Adrenocortical tumors encompass a spectrum of diseases with often seamless transition from benign (adenoma) to malignant (carcinoma) behavior.
The incidence of adrenocortical tumors in children is extremely low (only 0.2% of pediatric cancers).[
In children, 25 new cases are expected to occur annually in the United States, for an estimated annual incidence of 0.2 to 0.3 cases per 1 million individuals.[
Female sex is consistently predominant in most studies, with a female to male ratio of 1.6:1.0.[
Germline TP53 mutations are almost always the predisposing factor for adrenocortical tumors. The likelihood of a TP53 germline mutation is highest in the first years of life and diminishes with age. Predisposing genetic factors have been implicated in more than 50% of the cases in North America and Europe and in 95% of the Brazilian cases.[
Patients with Beckwith-Wiedemann and hemihyperplasia syndromes have a predisposition to cancer, and as many as 16% of their neoplasms are adrenocortical tumors.[
The distinctive genetic features of pediatric adrenocortical carcinoma have been reviewed.[
Unlike in adult adrenocortical tumors, histologic differentiation of pediatric adenomas and carcinomas is difficult. However, approximately 10% to 20% of pediatric cases are adenomas.[
Macroscopically, adenomas tend to be well defined and spherical, and they never invade surrounding structures. They are typically small (usually <200 cm3), and some studies have included size as a criterion for adenoma. By contrast, carcinomas have macroscopic features suggestive of malignancy. They are larger and show marked lobulation with extensive areas of hemorrhage and necrosis. Microscopically, carcinomas comprise larger cells with eosinophilic cytoplasm, arranged in alveolar clusters. Several authors have proposed histologic criteria that may help distinguish the two types of neoplasm.[
Morphological criteria may not allow reliable distinction of benign and malignant adrenocortical tumors. Mitotic rate is consistently reported as the most important determinant of aggressive behavior.[
A study performed on 71 pediatric adrenocortical tumors (37 in a discovery cohort and 34 in an independent cohort) provided a description of the genomic landscape of pediatric adrenocortical carcinoma.[
Paternal 11p15 uniparental disomy (UPD). A retrospective analysis of patients with adrenocortical tumors at the St. Jude Children's Research Hospital identified six children with wild-type TP53 and germline paternal 11p15 UPD.[
Because pediatric adrenocortical tumors are almost universally functional, they cause endocrine disturbances, and a diagnosis is usually made 5 to 8 months after the first signs and symptoms emerge.[
Because of the hormone hypersecretion, it is possible to establish an endocrine profile for each particular tumor, which may facilitate the evaluation of response to treatment and monitor for tumor recurrence.[
Nonfunctional tumors are rare (<10%) and tend to occur in older children.[
Overall, adverse prognostic factors for adrenocortical carcinoma include the following:
Stage I disease appears to be associated with a better prognosis.[
The overall probability of 5-year survival for children with adrenocortical tumors depends on stage and ranges from greater than 80% for patients with resectable disease to less than 20% for patients with metastases.[
A portion of patients with adrenocortical carcinoma do not have a germline TP53 mutation. A retrospective review of children with adrenocortical carcinoma identified 60 patients without germline TP53 mutations.[
Cancer in children and adolescents is rare, although the overall incidence has been slowly increasing since 1975.[
For information about supportive care for children and adolescents with cancer, see the summaries on Supportive and Palliative Care.
The American Academy of Pediatrics has outlined guidelines for pediatric cancer centers and their role in the treatment of pediatric patients with cancer.[
Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2020, childhood cancer mortality decreased by more than 50%.[
Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years.[
The designation of a rare tumor is not uniform among pediatric and adult groups. In adults, rare cancers are defined as those with an annual incidence of fewer than six cases per 100,000 people. They account for up to 24% of all cancers diagnosed in the European Union and about 20% of all cancers diagnosed in the United States.[
Most cancers in subgroup XI are either melanomas or thyroid cancers, with other cancer types accounting for only 2% of the cancers in children aged 0 to 14 years and 9.3% of the cancers in adolescents aged 15 to 19 years.
These rare cancers are extremely challenging to study because of the low number of patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the lack of clinical trials for adolescents with rare cancers.
Information about these tumors may also be found in sources relevant to adults with cancer, such as Adrenocortical Carcinoma Treatment.
At the time of diagnosis, two-thirds of pediatric patients have limited disease (tumors can be completely resected), and the remaining patients have either unresectable or metastatic disease.[
The European Cooperative Study Group for Pediatric Rare Tumors within the PARTNER project (Paediatric Rare Tumours Network - European Registry) has published consensus guidelines for the diagnosis and treatment of childhood adrenocortical tumors.[
Treatment options for childhood adrenocortical tumors include the following:
The stated goal of the study was to determine if RPLND would improve outcome for stage II patients. The operative notes to assess the adequacy of the RPLND were available for 11 of 15 patients. The median number of lymph nodes resected was 4 (range, 1–30). In a multivariable analysis performed in a cohort of 283 adult patients with adrenocortical carcinoma, patients who underwent RPLND (defined as >5 nodes resected) had a significantly reduced recurrence risk and disease-related death rate than patients who did not undergo nodal dissection.[
The use of radiation therapy in pediatric patients with adrenocortical tumors has not been consistently investigated. Adrenocortical tumors are generally considered to be radioresistant. Furthermore, because many children with adrenocortical tumors carry germline TP53 mutations that predispose them to cancer, radiation may increase the incidence of secondary tumors. One study reported that three of five long-term survivors of pediatric adrenocortical tumors died of secondary sarcomas that arose within the radiation field.[
For more information, see Adrenocortical Carcinoma Treatment.
Treatment options for relapsed childhood adrenocortical tumors include the following:
Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, see the ClinicalTrials.gov website.
The following is an example of a national and/or institutional clinical trial that is currently being conducted:
Patients with tumors that have molecular variants addressed by open treatment arms in the trial may be enrolled in treatment on Pediatric MATCH. Additional information can be obtained on the NCI website and ClinicalTrials.gov website.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Added text about the results of a retrospective analysis of patients with adrenocortical tumors at the St. Jude Children's Research Hospital that identified six children with wild-type TP53 and germline paternal 11p15 uniparental disomy (cited Pinto et al. as reference 2).
Added higher Ki-67 labeling index as an adverse prognostic factor. Also added text to state that a retrospective analysis of patients with adrenocortical carcinoma reported that higher Ki-67 labeling index correlated with worse overall survival and disease-free survival (cited Martins-Filho et al. as reference 10).
Special Considerations for the Treatment of Children With Cancer
Revised text to state that between 1975 and 2020, childhood cancer mortality decreased by more than 50% (cited National Cancer Institute as reference 4 and Surveillance Research Program, National Cancer Institute as reference 5).
Revised text to state that rare pediatric cancers account for about 5% of the cancers diagnosed in children aged 0 to 14 years and about 27% of the cancers diagnosed in adolescents aged 15 to 19 years. Also revised text to state that most cancers in subgroup XI are either melanomas or thyroid cancers, with other cancer types accounting for only 2% of the cancers in children aged 0 to 14 years and 9.3% of cancers in adolescents aged 15 to 19 years.
Treatment of Childhood Adrenocortical Carcinoma
Added text about the results of a Children's Oncology Group prospective, single-arm, risk-stratified, interventional study that examined whether retroperitoneal lymph node dissection would improve outcome for stage II patients (cited Rodriguez-Galindo et al. as reference 14 and level of evidence B4 and Reibetanz et al. as reference 15).
This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of pediatric adrenocortical carcinoma. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Childhood Adrenocortical Carcinoma Treatment are:
Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.
Levels of Evidence
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Pediatric Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
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The preferred citation for this PDQ summary is:
PDQ® Pediatric Treatment Editorial Board. PDQ Childhood Adrenocortical Carcinoma Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/adrenocortical/hp/child-adrenocortical-treatment-pdq. Accessed <MM/DD/YYYY>.
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Last Revised: 2022-12-08
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