Laparoscopic Excision of an Adrenal Ganglioneuroma Presented as an Incindentaloma of the Retro Peritoneum.

Adrenal ganglioneuroma (GN) is a benign tumor of retro-peritoneum that is presented as an incidentaloma. GNs most commonly have been diagnosed by imaging examinations notably by CT scan. Differential diagnosis from other malignant adrenal tumors is often difficult. The only examination that confirms diagnosis is only the histopathological one. Surgical excision of a GN has been proposed as the best solution for both diagnostic and therapeutic purposes. This case report is about a 68-year old male patient presenting with a non-typical abdominal pain. The imaging investigation showed an incidentaloma over 4cm at its large axis. The patient underwent laparoscopic excision of the tumor. We present the steps followed during the diagnosis the appropriate treatment and the follow up examinations as a result of this rare finding.

Introduction

Adrenal ganglioneuroma (GN) is a rare, slow-growing, benign, neuroblastic tumor that consists of neural crest cells [12]. They appear as solid, firm masses with a typical white color when observed with the naked eye. Histologically, the tumor is composed of Schwann mesenchymal cells, mature gangliocytes and fibrous tissue [3]. These tumors most commonly arise from sympathetic ganglia and may be situated at any site of the sympathetic chain from the skull base to the pelvis [4]. They are most commonly located in posterior mediastinum (39-43%), retroperitoneum (32-52%) and the adrenal medulla [56]. GNs are non-functioning tumors [1]. They are characterized as incindentalomas (IN) because of the absence of typical symptoms until the tumor gets large enough to cause symptoms due to compression of adjacent structures. The prevalence of an adrenal IN is about 0.2% in younger patients, 3% in populations past the fifth decade of their life, and 7% in those past their seventh decade [1]. GNs comprise about 0-6% of all of adrenal incidentalomas [78]. The mean age of patients that present GN is 38.4 years with a range about 25-52 years and with sex ratio 2:1 male to female [9]. Although GN is a benign non-secreting tumor there have been described in the literature some cases of malignant GNs with hepatic metastases [10] as well as cases with hormonal activity [1]. In some cases GNs may secrete catecholamines and patients present symptoms mimicking pheochromocytoma. As an incidentaloma GN most commonly has been diagnosed by imaging examinations including Ultra sound and CT scan that have been implemented for other clinical reasons. Adrenal inciltandenomas (AIs) were found in 2.5% of patients undergoing chest and abdomen CT [11]. The average mass size of AIs in multiple researches that have been published in literature is about 2,75cm [1213]. In a Chinese retrospective study the initial mean size of GNs in CT scan was about 6.27cm (range, 2.5-14cm) [8]. Differential diagnosis of adrenal tumors based on imaging characteristics is often difficult. Some tumors, many of them malignant like adrenocortical carcinoma (ACC) and pheochromocytoma may be misdiagnosed as GNs [1]. This must be taken seriously into account when deciding the treatment of choise. The diagnosis was actually later confirmed by histopathological examination [2]. Because the initial size of GNs is usually over 4cm and it is difficult to get an exact differential diagnosis with imaging criteria surgical exertion have been proposed as the best solution for both diagnostic and therapeutic reasons [11]. Laparoscopic excision is the procedure of choice. The prognosis after a surgical removal is excellent [114]. In this case report, we present the case of a 68-year old male patient with a GN adrenal tumor. The initial diagnosis of this adrenal incindentaloma was revealed after a CT scan of upper and lower abdomen during investigation of a non typical abdominal pain.

Case report

A 68-year old male patient visited his family doctor complained for atypical upper abdominal pain. After obtaining informed consent from the patient, we began with a typical clinical examination. This examination was based on medical history and any probable symptom and signs that were presented by the patient. No typical clinical finding was observed so the physician proposed further investigation with the ultrasound (US) of the upper abdomen. The US performed revealed a mass in the retroperitoneal space, possibly pertaining to the left adrenal gland. This mass was described with clear boundaries, dotted calcification and mild central tumor vasculature. This aspect made the differential diagnosis more complicated, spanning from adrenal adenoma to pheochromocytoma. The size of the tumor was approximately 5cm as measured by US. For this reason imaging procedure included CT scan for further investigation of this mass. CT scan confirmed the presence of the mass and described a tumor in the left adrenal gland, with mild inhomogeneous solid characteristics and an oval size of approximately 42x38x32mm (Fig.1). The tumor had also low electron levels on the Hounsfiled scale (about 15 ΗU) and the CT showed a small dot calcification over the tumor. The washout percentage of the tumor was measured at a minute and 15 minutes later after intravenous administration of a radiocontrast agent. The washout percentage did not help the differential diagnosis of this adrenal incindentaloma because there observed further intake of the radiocontrast agent in the late CT images of the tumor (about 40-45 ΗU 15 minute later). Retroperitoneal lymph node involvement or other metastases was not detected.

Fig.1

A,B,C: CT scan shows a mass with mild inhomogeneous solid characteristics and an oval size about 42x38x32mm

However the imaging criteria weren’t sufficient for the investigation of the AI. Naturally the hormonal activity of the tumor had to be investigated. The patient was referred to the department of endocrinology of the University hospital of AHEPA Thessaloniki to complete the examinations required. These included a 24hr urinary free cortisol and 24hr urinary metaneprine levels as well as catecholamines levels. Plasma aldosterone and renine levels were not required because the patient did not present with medical history of hypertention. Both biochemical examinations showed that hormone levels were within normal parameters.

VMA was 2.67mgr/24h (2-7mg/24 hours) and cortisol was 28.5μgr/24h (3.5-45µg/24h). In conclusion and taking into account the above measured parameters the AI seemed to be a non-secretive adrenal tumor. Only the increased size of the tumor (42mm>40mm) was an inclusion criteria for the surgical excision of this AI. The non diagnostic washout percentage gave us a little evidence about the malignancy of the tumor. The patient underwent to laparoscopic excision of the tumor for both therapeutic and diagnostic purposes. The surgical specimen had an oval shape and its size was in its longest axis was 4,8cm. The tumor was solid, with no hemorrhage and necrotic signs with its cut surface showing a white color as described in literature (Fig.2,Fig.3). The histological examination showed many Schwann cells inside fat tissue as well as gangliocytes. Immunohistochemically Schwann cells were at S100 protein positive [S100(+)] and gangliocytes NSE (+) (Fig.4,Fig.5,Fig.6, Fig.7). The postoperative period was free of complications. Six months later a scheduled follow up examination was performed, with a new CT scan. There was no evidence of recurrence of the tumor in the retroperitoneum.

Fig.2

The surgical specimen with its longest axis at 4,8cm

Fig.3

The surgical specimen appears with an oval shape, solid, with no hemorrhage and necrotic signs, with its cut surface showing a white color

Fig.4

Borderlines form adrenal gland cortex to the tumor with Schwann cells into the fat tissue

Fig.5

Schwann cells with large gangliocytes

Fig.6

Schwann cells positive at S100 protein

Fig.7

Gangliocytes positive at NSE protein

Discussion

Adrenal Ganglioneuroma (GN) is a non-functional benign tumor that develops slowly. Although there have been described in literature cases of malignant GNs with hepatic metastases and hormonal activity GN is most commonly presented as an adrenal incidentaloma. Adrenal Incidentalomas are the tumors found by coincidence (incidentally) without clinical symptoms or suspicion. Symptoms are presented only if the tumor becomes large enough to cause symptoms by pressure on adjacent organs or if the tumor exhibits any hormonal activity. The examination that confirms the existence of an adrenal incidentaloma is the CT scan. Incidental adrenal masses on imaging are common (0.6 to 1.3% of all abdominal CT). GN comprise about 0-6% of all of adrenal incidentalomas. The initial size of a GN that has been measured by CT is often large. Although the average mass size of AIs is about 2,75cm, in a Chinese retrospective study the initial size of GNs shows a range about 2.5-14cm with a mean size about 6.27cm. There are many indications about the surgical excision of an AI for the risk of malignancy. The most common have to do with the size, the presence hormonal activity and the radiologic appearance of the tumor. Masses with size over 4.0cm should be removed. Incidentalomas of any sizes that display either clinical, imaging or serum abnormalities that may plead for an adrenal hyperfunction or malignancy are candidates for surgery. The differential diagnosis only with imaging criteria is often difficult. It comprises of a long list of tumors witch include pheochromocytoma, adrenocortical carcinoma, lipoma, myelolipoma, cyst, metastases or inflammation from any cause. All these tumors show similar results about their appearance in the Hounsfiled scale and the washout percentage [15,16]. In most cases (71%) other malignant tumors like pheochromocytoma and paraganglioma coexist with GN. Because the initial size of GN is often over 4cm and it appears at CT scan with calcifications, similar Hounsfiled levels and washout percentage and usually coexists with other malignant tumors complete surgical resection is the preferred approach for both therapeutic and diagnostic reasons. Laparoscopic excision is the gold standard for the surgical treatment of GNs of the adrenal gland. A follow-up is recommended in any case. Histopathological examination is the only way to confirm the diagnosis of an AI. There isn't a commonly accepted procedure for an optimal follow up in each case. Patients with AI that surgery is not an initial option should be followed up by their physician. It is recommended that imaging follow-up should be performed at 3-6 months intervals for masses having a high suspicion of malignancy or at one year for lesions that may appear benign. If the tumor secretes hormones such as catecholmines or cortisole, the attending team should perform annual clinical and laboratory follow-up, focusing on hormonal disorders, for at least four years.

Conclusion

The prognosis of an AI depends mostly on the histopathological type of the tumor. Following surgical removal, prognosis tends to be very good in the case of GN, with no further chemotherapy or radiotherapy required