This can be fatal. Longer term disease may lead to cardiomyopathy.
Tumour/Normal Tissue Features
Macroscopically the tumour enlarges the adrenal gland which is often distorted by the mass. The tumour is usually tan or yellow; the mean weight is 100 g in weight but this varies considerably. Microscopically the tumour is formed by large polygonal chief cells (significant clear or eosinophilic cytoplasm, small regular nuclei) with surrounding vascular stroma which surrounds nests of chief cells. Immunohistochemistry is positive for neuroendocrine markers in the chief cells and S100 in the stroma.
