Adrenal Primary Ganglioneuroblastoma Presenting in Adulthood: A Case Report

ABSTRACT

Introduction

Ganglioneuroblastoma is a rare neuroblastic tumor derived from embryonic neural crest cells, composed of mature gangliocytes and immature neuroblasts. Although most neuroblastic tumors present in children and commonly involve the adrenal glands, adrenal ganglioneuroblastoma is rare in adults, with only 25 previously reported cases.

Case Presentation

A 20‐year‐old female presented with epigastric pain, and imaging revealed a 13 cm left adrenal mass with calcification and heterogeneous enhancement. Endocrinological tests were normal, except for a mildly elevated urinary metanephrine level. Open adrenalectomy was performed, and histopathological examination confirmed a mixed‐type adrenal ganglioneuroblastoma with low proliferative activity (Ki‐67, < 1%). Adjuvant therapy was not administered. The patient has remained recurrence‐free for 39 months post‐operatively.

Conclusion

We report a rare case of primary adrenal ganglioneuroblastoma in an adult, emphasizing its diagnostic challenges, histopathological characteristics, and favorable post‐operative course.

Keynote Message

Primary adrenal ganglioneuroblastoma is rare in adults. This case highlights the importance of considering neuroblastic tumors in the differential diagnosis of adrenal masses, even beyond childhood. Surgical resection remains the cornerstone of treatment, and long‐term follow‐up is essential to monitor recurrence.

Abbreviations

CT

computed tomography

GNB

ganglioneuroblastoma

INRG

International Neuroblastoma Risk Group

1. Introduction

Ganglioneuroblastoma (GNB) is a cancerous transformation of embryonic neural crest cells and it belongs to the neuroblastic tumor group. Neuroblastic tumors are histopathologically classified into three types: neuroblastoma, GNB, and ganglioneuroma [1, 2]. These three tumors vary in malignancy, with neuroblastoma being the most malignant and the most common extracranial solid tumor in children [3]. In contrast, ganglioneuroma is categorized as a benign tumor, while GNB is positioned as a tumor with an intermediate malignant potential [3]. Neuroblastic tumors can be present anywhere in the sympathetic nervous system, but most are in the adrenal glands [1]. Greater than 90% of neuroblastic tumors are in children less than five‐years‐old [1].

GNB contains mature gangliocytes and immature neuroblasts, and it is divided into two subtypes by presence or absence of visible nodules: nodular‐GNB (stroma‐poor) and intermixed‐GNB (stroma‐rich) [1]. Intermixed‐GNB is classified into a favorable histology group [4]. To our knowledge, there have been only 25 reported cases of GNB in the adrenal glands of adults. The 25 cases are reviewed, with a focus on symptoms, treatment methods, patient age and sex, and the presence of tumor metastases and calcification. We report the case of a 20‐year‐old female with primary adrenal GNB, and a literature review.

2. Case Presentation

A 20‐year‐old female presented at the emergency department with epigastric pain. Computed tomography (CT) of the abdomen revealed a 12 cm tumor in the left adrenal gland, and she was referred to our department. Her medical history included atopic dermatitis. There were no special notes on family or oral medication history. During the visit, dull pain was noted in the left hypochondrium. The blood pressure and heart rate were 138/88 mmHg and 82 beats per minute, and no apparent catecholamine‐related symptoms were observed. Endocrinological tests, including blood tests and 24‐h urine tests, were within the normal ranges, except for a mildly high urine metanephrine level (0.25 mg/day; normal range 0.04–0.2 mg/day). CT revealed a 13 cm mass lesion in the left adrenal gland with calcification and uneven contrast (Figure 1a,b). There were no findings suggestive of invasion of surrounding organs or large blood vessels. There was no abnormal accumulation in the left adrenal gland on ¹²³I‐metaiodobenzylguanidine scintigraphy (Figure 1c). The mass lesion had a partial contrast effect, and the suspected diagnosis of an endocrine‐inactive left adrenal malignant tumor of neurogenic origin led to an open left adrenalectomy. The differential diagnosis included pheochromocytoma, adrenocortical carcinoma, malignant lymphoma, and other mesenchymal tumors.

FIGURE 1.

(a, b). Computed tomography (CT) showing a 13 cm tumor in the left adrenal gland with heterogeneous enhancement and calcification. (a) Non‐contrast‐enhanced CT image, (b) Contrast‐enhanced CT image, and (c) ¹²³I‐metaiodobenzylguanidine scintigraphy with no abnormal accumulation in the left adrenal gland.

A central venous catheter was inserted for perioperative hemodynamic monitoring. The patient underwent an open left adrenalectomy with a chevron incision in order to obtain a clear operative field encompassing the entire tumor and to safely mobilize the pancreas and spleen for secure dissection along the tumor margin. There were no adhesions between the tumor and surrounding tissues. The adrenal tumor was separated from the left kidney along the anatomical plane. The left renal vein and the central adrenal vein were identified. The central adrenal vein was temporarily clamped to confirm the absence of venous congestion, after which it was transected. There were no blood pressure fluctuations associated with surgery. Duration of surgery was 331 min, and blood loss was 1020 mL. The resected sample weighed 910 g, and it was a grayish‐white to pale yellow‐brown, with a well‐defined capsule (Figure 2). The tumor had areas of hemorrhage and necrosis with an internal dark reddish coloration. There were punctate and coarse calcifications within the tumor without visible nodules. Histopathological examination revealed proliferation of tumor cells with eosinophilic cytoplasm and enlarged nuclei, coexisting with ganglion‐like cells characterized by prominent nucleoli (Figure 3a,b). There was normal adrenal tissue at the margin of the tumor, and the tumor was considered to have originated from the adrenal gland. Based on these findings, the histopathological diagnosis was intermixed‐GNB of the adrenal gland. As the Ki‐67 positivity rate was < 1% (Figure 3c), it was considered to have low proliferative potential.

FIGURE 2.

Macroscopic image of resected specimen.

FIGURE 3.

(a, b). Ganglion‐like cells with distinct nucleoli in the tumor (hematoxylin and eosin stain). Blue arrows indicate ganglion‐like cells. (c) Ki‐67 positivity rate is < 1% (Ki‐67 stain).

There were no severe postoperative complications other than mild pain, vomiting, and anemia. The duration of hospital admission was 20 days. Post‐operative adjuvant treatment was not provided. Follow‐up has been performed on an outpatient basis, and there has been no evidence of recurrence 39 months post‐operatively.

3. Discussion

GNB is one of the neuroblastoma group of tumors [1, 2]. Neuroblastoma tumors originate in the neural crest and can present in the sympathetic ganglia and adrenal medulla, and they may also have adrenal medullary hormone activity [5]. They are classified into three categories in descending order of malignancy: neuroblastoma, GNB, and ganglioneuroma [1, 2]. More than 90% of the cases are in children under the age of 5 years and they are rarely diagnosed in adults [1]. The International Neuroblastoma Risk Group (INRG) risk classification, which takes into account the stage, age, and histopathology, is used as a prognostic predictor [6]. In the very low‐risk group, the five‐year disease‐free survival rate is ≥ 85% with surgical resection alone [6]. In the high‐risk group, the five‐year disease‐free survival rate is < 50% even with multidisciplinary treatment including chemotherapy or radiation therapy [6]. In the present case, the tumor was localized with no distant metastases, no infiltration into surrounding organs or the vasculature, and the histopathological diagnosis was intermixed‐GNB. Based on the above, the case was classified into the very low‐risk group according to the INRG risk classification, although the usefulness of the INRG classification in adults remains unclear. Additionally, it was considered that complete resection had been achieved through surgery and the Ki‐67 positivity rate was < 1%. The pediatric guidelines were followed and adjuvant therapy was not administered; instead, there has been regular follow‐up with imaging examinations.

As far as can be determined, including the present case, there have been only 26 reported cases of primary adrenal GNB in adults worldwide [3, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19]. The 26 cases are summarized in Table 1. There were no sex‐based differences; most patients were diagnosed in their 20s, and metastases were observed at the time of diagnosis in 10 patients. In 6 cases, the presence of calcifications within tumors was reported. This finding might improve the diagnostic accuracy of adrenal tumor [20]. Surgical resection was performed in only 18 patients. Radiation therapy and chemotherapy were administered in addition to surgical resection for two patients. Of the 13 patients whose outcomes were described, 10 had no evidence of recurrence, two had tumor recurrence, and one having bone marrow metastases at the time of diagnosis died at 3 months post‐operatively. In the present case, there has been no evidence of recurrence at 39 months post‐operatively. Given the limited number of reported cases, it is difficult to draw definitive conclusions regarding the differences between rare adult‐diagnosed and usual pediatric cases. Nevertheless, the INRG classification may provide a useful reference when determining treatment strategies in adult‐diagnosed patients.

TABLE 1.

Summary of the reported cases of adrenal GNB found in adulthood.

First Author (Year)	Age (years)	Sex	Affected side	Size (cm)	Metastasis	Presence of calcification	Treatment	Survival
Butz (1940)	25	Male	N/A	N/A	Liver; paraaortic nodes	N/A	N/A	N/A
Cameron (1967)	54	Female	Right	N/A	None	N/A	Surgical removal	3.5 years, NED
Takahashi (1988)	21	Male	Left	8.8	Lymph nodes	N/A	Surgical removal combined with CRT	11 months, NED
Koizumi (1992)	47	Female	Right	9	Bone marrow	N/A	None	3 months, DOD
Kishikawa (1992)	29	Male	N/A	11	Bone	N/A	N/A	N/A
Higuchi (1993)	29	Male	N/A	11	Bone marrow	N/A	Surgical removal	10 months, AWD
Hiroshige (1995)	35	Male	Left	9	None	Yes	Surgical removal	2 years, NED
Mehta (1997)	22	Male	Right, Left	8, 9	None	N/A	N/A	N/A
Rousseau (1998)	N/A	Female	Left	N/A	Liver	N/A	Surgical removal combined with CRT	N/A
Fujiwara (2000)	25	Female	Left	9	None	Yes	Surgical removal	N/A
Slapa (2002)	20	Female	Right	18	None	Yes	Surgical removal	N/A
Koike (2003)	50	Male	Right	4.5	None	No	Surgical removal	2.5 years, NED
Gunlusoy (2004)	59	Male	N/A	12	Lymph nodes	N/A	Surgical removal	N/A
Sargazi (2006)	45	Female	Right	N/A	None	N/A	N/A	5 years, AWD
Mizuno (2010)	53	Male	Right	11	Bone	No	Surgical removal	30 months, AWD
Sorrentino (2014)	28	Male	N/A	N/A	Lymph nodes	N/A	Surgical removal	N/A
Bolzacchini (2015)	63	Male	Left	5	None	N/A	Surgical removal	N/A
Qiu (2015)	27	Female	Left	11.4	None	Yes	Surgical removal	5 months, NED
Ding (2015)	27	Female	Left	N/A	None	N/A	Surgical removal	N/A
Ohtaki (2016)	37	Female	N/A	6.5	None	N/A	N/A	N/A
Benedini (2017)	20	Female	Left	11	None	N/A	N/A	21 months, NED
Lonie (2017)	27	Male	Right	13	None	N/A	Surgical removal	N/A
Kumata (2018)	73	Female	Right	8	None	N/A	Surgical removal	3 months, NED
Heidari (2018)	38	Male	Right	N/A	None	N/A	Surgical removal	N/A
Vassalo (2021)	22	Male	Right	4	None	Yes	Surgical removal	N/A
Present case (2025)	20	Female	Left	13	None	Yes	Surgical removal	39 months, NED

Abbreviations: AWD, alive with disease; CRT, chemotherapy and radiotherapy; DOD, dead of disease; GNB, ganglioneuroblastoma; N/A, not available; NED, no evidence of disease.

In conclusion, we encountered a rare case of primary adrenal GNB in an adult.

Disclosure

Editorial assistance: Editorial assistance was provided by Editage (www.editage.jp) for English language editing.

Ethics Statement

The authors have nothing to report.

Consent

We obtained consent from the patient for publication.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.