Incidence and Pathology
Adrenocortical carcinomas are rare malignancies, accounting for approximately 0.02% of all carcinomas with a reported incidence of 2 cases per million population (106). Tumours most commonly present in the 30-50 year age group with a female to male ratio of 2:1. Most lesions are large (> 5 cm) and occasionally palpable. Local invasion into adjacent structures, local lymph node and distant metastases are frequently present at initial assessment.
Macroscopically areas of haemorrhage and necrosis are present in a firm, lobulated tumour which is grey/pink in colour on cut section. Microscopic features include numerous mitosis and vascular invasion. These features, however, may also be present in benign adrenal tumours, thus histological diagnosis ofmalignancy is often difficult.
Approximately 60% of adrenocortical carcinomas are functioning, secreting steroid hormones which lead to a wide spectrum of clinical conditions.
Patients may present with an abdominal mass (tumours can grow to >20 cm), symptoms of weight loss, lassitude, fatigue, flank pain, a low grade pyrexia of unexplained origin. Despite the term non-functioning, subtle clinical changes, including mild hirsuitism can be evident. These changes may result from dehydroepiandrosterone production which has some value as a marker of malignancy. On rare occasions patients have presented with acute haemorrhagic shock from a sudden bleed into the tumour.
Functioning adrenocortical carcinomas are responsible for Cushing's syndrome in 10% of patients presenting with the syndrome. In contrast to benign secreting tumours, onset of signs and symptoms is frequently rapid and distressing. Women are affected four times as commonly as men. The onset of Cushing's syndrome in a child or young adult should raise the suspicion of malignancy. Secreting tumours produce a diversity of clinical syndromes including hypercortisolism (30%), virilisation (22%), feminisation (10%). Mixed hormonal secretions resulting in a varied clinical picture are present in 35% of tumours and when present are almost always associated with malignancy. As with non-functioning carcinomas, tumours can be large at initial presentation, illustrated by the fact that over 15% of tumours > 6 cm are malignant (2).
Initial Surgical Management of Adrenocortical Carcinoma
Aggressive surgical resection is the treatment of choice for stage I and II cancers and in selected patients with stage III cancers (Table 4). Unfortunately, 45%-70% of patients have either stage III or stage IV disease at presentation, reflected in the very poor overall survival figures of this highly malignant cancer. Wide resection with en-bloc tissue removal and lymphadenectomy is necessary in an attempt to gain local control of the cancer. Adjacent structures, including spleen, kidney and pancreas may also be sacrificed to achieve adequate clearance.
Suspected recurrent loco-regional disease or distant metastases to the liver and lung may be imaged with chest X-ray, CT or MRI. Tumour spread into the inferior vena cava may also be accurately assessed by MRI, making caval venography obsolete. T2 weighted MRI images are useful in differentiating recurrent tumour from scar tissue in the operative field. USS or CT guided FNAC or needle biopsy provides histological confirmation of local recurrence, hepatic or other metastatic disease.
Table 4. Staging of Adrenocortical Carcinoma Stage Size (cm) Local
MANAGEMENT OF RECURRENT OR METASTATIC ADRENOCORTICAL CARCINOMA
Survival rates in patients with adrenocortical carcinoma are abysmal. Careful assessment is therefore necessary to identify at an early stage patients with locally recurrent or distant metastatic in whom repeated surgical resection may be of benefit in alleviating symptoms and controlling local disease (2,107,108). Few patients are suitable for repeated surgical resection. Only 7 of 41 patients in one series and 3 of 19 in another report were considered candidates undergo repeated surgical excision (109,110).
Nodal metastases are present in 10% to 45% of operative patients. Lymph nodes should be included in the primary surgical procedure as an en-bloc excision. Lymph node metastases in adrenocortical carcinoma are associated with a poor overall survival.
Patients Stage IV adrenocortical carcinoma have very short life expectancies. Surgical excision is not warranted ifwidespread disease is present. Symptomatic, solitary hepatic or
Regional Lymph Distant
pulmonary metastases, however, may be considered for surgical resection in suitable patients (111).
Adrenocortical carcinoma is not particularly radiosensitive and radiotherapy has had little effect in controlling local disease or decreasing local recurrence (112).
Mitotane (o,p' DDD) is the only agent which has been shown to be of some value in patients with advanced disease. It is most effective when used in patients prior to the development of metastatic disease following surgical resection for stage I and II disease and in patients undergoing repeated surgical resection for recurrent disease (113). This drug destroys the contra-lateral adrenal gland and steroid replacement is therefore essential.
Mitotane has been shown to decrease multidrug resistance in vitro in adrenocortical carcinoma. Recent reports, however, describing mitotane used in association with combination chemotherapy including etoposide, doxorubicin and cisplatin have described high toxicity and morbidity with no significant improvement in either overall or disease free survival (114,115).
Survival rates for adrenocortical carcinoma are dependent upon disease stage at presentation. A recent, multicentre French study of 156 patients reported an overall 5 year survival of 34% but only 9% 1 year survival in patients undergoing palliative resection (109).
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