Adrenal Cortical Carcinoma Metastatic to the Brain in a Child
Alejandra Montenegro Piniella, MD, and R. Michael Siatkowski, MD
A 9-year-old girl presented with profoundly decreased vision in both eyes and bilateral optic disc swelling. Magnetic resonance imaging showed a large intraventricular mass. Excisional bi- opsy diagnosed metastatic adrenal cortical carcinoma (ACC). This is, to the best of our knowledge, the first reported case of ACC metastatic to the brain in a child. It also illustrates the importance of differentiating optic neuritis from papilledema in children.
Key Words: Adrenal cortical carcinoma-Optic neuritis- Papilledema.
Adrenal cortical carcinoma (ACC) is quite rare, con- stituting only 0.05% to 0.2% of all cancers, equivalent to a rate of 2 per million worldwide (1). Common meta- static sites are regional lymph nodes, lung, liver, and bone. Only a handful of cases of adrenal cortical carci- noma metastatic to the brain have been reported in adults (2) and none in children. We report such a case with isolated visual loss.
CASE REPORT
A 3-year-old white girl presented with precocious pu- berty and Cushing syndrome. Workup indicated a large left-sided adrenal tumor, which was excised. Histopath- ologic interpretation was adenocarcinoma of the adrenal cortex. Postoperatively, endocrine function normalized, and regular follow-up with the pediatric endocrine ser- vice indicated normal growth and no sign of recurrent disease.
In June 1998, at age 9 years, she experienced blurred vision for 2 weeks, which became severe enough to pro- duce difficulty ambulating. Optometric evaluation diag- nosed bilateral optic neuropathy, and she was referred to a pediatric neurologist, who diagnosed optic neuritis, with referral to the pediatric neuro-ophthalmology ser- vice. On presentation, visual acuity was 4/120 OD and 1.5/180 OS. Ocular motility, anterior segments, and in-
From the Bascom Palmer Eye Institute (AMP), University of Miami School of Medicine, Miami, Florida; and the Dean A. McGee Eye Institute (RMS), University of Oklahoma School of Medicine, Okla- homa City, Oklahoma.
Address correspondence to R. Michael Siatkowski, MD, Dean A. McGee Eye Institute, University of Oklahoma School of Medicine, 608 Stanton L. Young Boulevard, Oklahoma City, OK 73104.
traocular pressures were normal. Dilated fundus exami- nation indicated chronic bilateral optic disc swelling with axoplasmic stasis, narrowed retinal arteries, and venous collapse to only firm compression of the globe (Fig. 1). Orbital echography showed bilateral disc elevation with a positive 30° test, indicating increased subarachnoid fluid around both optic nerves (3).
The patient was admitted to the hospital and begun on Solumedrol (Pharmacia-Upjohn, Kalamazoo, MI), 100 mg intravenously every 6 hours. The following morning, magnetic resonance imaging (MRI) of the brain was per- formed, which showed a large lobulated mass in the left lateral ventricle suggestive of a choroid plexus papil- loma. There was marked hydrocephalus and occipitopa- rietal vasogenic edema, as well as chiasmal compression and early tonsillar herniation (Fig. 2). A difficult but complete resection was performed along with ventricu- lostomy. Histopathologic examination indicated meta- static adrenal carcinoma with cellular morphology iden- ” tical to the adrenal mass excised 6 years earlier. Systemic workup for further metastatic disease (MRI of thorax, abdomen, and pelvis, and bone scan) was negative. One year later, she remained disease-free. Visual acuity was hand motion OD and no light perception OS.
DISCUSSION
To our knowledge, this is the first report of childhood adrenal carcinoma metastatic to the brain. It is even more unusual in that the presenting symptoms were com- pletely visual. This made optic neuritis the likeliest of the differential diagnoses at presentation. Optic neuritis in children frequently presents with bilateral optic disc swelling (4). Although this was present, there was no history of preceding viral illness or vaccination, common factors associated with pediatric optic neuritis (4). The temporal profile of this case would be typical for optic neuritis, because our patient had a chief complaint of rapid and profound visual loss. However, the optic nerves had features of chronic edema such as axoplasmic stasis, retinal arteriolar narrowing, and venous distention. Disc swelling in optic neuritis is more acute-appearing with hyperemia and only rare nerve fiber layer hemor- rhages. Finally, MRI of the brain showed the cause of the optic nerve swelling: chronic papilledema secondary to an intracranial mass. The mass was identified as adrenal cortical carcinoma, 6 years after resection of the primary.
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Adrenal cortical carcinoma is a rare tumor. It has a bimodal occurrence by age, with the first peak being before 5 years of age and the second being in the fourth and fifth decades of life (1,5). Adrenal cortical carci- noma is a malignant neoplasm showing partial or com- plete histologic and functional differentiation (1). The distinction between ACC and adenoma is pathologically based on tumor weight, necrosis, vascular invasion, and number of mitotic figures (1,6). Clinically, it is based on constitutional symptoms, feminization, and distant me- tastases (1,6). Virilization and extension of the tumor beyond the adrenal capsule are suggestive, but not diag- nostic, of malignancy (1,6). Therefore, diagnosis of ACC is often not clear-cut. Our patient’s primary tumor at the age of 3 was thought to be malignant, based primarily on
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the gross tumor size. Because ACC is highly malignant, surgical resection is the only potentially curable treat- ment (7). Chemotherapy with mitotane (o,p-DDD) has been shown to induce partial remission in 22% to 60% of patients and complete but temporary remission in a hand- ful of patients (8,9). Other chemotherapeutic agents have had no success in ACC (1). Abdominal radiation has been palliative in some inoperable masses or in bony metastases (10). Prolonged remissions have been re- ported after resection of hepatic and pulmonary me- tastases (11).
Local spread characterizes ACC. Tumor spreads into the kidneys, retroperitoneal and peritoneal spaces, dia- phragm, and vena cava. Metastases to regional lymph nodes, lung, liver, and bone are also seen (1). Only six cases of ACC metastasis to the central nervous system have been previously reported, all in adults (2,12).
Prognosis in ACC is poor. In one analysis of 105 patients (adults and children), the 5-year survival was 22% and depended mostly on the stage of disease at diagnosis (8). Mean survival was 18 months (8). Seventy percent of patients have local spread or distant metastasis at presentation. Children tend to present earlier because they are more likely to have hormonal disturbances caused by their malignancy. Up to 93% present with virilization, but only rarely (as in our case) with preco- cious puberty or Cushing syndrome (5). In one report, 17 of 26 (65%) of children remained in complete remission after complete tumor resection (13).
This case illustrates an extremely unusual presentation of an uncommon disease. It emphasizes the importance of a detailed medical history and reinforces the concept that bilateral visual acuity loss with disc swelling in chil- dren is not always attributable to optic neuritis.
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