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Three cases of pediatric adrenocortical carcinoma with intermediate malignant potential: a case report with literature review
Marwa Messaoud1^, Amer Alsaied2^, Sana Mosbahi1, Nouha Boukhrissa1, Rania Sakka3, Amani N. Alansari2^
1Pediatric Surgery Department, Fattouma Bourguiba Hospital, Faculty of Medicine, University of Monastir, Monastir, Tunisia; 2Pediatric Surgery Department, Hamad Medical Corporation, Doha, Qatar; ‘Genetics Department, Fattouma Bourguiba Hospital, Faculty of Medicine, University of Monastir, Monastir, Tunisia
Contributions: (I) Conception and design: M Messaoud, A Alsaied, AN Alansari; (II) Administrative support: None; (III) Provision of study materials or patients: S Mosbahi, N Boukhrissa, R Sakka; (IV) Collection and assembly of data: S Mosbahi, N Boukhrissa, R Sakka; (V) Data analysis and interpretation: M Messaoud, N Boukhrissa, AN Alansari; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.
Correspondence to: Amani N. Alansari, MD, FRCS. Pediatric Surgery Department, Hamad General Hospital, Hamad Medical Corporation, Al Rayyan Road, Doha 3050, Qatar. Email: aalansari9@hamad.qa.
Background: Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy of the adrenal glands, characterized by a high potential for local invasion and metastasis. In pediatric patients, it often presents as a localized tumor with either benign or intermediate malignant potential. While ACC is considered rare in children, early diagnosis and intervention are critical for improving outcomes. This case report presents three children diagnosed with intermediate-potential malignant ACC, diagnosed at an early stage, and successfully treated with complete surgical resection.
Case Description: The first case involves a 2-month-old female neonate presenting with signs of Cushingoid syndrome and a 5.5 cm left-sided stage II ACC. The second case describes a 3-year-old male who exhibited peripheral signs of precocious puberty with a 7 cm androgen-secreting right-sided stage II ACC. The third case involves a 2.5-year-old boy who presented with a hypertensive crisis-related seizure, adrenocorticotropic hormone (ACTH)-independent Cushing’s syndrome, and peripheral precocious puberty due to a 3.5 cm right adrenal stage I ACC. All three patients underwent successful complete resection of their respective tumors, with no signs of locoregional invasion or distant metastasis. Postoperatively, there was a complete resolution of the endocrine manifestations, such as Cushingoid features and precocious puberty. All three children underwent successful complete tumor resection, resolution of the endocrine findings and no recurrences after up to 4 years of follow-up.
Conclusions: This case report highlights the diverse clinical presentations of pediatric ACC, showcasing the various hormonal profiles and symptoms associated with the disease. It emphasizes the critical importance of early detection and complete surgical resection in improving patient outcomes. Although pediatric ACC is a rare and aggressive disease, these cases demonstrate that with appropriate intervention, favorable outcomes can be achieved, even in cases with intermediate malignant potential.
Keywords: Adrenocortical carcinoma (ACC); pediatrics; adrenal gland neoplasms; case report
Received: 09 August 2025; Accepted: 30 October 2025; Published online: 22 January 2026. doi: 10.21037/acr-2025-204
View this article at: https://dx.doi.org/10.21037/acr-2025-204
^ ORCID: Marwa Messaoud, 0009-0006-1314-6713; Amer Alsaied, 0000-0003-2939-9716; Amani N. Alansari, 0000-0002-9369-1933.
Introduction
Adrenocortical carcinoma (ACC) is a rare but exceptionally aggressive malignancy that may affect children (1). Its incidence is estimated at approximately 0.2-0.3 cases per million children per year, accounting for less than 0.2% of all pediatric malignancies (2). However, this rate varies geographically notably; the incidence in southern Brazil is 10-15 times higher, mainly due to the prevalence of the TP53 R337H germline mutation (3). Most pediatric ACC cases are confined to a local region (benign and intermediate potential malignant) (1).
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Key findings
· This case report details three pediatric adrenocortical carcinoma (ACC) cases, all classified as intermediate-potential malignant tumors, which exhibited an exceptionally favorable prognosis with no recurrence after up to 4 years of follow-up.
· The patients were diagnosed at early stages and successfully treated with complete surgical resection alone (adrenalectomy), without the need for adjuvant therapy.
· These cases, presenting with distinct hormonal features (Cushing syndrome, peripheral precocious puberty, and mixed syndrome), underscore the diversity of ACC presentation even in localized tumors.
· In children, ACC typically presents as a functional hormone- secreting tumor, most frequently with virilization, whereas Cushing syndrome is less common.
· Although symptom duration alone may not predict prognosis, patients diagnosed with pediatric ACC at localized stages (I-II) consistently demonstrate better survival outcomes compared with those presenting with advanced disease stages (III-IV).
What is known and what is new?
· Pediatric ACC is a rare and aggressive cancer typically presenting as a functional tumor (most often virilization), and localized stages (I-II) are correlated with better survival.
· This study demonstrates that ACC with intermediate malignant potential-characterized by limited microscopic features of malignancy-can achieve long-term, cured outcomes with surgery alone, thereby questioning the need for routine adjuvant therapy in all localized cases.
What is the implication, and what should change now?
· The excellent prognosis observed in this case report suggests that complete tumor resection remains the cornerstone of management, particularly for intermediate-potential ACC in early stages.
. Further studies are needed to refine the sub-classification of localized ACC and identify molecular markers that accurately predict which patients will benefit from adjuvant therapy, thus avoiding unnecessary treatment-related toxicity.
Pediatric ACC displays a bimodal distribution, with the first peak occurring under the age of 5 and the second after 10 years of age, and it is more commonly observed in females than males (1). Childhood ACC can be associated with genetic cancer predisposition syndromes, including Li- Fraumeni syndrome, Beckwith-Wiedemann syndrome, and multiple endocrine neoplasia type 1 (MEN1) (4).
Surgery remains the cornerstone of treatment (5). Neoadjuvant chemotherapy which has evolved from adult studies has shown promising results (6). There is also room for mitotane- and cisplatin-based regimens as adjuvant and salvage therapy (7). Radiotherapy is generally avoided in pediatric ACC, even in relapse settings, because many affected children harbor TP53 germline mutations that markedly increase their susceptibility to radiation-induced secondary cancers (8,9). The treatment protocols have not yet been fully standardized (8). The prognosis of pediatric ACC is highly variable and largely dependent on stage at diagnosis.
According to the European Cooperative Study Group for Paediatric Rare Tumours (EXPERT), 5-year survival exceeds 80% in localized disease (stages I-II) but falls below 20% in metastatic cases (stages III-IV) (8-10).
The histological characteristics of pediatric ACC are similar to those observed in adults; however, their histological interpretation and classification differ (6). These tumors are primarily composed of adrenal cortical cells with eosinophilic or clear cytoplasm, often exhibiting nuclear pleomorphism with frequent mitoses. Nevertheless, atypical mitoses are not always present (1). Areas of necrosis and sometimes signs of invasion are observed in tumors. The Weiss criteria, initially developed for adult ACCs, often overestimate malignancy potential when applied to pediatric cases, leading to misclassification of tumors with otherwise benign clinical behavior (6). The Wieneke scoring system (11), proposed in 2003, is currently preferred for children as it incorporates pediatric-specific morphological features (8,11,12). More recent work, such as that by Picard et al. (2019), has proposed refined prognostic models that integrate mitotic activity, Ki-67 index, and molecular alterations to improve outcome prediction in pediatric ACC (13).
In contrast to adult ACC, pediatric ACCs are typically functional, leading to excess hormonal secretion, particularly corticosteroids and androgens, resulting in a broad spectrum of clinical manifestations such as Cushing’s syndrome, sexual precocity, and secondary hypertension (5,11).
The objective of this study is to highlight the diverse
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clinical presentation and the outcome of three pediatric ACC cases from the Middle East North Africa (MENA) region. We present this article in accordance with the CARE reporting checklist (available at https://acr. amegroups.com/article/view/10.21037/acr-2025-204/rc).
Case presentation
Case 1
Clinical course
A 2-month-old female infant was born to non- consanguineous parents via cesarean section due to fetal distress. There was no family history of cancer. The patient subsequently presented with a progressively developing round moon face, diffuse cutaneous infiltration, and hypertrichosis (Figure 1). Physical examination revealed normal female external genitalia with no signs of sexual precocity and a firm left-sided abdominal mass.
The patient’s blood pressure was within normal limits for her age, measuring 95/45 mmHg.
Diagnostic workup
Routine laboratory tests, including glycemia and electrolytes, were within normal limits. However, hormonal workup revealed an altered cortisol circadian rhythm with elevated late-night plasma cortisol levels at 162.1 ng/ml and suppressed plasma adrenocorticotropic
hormone (ACTH) (4.6 pg/mL), consistent with ACTH- independent Cushing syndrome. Urinary-free cortisol and dexamethasone suppression tests were not performed due to the patient’s young age. There was no associated adrenal hypersecretion of androgens, mineralocorticoids, or catecholamines.
Hormonal workup revealed mildly elevated luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels (at 4.13 ng/ml), which were consistent with the physiological mini-puberty of infancy rather than tumor-related androgen secretion.
Abdominal computed tomography (CT) revealed a large, 60 mm × 55 mm × 45 mm heterogeneously hypervascular left-sided adrenal tumor with tissue necrosis (Figure 2). Although the tumor exceeded the median line, there were no signs of local invasion or distant metastases. Based on these findings, the patient was diagnosed with a cortisol-secreting adrenal tumor with a high suspicion of malignancy.
Management
The patient underwent surgical treatment, and intraoperative findings showed a large, heterogeneously hypervascular left-sided adrenal tumor with no locoregional invasion, allowing for macroscopically complete tumor resection. With a Wieneke score of 3 (11), stage II ACC (14) was confirmed by histopathological analysis, indicating a
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moderate risk of aggressive behavior typically associated with this stage. The surgical margins were safe (R0), and no adjuvant systemic therapy was indicated.
Follow-up and outcomes
The patient exhibited favorable postoperative outcomes, with a notable regression of Cushingoid features observed within a few months following surgery. At the four-year follow-up, no recurrence was detected.
Case 2
Clinical course
Patient B was a 3-year-old boy with a medical history of recurrent otitis externa, who was referred for the progressive onset of pubertal signs over the past 7 months. Physical examination revealed Tanner stage II features, including mild testicular (2.5 mL bilaterally) and penile enlargement, with long, thin pubic hair. Bone age was advanced (7 years vs. chronological age 3 years), consistent with chronic androgen exposure.
This testicular enlargement, although atypical in peripheral precocious puberty, was likely due to peripheral androgenic stimulation rather than central gonadotropin activation. The patient’s blood pressure was normal for his age, measuring 100/60 mmHg.
Diagnostic workup
Routine laboratory tests were normal. However, hormonal workup showed an elevated total plasma testosterone level at 9.6 ng/ml, low gonadotropins (LH =0.1, FSH =0.1), and
increased DHEA-S concentration (18 pmol/L), consistent with a peripheral isosexual precocious puberty pattern, whereas, the gonadotropin-releasing hormone (GnRH) stimulation test was unavailable. Concomitant hormone hypersecretions, including corticoids and catecholamines, were ruled out. Alpha-fetoprotein, human chorionic gonadotropin (HCG), thyroid-stimulating hormone (TSH), and free thyroxine (FT4) were normal. An abdominal CT scan exhibited a 70 mm × 50 mm × 50 mm well-defined right adrenal tumor with peripheral calcifications. This heterogeneous mass was moderately enhanced with contrast media, with zones of necrosis. The provisional diagnosis was an androgen-secreting adrenal tumor with radiological features suggesting malignancy.
Management
A complete surgical resection of the tumor was successfully achieved via laparotomy. The histopathological findings were consistent with stage II ACC and a Wieneke score of 3. No adjuvant therapy was recommended for this patient.
Follow-up and outcomes
Postoperative outcomes were favorable, with stabilization of pubertal progression and normalization of growth velocity. No evidence of tumor recurrence was observed over a three-year follow-up period.
Case 3
Clinical course
Patient C was a 2.5-year-old boy with no family history of cancer. He was initially admitted to the pediatric emergency department due to seizures with altered consciousness status related to a hypertensive crisis. After the management and resolution of this acute episode, the child was referred for further investigations. Upon physical examination, his blood pressure was high at 130/100 mmHg. He exhibited a moon face with hypertrichosis on the back. Signs of sexual precocity were noted, including enlargement of the testes (G2), pubic hair (P2), and axillary hair (A1) according to Tanner staging. The child weighed 15 kg (+2 SD) for a height of 84 cm (median). The parents reported recent excessive weight gain, with a body mass index (BMI) of 22 kg/m2 (grade II obesity).
Diagnostic workup
The biochemical findings showed moderate fasting hyperglycemia of 5.75 mmol/L. The potassium level was
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normal. Cortisol was unresponsive (22 ng/mL) despite a 2-day dexamethasone suppression test (2DDST). Urinary free cortisol was elevated with suppressed ACTH at 3.6 pg/mL. These findings confirmed ACTH-independent Cushing syndrome. A left-hand radiograph showed bone age corresponding to approximately 5 years (chronological age 2.5 years). Despite mild bilateral testicular enlargement (Tanner G2), LH and FSH were suppressed, confirming a non-GnRH-dependent etiology of precocious puberty.
There was no associated mineralocorticoid or catecholamine hypersecretion. Hypertension was complicated by concentric left ventricular and septal hypertrophy with no renal damage.
Abdominal CT scan revealed a 32 mm × 30 mm × 29 mm well-defined spontaneously hypodense tumor originating from the right adrenal gland, which was heterogeneously enhanced after the injection of contrast media with necrotic zones (Figure 3). The diagnosis of a malignant adrenal tumor with mixed glucocorticoid and androgen secretion was highly suspected.
Management
The child underwent right adrenalectomy with complete tumor resection. The histopathological examination featured a stage I ACC with a Wieneke score of 3. This neoplasm did not require any further systemic adjuvant therapy.
Follow-up and outcomes
Postoperative outcomes were favorable. Antihypertensive therapy was discontinued following resolution of
hypertension, and prediabetes remitted with normalization of fasting plasma glucose. Pubertal progression stabilized, and the patient achieved normal growth velocity and BMI. No tumor recurrence has been observed over 3.5 years of follow-up. A summary of all three cases is presented in Table 1.
Ethical statement
All procedures performed in this study were in accordance with the ethical standards of the University of Monastir Research Committee and the principles of the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patients’ parents for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.
Discussion
Cushing’s syndrome is a rare presentation in pediatric ACC, and isolated Cushing’s syndrome is even less frequent. On the other hand, adrenocortical tumors account for the cases of neonatal Cushing’s syndrome (11). In neonates, the clinical features of Cushing’s syndrome may mimic other conditions associated with weight gain or endocrine dysregulation, such as exogenous obesity or McCune- Albright syndrome (12,15).
The diagnostic workup of glucocorticoid hypersecretion can be challenging, as the circadian rhythm of neonates and infants is not always in sync with that of older children and adults. The 24-hour urine collection test is difficult to obtain, and the oral dexamethasone suppression test is not always easy to perform (16). Cushing’s syndrome is a poor prognostic factor while virilisation alone is a better prognostic factor (6). Two of our cases presented with Cushing’s syndrome (A and C) and one of them presented with isolated neonatal Cushing’s. In our patients, normal birth weight, moon-shaped face, erythroses, lack of café-au-lait macules and ACTH-independent Cushing syndrome helped in diagnosis of adrenal tumor origin of the inappropriate cortisol secretion leading to the Cushing’s syndrome.
In our cases, both children with androgen-secreting ACC exhibited mild testicular enlargement despite suppressed gonadotropins, an unusual finding in peripheral precocious puberty. This phenomenon may result from paracrine or local androgenic effects on testicular tissue, as reported in rare cases of peripheral androgen excess (6,17).
| Characteristics | Case 1 | Case 2 | Case 3 |
|---|---|---|---|
| Age/gender | Newborn female | 3-year-old male | 2.5-year-old male |
| Symptoms | . Round moon face · Diffuse cutaneous infiltration . Hypertrichosis | · Progressive onset of pubertal signs over the past 7 months | · Seizures with altered consciousness · Hypertensive crisis · Excessive weight gain |
| Signs | - Firm left-sided abdominal mass, normal feminine external genitalia, no signs of sexual precocity, blood pressure 95/45 mmHg | - Testicular and penile enlargement (G2), pubic hair development (P2), accelerated growth (weight +5.53 SD, height +4 SD), advanced bone age of 7 years, blood pressure: 100/60 mmHg (normal for age) | - Moon face, hypertrichosis on the back, enlargement of testes (G2), pubic hair development (P2), axillary hair development (A1), weight: 15 kg (+2 SD), height: 84 cm (Median), high blood pressure: 130/100 mmHg, BMI: 22 kg/m2 (Grade II obesity) |
| Lab investigations | . Normal glycemia and electrolytes | . Normal routine laboratory tests | · Moderate fasting hyperglycemia: 5.7 mmol/L, normal potassium level |
| . Altered cortisol circadian rhythm | · Elevated total plasma testosterone level: 9.6 ng/ml | · Cortisol unresponsive to 2-day dexamethasone suppression test (2DDST) | |
| · Elevated late-night plasma cortisol levels | . Low gonadotropins (LH =0.1, FSH =0.1) | . Elevated urinary free cortisol with suppressed ACTH and elevated | |
| · Suppressed plasma ACTH | . Increased DHEA-S concentration | DHEA-S and testosterone with low gonadotropins | |
| . Elevated LH, FSH, and testosterone levels | . Normal levels of alpha-fetoprotein, HCG, TSH, and FT4 | ||
| Radiology | Abdominal CT: 60 mm × 55 mm × 45 mm heterogeneously hypervascular left-sided adrenal tumor with tissue necrosis. No locoregional invasion or distant metastases | Abdominal CT: 70 mm × 50 mm × 55 mm well-defined right adrenal tumor with peripheral calcifications. Heterogeneous mass with moderate contrast enhancement and zones of necrosis | Abdominal CT: 32 mm x 30 mm × 29 mm well-defined spontaneously hypodense tumor from the right adrenal gland. Heterogeneous enhancement with necrotic zones |
| Treatment | - Surgical excision with macroscopically complete resection | - Laparotomy and complete surgical excision of the tumor | - Right adrenalectomy with complete tumor resection |
| Histopathology | · Stage II ACC with a Wieneke score of 3. Safe surgical margins (R0) | · Stage II ACC with a Wieneke score of 3. No adjuvant therapy recommended | · Stage I ACC with a Wieneke score of 3. No further systemic adjuvant therapy required |
| Follow-up | Four years postoperatively, no recurrence detected; Cushingoid features regressed within a few months after surgery | Three years postoperatively, satisfactory outcomes; stabilization of pubertal signs and normal growth velocity; no tumor recurrence detected | 3.5 years postoperatively; favorable outcomes: antihypertensive drugs discontinued. Reversal of prediabetes. Pubertal signs did not progress; normal growth pattern and BMI. No recurrence noted for 3.5 years |
2DDST, 2-day dexamethasone suppression test; ACC, adrenocortical carcinoma; ACTH, adrenocorticotropic hormone; BMI, body mass index; CT, computed tomography; DHEA-S, dehydroepiandrosterone sulfate; FSH, follicle-stimulating hormone; FT4, free thyroxine; HCG, human chorionic gonadotropin; LH, luteinizing hormone; SD, standard deviation; TSH, thyroid-stimulating hormone.
In addition to Cushing’s syndrome, Patient C presented with hypertension and sexual precocity. Hypertension in children with ACC is more frequently related to elevated
glucocorticoids and subsequent mineralocorticoid receptor activation rather than either recruitment of the renin angiotensin system or direct elevation of aldosterone (14).
Aldosterone-secreting adrenocortical tumors are exceptionally rare in children and, when present, are usually associated with malignant behavior or advanced disease rather than benign pathology (6,15,17). Hypertension is a relatively common clinical manifestation in pediatric ACC, especially in cortisol- and androgen-secreting tumors. According to Michalkiewicz et al. (17), approximately one- third of affected children present with hypertension, often secondary to glucocorticoid-induced mineralocorticoid receptor activation. The management of hypertension in the pediatric population is challenging, and it is a serious finding. In previous literature, several hypertensive complications have been reported, such as seizures, intracerebral hemorrhage, and life-threatening hypertensive crises in children with ACC. For instance, Chen et al. documented a case of a girl diagnosed with ACC who presented with stroke and hemiparesis at a blood pressure of 225/150 mmHg. Patient C experienced neurological and cardiac organ damage due to severe secondary hypertension (18). Pediatric ACC is frequently associated with germline TP53 mutations, which represent the hallmark of Li-Fraumeni syndrome and account for the majority of genetic predispositions, even outside the Brazilian population (1,2,19). Other syndromes such as Beckwith-Wiedemann, MEN1, and Lynch are much less common but should still be considered in the genetic evaluation of affected children. These conditions are autosomal dominant and predispose to multiple primary malignancies involving various organs (1). Our patients did not exhibit any features or family history of Beckwith-Weidman syndrome, Li-Fraumeni, MEN1 or relevant family history of cancerous or precancerous lesions. However, germline mutations in predisposing genes cannot be excluded due to the variable expressivity and typical late onset of most primary cancers.
Therefore, long-term clinical and radiological follow-up is planned. Genetic testing for key predisposing genes (e.g., TP53) was not feasible during the study period.
The Children’s Oncology Group (COG) clinical staging system, updated in 2012, defines stage I as completely resected tumors ≤5 cm or ≤200 g without capsular rupture or nodal involvement; stage II as completely resected tumors >5 cm or >200 g; stage III as incompletely resected tumors, those with capsule rupture, local invasion, or positive lymph nodes; and stage IV as tumors with distant metastases (commonly liver, lung, or bone). This framework remains the reference for pediatric ACC classification (3,11,20). ACC has a poor prognosis in adults (5-year survival: 20-50%) (21), whereas children show better
outcomes (30-70%), largely influenced by disease stage (3,21).
Complete resection yields survival rates of 80-90%, while metastatic cases drop to 0-10% (3). Rodriguez- Galindo et al. reported 5-year event-free survival rates of 86.2% for stage I, 53.3% for stage II, 81% for stage III, and 7.1% for stage IV (14). In a separate study, Chafaaoui et al. identified six Weiss malignancy criteria in the tumor, including high nuclear grade, >5 mitoses per 50 high-power fields, <25% clear cells, tumor necrosis, venous invasion, and capsular invasion (22). Our three cases were stages II (A and B) and stage I (Patient C). All three of them underwent R0 resection and showed moderate Wieneke score with no adjuvant chemotherapy.
The management of pediatric ACC has been largely based on adult ACC treatment protocols. The European Cooperative Study Group for Pediatric Rare Tumors has published consensus guidelines that suggest complete en bloc resection as the mainstay of a potentially curative approach. An experienced surgeon in adrenal and oncological surgery is essential for successful outcomes. Open adrenalectomy remains the gold standard for pediatric ACC. Laparoscopic resection may be cautiously considered only in highly selected cases with small (<6 cm), well-encapsulated, non- invasive tumors, and when performed by an experienced pediatric surgical team. However, evidence supporting this approach in children remains limited compared with adult data (5,6). Locoregional lymphadenectomy is recommended when feasible (9,14). Despite significant advances in pediatric oncological interventions in general, children with ACC have still not experienced its benefits (6). Mitotane is an adrenolytic agent that inhibits steroidogenesis and exhibits anti-proliferative effects. Adjuvant mitotane is recommended for high-risk pediatric cases, including stage III disease or incomplete resection (R1-RX) (9,11). Chemotherapy in pediatric ACC remains an evolving field, but several international collaborative trials have been conducted. These include the GPOH-MET 97 (Germany), TREP (Italy), and FRACTURE (France) protocols under the European EXPERT network, as well as the COG- ARAR0332 trial (North America). These studies have collectively supported the selective use of mitotane and platinum-based regimens, particularly in high-risk or incompletely resected cases (5,20). On the other hand, the ADIUVO trial recently published showed no advantage of the use of using mitotane as an adjuvant agent in children with stage I, II, and III ACC who have undergone complete resection and have low Ki-67 marker on histopathology, as
well as in cases with incomplete resection (20,23,24).
In this series, complete tumor resection was achieved in all patients, with favorable postoperative outcomes, and no case required adjuvant chemotherapy.
This case report highlights the diverse clinical presentations of pediatric ACC. Pediatric ACC is an entity that is inherently rare and diagnostically challenging. Our report highlights three distinct cases of intermediate- potential malignant ACC with a broad phenotypic spectrum, coupled with consistent histopathological findings of intermediate malignancy (Wieneke score of 3 for all cases), underscoring the critical need for a high index of suspicion for successful diagnosis in the early stages. Furthermore, the favorable outcomes observed across all three cases, despite the aggressive nature of the disease, provide valuable insights into the management and prognosis of pediatric intermediate-potential malignant ACC.
Conclusions
ACCs are rare and aggressive tumors in the pediatric population with the diverse clinical presentation and hormonal profile. We present three unique cases and an updated literature review of the advances in management. Early diagnosis of these tumors at the localized stage is a crucial factor for favorable outcomes and improved survivability. Although our case report did not explore molecular-targeted therapy, recent literature suggests a growing role for biological markers and emerging targeted agents in pediatric ACC management, an area that remains under active investigation. Future studies are needed in order to provide oncological target therapies for children with ACC based on the significant advances in our understanding of its molecular biology.
Acknowledgments
We would like to express our sincere gratitude to all the patients who participated in this case report. Their willingness to share their experiences has been invaluable. We also acknowledge the contributions of our clinical and research staff, whose dedication ensured the successful completion of this work.
Footnote
Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://acr.amegroups.com/
article/view/10.21037/acr-2025-204/rc
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Funding: None.
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups. com/article/view/10.21037/acr-2025-204/coif). The authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the University of Monastir Research Committee and the principles of the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patients’ parents for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non- commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
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doi: 10.21037/acr-2025-204
Cite this article as: Messaoud M, Alsaied A, Mosbahi S, Boukhrissa N, Sakka R, Alansari AN. Three cases of pediatric adrenocortical carcinoma with intermediate malignant potential: a case report with literature review. AME Case Rep 2026;10:3.