Pediatric adrenocortical carcinoma

Ilanchezhian, Maran; Varghese, Diana Grace; Glod, John; Reilly, Karlyne M.; Widemann, Brigitte C.; Pommier, ﻿Yves; Kaplan, Rosandra N.; Rivero, Jaydira Del

doi:10.3389/fendo.2022.961650

Cited by 15 publications

(30 citation statements)

References 91 publications

(132 reference statements)

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“…ACC is a rare but very aggressive childhood cancer with an annual worldwide incidence of 0.3–0.38 cases/million children below 15 years old, with female preponderance (0.2% of all cancers diagnosed in children) [ 4 , 5 ]. About 65% of adrenocortical tumours occur at < 5 years of age [ 6 ].…”

Section: Discussionmentioning

confidence: 99%

Precocious puberty and other endocrine disorders during mitotane treatment for paediatric adrenocortical carcinoma – case series and literature review

Moszczyńska,

Baszyńska-Wilk,

Tutka

et al. 2024

pedm

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Introduction Adrenocortical carcinoma (ACC) is rare and an aggressive tumour. Mitotane is the mainstay adjuvant drug in treating ACC. The study aimed to describe patients diagnosed with precocious puberty (PP) and other endocrinological complications during mitotane therapy. Material and methods This retrospective study enrolled 4 patients with ACC treated with mitotane therapy complicated by PP. We analysed clinical manifestations, radiological, histopathological findings, and hormonal results. Results The median age at the diagnosis of ACC was 1.5 years. All patients were treated with surgery and mitotane, accompanied by chemotherapy regimens in 2 cases. The median time from surgery to the initiation of mitotane therapy was 26 days. During mitotane treatment, PP was confirmed based on symptoms, and hormonal and imaging tests. In one patient, incomplete peripheral PP was followed by central PP. The median time from the therapy initiation to the first manifestations of PP was 4 months. Additionally, due to mitotane-induced adrenal insufficiency, patients required a supraphysiological dose of hydrocortisone (HC), and in one patient, mineralocorticoid (MC) replacement with fludrocortisone was necessary. In 2 patients, hypothyroidism was diagnosed. All patients presented neurological symptoms of varying expression, which were more severe in younger children. Conclusions The side effects of using mitotane should be recognized quickly and adequately treated. In prepubertal children, PP could be a complication of therapy. The need to use supraphysiological doses of HC, sometimes with MC, should be highlighted. Some patients require levothyroxine replacement therapy. The neurotoxicity of mitotane is a significant clinical problem.

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Section: Discussionmentioning

confidence: 99%

Precocious puberty and other endocrine disorders during mitotane treatment for paediatric adrenocortical carcinoma – case series and literature review

Moszczyńska,

Baszyńska-Wilk,

Tutka

et al. 2024

pedm

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“…BWS is a genetic disorder characterized by overgrowth. This syndrome is caused by defects in chromosome 11p15.5, which result in the overexpression of insulin-like growth factor 2 (IGF2) [ 41 ]. Several molecular mechanisms including imprinting control region 1 (IC1) gain of methylation or paternal uniparental disomy of 11p15 induce overexpression of IGF2 [ 42 ].…”

Section: Hereditary Malignancies Associated With Adrenal Tumorsmentioning

confidence: 99%

Current prospects of hereditary adrenal tumors: towards better clinical management

Ohmoto,

Hayashi,

Takahashi

et al. 2024

Hered Cancer Clin Pract

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Adrenocortical carcinoma (ACC) and pheochromocytoma/paraganglioma (PPGL) are two rare types of adrenal gland malignancies. Regarding hereditary tumors, some patients with ACC are associated with with Li-Fraumeni syndrome (LFS), and those with PPGL with multiple endocrine neoplasia type 2. Recent studies have expanded this spectrum to include other types of hereditary tumors, such as Lynch syndrome or familial adenomatous polyposis. Individuals harboring germline TP53 pathogenic variants that cause LFS have heterogeneous phenotypes depending on the respective variant type. As an example, R337H variant found in Brazilian is known as low penetrant. While 50–80% of pediatric ACC patients harbored a LFS, such a strong causal relationship is not observed in adult patients, which suggests different pathophysiologies between the two populations. As for PPGL, because multiple driver genes, such as succinate dehydrogenase (SDH)-related genes, RET, NF1, and VHL have been identified, universal multi-gene germline panel testing is warranted as a comprehensive and cost-effective approach. PPGL pathogenesis is divided into three molecular pathways (pseudohypoxia, Wnt signaling, and kinase signaling), and this classification is expected to result in personalized medicine based on genomic profiles. It remains unknown whether clinical characteristics differ between cases derived from genetic predisposition syndromes and sporadic cases, or whether the surveillance strategy should be changed depending on the genetic background or whether it should be uniform. Close cooperation among medical genomics experts, endocrinologists, oncologists, and early investigators is indispensable for improving the clinical management for multifaceted ACC and PPGL.

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“…In the paediatric population, ACC has been shown to improve outcomes in grades III and IV, although it is poorly tolerated. In a review of 11 children with advanced ACC treated with mitotane and cisplatin, 7 patients showed a measurable response, suggesting that it may be considered in patients in whom complete surgical resection is not possible [8]. Terzolo et al conducted a retrospective analysis of 177 adult patients with stage ACC I and II, who initially had complete tumour resection and then received complementary mitotane therapy.…”

Section: Treatmentmentioning

confidence: 99%

Adrenal cortical carcinoma: Paediatric aspects – literature review

Dasiewicz,

Moszczyńska,

Grajkowska

2024

pedm

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Introduction: Adrenocortical carcinoma (ACC) is a rare malignancy in children. Because of this, each patient with suspected ACC requires individualised management, which should be determined at a meeting of a team of multidisciplinary experts in the field. Aim of the study: To summarise data on symptoms, genetic predisposition, and diagnostic procedures for ACC in children. Material and methods: Papers were searched in the PubMed database to identify published randomised clinical trials, reviews, systematic reviews, meta-analyses, and case reports. Results: Most cases of ACC in children occur under the age of 5 years. The most common presenting symptom in 60-80% of paediatric patients is rapidly progressive virilisation. Diagnostics are based on laboratory and imaging evaluation. The mainstay of treatment is surgery, with laparotomy being the preferred method of surgery. Diagnosis is based on histological examination of surgically removed tissue. The Wieneke index is most commonly used in paediatric practice. However, some cases are still classified as "indeterminate histology". Predisposing genetic factors are found in most children with ACC, most commonly a mutation of the TP53 gene. Conclusions: Patients should be diagnosed in large clinical centres with experience in this field. The treatment strategy should be individualised. Genetic testing for TP53 gene mutations is indicated in patients with ACC.

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Pediatric adrenocortical carcinoma

Cited by 15 publications

References 91 publications

Precocious puberty and other endocrine disorders during mitotane treatment for paediatric adrenocortical carcinoma – case series and literature review

Precocious puberty and other endocrine disorders during mitotane treatment for paediatric adrenocortical carcinoma – case series and literature review

Current prospects of hereditary adrenal tumors: towards better clinical management

Adrenal cortical carcinoma: Paediatric aspects – literature review

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