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

Daniel Weiser, MD

Raul C. Ribeiro, MD

Terry L. Levin, MD

Walter E. Berdon, MD

Radiology Case Reports

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Adrenocortical carcinoma with extension to the inferior vena cava and right atrium: 20-month-old girl with TP53 mutation

AbstractA 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

Levin, Terry L.

Berdon, Walter E.

Weiser, Daniel

Ribeiro, Raul C.

Elsevier - Publisher Connector 

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. 
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! 1! 2015 | Volume 10 | Issue 2
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. 
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
Radiology Case Reports
Volume 10, Issue 2, 2015
Fig. 1. Contrast-enhanced computed tomographic image of 
the chest and abdomen. A large suprarenal mass (asterisk) 
displaces the right kidney inferiorly. The aygous is enlarged 
(arrow). 
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
1.  McAteer JP, Huaco JA, Gow KW. Predictors of  sur-
vival in pediatric adrenocortical carcinoma: A Surveil-
lance, Epidemiology, and End Results (SEER) pro-
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1031. [PubMed]
2.  Ribeiro RC, Sandrini F, Figueiredo B, et al. An inher-
ited p53 mutation that contributes in a tissue specific 
ACC with extension to inferior vena cava and right atrium: 20-month-old girl with TP53 mutation
RCR Radiology Case Reports | radiology.casereports.net! 2! 2015 | Volume 10 | Issue 2
Fig. 2. Tumor extension into the IVC and right atrium is 
demonstrated.
manner to pediatric adrenal cortical carcinoma. Proc 
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6. 	 Godine LB, Berdon WE, Brasch RC, Leonidas JC. 
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8. 	 Ribeiro RC, Schettini ST, Abib C,da Fonseca JH, 
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9. 	 Ribeiro RC,Pinto EM, Zambetti GP, Rodriguez-
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nocortical tumors. Mol Cell Endocrinol 2012:351:37-43. 
[PubMed]
ACC with extension to inferior vena cava and right atrium: 20-month-old girl with TP53 mutation
RCR Radiology Case Reports | radiology.casereports.net! 3! 2015 | Volume 10 | Issue 2


Adrenocortical carcinoma with extension to the inferior vena cava and right atrium: 20-month-old girl with TP53 mutation 

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Adrenocortical carcinoma with extension to the inferior vena cava and right atrium: 20-month-old girl with TP53 mutation

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