Case Description

A 40-year-old man was referred to our clinic with a recurrent tumor in the right adrenal area on health examination, since he had undergone retroperitoneal laparoscopic resection of adrenal tumor with a diagnosis of pheochromocytoma by pathology 5 years prior (fig. 1). The patient denied hypertension, hyperglycemia, low back pain or hematuria. There was no family history of tumors. Radionuclide imaging revealed that the expression of somatostatin receptor was increased, indicating the possibilities of neuroendocrine tumor. Multiple nodules and masses were observed in the retroperitoneal right adrenal gland area, around the pancreatic head as well as the inferior vena cava and at the upper pole of the right kidney on magnetic resonance imaging, some of which were fused, and the maximum cross section was approximately 5.1×4.1 cm (fig. 2). The patient subsequently underwent robot-assisted laparoscopic right retroperitoneal tumor resection and nephrectomy (fig. 3). Postoperative pathological results revealed an intermixed variant of ganglioneuroblastoma (fig. 4).

Figure 1. Pathological results of the patient 5 years prior.

Figure 2. Magnetic resonance imaging findings of the patient.

Figure 3. Representative image during the second operation.

Figure 4. Hematoxylin and eosin staining of the postoperative specimen.

Discussion

Ganglioneuroblastoma, a borderline and favorable-risk tumor, combines the biological characteristics of poorly differentiated neuroblasts and well-differentiated gangliocytes.¹ It is a rare tumor which mostly occurs in children aged 2–4 years. The pathological subtypes of ganglioneuroblastoma include ganglioneuroblastoma-maturing, ganglioneuroblastoma-intermixed and ganglioneuroblastoma-nodular. The prognosis of patients with ganglioneuroblastoma depends on the pathological subtype and clinical staging.² In our case, the patient was 40 years old. It must be highlighted that ganglioneuroblastoma is extremely rare in adults. In addition, the pathology of the mass changed with disease progression because pheochromocytoma is completely different from ganglioneuroblastoma. Although it has been reported that pheochromocytoma and ganglioneuroblastoma of the adrenal gland are concurrent in some cases,^3,4 it is intriguing to explore whether pheochromocytoma could be transformed into ganglioneuroblastoma in our case. Pheochromocytoma of the adrenal gland originates from chromaffin cells of the adrenal medulla, and ganglioneuroblastoma is caused by the obstacle of differentiation from partial neuroblasts to ganglion cells.⁵ However, both medullary cells and neuroblasts differentiated from the primitive neural crest. To our knowledge, this is the first study to report this possible transformation. Hence, we speculate that the second emergence of ganglioneuroblastoma is likely due to the tumor microenvironment of pheochromocytoma, which induces the repopulation of residual primordial cells but blocks differentiation and maturation. Moreover, the patient developed a new tumor with rapid growth rate during the routine postoperative followup period. The presence of primary retroperitoneal ganglioneuroblastoma, which is unrelated to previous pheochromocytoma, cannot be ruled out. Subsequent followup is of great importance in the future, and compositional analysis of the 2 surgical specimens and single-cell sequencing analysis are needed to determine the origins of pheochromocytoma and ganglioneuroblastoma, and the possible correlation between these 2 types of tumors. In addition, it is still unknown whether postoperative radiotherapy and chemotherapy should be performed because of the lack of evidence-based medicine for oncologists and patients with regard to the treatment of adult ganglioneuroblastoma. Clinical analysis and tumor biological behavior research on the differences between children and adults with ganglioneuroblastoma are needed in the future as more cases are available.