ACC

What it is

Overview

Adrenocortical carcinoma (ACC) is a rare malignancy arising from the cortex of the adrenal gland. It can be functional (secreting excess hormones like cortisol, aldosterone, or androgens) or nonfunctional. ACC carries a poor prognosis, with many patients presenting at an advanced stage. It is one of the few adrenal tumors that poses a significant mortality risk.

Biology

How It Develops

ACC arises from adrenocortical cells with mutations in TP53, CTNNB1 (Wnt pathway), PRKAR1A, and copy number alterations across the genome. Li-Fraumeni syndrome (germline TP53 mutation) is associated with familial ACC, particularly in children. Genomic profiling has identified two distinct molecular subtypes with very different prognoses.

Warning signs

Symptoms

• —Cushing's syndrome (weight gain, moon face, purple striae) from cortisol excess
• —Virilization in women from androgen excess
• —Abdominal pain or mass
• —Hypertension and hypokalemia
• —Incidental adrenal mass found on imaging

Detection

Diagnosis Methods

• —CT and MRI of adrenal glands
• —Hormonal evaluation (24-hour urinary cortisol, DHEA-S, aldosterone)
• —PET scan
• —Adrenal biopsy (avoided if primary surgery is planned)
• —Germline TP53 testing

Medical care

Treatment Options

• —Adrenalectomy (primary curative intent)
• —Mitotane (adrenolytic agent — adjuvant and palliative)
• —Chemotherapy (EDP-M: etoposide, doxorubicin, cisplatin + mitotane)
• —Radiation therapy (for local recurrence or bone metastases)
• —Clinical trials (immunotherapy, targeted therapy)

Data

Statistics

Prevention

Risk Factors

• —Li-Fraumeni syndrome (TP53 germline mutation)
• —Beckwith-Wiedemann syndrome
• —MEN1 syndrome
• —No modifiable risk factors identified

Further reading

Resources