Introduction
Ganglioneuroma is a rare benign tumor of neural crest origin that develops along the sympathetic ganglion chains and belongs to the spectrum of neurogenic tumors, which also includes ganglioneuroblastoma and neuroblastoma.
With the widespread use of cross-sectional imaging, the incidental detection of adrenal masses has markedly increased. Among these adrenal incidentalomas, ganglioneuroma represents an uncommon and often unsuspected entity. Its diagnosis is particularly challenging because the tumor is typically hormonally silent and lacks specific radiological characteristics. Imaging findings are frequently non-specific and may overlap with those of malignant adrenal tumors, often necessitating histopathological confirmation for definitive diagnosis.
This diagnostic challenge becomes even more complex in patients with known malignancy, in whom an adrenal mass is more readily interpreted as a malignant lesion. We report the case of a patient with multiple myeloma in whom an adrenal mass discovered during staging imaging was ultimately diagnosed as an adrenal ganglioneuroma.
Case report
A 60-year-old man with a recent diagnosis of multiple myeloma was referred for imaging as part of the initial staging work-up. The patient was asymptomatic. Contrast-enhanced computed tomography (CT) performed for staging incidentally revealed a large left adrenal mass, in addition to a lytic bone lesion consistent with the known myeloma ( Fig. 1 , Fig. 2 ).
CT demonstrated a well-circumscribed heterogeneous left adrenal mass measuring 109 × 75 × 95 mm in the anteroposterior, transverse, and craniocaudal planes, respectively. The lesion showed an unenhanced attenuation of 43 HU, increasing to 58 HU on the portal venous phase, without significant washout on delayed imaging (absolute and relative washout: 0%). Areas of low attenuation were also noted within the lesion, without visible calcifications. No signs of local invasion of adjacent structures, vascular encasement, or regional lymphadenopathy were observed ( Fig. 1 ).
To further characterize the lesion, magnetic resonance imaging (MRI) of the adrenal gland was performed. Owing to deterioration of renal function between the CT and MRI examinations, the MRI study was conducted without contrast administration. The mass showed low signal intensity on T1-weighted images relative to the liver, with focal hyperintense areas suggestive of intralesional hemorrhage. Chemical-shift imaging demonstrated no significant signal loss on opposed-phase images compared with in-phase images, indicating the absence of substantial intracellular lipid content. On T2-weighted sequences, the lesion demonstrated heterogeneous high signal intensity. Diffusion-weighted imaging showed focal areas of high signal intensity with corresponding low signal intensity on the ADC map. These findings suggested restricted diffusion but remained non-specific and did not allow reliable differentiation between benign and malignant adrenal lesions ( Fig. 3 ).
Prior to biopsy, a complete hormonal evaluation was performed to exclude a functioning adrenal tumor. Plasma and urinary catecholamines and metanephrines were within normal limits, thereby excluding the possibility of pheochromocytoma.
Given the indeterminate imaging findings and the patient's known malignancy, histological confirmation was considered necessary to distinguish between metastasis, plasmacytoma, and a primary adrenal tumor. Following biochemical exclusion of pheochromocytoma, CT-guided percutaneous biopsy was therefore considered appropriate and was performed without complication.
Histopathological examination confirmed the lesion as an adrenal ganglioneuroma. Histological sections showed a benign tumor proliferation composed of mature ganglion cells with round nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm, embedded within a rich Schwannian stroma, findings consistent with ganglioneuroma ( Fig. 4 ).
Following histological confirmation of adrenal ganglioneuroma, a conservative management strategy with imaging surveillance was adopted. Follow-up CT performed one year later demonstrated no appreciable interval change in lesion size, morphology, or attenuation characteristics compared with the initial examination, supporting the decision for conservative management. The patient remained clinically stable.
Discussion
Ganglioneuroma is a rare benign tumor that develops along the sympathetic chains, explaining its preferential locations in the cervical region, posterior mediastinum, retroperitoneum, and pelvis. The retroperitoneum is the most frequent site, accounting for 32%-52% of cases, with approximately half of these tumors arising from the adrenal gland and the remainder being extra-adrenal. Adrenal ganglioneuromas are particularly uncommon and represent only 0.2%-1.6% of all adrenal tumors in population-based studies [ 1 ]. Ganglioneuromas may arise de novo or from the maturation of ganglioneuroblastoma or neuroblastoma, whereas malignant transformation in adults is exceptionally rare [ 2 , 3 ].
The mode of presentation is frequently incidental, as adrenal ganglioneuromas are usually hormonally silent and may remain asymptomatic even when they reach a large size [ 4 , 5 ], as illustrated in our patient.
From a radiological perspective, adrenal ganglioneuroma lacks specific imaging features and may closely resemble other adrenal neoplasms, creating significant diagnostic uncertainty, particularly in patients with known malignancy. On computed tomography, these tumors are typically well circumscribed and show soft-tissue attenuation, sometimes with low-density areas that may be related to myxoid stroma, cystic degeneration, or necrosis. Calcifications are present in a substantial proportion of cases. After contrast administration, enhancement is often heterogeneous and progressive, which may be associated with the tumor's stromal composition [ 6 , 7 ].
Magnetic resonance imaging findings are likewise nonspecific. Ganglioneuromas typically demonstrate low signal intensity on T1-weighted images and heterogeneous high signal intensity on T2-weighted sequences. Areas of hemorrhage, cystic change, or myxoid matrix may contribute to this heterogeneity. Diffusion-weighted imaging may show variable degrees of restriction, further complicating differentiation from malignant adrenal tumors [ 6 , 8 ].
In patients with multiple myeloma, adrenal masses raise a distinct diagnostic consideration: extramedullary plasmacytoma. Although extremely rare, plasmacytomas may present as adrenal incidentalomas in this context, and their imaging appearance can be indistinguishable from other adrenal lesions, including ganglioneuroma and metastasis [ 9 , 10 ]. Several case reports have documented adrenal plasmacytomas in patients with plasma cell disorders, underscoring the need to include this entity in the differential diagnosis when evaluating adrenal masses in oncological patients [ 9 , 10 ].
In addition to plasmacytoma, the imaging differential diagnosis included adrenal adenoma, pheochromocytoma, adrenocortical carcinoma, and metastasis. In our patient, an adenoma was considered unlikely because of the relatively high unenhanced attenuation (43 HU) and the absence of contrast washout, findings that are atypical for lipid-rich adrenal adenomas [ 11 ]. Pheochromocytoma was also considered; however, normal plasma and urinary catecholamine and metanephrine levels argued against this diagnosis despite some overlapping imaging features [ 12 ]. Adrenocortical carcinoma was included in the differential diagnosis because of the large size of the lesion, but the absence of local invasion, vascular encasement, regional lymphadenopathy, or distant metastatic spread made this diagnosis less likely [ 13 ]. Adrenal metastasis remained an important consideration given the patient's underlying malignancy, although the well-circumscribed appearance and subsequent radiological stability were less suggestive of metastatic disease [ 14 ].
In the present case, despite the patient’s oncologic background, several imaging features favored a benign lesion. The mass was well circumscribed and showed no evidence of local invasion, vascular encasement, regional lymphadenopathy, or distant metastatic disease despite its large size [ 15 , 16 ]. Nevertheless, these findings were insufficient to confidently exclude malignant entities, particularly in the context of multiple myeloma, and histological confirmation remained necessary.
As reported in the literature, preoperative diagnosis of adrenal ganglioneuroma remains particularly challenging because of its non-specific imaging characteristics and its potential to mimic malignant adrenal tumors. Consequently, most published cases are diagnosed only after surgical excision performed for suspected malignancy [ 17 ].
However, current recommendations for the management of adrenal incidentalomas state that adrenal biopsy should not be performed routinely and should be reserved for specific situations [ 18 ]. According to these guidelines, adrenal biopsy may be considered in patients with a known extra-adrenal malignancy when the adrenal lesion is hormonally inactive, indeterminate on imaging, and when histological confirmation would directly influence patient management [ 18 ].
This was precisely the situation in our patient, who had a recent diagnosis of multiple myeloma and presented with an atypical adrenal mass that raised suspicion for metastasis or plasmacytoma. In this context, CT-guided percutaneous biopsy was fully justified and allowed a definitive diagnosis to be established, thereby avoiding unnecessary adrenal surgery.
Histologically, adrenal ganglioneuroma is characterized by abundant Schwannian stroma composed of spindle cells without cytological atypia, within which mature ganglion cells are scattered. These histopathological findings support the benign nature of the tumor and help distinguish it from other neurogenic tumors of the sympathetic chain [ 6 ].
Surgical excision is considered the treatment of choice when the diagnosis is uncertain, when the lesion is symptomatic, hormonally active, or radiologically suspicious for malignancy. However, when a definitive diagnosis is established by biopsy and the lesion is asymptomatic, conservative management with imaging follow-up may be an appropriate alternative, particularly in patients with significant comorbidities [ 7 , 19 ].
Given the benign behavior and extremely low risk of malignant transformation, the long-term prognosis is excellent. Follow-up is mainly radiological and aims to monitor the stability of the lesion over time [ 20 ].
Conclusion
Adrenal ganglioneuroma is a rare benign tumor that can present as an incidental adrenal mass with nonspecific imaging features, often mimicking malignant lesions. This diagnostic challenge is particularly pronounced in patients with known malignancy, in whom adrenal involvement is more readily attributed to metastatic or plasmacytic disease. Recognition of this entity and an appropriate diagnostic approach are essential to avoid overtreatment and to ensure optimal patient management.
Ethics approval
Our institution does not require ethical approval for reporting individual cases or case series.
Author contributions
O. Taibi: Conceptualization, data curation, imaging analysis, writing – original draft, and final approval of the manuscript. Agrees to be accountable for all aspects of work ensuring integrity and accuracy. Z. Iraqi Houssaini: Imaging analysis, data interpretation, writing – review and editing. Agrees to be accountable for all aspects of work ensuring integrity and accuracy. R. Bouanane: Data collection, imaging interpretation, writing – review and editing. Agrees to be accountable for all aspects of work ensuring integrity and accuracy. S. Mesmoudi: Histopathological analysis, data interpretation. Agrees to be accountable for all aspects of work ensuring integrity and accuracy. M. Boubekri: Histopathological analysis and critical revision of the manuscript. Agrees to be accountable for all aspects of work ensuring integrity and accuracy. K. Znati: Supervision of histopathological findings and critical revision of the manuscript. Agrees to be accountable for all aspects of work ensuring integrity and accuracy. O. El Aoufir: Clinical data collection and manuscript review. Agrees to be accountable for all aspects of work ensuring integrity and accuracy. Z. Labbi: Clinical data interpretation and manuscript review. Agrees to be accountable for all aspects of work ensuring integrity and accuracy. L. Jround: Literature review and manuscript editing. Agrees to be accountable for all aspects of work ensuring integrity and accuracy. O. Messaoud: Supervision, project administration, and final validation of the manuscript. Agrees to be accountable for all aspects of work ensuring integrity and accuracy.
Patient consent
A written informed consent was obtained from the patient for the publication of this case report.
Footnotes
Acknowledgment: I would like to express my gratitude to my professors and all the colleagues who participated in the completion of this work.
Competing Interests: The authors have declared that no competing interests exist.
References
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