Radiology Case Reports
Adrenocortical carcinoma with extension to the in- ferior vena cava and right atrium: 20-month-old girl with TP53 mutation
Terry L. Levin, MD; Walter E. Berdon, MD; Daniel Weiser, MD; and Raul C. Ribeiro, MD
A 20-month-old female presented with respiratory distress and a right adrenal mass extending into the inferior vena cava and right atrium. The mass was initially thought to be neuroblastoma. Pathology later revealed adrenocortical carcinoma. Inferior vena cava extension is far more common in adrenocortical carcinoma than neuroblastoma, and its presence should prompt clinical and laboratory evaluation for an adrenocortical tumor. The genetic findings in TP53 associated with this disease are discussed.
Case report
A 20-month-old female presented with respiratory dis- tress, fever, and anorexia. Physical examination revealed hypertension, tachycardia, tachypnea, and presumed hepa- tomegaly. A chest radiograph revealed cardiomegaly and a right paratracheal density (subsequently noted to represent a large azygous vein), prompting an echocardiogram. This demonstrated a large right atrial mass. Contrast-enhanced computed tomography demonstrated a large right suprare- nal mass with occlusive thrombus in the inferior vena cava (IVC) extending to the right atrium (Figs. 1, 2). The right adrenal gland was not identified, and pulmonary metasta- ses were absent. Based on the patient’s age and the pres- ence of an adrenal mass, a presumptive diagnosis of neu- roblastoma was made.
Citation: Levin TL, Berdon WE, Weiser D, Ribeiro RC. Adrenocortical carcinoma with extension to the inferior vena cava and right atrium: 10-month-old girl with TP53 mutation. Radiology Case Reports. (Online) 2015;10(2);1084.
Copyright: @ 2015 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs 2.5 License, which permits reproduction and distribution, provided the original work is properly cited. Commercial use and derivative works are not permitted.
Dr. Levin is in the Department of Radiology, Division of Pediatric Radiology, at Chil- dren’s Hospital at Montefiore Medical Center, Bronx, NY. Dr. Berdon is in the Depart- ment of Radiology, Division of Pediatric Radiology, at Columbia Presbyterian Medical Center, New York, NY. Dr. Weiser is in the Department of Pediatrics, Division of Pediatric Hematology and Oncology, at the Children’s Hospital at Montefiore Medical Center, Bronx, NY. Dr. Ribeiro is in the Department of Oncology, Leukemia and Lym- phoma Division, at St. Jude’s Children’s Research Hospital, Memphis TN. Contact. Dr. Levin at tlevin@montefiore.org.
Competing Interests: The authors have declared that no competing interests exist. DOI: 10.2484/rcr.v10i2.1084
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The child, who was critically ill, was treated with etopo- side and cyclophosphamide in an effort to shrink the tumor
RCR Radiology Case Reports | radiology.casereports.net
ACC with extension to inferior vena cava and right atrium: 20-month-old girl with TP53 mutation
and stabilize her, despite the absence of a tissue diagnosis. One cycle of chemotherapy complicated by marked mar- row suppression resulted in no change in tumor size. MIBG scan and urine catecholamines were negative. Transjugular biopsy of the right atrial mass was performed, and pathol- ogy revealed adrenocortical carcinoma (ACC). Laboratory workup was notable for elevated cortisol 25.7 ug/dL (nor- mal, 5-25 ug/dL), testosterone 253 ng/dL (normal, 5-81 ng/dL), and androstenedione 473 ng/dL (normal, 5-51 ng/dL). Mild clitoromegaly was appreciated. There were no other signs of virulization.
Gross tumor resection was performed with normalization of endocrine biomarkers. Despite residual disease, the fam- ily declined chemotherapy after one cycle. Germline exome analysis of the TP53 gene identified a disease-causal het- erozygous c.818G>A (p.R273H) mutation. The tumor re- curred after three months, and the patient died 5 weeks later. No family history of neoplasm was elicited, and the parents declined further genetic testing.
Discussion
ACC is rare in children in the United States, with an incidence of 0.3-0.4 cases/million children. The median age at diagnosis is 3 years, and females are affected twice as often as males (1).
TP53 is a tumor suppressor gene that is mutated in at least 2/3 of children with ACC in North America. Germ- line TP53 mutations are less frequently identified in chil- dren with ACC over ten years of age. Lack of normal p53 protein function leads to proliferation of cells containing damaged DNA, and malignant transformation (2). Most germline TP53 mutations are associated with Li-Fraumeni
syndrome, an autosomal dominant disorder characterized by a wide range of early-onset malignancies including ACC, soft-tissue and bone sarcomas, leukemia, brain tu- mors, and breast cancer (3).
It has been recognized for forty years that there is a much higher incidence of childhood ACC in southern Brazil compared to North America. Ninety percent of af- fected children in Brazil exhibit a founder germline TP53 mutation (p.R337H) that is not found in North American cases (4).
Whether in North America or Brazil, almost all ACCs secrete excess adrenal hormones causing virilization, feminization, Cushing syndrome, or Conn syndrome. Hy- pertension is common. Levels of urinary 17-ketosteroids and plasma biomarkers, including testosterone, andros- tenedione, cortisol, and DHEA-S are often elevated. Prog- nosis is poor in cases with local invasion or metastases.
In the present case, a presumptive diagnosis of neuro- blastoma was made based on the presence of an adrenal mass and the patient’s age. However, tumor thrombus in- volving the IVC and right atrium is exceedingly uncom- mon in neuroblastoma, with few reported cases in the lit- erature (5). In contrast, there are repeated examples of ACC extending into the IVC and right atrium (6). In a series of 92 patients, venous extension of the tumor was noted in 19.6% of patients. Right atrial extension was much less common, occurring in approximately 1% of cases (7).
Thus, the identification of vascular extension in this pa- tient might have favored the correct diagnosis of ACC since, in a young child with a right-upper-quadrant mass extending into the IVC and right atrium, the diagnosis is much more likely to be ACC than neuroblastoma.
Differentiation of ACC from Wilms tumor requires ac- curate identification of the organ of origin, which in the presence of a large mass may be difficult using ultra- sonography alone and may require imaging with computed tomography or MRI. Vascular extension of the tumor is a well-recognized feature of Wilms tumor, with IVC and right atrial extension occurring in 4% and 1% of cases, respectively (8).
In a child with an adrenal mass and IVC thrombus, ACC should be considered. A prompt, detailed physical exami- nation and laboratory testing for adrenocortical hormone excess should be performed. As childhood ACC is often the first manifestation of Li-Fraumeni syndrome (9), a familial history of cancer should be sought and genetic testing performed.
References
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2. Ribeiro RC, Sandrini F, Figueiredo B, et al. An inher- ited p53 mutation that contributes in a tissue specific
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