Phaeochromocytoma

Definition

A catecholamine-secreting tumour arising from the chromaffin cells of the sympathoadrenal system. The vast majority are adrenal phaeochromocytomas. Those arising in the organ of Zuckerkandl are referred to as extra-adrenal phaeochromocytomas. The same tumour arising at other sites are called paragangliomas.

Epidemiology

Patients range from children to the elderly. 8-12% of cases are familial and there are associations with MEN syndrome, neurofibromatosis, von Hippel-Lindau syndrome and Turner's syndrome. Non-sporadic phaeochromocytomas are more likely to be bilateral. The mean age at presentation is 47 years, 34 years for those with a syndromic association.

Clinical features

Patients may present with symptoms of flushing, nausea, vomiting headache, palpitations, pain at diverse sites. They are commonly hypertensive: the hypertension may be sustained or episodic. Serum catecholamines are commonly raised.

Radiology

T2-weighted images or angiography show the adrenal mass to be hypervascular. The guanethidine analog ¹³¹I MIBG is taken up by neurotransmitter vesicles of the adrenal medulla and by phaeochromocytomas. Metastatic lesions may also be characterised as hypervascular.

Macroscopic appearances

The tumours are encapsulated or well-demarcated. The cut surface is variegated grey-tan to brown-red with areas of haemorrhage and cystic degeneration. The residual adrenal cortex is bright yellow.

Histopathology

The cells are arranged in characteristic "zellballen". In areas, the cells may form larger nests or show a diffuse architecture. There may be nuclear pleomorphism with tumour giant cells.

Criteria for malignancy

About 6.5% of phaeochromocytomas show malignant behavior. The only absolute criterion is metastasis to a site where chromaffin tissue is not normally found. The most common sites for metastases are the axial skeleton, lymph nodes, liver, lung and kidney. Syndromic cases are benign. A scoring system has ben proposed¹:

Feature	score
vascular invasion	1
capsular invasion	1
extension into periadrenal adipose tissue	2
large nest size of diffuse architecture	2
necrosis (focal or confluent)	2
high cellularity	2
tumour cell spindling	2
cellular monotony	2
more than 3 mitoses per 10 HPF	2
atypical mitotic figures	2
profound nuclear pleomorphism	1
tumour cell hyperchromasia	1

In the series of 100 patients, a score of 3 or less identified 50 patients, none of who developed metastases. Of those with a score of 4 or more, 33 of 50 patients developed metastases.

Positivity for tenascin may help to differentiate malignant from benign phaeochromocytomas.

Immunohistochemistry

Chromogranin	76/761
Synaptophysin	74/761
CD56	69/741
S-100	61/74 (sustentacular cells)1
Serotonin	5/741
Somatostatin	11/741
Pancytokeratin (AE1/AE3, Cam5.2 and 34bH11)	29%2
AE1/3 and CK1	6/741
Cytokeratin 7	1/741
Cytokeratin 20	1/741

Differential diagnosis

• Adrenal cortical carcinoma: the cells have eosinophilic, vesicular or microvacuolated cytoplasm. Mitoses are common.

• Metastatic carcinoma

• Malignant transformation of sustentacular cells: this closely resembles a malignant peripheral nerve sheath tumour and is S-100 positive.

Prognosis

The prognosis for malignant phaeochromocytoma is poor, due to metastatic spread and the effects of excess catecholamines, inducing heart failure.

References

¹Thompson, L.D. Phaeochromocytoma 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;26:551-66.

²Erickson, L. A. and R. V. Lloyd (2004). "Practical markers used in the diagnosis of endocrine tumors." Adv Anat Pathol 11(4): 175-89.

This page last revised 21.7.2004.

©SMUHT/PW Bishop