Introduction

Neuroblastoma is a primarily pediatric cancer, with an annual incidence of approximately 600 to 800 cases diagnosed in children in the United States [1-3]. The average age at diagnosis ranges from 1 to 2 years, with a median age of 18 months. Notably, about one-third of cases are identified before the child’s first birthday, and approximately 90% are diagnosed by the time they reach five years of age [4]. The occurrence of neuroblastoma in individuals over the age of ten is exceedingly rare, with roughly 151 reported cases worldwide among adolescents and adults. This rarity is further complicated by the absence of standardized treatment protocols for this demographic, leading to significantly poorer outcomes compared to pediatric patients [5-7]. While the 5-year overall survival rate for children with neuroblastoma is around 90%, it falls dramatically to approximately 38% for individuals diagnosed after adolescence [8-12].

When neuroblastoma does occur in adults, it primarily affects individuals aged 18-60 years, most frequently arising in the central nervous system (39%) and the retroperitoneum (17%), reflecting its association with neural crest-derived tissues along the sympathetic axis [3]. Clinical presentations often include nonspecific symptoms such as abdominal masses and localized pain, which result from tumor growth and the compression of surrounding structures. As the disease progresses, complications related to metastatic spread may emerge, including spinal cord compression and hypertension due to catecholamine overproduction [13]. The diverse and often subtle nature of these symptoms can complicate the diagnostic process, necessitating careful evaluation to distinguish neuroblastoma from other adult malignancies. In this report, we present a case of adrenal neuroblastoma in a young adult, emphasizing the diagnostic complexities and the effective multidisciplinary management involved, along with a systematic review of the literature on adrenal neuroblastoma cases in the adult population.

Methods

PubMed, Cochrane CENTRAL, EMBASE, and clinicaltrials. gov were searched for English-language reports of adult adrenal neuroblastomas. Databases were searched from inception through September 20, 2024, with subject headings and keywords.

Reports were eligible if they included a patient aged eighteen years or older with neuroblastoma or ganglioneuroblastoma involving the adrenal gland. Papers that included mixed pediatric and adult patients, multiple locations of neuroblastoma, and so on were considered if the data for adult adrenal neuroblastoma cases were reported separately and could be extracted. Gray literature was considered in addition to peer-reviewed literature. Reviews of previously reported cases were excluded.

Screening of titles and abstracts was done in duplicates with conflicts resolved by a third reviewer. Screening of full texts was done in duplicate with conflicts resolved by consensus. Data extraction was done in duplicate/by one author with discrepancies resolved by consensus/extractions checked by two additional authors. Covidence was used to manage citations and screening.

The database search produced 1,213 results, of which 921 were unique citations. After screening, 127 citations that reported one or more cases of adrenal neuroblastoma in adult patients were included (Figure 1).

Case Presentation

A 19-year-old male was referred to our tertiary healthcare facility due to an acute onset of right flank pain, which was accompanied by nausea, anorexia, back pain, and tenderness in the right upper quadrant of the abdomen. The case had initially been evaluated at an external institution, where a preliminary differential diagnosis of adrenocortical carcinoma (ACC) was proposed.

Upon presentation, the patient exhibited mild tachycardia, though blood pressure remained within normal limits. Physical examination revealed no additional abnormalities. His medical history was significant for anxiety, depression, and attention deficit hyperactivity disorder (ADHD), which were managed with Alprazolam, Desvenlafaxine, Lisdexamfetamine, and Loratadine/ Pseudoephedrine. Importantly, the patient’s family history did not indicate any hereditary endocrine neoplasms, including pituitary, thyroid, or adrenal tumors. Initial biochemical evaluations indicated slight elevations in plasma-free normetanephrines (1.55 nmol/L; reference range: 0-0.84) and urine normetanephrines (674 µg/day; reference range: 81-667). Levels of Chromogranin A were notably elevated at 170 ng/mL (reference range: 0-103).

Furthermore, mild hypercalcemia was recorded (10.8 and 10.4 nmol/dL; reference range: 8.4-10.2), accompanied by low-normal PTH. Other endocrine markers, including plasma and urine metanephrines as well as aldosterone, renin, and androgen levels, were within the reference ranges. Random cortisol levels were mildly elevated at 19.8 µg/dL (reference range: 2.9-17.3), and a low-dose dexamethasone suppression test yielded normal results. Additional details regarding the patient’s pre-operative hormonal profile can be found in Table 1.

Genomic analysis identified a pathogenic variant in the CDKN2A gene, a finding associated with tumorigenesis and endocrine malignancies. A comprehensive summary of pre-operative genetic findings is presented in Table 2. Based on the integration of clinical, biochemical, and genomic data, the differential diagnosis included ACC with possible underlying familial endocrine syndromes.

Other considerations included malignant pheochromocytoma, adrenal metastasis, and lymphoma.

The patient underwent imaging and diagnostic evaluations, revealing a large, heterogeneous mass measuring 12.3 × 9.9 × 7.8 cm in Morrison’s pouch on ultrasound. The mass was inseparable from the superior pole of the right kidney and the liver. A subsequent abdominal CT scan showed a 10 cm calcified lesion originating from the right adrenal gland, which was adherent to the liver, inferior vena cava (IVC), and diaphragm, along with bulky retroperitoneal lymphadenopathy. Additionally, there was an 8 cm conglomerate of lymph nodes encasing both right renal arteries and the left renal vein (Figure 2A-B).

MRI confirmed that the lesion originated from the adrenal gland and did not definitively exclude liver invasion. The retroperitoneal lymphadenopathy was noted, with nodes measuring up to 3 cm located in the retrocaval region behind the IVC and between the IVC and aorta. A whole-body 18-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)/CT scan revealed intense focal uptake of FDG, with a maximum standardized uptake value (SUVmax) exceeding 25, which strongly suggested malignancy. Notably, the PET/CT scan also ruled out distant metastases. Collectively, these imaging findings indicated a malignant process originating from the adrenal gland, with significant retroperitoneal involvement but no evidence of distant disease, thereby informing multidisciplinary treatment planning (Figure 2C-D).

A preoperative biopsy of the adrenal mass was not conducted due to concerns about procedural risks and diagnostic limitations. Adrenal biopsies frequently cannot reliably differentiate between benign and malignant lesions and carry significant risks, particularly in cases of pheochromocytoma, where complications may arise, or in ACC, which poses a risk of neoplastic seeding. The differential diagnosis included pheochromocytoma, lymphoma, and ACC, alongside complex retroperitoneal anatomy and bulky lymphadenopathy encasing vital structures, complicating a safe biopsy approach. Given that a definitive diagnosis could not be established before surgery, the Endocrine Tumor Board recommended performing an intraoperative frozen section of the lymph nodes to rule out lymphoma or other conditions that might not necessitate resection.

The proposed surgical plan included open resection of the right adrenal mass, right nephrectomy, potential vena caval reconstruction, and, if necessary, left kidney resection with autotransplantation. The goal was to achieve complete resection of all gross disease, including liver resection and lymph node excision, contingent on intraoperative findings. At surgery (Figure 3), the large right adrenal mass was found to be densely adherent to the liver and matted lymph nodes were identified in the retrocaval, paraaortic, and pararenal areas, the latter encasing both right renal arteries.

Retroperitoneal lymph nodes were biopsied and sent for intraoperative frozen section analysis the results of which indicated a diagnosis of neuroblastoma. Based on this finding, and after consultation with pediatric oncology and pediatric surgery, an adrenal biopsy was performed for comparison with the nodal pathology, and the initial plan for surgical resection was aborted to pursue the optimal treatment for neuroblastoma of neoadjuvant chemotherapy. Systemic therapy would be further managed by pediatric oncology.

During intraoperative frozen section analysis, the presence of Homer-Wright rosettes, a classical histopathological hallmark, provided a strong indication of neuroblastoma. These rosettes are characterized by clusters of poorly differentiated neuroblasts arranged around a central neuropil, reflecting the tumor’s neuroectodermal origin. While other small round blue cell tumors such as Ewing sarcoma, rhabdomyosarcoma, or lymphoma could be considered in the differential diagnosis, the identification of these rosettes, along with immunohistochemical markers (e.g., CD56, synaptophysin, and chromogranin A), narrowed the diagnosis to neuroblastoma (Figure 4).

Final pathology confirmed the diagnosis of poorly differentiated, high-risk neuroblastoma in both lymph nodes while the biopsy of the adrenal gland showed significant differentiation (less than 50%) and suggested the possibility of underlying nodular ganglioneuroblastoma. The tumor exhibited an intermediate mitotic-karyorrhectic index (2%-4%). Classified as unfavourable under the International Neuroblastoma Pathology Classification (age >5 years). This intraoperative decision exemplified the critical role of real-time pathology in guiding surgical and therapeutic strategies, ensuring the patient’s safety while enabling appropriate oncological management.

Postoperative evaluation included repeat PET and MIBG scans, which demonstrated no evidence of distant or bony metastases. Bilateral bone marrow aspiration and biopsies were also negative for malignant involvement. These findings confirmed that the disease was localized, albeit high-risk due to the tumor’s size and poorly differentiated histology.

Following multidisciplinary discussions with the Pediatric Endocrine Tumor Board, a decision was made to pursue stem cell harvest followed by neoadjuvant chemotherapy. The selected regimen included five cycles of doxorubicin, cyclophosphamide, etoposide, and anthracycline. This approach aimed to achieve significant tumor shrinkage, reduce vascular and lymphatic encasement, and enhance the feasibility and safety of a subsequent complete surgical resection without need for nephrectomy or resection of other surrounding structures.

This treatment strategy underscores the importance of a tailored, multidisciplinary approach in managing rare, high-risk malignancies such as adult-onset neuroblastoma, integrating pediatric oncology expertise to optimize therapeutic outcomes.

The patient showed a strong clinical response after a multidisciplinary approach involving neoadjuvant chemotherapy, right adrenalectomy, and postoperative care. Initially, the patient had a large, high-risk neuroblastoma affecting the adrenal gland and regional lymph nodes. Imaging after chemotherapy showed a 75% decrease in tumor size, with complete resolution of retroperitoneal lymphadenopathy and vascular encasement, highlighting treatment efficacy. At surgery, complete resection of the residual tumor was achieved, crucial for improving outcomes in high-risk neuroblastoma. Final pathology confirmed adrenal neuroblastoma (6 x 3.8 x 5.5 cm) with a 75% treatment effect and 20% maturation. No regional nodes or distant metastases were identified. The positive response to therapy and absence of distant metastases on scans suggest an improved prognosis. Nonetheless, the poorly differentiated histology and high-risk classification still significantly affect long-term survival (Figure 6).

Results

The database searches produced 1,213 results, of which 921 were unique citations. After screening, 127 citations that reported one or more cases of adrenal neuroblastoma in adult patients were included (Figure 1).

This table summarizes key demographic, clinical, diagnostic, and pathological characteristics of adult adrenal neuroblastoma cases from the literature (Table 2). It includes patient age, sex, tumor size, laterality, imaging modalities (e.g., CT, MRI, PET), secreted hormones, abnormal laboratory findings, and preoperative biopsy status. Diagnosis methods, differential diagnoses, tumor composition, neoadjuvant chemotherapy, pathology, immunohistochemical markers (e.g., CD56, synaptophysin), adjuvant therapies, long-term follow-up outcomes, and additional observations are also detailed. This comprehensive overview underscores the importance of a multidisciplinary approach to managing this rare malignancy.

Adrenal neuroblastoma in adults is an exceptionally rare malignancy, diverging significantly in presentation, prognosis, and treatment from its pediatric counterpart. This systematic review synthesizes data from reported cases to delineate key trends and knowledge, providing a foundation for future diagnostic and therapeutic strategies.

Figure 1: PRISMA flow diagram. Illustrating the systematic review process for adult adrenal neuroblastoma studies. A total of 1,213 records were identified through database searches, including PubMed (n = 506), EMBASE (n = 679), Cochrane CENTRAL (n = 11), and ClinicalTrials.gov (n = 17). After the removal of 292 duplicates, 921 studies were screened for relevance. Of these, 49 studies were excluded due to wrong diagnosis (n = 4), wrong study design (n = 7), or inclusion of pediatric populations (n = 38). Following the eligibility assessment of 177 studies, 128 were included in the final review, providing a comprehensive analysis of adult-onset adrenal neuroblastoma.

Figure 2: Multimodal Imaging of Adrenal Lesion. (A) Ultrasound: 12.3 x 9.9 x 7.8 cm heterogeneous mass in Morrison’s pouch, inseparable from the right kidney and liver. (B) CT: 10 cm calcified adrenal mass adherent to the liver, IVC, diaphragm, with bulky retroperitoneal lymphadenopathy. (C) MRI: Hyperintense adrenal mass on T2-weighted imaging with regional lymphadenopathy. (D) FDG PET: Partially necrotic, FDG-avid adrenal mass with retroperitoneal lymph node involvement; no distant disease. This imaging highlights tumor size, spread, and metabolic activity for clinical management.

Figure 3: : Intraoperative View. Right adrenal mass in the retroperitoneum, adherent to the liver, IVC, and diaphragm, with paracaval nodes encasing right renal vessels. Highlights complex anatomy and need for meticulous surgical planning in high-risk adrenal neuroblastoma resection.

Figure 4: Histopathological and Immunohistochemical Findings. (A) H&E staining shows poorly differentiated neuroblasts with scant cytoplasm and high nuclear-to-cytoplasmic ratio. (B) CD56 staining demonstrates strong membranous positivity, confirming neuroendocrine origin. (C) Chromogranin A shows robust cytoplasmic expression, supporting neuroendocrine lineage. (D) NSE staining reveals diffuse cytoplasmic positivity, confirming neuroendocrine differentiation. (E) Synaptophysin staining highlights sympathetic ganglia-derived neuroblasts with diffuse positivity. These findings confirm high-risk neuroblastoma with neuroendocrine differentiation.

Figure 5: P Post-Chemotherapy CT Imaging. Contrast-enhanced CT shows the right adrenal mass reduced to 6 x 3.8 x 5.5 cm. Retroperitoneal lymphadenopathy and vascular encasement have resolved, demonstrating a favourable response to neoadjuvant chemotherapy and improved surgical feasibility.

Figure 6: Gross Specimen of Resected Adrenal Mass. Post-resection specimen measuring 6 x 3.8 x 5.5 cm after neoadjuvant chemotherapy. The irregular, encapsulated mass shows necrosis and hemorrhage, reflecting significant tumor reduction and the efficacy of preoperative treatment. Surgical ruler included for scale.

Table 1: Laboratory test results of our patient with adrenal neuroblastoma. This table summarizes the biochemical and hormonal profile of our patient on admission. Key findings include elevated chromogranin A (170 ng/mL), plasma normetanephrines (1.55 nmol/L), and urine normetanephrines (674 µg/day), indicative of catecholamine hypersecretion and neuroendocrine tumor activity. Mild hypercortisolism (19.8 µg/dL) and hypercalcemia (10.8 mg/dL) suggest paraneoplastic or tumor-related effects. All results are compared against clinical reference ranges, highlighting abnormalities highlighting the index of suspicion for diagnosing this rare malignancy in adults.

Table 2: Clinical, diagnostic, and treatment characteristics of adult-onset adrenal neuroblastoma cases. This table summarizes data from reported cases, including demographic details (age, sex), tumor characteristics (size, laterality), diagnostic approaches (imaging modalities, biopsy), and therapeutic interventions (neoadjuvant/adjuvant chemotherapy, radiotherapy, surgery). Outcomes, including recurrence rates, disease-free survival, and overall survival, are provided to highlight the impact of multidisciplinary approaches on prognosis. NR = Not reported, *Age range estimate, limited data.

Patient Demographics

The patient demographics reveal an age range from late adolescence to over 60 years. The mean patient age was 41.6 years. This wide variability suggests that adrenal neuroblastoma lacks a consistent age-related presentation in adults. Male patients constituted a slight majority (~60%), which may indicate sex-specific tumor biology. This skewed distribution raises questions about the hormonal or genetic underpinnings that could influence adult tumorigenesis.

Tumor Size and Laterality

Tumor size at diagnosis was typically large, with dimensions ranging from 6.5 cm to 34 cm, suggesting prolonged asymptomatic growth. The average tumor size across cases was 9.95 cm, with sizes ranging from 4.5 cm to 34 cm. Tumors >10 cm were reported in 56% of cases, indicating a tendency for large tumors at presentation. Examples include Nzegwu (2009) [90] reported a massive 34 cm tumor in a 35-year-old male, one of the largest tumors in the dataset. Sousa (2016) [114], in contrast, described a relatively smaller 2 cm tumor, likely identified earlier due to advanced imaging techniques.

Tumor laterality was evenly distributed between the left and right adrenal glands. Right-sided tumors comprised 31.7% of cases, often larger (mean size 10.4 cm) and associated with more vascular encasement. Left-sided tumors accounted for 32.5% and were diagnosed slightly earlier, with less extensive lymphadenopathy, but had similar outcomes to right-sided tumors. This balance indicates no significant anatomical predisposition. Surgical complexity was higher for right-sided tumors due to their proximity to the IVC, as noted in studies by Cho (2018) [30] and Taylor (1977) [121].

Imaging Modalities

Imaging is crucial for diagnosing and characterizing adrenal neuroblastoma. Ultrasound is used in 21% of cases, primarily for initial evaluations or intraoperative localization. CT scans are the primary imaging modality in 96% of cases, helping to identify tumor size, location, and regional involvement. Tumors found via ultrasound average 9.8 cm in size. Modern imaging methods, including MRI (58%) and PET/CT (36%), offer clear visuals of tumor morphology and metabolic activity. For example, Cetin (2023) [23] used PET/CT to show intense FDG uptake SUVmax malignancy and ruling out metastases. Liu (2022) [77] employed contrast-enhanced CT and MRI to define tumor boundaries and evaluate retroperitoneal involvement.

In earlier studies, older imaging modalities were used: Krikke (1989) [71] described the use of intravenous urography (IVU) and aortography, which provided less precise anatomical detail but helped identify vascular encasement. Advancements in imaging, especially MRI have improved diagnostic accuracy and facilitatedbetter preoperative planning by identifying vascular and lymphatic involvement.

Preoperative Biopsy

The majority, 78% of cases, did not include a preoperative biopsy. Biopsy was rarely performed due to concerns about tumor seeding, hemorrhage, or inadequate sampling, particularly in large, vascularized tumors. Preoperative biopsy was reserved for diagnostically ambiguous cases, such as those reported by Liu (2022) [77]. Manoharan (2018) [81] explicitly avoided preoperative biopsy due to concerns about misdiagnosis and potential complications. Cetin (2023) [25] deferred biopsy due to the tumor’s proximity to critical retroperitoneal structures and the low diagnostic yield in differentiating benign from malignant lesions. This trend highlights the reliance on imaging and biochemical markers over invasive diagnostic techniques for adrenal masses.

Laboratory and Biochemical Findings

Hormonal and biochemical analyses varied. Elevated catecholamine levels (urine/plasma) were found in 71% of cases, confirming the neuroendocrine nature of these tumors. Matsuno (2020) [85] noted significantly high urinary vanillylmandelic acid (VMA), indicating active hormone secretion. Chromogranin A (CgA) was elevated in 63% of cases and is a reliable neuroendocrine marker. Shida (2015) [111] reported a 53-year-old man with adrenal neuroblastoma and serum norepinephrine levels over 3,801 pg/mL (normal: <450 pg/mL), correlating with high tumor burden. Elevated lactate dehydrogenase (LDH) levels were seen in 58% of cases, often indicating tumor aggressiveness. These results highlight the need for standardized biochemical testing in suspected adrenal neuroblastomas to improve diagnostic consistency.

Histological Findings

Poorly differentiated neuroblastoma was found in 68% of cases and is linked to a high mitotic-karyorrhectic index (MKI), poor prognosis, and aggressive behaviour. Heideri (2018) [57] reported a case in a 38-year-old male with diffuse CD56 and synaptophysin expression, typical of aggressive tumors. Ganglioneuroblastoma occurred in 22% of cases, often featuring Schwannian stroma and ganglionic differentiation, which suggest better outcomes. Ganglioneuroblastoma occurred in 22% of cases, often featuring Schwannian stroma and ganglionic differentiation, which suggest better outcomes. Undifferentiated neuroblastoma is rare, seen in only 7% of cases, characterized by a lack of neuroblastic differentiation and a poor prognosis. Masaoutis (2019) [83] documented a 71-year-old male with an undifferentiated tumor lacking neuropil formation, leading to rapid disease progression despite treatment.

Immunohistochemical Staining

CD56 was positive in 93% of cases, serving as a hallmark marker for neuroblastomas. Synaptophysin and Chromogranin A: Expressed in 89% and 78% of cases, respectively, confirming neuroendocrine differentiation. Lee (2016) highlighted strong chromogranin A positivity in a 42-year-old male, aiding in the differential diagnosis of pheochromocytoma. Ki-67 Proliferation Index: High (>30%) in 62% of cases, correlating with poor outcomes.

Surgical Intervention

Complete resection (R0) was achieved in 72% of cases, resulting in better outcomes. Patients with complete resection had a 5-year survival rate of 41.2%, compared to 18.7% for those with residual disease (R1/R2). Fujiwara (2000) [46] reported a 25-year-old female with a 9 cm adrenal tumor who had R0 resection, leading to a 5-year disease-free survival. Only 16% of cases involved partial or incomplete resection (R1/R2), primarily due to vascular encasement, lymph node involvement, or proximity to vital organs, which are linked to higher recurrence rates and lower overall survival. Custodio (1999) [33] documented incomplete resection in a 32-year-old female with extensive IVC encasement, resulting in recurrence within 3 months despite adjuvant chemotherapy.

Neoadjuvant Chemotherapy

High-risk neuroblastoma often requires pre-surgery chemotherapy to shrink tumors, which helps reduce complications and improve outcomes. This treatment is used in 37% of cases, mainly for tumors with high-risk features such as large size, vascular encasement, or regional lymphadenopathy. Neoadjuvant therapy resulted in tumor size reduction in 89% of cases, with an average decrease of 55% to 75%. Platinum-based regimens were utilized in 68% of the chemotherapy cases, commonly including combos like cisplatin/etoposide or carboplatin/doxorubicin. Chemotherapy is critical for cases with incomplete resection or minimal residual disease (MRD), resolving lymph node involvement or vascular encasement in 58% of cases.

Radiotherapy, though less frequently cited, is important for the high risk of local recurrence, especially in cases with large tumors or extensive retroperitoneal involvement. It is generally used when there is residual disease or close surgical margins.

The lack of long-term data in adults limits our understanding of optimal treatment. While chemotherapy dominates, radiotherapy and new approaches like immunotherapy may have supportive roles in high-risk cases. The variation in reported practices emphasizes the need for standardized protocols for adults. Future research should integrate new treatments and enhance access to advanced therapies while establishing long-term survival data for better evidence-based strategies.

Adjuvant Therapy

Adjuvant chemotherapy was given in 61% of cases, mainly for highrisk tumors or residual disease after surgery, with platinumbased regimens like cisplatin/etoposide and carboplatin/ doxorubicin being the most common. Sharma (2015) [110] described a 50-yearold male who underwent postoperative chemotherapy following an R0 resection and showed no recurrence after 4 years. Adjuvant radiotherapy was used in 18% of cases, particularly for incomplete resections or close margins, targeting the tumor bed and regional lymph nodes to prevent local recurrence. Jrebi (2014) [62] reported a 22-year-old female with residual disease who received adjuvant radiotherapy and had a stable disease-free interval of 7 years. Immunotherapy, including anti-GD2 monoclonal antibodies, was applied in 9% of cases, primarily in research settings, often combined with chemotherapy to enhance the immune response against residual tumor cells.

Outcomes

Long-term follow-up data show key trends in neuroblastoma treatment. Patients receiving adjuvant chemotherapy and radiotherapy had a 25% lower recurrence risk compared to those who had surgery alone. Adjuvant therapy improved 5-year survival rates for high-risk patients from 28.5% with surgery alone to 42.8% with added therapy. Compared to poorly differentiated neuroblastomas, better outcomes were observed with complete resection and favourable histology, such as ganglioneuroblastoma. Effective multimodal therapy, which includes complete surgicalresection, led to improved survival. Studies by Sharma (2015) [110] and Jrebi (2014) [62] highlight the positive impact of adjuvant therapies on overall outcomes and disease-free intervals.Overall, complete resections are linked to better survival, whileincomplete resections and poor histology lead to worse prognoses and a need for more aggressive treatments.

Discussion

The decision to forgo a preoperative biopsy was based on several factors: adrenal biopsies often fail to differentiate benign from malignant lesions, there was a significant risk of complications from a potential pheochromocytoma, the patient’s history of adrenal hemorrhage posed a recurrence risk, tumor seeding in ACC was a concern, and the complex retroperitoneal anatomy made the biopsy unsafe. Although an endoscopic ultrasound (EUS) guided biopsy was an option, its risks made it unnecessary.

Intraoperative frozen section pathology confirmed a diagnosis of neuroblastoma, leading to a treatment shift from immediate surgical resection to neoadjuvant chemotherapy. This approach reduced surgical risks and preserved renal function, a highly important consideration given the nephrotoxicity of the chemotherapeutic agents. The collaboration among the Endocrine Surgery, Endocrine Tumor Board and Pediatric Surgery and Oncology teams highlighted the importance of a multidisciplinary approach in managing complex malignancies.

Neuroblastomas originate from neural crest cells that form primitive sympathetic ganglia during fetal development and are predominantly pediatric malignancies, with a median age of diagnosis of 17.3 months. The exceedingly rare presentation of adult-onset neuroblastoma, as demonstrated in this case, highlights the need to consider this diagnosis in atypical clinical scenarios. This case underscores the critical importance of a multidisciplinary approach to rare malignancies, integrating expertise from multiple specialties to achieve precision in diagnosis and optimize therapeutic outcomes.

We recommend a multimodal case management strategy based on our systematic review and current guidelines [14]. Key components include achieving complete surgical resection with negative margins to improve outcomes, and effectively using neoadjuvant and adjuvant therapies, such as chemotherapy and immunotherapy, for high-risk cases. Advanced imaging techniques like CT, MRI, and PET are essential for early identification and monitoring, enhancing long-term survival. Other modalities, such as local radiation therapy, autologous stem cell transplant, and the use of agents with confirmed activity, may improve the poor prognosis for adolescents and adults [12]. Standardized reporting practices for long-term follow-up data will improve our understanding of outcomes. Future research should focus on high-risk subgroups, particularly poorly differentiated neuroblastomas, and explore the broader use of novel therapies, including targeted therapies and immunotherapy, in adult populations to reduce the survival gap with pediatric neuroblastoma.

Conclusion

This case underscores the clinical complexity of diagnosing rare adrenal malignancies in young adults and highlights the necessity of a multidisciplinary approach, leveraging biochemical, genetic, and imaging studies to refine the differential diagnosis and guide therapeutic decision-making.

The systematic review highlights the rarity, diagnostic complexity, and high-risk nature of adult adrenal neuroblastoma. Key takeaways include the pivotal role of imaging, the diagnostic value of immunohistochemistry, and the necessity of neoadjuvant chemotherapy in high-risk cases. The limited availability of long-term follow-up data underscores the need for standardized reporting and management protocols. By consolidating these insights, this review aims to inform clinical practice and stimulate further research into the optimization of outcomes for adult-onset adrenal neuroblastoma.

Statements and Declarations: Not applicable

Acknowledgments: The authors would like to acknowledge Norton Children’s Hospital Oncology, Surgery, and Pathology department for their collaboration on the management of this case.

Author’s contribution:

- D A. Malik: protocol/project development, literature review, data collection, data analysis, manuscript writing, manuscript proofreading

- P. Hill: literature review, data collection, manuscript proofreading

- G. Genova: literature review, manuscript writing, manuscript proofreading

- R. Kulkarni: data collection, manuscript proofreading

- D D. Mais: data collection, data analysis, manuscript proofreading

- M. Javid: protocol/project development, literature review, data collection, data analysis, manuscript writing, manuscript proofreading

Compliance with Ethical Standards

Funding: None.

Conflicts of Interest: The authors of this manuscript declare no conflict of interest.

Consent: Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editorin-chief of this journal.

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