Composite paraganglioma-ganglioneuroma in the retroperitoneum
© Hirasaki et al; licensee BioMed Central Ltd. 2009
Received: 23 August 2009
Accepted: 05 November 2009
Published: 05 November 2009
Paragangliomas occur most commonly in head and neck region and much less frequently, they are found in the retroperitoneum. Composite paraganglioma-ganglioneuroma of the retroperitoneum is very rare.
We present an unusual case of retroperitoneal composite paraganglioma-ganglioneuroma discovered on computed tomography in a 63-year-old female patient. Routine hematological examination and biochemical tests were within normal limits. Plasma adrenaline was 0.042 ng/ml, plasma noradrenaline 0.341 ng/ml, and plasma dopamine <0.01 ng/ml. An abdominal contrast-enhanced CT scan and magnetic resonance imaging revealed a 6.5 cm heterogeneous retroperitoneal mass with a cystic component. The retroperitoneal tumor accumulated 131I-Metaiodobenzylguanidine (131I-MIBG) 48 hours after radioisotope injection. Under the diagnosis of paraganglioma in the retroperitoneum, the patient underwent surgery. The resected tumor (6.5 × 5 × 3 cm) was solid and easily removed en bloc. The cut surface of the tumor and histology revealed two different components in the tumor: paraganglioma centrally and ganglioneuroma on the periphery. She remains disease-free 18 months after surgery.
This case reminds us that neuroendocrine tumor should be included in the differential diagnosis of a retroperitoneal mass although composite paraganglioma-ganglioneuroma in the retroperitoneum is very rare.
Pheochromocytomas arising from outside the adrenal glands are called paragangliomas  and constitute a relatively rare disease, arising from undifferentiated cells of the primitive neural crest [2, 3]. Paragangliomas occur most commonly in head and neck region , and much less frequently, they are found in the retroperitoneum . Extraadrenal paragangliomas, which account for 5-10% of these tumors, are found in the retroperitoneum, thorax, and urinary bladder ; composite tumor of the retroperitoneum is rare. To our knowledge, at least 4 cases of composite paraganglioma-ganglioneuroma in the urinary bladder have been reported [5–7]; however, there have been only few reports of retroperitoneal composite paraganglioma-ganglioneuroma. Herein, we report an unusual case of composite paraganglioma-ganglioneuroma in the retroperitoneum successfully treated with surgery.
The paraganglia are widely dispersed collections of specialized neural crest cells that lie adjacent to the sympathetic ganglia and plexuses throughout the body. The paraganglionic system includes the adrenal medulla, the chemoreceptors, vagal body, and small groups of cells associated with the thoracic as well as intraabdominal and retroperitoneal ganglia . Tumors that arise from chromaffin cells of the adrenal medulla are called pheochromocytomas, whereas those that occur in paraganglia at other sites are referred to as paragangliomas . Ganglioneuroma is a benign neoplasm composed of Schwann cells and ganglion cells. The most affected anatomical sites are the posterior mediastinum, retroperitoneum, adrenal gland and head and neck soft tissue . Solitary ganglioneuromas most commonly occur in infants and young children, slightly more often in girls than boys, with a female-to-male ratio of about 3:1 . The majority is diagnosed before the patient is 10 years of age.
Paraganglioma shows marked contrast enhancement on contrast-enhanced CT scan [12, 13]. MRI can be used to help to locate a paraganglioma; however, only about 80% of T2-weighted MRI studies will show the characteristic uniform high-signal-intensity image because the presence of internal hemorrhage may reduce signal intensity . In the present case, diagnostic images obtained by contrast-enhanced CT scan, MRI and 131I-MIBG scintigraphic scan tomography were compatible with paraganglioma. But we could not diagnose this tumor as composite paraganglioma-ganglioneuroma.
Paraganglioma-ganglioneuroma is a rare composite tumor, and at least one case of extra-adrenal retroperitoneal ganglioneuroma-pheochromocytoma has been reported . Usuda et al reviewed 4 patients with paraganglioma-ganglioneuroma in the urinary bladder . All 4 patients were older than 40 years of age (range, 49-81 years), 3 of 4 patients with composite tumor were women, and 2 patients had a symptom of headache. They reported that it was difficult to predict the clinical behavior of composite tumors. These 4 reported cases of composite paraganglioma-ganglioneuromas in the urinary bladder showed no malignant features such as extra-bladder infiltration or metastasis. The natural history of composite paraganglioma-ganglioneuromas remains unclear. Thus, accumulation of long-term follow-up cases may provide valuable prognostic information on this composite tumor. The pathogenesis of composite paraganglioma-ganglioneuroma also remains unknown. Although we could not make a conclusive remark, we thought that the tumor might be a collision tumor because two components (paraganglioma and ganglioneuroma) were separated in the greater part of the tumor and transitional zone was not recognized in the present case.
It is not possible to differentiate benign from malignant paraganglioma confidently with imaging alone. With the exception of the presence of distant metastases, there are no absolute criteria for malignancy in paragangliomas. However, features more frequently noted in malignant tumors are extraadrenal location, greater tumor weight, confluent necrosis, and the presence of vascular invasion and/or extensive local invasion . According to Hayes et al , malignant paragangliomas tend to be large and their four cases had average diameter of 13.8 cm (range, 10.7-17.0). Thus a tumor size of larger than 10 cm may be indicative of malignant behavior. Assessing the proliferative index seems to be important, because all of the analyzed benign tumors showed <1% of MIB-1-positive cells .
In the present case, there were no histological features suggesting malignancy, and MIB-1-positive cells were <1%; however, we should be attentive to recurrence in this case. Sclafani et al found that 11 of 22 (50%) retroperitoneal paragangliomas metastasized to distant organs  and 2 of 11 (18%) patients developed their first metastases more than 7 years after diagnosis; thus, a longer follow-up is needed for this disease.
Retroperitoneal paraganglioma is treated in principle by surgical resection. Composite paraganglioma-ganglioneuroma in the retroperitoneum is very rare. However, as probably most of the retroperitoneal paragangliomas are benign, it is likely that there are patients with latent retroperitoneal paraganglioma, which may be incidentally discovered in the future as a result of advances in diagnostic imaging, such as improved CT and MRI.
Although composite paraganglioma-ganglioneuroma in the retroperitoneum is not common, the possibility of a neuroendocrine tumor should be considered in the differential diagnosis of a retroperitoneal mass. When a large retroperitoneal mass is incidentally found by diagnostic imaging, it should be carefully examined and resection should be considered, especially in patients with tumor size of larger than 10 cm.
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 Editor-in-Chief of this journal.
The authors are deeply grateful to Dr Atsuko Shirakawa, Department of Pathology, Sumitomo Besshi Hospital, for her assistance in the pathological study.
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