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WILEY
Pediatric Blood & Cancer
SOCIÉTÉ INTERNATIONALE D’ONCOLOGIE PÉDIATRIQUE
SIOP INTERNATIONAL SOCIETY OF PAEDIATRIC ONCOLOGY
aspho The American Society of Pediatric Hematology/Oncology
A Case of Pediatric Adrenocortical Carcinoma With McCune-Albright Syndrome Masquerading as Spontaneously Regressing Neuroblastoma
Yu Lin1 Qi Zhang1 Shen Yang1 Haiyan Cheng1 Xiaofeng Chang1 Jianyu Han1 Jun Feng1 Ziyun Zhu1 Hong Qin1 Nan Zhang2 Wei Yang1 Huanmin Wang1
1Department of Oncology Surgery, Beijing Children’s Hospital, Capital Medical University, National Center For Children’s Health, Beijing, China | 2Department of Pathology, Beijing Children’s Hospital, Capital Medical University, National Center For Children’s Health, Beijing, China
Correspondence: Wei Yang (yw092011@aliyun.com) Huanmin Wang (wanghuanmin@bch.com.cn)
Received: 2 February 2026 Revised: 2 February 2026 Accepted: 13 February 2026
To the Editor:
Pediatric adrenocortical carcinoma (ACC) is a rare malignant tumor, with an incidence of 0.5-2.0 new cases per million chil- dren annually [1, 2]. McCune-Albright syndrome (MAS), caused by somatic GNAS mutations, with an incidence rate ranging from one in a million to one in a hundred thousand [3]. Both are etiologies of adrenal Cushing syndrome, and their concurrence is extremely rare. Herein, we report the case of pediatric ACC with MAS, initially suspected of spontaneously regressed neuroblas- toma due to spontaneous regression of bilateral space-occupying lesions.
Bilateral adrenal lesions were detected prenatally in the third trimester (left: 3.6 x 3.4 x 3.4 cm; right: 2.3 x 2.2 x 2.1 cm), sug- gestive of hematoma or neurogenic tumors. Postnatally, lesions gradually regressed; normal neuron-specific enolase (NSE) and age suggested spontaneously regressed neuroblastoma, with reg- ular follow-up. The left lesion enlarged first (maximum: 6.0 x 5.5 × 4.0 cm) then regressed to undetectable; the right lesion enlarged, regressed (minimum: 0.9 × 0.6 × 0.9 cm), then re- enlarged to 6.8 x 5.2 × 4.8 cm (Figure 1). At 4 years and 2 months, the patient was admitted for Cushing syndrome, preco- cious puberty, erythrocytosis, and asymmetric limb development. Physical examination: Maximum blood pressure 176/142 mmHg, moon facies (Figure 2A), right limb hypertrophy, penis: 6 x 2 cm; left testis: 2 mL, right testis: 5 mL; Tanner stage II (Figure 2B), left back café-au-lait spot (4.3 x 2.7 cm, Figure 2C), and right
posterior helical pits (Figure 2D). Unremarkable past and family history. Hemoglobin 182 g/L, NSE 18 ng/mL, testosterone 45.32 ng/dL; normal urinary homovanillic acid/vanillylmandelic acid. Negative bone marrow smear. Bilateral diffuse medullary nephro- calcinosis, and renal size: left: 8.3 × 3.1 cm; right: 9.3 × 4.0 cm (Figure 2E). Preoperative enhanced CT showed a right adrenal mass 6.8 x 5.2 × 4.8 cm, 47 HU, heterogeneous enhancement (Figure 2F), PET-CT imaging of spontaneous rib fracture healing (Figure 2G).
After blood pressure control, bilateral adrenal lesion resec- tion was performed: complete resection of the right lesion (with liver/kidney invasion, Figure 2H) and partial left adrenal preservation. Pathology confirmed right ACC, Wieneke score 6, with vascular invasion, intravascular tumor thrombi, signif- icant pleomorphism, tumor giant cells, >20 mitoses/10 HPF, necrosis, and Ki-67: 15% focal [4-6] (Figure 2J,K). The left lesion showed cysts with hemorrhage, necrosis, calcification, hemosiderin deposition, and atrophic cortical glands. Postoper- atively, with the Children’s Oncology Group (COG) stage II, the European Network for the Study of Adrenal Tumors (ENSAT) stage III, the patient received 8 cycles of EDP chemother- apy (cisplatin, doxorubicin, etoposide, q21d) and 2-year oral mitotane.
A differential diagnosis of Beckwith-Wiedemann syndrome (BWS) was considered [7]. Multiplex ligation-dependent probe amplification (MLPA) results showed no abnormalities in gene
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copy number or methylation status in the 11p15.5 region (Figure 2I). Next-generation sequencing (NGS) for both somatic and germline variants identified the following somatic mutations: CTNNB1: c.122C>T (p.T41I) in exon 3, and GNAS: c.601C>T (p.R201C) in exon 8. Based on the above findings combined with the patient’s clinical manifestations including precocious
puberty, café-au-lait spot, spontaneous bilateral rib fractures, and diffuse medullary nephrocalcinosis, the diagnosis of MAS was confirmed. Meanwhile, the CTNNB1 mutation was identified as the pathogenic driver of ACC. At the 3-year postoperatively follow-up, the patient had discontinued mitotane and remained in tumor-free survival status.
MAS is caused by somatic GNAS gain-of-function mutations, and its concurrence with ACC is extremely rare [8]. Bilateral adrenal space-occupying lesions in this patient continued to enlarge during pregnancy. This was considered to be adrenal cortical hyperplasia induced by MAS, while the significant changes in the left lesion suggested the presence of adrenal hematoma during pregnancy. Both lesions gradually decreased in size within 6 months after birth. At the initial diagnosis, we optimistically considered the possibility of spontaneously regressed neuroblastoma.
Regarding the causes of the size changes of the lesions: the regression of the right lesion may be related to the atrophy of the original fetal cortex after birth due to the interruption of maternal placental hormones, while the regression of the left lesion was attributed to the absorption of the hematoma. Usually, by the age of 3 years, the three-zone structure of the adrenal gland is fully formed, and the adrenal gland resumes growth with its weight returning to 4-5 g. At this stage, the cortical cells of the right adrenal gland, driven by the CTNNB1-mediated WNT/B-catenin signaling pathway, began to proliferate in accordance with onco- logical rules, manifesting as progressive tumor enlargement [9]. Therefore, the right tumor grew to 6.8 cm in diameter when the patient was 4 years old. In contrast, the left adrenal cortical lesion showed atrophy due to the inhibition of adrenocorticotropic hormone negative feedback caused by cortisol secretion from the right adrenal cortical carcinoma. This explains the presence of hemosiderin-laden cell deposition and atrophic adrenal cortical glands in the cyst wall observed in the postoperative pathology of the left adrenal lesion. Hypercortisolism and precocious puberty are common in 1.7%-7.5% of MAS cases and most functional ACC [2, 10]. Regardless of whether the hyperhormonal state is caused by MAS or ACC, surgery effectively normalizes hormone levels, as observed in this case.
In conclusion, the combination of MAS and ACC is extremely rare. Genetic testing is an important means for diagnosis and etiological identification, and comprehensive and personalized management involving pediatric surgical oncology, medical oncology, and endocrinology-genetic metabolism is required for such patients.
Acknowledgments
We are grateful to the patient and the families of the patient who have made this research possible.
Ethics Statement
The patient’s parents give written consent to the release of the medical history and images.
Funding
This work was supported by the Capital’s Funds for Health Improvement and Research (CFH) (No. 2024 - 1 - 2091).
Conflicts of Interest
The authors declare no conflicts of interest.
Yu Lin Qi Zhang Shen Yang Haiyan Cheng Xiaofeng Chang Jianyu Han Jun Feng Ziyun Zhu Hong Qin Nan Zhang Wei Yang Huanmin Wang
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