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Urology Case Reports
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UROLOGY CASE REPORTS
Partin, MD, PHD Alan J. Wein, MD, Editors-in-Chief
Oncology
Report of a rare case of childhood adrenocortical carcinoma and literature review
Zhihuang Wuª,*®, Lianyu Qiub, Minjie Zhangª, Guoqiang Chen ℃
a Department of Urology, Master’s Degree, The Second Hospital of Longyan, Fujian, China
b Department of Pediatrics, Bachelor’s Degree, The Second Hospital of Longyan, Fujian, China
” Department of Urology, Bachelor’s Degree, The Second Hospital of Longyan, Fujian, China
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| ARTICLE INFO | ABSTRACT |
|---|---|
| Keywords: | Adrenocortical carcinoma (ACC)in children is rare, and its nonspecific clinical presentation renders early diag- nosis challenging. Surgery remains the primary therapeutic approach. A multidisciplinary, multimodal treatment strategy and long-term follow-up are essential to improve prognosis. A retrospective analysis was conducted on the clinical data of a child diagnosed with ACC at our hospital, including symptoms, signs, imaging findings, surgical procedures, pathological results, and postoperative follow-up, We also perform a literature review to increase disease awareness and provide references for similar clinical cases in the future. |
| Adrenal tumor | |
| Adrenal cortical carcinoma Precocious puberty Endocrine diseases |
1. Introduction
Adrenocortical carcinoma (ACC) is a rare and highly malignant tumor originating from the adrenal cortex cells. Epidemiological data indicate that ACC occurs infrequently in children and adolescents, ac- counting for approximately 1 %-2 % of all adrenal tumors.1 The etiology of ACC remains unclear, but potential associations include genetic fac- tors, endocrine disorders, and environmental conditions. ACC manifests with various clinical features, most notably precocious puberty, weight gain, skin pigmentation, and hypertension. Due to symptomatic simi- larity with other endocrine disorders, ACC is frequently misdiagnosed.2 The diagnosis is primarily established through imaging studies, hor- mone level analyses, and pathological examinations. Early detection and timely intervention are critical for improving patient prognosis.3 This case study reports a 3-year-and-6-month-old female who presented with pubic hair development, initially suggestive of an endocrine disorder. However, subsequent comprehensive evaluation confirmed a diagnosis of ACC. The occurrence of such a rare condition in a child and the associated significant endocrine abnormalities highlight the necessity of including ACC in differential diagnoses, thus facilitating prompt inves- tigation and treatment. The study was conducted following the SCARE criteria. 4
2. Presentation of case
The patient, a 3-year and 6-month-old girl, was admitted due to pubic hair growth observed on the vulva for two months. Physical ex- amination revealed blood pressure of 88/66 mmHg, weight of 19 kg, and height of 106 cm (+1.74 SD). No distinct facial features were observed; however, the patient exhibited balanced body proportions, acne on the head, face, and trunk, and extensive dark hair on the limbs and back. Breast development was classified as Tanner stage B1. The vulva was at Tanner stage PH2, showing pigmentation, visible pubic hair, and clitoral hypertrophy measuring 2 cm in length and 1 cm in width, with white discharge present. Laboratory results were as follows: Dehydroepian- drosterone (DHEA) at 0.63 ng/ml, Androstenedione (A4) at 9.41 nmol/ L, Neuronal Enolase (NSE) at 34.66 ng/ml, Testosterone (T) at 8.21 nmol/L, and Adrenocorticotropic Hormone (ACTH) at 77.3 pg/ml. Pe- ripheral blood chromosomal analysis revealed a 46, XX karyotype. Basic G-banding analysis of 20 metaphase cells revealed no numerical or structural chromosomal abnormalities. Bone age assessment indicated a carpal bone age of 7 years and 4 months compared to the chronological age of 3 years and 7 months, revealing advancement by approximately 3 years and 9 months. Pituitary MRI with and without contrast did not reveal significant abnormalities. A whole-body bone scan showed no evidence of skeletal metastasis. Routine bone marrow examination re- sults were within normal limits. Adrenal ultrasound revealed an irreg- ular echoic mass in the left adrenal region, approximately 5.60 cm x
* Corresponding author. Department of Urology, The Second Hospital of Longyan, Fujian, China. E-mail address: wuzhihuang871111@163.com (Z. Wu).
https://doi.org/10.1016/j.eucr.2025.103113
3.80 cm in size, with unclear boundaries and heterogeneous internal echoes, including areas of slightly increased echogenicity; color Doppler flow imaging (CDFI) demonstrated minimal peripheral and internal blood flow signals (Figure_1). Adrenal CT imaging revealed an abnormal mass in the left adrenal area, suggestive of neuroblastoma (Figure_2).
A preliminary diagnosis of a left adrenal mass was established based on the patient’s medical history, physical signs, and examination results. After comprehensive preoperative preparation, laparoscopic resection of a large left adrenal tumor was performed under general anesthesia.
The surgical procedure involved the following steps: (1) releasing the adherent mesentery on the surface of the left kidney; (2) incising the peritoneum lateral to the descending colon to expose a mass approxi- mately 8.0 x 5.0 × 3.0 cm in the left adrenal region; (3) dissecting the
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R
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avascular zone at the upper pole of the left kidney and the junction between the left adrenal gland and the spleen, subsequently removing the left adrenal mass along with the adrenal gland; Notably, the child’s blood pressure remained stable throughout the surgery, and the opera- tion was successfully completed.
The postoperative pathology revealed an adrenal cortical tumor exhibiting focal necrosis, approximately 18 mitotic figures per 4 mm2 including atypical forms, capsular invasion, and vascular involvement. The Wieneke score was at least 4, indicative of ACC. The tumor measured approximately 8.5 x 2.2 cm. Immunohistochemical analysis demonstrated tumor cells positive for Syn, SF-1, and Inhibin, partially positive for IGF2 in cytoplasmic granules, with loss of ATRX expression, and ß-catenin positivity at the cell membrane. The tumor exhibited wild- type expression of P53 and was negative for TFE-3, CgA, AR, S100, Melan-A, CYP11B2, and Pax-8. Additionally, Ki67 labeling index was approximately 25 % in hotspot areas (Figure_3). The final diagnosis was primary ACC with pathological staging of T2N0M0. At one-month postoperative follow-up, imaging studies showed no evidence of tumor recurrence.
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Given the tumor characteristics and pathological features, radio- therapy and chemotherapy are recommended as part of the patient’s treatment regimen. To date, the patient and her family have not returned for follow-up examinations or further treatment.
3. Discussion
ACC is a malignant epithelial tumor derived from adrenal cortical cells. It is clinically rare, with an incidence of 1-2 cases per 100,000, representing 0.02 % of all malignant tumors and accounting for 0.2 % of cancer-related deaths.5 In children, the incidence is approximately 0.3 cases per 100,000 annually, frequently associated with a specific TP53 exon 10 mutation (R377H).6 The precise molecular mechanisms un- derlying ACC remain unclear but may involve the inactivation of tumor suppressor genes (TP53, MEN-1, P57Kip2, and H19), abnormal activa- tion of oncogenes (Gas, Ras, ACTH receptor), overexpression of growth factor IGF-2, and abnormal activation of the ß-catenin gene.7 Concurrent analysis of the DL7, BUB1, and PINK1 genes is useful for subtype clas- sification and prognostic evaluation of ACC.8 While most ACC cases are sporadic, approximately 20 % may be associated with other malig- nancies or familial cancer syndromes, including Li-Fraumeni syndrome, Beckwith-Wiedemann syndrome, multiple endocrine neoplasia type 1 (MEN1), familial adenomatous polyposis, neurofibromatosis type 1, and Lynch syndrome.9 The clinical diagnosis of ACC relies upon clinical manifestations, radiological imaging, and endocrine evaluations, though pathological confirmation is essential. Clinical presentations of ACC vary depending on tumor stage, hormone secretion type, and functional status. Approximately 50 %-79 % of ACC cases exhibit endocrine activity,8 with mixed secretion of cortisol and androgens being most common (35 %-40 % of cases).8 Pure Cushing syndrome (CS) accounts for approximately 30 %, and isolated androgen secretion (characterized by acne, hirsutism, breast atrophy, menstrual abnor- malities, and voice deepening) occurs in about 20 % of cases. Abnormal estrogen and aldosterone secretion are less frequent, with female masculinization occurring in approximately 10 % of cases, while aldosterone-secreting ACC is rare (approximately 2 %).10 In adults, ACC displays higher endocrine functionality (approximately 90 %), pre- dominantly androgen secretion (55 % pure androgen secretion) or mixed cortisol secretion (30 %), whereas pure cortisol syndrome is un- common (<5 %). Symptoms in adults predominantly include virilization or pseudo-pubertal manifestations.11
Surgical intervention is currently the only potentially curative treatment for ACC, with the outcomes of the initial surgery frequently determining patient prognosis. Therefore, the choice of surgical
procedure requires careful consideration. Surgical indications include: (1) Clinical stage I to III tumors11; however, due to the infiltrative growth of ACC, complete resection is typically feasible only in stages I, II, and some stage III tumors.12 (2) For stage IV tumors,13 surgery is indicated if complete resection of both primary and metastatic lesions is achievable. Alternatively, palliative debulking may be performed to alleviate hypercortisolism and enhance the effectiveness of subsequent therapies, although prognosis remains poor, with survival generally less than 12 months.14
Follow-up: Patients with clinical stage I-III tumors that have un- dergone complete resection should receive follow-up every 3 months during the first 2 years postoperatively, followed by every 6 months thereafter. Patients with clinical stage I-III tumors not fully resected and those with clinical stage IV disease should be monitored every 2 months for the first 2 years, and the follow-up period should extend to at least 10 years.15 After the initial 2 years, the follow-up frequency should be adjusted based on tumor progression. Follow-up evaluations should include adrenal ultrasound, CT or MRI, PET-CT,15 and adrenal-related endocrine hormone measurements.15
This case highlights the atypical presentation of ACC in pediatric patients and emphasizes the importance of accurate diagnosis, espe- cially in cases involving precocious puberty and other endocrine ab- normalities. Clinical features of pediatric ACC differ from those observed in adults, with children frequently presenting prominent signs of endocrine disturbances, such as precocious pubic hair, acne, and extensive body hair.16 The emergence of these symptoms results from abnormal adrenal hormone secretion, underscoring the need for heightened clinical vigilance in similar cases. Hormone level assess- ments and imaging studies are essential for diagnosing ACC, while pathological examination confirms tumor malignancy and supports the diagnosis.17 Surgical resection remains the primary treatment option for ACC. In this patient, laparoscopic resection of the left adrenal mass was performed, and postoperative pathology confirmed the diagnosis of ACC. Timely and effective surgical management is critical to improving patient outcomes.18 Literature review further confirms that pediatric ACC is uncommon and presents with diverse clinical manifestations.
4. Conclusion
This case report presents a rare instance of ACC in a child. Due to its low incidence and limited clinical data, the identification, diagnosis, and treatment of pediatric ACC remain significantly challenging. The pa- tient’s clinical history was notable for atypical early symptoms. A definitive diagnosis was established through comprehensive diagnostic
evaluations, and the tumor was successfully resected via standard sur- gical procedures. Pathological examination confirmed the preoperative diagnosis. Postoperative pathology is crucial for determining the tu- mor’s pathological type and stage, guiding subsequent therapeutic de- cisions. Pediatric ACC is characterized by high invasiveness and significant recurrence risk, as highlighted by the existing literature. Therefore, close, long-term follow-up-including clinical assessments, laboratory testing, and imaging studies-is necessary to promptly detect recurrence or metastasis. In conclusion, this case contributes valuable clinical insights into pediatric ACC, providing reference points for diagnosis, management, and prognosis. It underscores the importance of multimodal diagnostic approaches, personalized surgical strategies, and sustained postoperative surveillance in improving patient outcomes. Further research and accumulation of case data are required to optimize diagnostic and therapeutic strategies for pediatric ACC.
CRediT authorship contribution statement
Zhihuang Wu: Writing - review & editing. Lianyu Qiu: Writing - original draft. Minjie Zhang: Data curation. Guoqiang Chen: Data curation.
Informed consent
Written informed consent was obtained from the patient’s guardian for publication of this case report and accompanying images.
Ethical approval
All data used in this study were derived from the patient’s medical records. This report contains no personal information that could identify the patient; thus, ethical approval was waived.
Funding
This research did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors.
Declaration of competing interest
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Acknowledgement
Not applicable.
Abbreviations
| ACC | Adrenocortical Carcinoma |
| DHEA | Dehydroepiandrosterone |
| ACTH | Adrenocorticotropic hormone |
|---|---|
| A4 | Androsterone |
| NSE | Neuronal |
| T | Testosterone |
| CS | Cushing's syndrome |
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