Adrenocortical carcinoma in childhood

A 10-month-old healthy female of Brazilian origin presented to the emergency department where an upper tract respiratory infection was diagnosed. On physical examination, there were abdominal distension and signs of virilization with hypertrophy of the clitoris and hirsutism.

An abdominal ultrasound scan was requested, which revealed a left adrenal with calcifications solid lesion (figure 1). On magnetic resonance (MR) this well-circumscribed mass measured 8 x 6 x 7 cm (ap tr cc), showed high cellularity and heterogenous vascularity, and displaced the adjacent structures without invading them (figure 2). It was meta-iodo-benzyl-guanidine – (mIBG) – negative but it exhibited 18F-fluorodeoxyglucose avidity; no metastasis was demonstrated on positron emission tomography / computed tomography (PET/CT) (figure 3).

Seric levels of testosterone, dehydroepiandrosterone sulfate, and androstenedione-4 were elevated; whereas, serum cortisol, adrenocorticotropic hormone, 24-hour urinary free cortisol, catecholamines, and metanephrines were within the normal range.

Clinical, laboratory and imaging findings were compatible with a secreting adrenal tumour, more probably adrenocortical carcinoma. The child underwent complete surgical resection; on pathology, a stage 3 adrenocortical carcinoma was diagnosed due to the rupture of its capsule (figure 4). She was started on mitotane therapy.

Adrenocortical carcinoma (ACC) is a rare but aggressive paediatric cancer (less than 1% of malignancies)[1]. It has a bimodal distribution, with the first peak in children younger than 5 years and the second in the fourth to fifth decade[1-3], with higher incidence in females[1,2].

The majority of ACC are sporadic but may be associated with a genetic defect (for example Li–Fraumeni or Beckwith–Wiedmann syndrome)[1,4-9]. The incidence of ACC is higher in southern Brazil, due to a mutation of the p53 gene[6,10].

About 90% of the cases of ACC is functional in children (less of 50% cases in adults)[3,4]. It mostly presents as virilisation comprising acne, hirsutism, and clitoris hypertrophy[2-7], and Cushing syndrome; a few cases are non-functional and diagnosed incidentally [5]. Conn syndrome can also be present.

Ultrasound is usually the first test performed[1,9]; MR is used to characterise the lesion, to help differentiate benign from malignant nature, evaluate the locoregional mass effect, and the metastases[1,5,6,8]. Therefore, the latter is the golden standard. On CT and MR, ACC is typically circumscribed, with variable heterogeneity due to haemorrhage and necrosis[1,9]. Larger lesions tend to have heterogeneous[1,9].

It is challenging to differentiate among ACC and other malignant neoplasms arising from the same organ. Features suggesting the former are a locally-invasive mass larger than 8.5 cm, with irregular margins, heterogeneous architecture and vascularity, containing some calcifications, and with metastases (mainly to liver, lungs, and bones)[1,5,7]. However, biopsy is necessary as pheochromocytoma can mimic it.

ACC tends to grow and metastasize rapidly if untreated[5]. Complete surgical resection is the only potentially curative treatment[2,4,6]. Mitotane and in some cases chemotherapy is recommended in advanced stages, unresectable lesion or positive surgical margins[2,5,10].

Despite neuroblastoma being the most common solid neoplasm arising from the adrenal gland in infants[7], in our case virilisation and laboratory tests were compatible with a functioning adrenal tumour. Besides, urinary catecholamines and mIBG scans were negative, which disregards neuroblastoma.

Pheochromocytoma is another differential diagnosis to consider. In children the majority are functional and actively secrete norepinephrine and epinephrine, which are responsible for clinical manifestations[7]. Metanephrine and normetanephrine were negative, which together with the mIBG scan result exclude this hypothesis.

Imaging favoured malignancy and the diagnosis was confirmed by histology.

ACC is rare, and delays in diagnosis carry a poorer prognosis. Imaging plays a key role in identifying and differentiate malignant and benign adrenal neoplasms.

Written informed patient consent for publication has been obtained.