JBR–BTR, 2014, 97: 109-112.

Dopamine-Secreting Giant Adrenal Ganglioneuroma: Clinical and Diffusion-Weighted Magnetic Resonance Imaging Findings

A.V. Polat1, A. Kamali Polat2, K. Aslan1, H. Atmaca3, F. Karagoz4

We report a case of a -secreting giant primary adrenal ganglioneuroma (GN) in a 29-year-old male patient. Although the patient was clinically silent, the 24-hour urine levels of dopamine, , homovanillic acid and vanillyl mandelic acid were elevated. Abdominal ultrasonography and magnetic resonance imaging showed a large solid tumor with calcifications and a slightly lobular edge on the left adrenal gland. A tumor, 13 × 23 × 25 cm in size, was completely resected without morbidity. A 2-year follow-up with computed tomography showed that the postoperative course of the patient was uneventful.

Key-words: Ganglioneuroma – Magnetic resonance imaging – Diffusion-weighted imaging – Adrenal gland.

Ganglioneuroma (GN) is a rare well-differentiated benign slow- growing tumor, arising from the pri- mordial neural crest tissue anywhere along the paravertebral sympathetic plexus. It is most commonly located in the posterior mediastinum, aorto- caval sympathetic ganglia, and retro- peritoneum. However, the adrenal gland is a rare location for a GN, and primary adrenal GNs in adults have been reported in small series so far. The increased use of various imag- ing modalities has led to an increase in the number of incidentally identi- fied GNs. GN is composed of mature ganglion cells and Schwann cells in a fibrous stroma. Adrenal GN is usu- ally asymptomatic and hormonally inactive, but some of them secrete Fig. 1. — Abdominal ultrasonography showed a hetero­ and their metabo- geneous hypoechogenic left adrenal solid mass with faint calci- lites — cortisol or androgens (1-3). fications and a slightly lobular edge. Differential diagnosis in the case of adrenal incidentalomas is a crucial point before performing surgery. GN is considered benign; however, adre- admitted to the clinic, a palpable 105–354 µg/dl); homovanillic acid nal and pheochromocy- mass located in the left upper (HMA), 280.84 mg (normal range, tomas are the differential diagnoses ­quadrant was found on physical 2–7.4 mg); and vanillyl mandelic acid that need detailed evaluation and ­examination. He had no headache, (VMA), 10.62 mg (normal range, special preoperative intervention. palpitation, flushing, hypertension, 0–6.6 mg). On the other hand, levels We report diffusion-weighted or Cushingoid phenotype. His blood of 5-hydroxy-indol-acetic acid (5- magnetic resonance imaging (MRI) pressure was 120/70 mm Hg and HIAA), , noradrenaline, findings in a giant primary adrenal pulse was 72. , and 5-hydroxy-trypt- GN, which was found to secrete do- Laboratory tests, including peri­ amine () were within nor- pamine, and to the best of our knowl- pheral blood examination, liver func- mal ranges. Plasma levels of cortisol, edge, this case presents the largest tion tests, renal function tests, adrenocorticotropin, dehydroepian- pure GN in the literature. ­urinalysis, and electrolyte determi- drosterone sulfate, and nation, conducted on admission were within normal ranges. Cortisol Case showed no abnormal findings. Endo- response on 1 mg dexamethasone crine examination revealed increased suppression test was < 1 µg/dl. A 29-year-old male patient was levels of 24-hour urinary concentra- Based on these findings, the pa- suffering from chronic abdominal tions of dopamine, 18695 µg/dl (nor- tient’s condition was diagnosed as a discomfort in the left upper quadrant mal range, 0–500 µg/dl); normeta- selectively se- for the past 2 years. When he was nephrine, 461 µg/dl (normal range, creting dopamine. Preoperatively, he was administered 2 mg doxazosin daily and was recommended ade- quate hydration. Ultrasonography (US) was per- From: Department of 1. Radiology, 2. General Surgery, 3. Endocrinology and formed using Toshiba Aplio XG SSA- 4. Pathology, University of Ondokuz Mayis, Faculty of Medicine, Samsun, Turkey. Address for correspondence: Dr A. Veysel Polat, M.D., Ondokuz Mayis University, 790A (Toshiba Medical Systems, ­Faculty of Medicine, Department of Radiology, 55139 Atakum, Samsun, Turkey. ­Tokyo, Japan) with 3.5 MHz convex E-mail: [email protected] probes. US examination revealed a

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D A

B E

Fig. 2. — Axial magnetic resonance images showed a large mass in the left adrenal gland with a hypointense signal inten- sity on T1-weighted image (A) and hyperintense and heteroge- neous signal intensity on T2-weighted HASTE image (B). An en- hanced T1-weighted image showed heterogeneously enhanced adrenal mass (C). In the left adrenal gland, there is a lesion that is hyperintense on transverse echo-planar diffusion-weighted images at b = 1000 s/mm2 (D). The ADC value of this lesion was 1.65 × 10-3 mm2 (E).

­tissue (Fig. 2D). The apparent diffu- sion coefficient (ADC) measurements were done on ADC maps. ADC val- ues were obtained using a circular region of interest in the tumor. T2- weighted and contrast enhanced T1- weighted MR images compare local- izing solid portion of the lesion in C ADC map. The ROI was placed man- ually within the solid portion of the lesion. Multiple measurements were heterogeneous hypoechogenic lobu- (Fig. 2A), and a heterogeneous high- done for lesion, and the lowest one lated mass calcified in the left upper signal intensity and millimetric hypo­ was accepted as the ADC value. This quadrant (Fig. 1). intensities consistent with calcifica- lesion showed lowest ADC value of Abdominal MRI was performed tions on T2-weighted MRI (Fig. 2B). 1.65 × 10-3 mm2/s (b = 1000 s/mm2) for further lesion characterization by The mass demonstrated heteroge- (Fig. 2E). MRI showed signs of dis- using the 1.5-T Siemens Symphony neous contrast enhancement after placement of the left diaphragm, tail system (Siemens Medical Solutions, intravenous injection of gadolinium of the pancreas, and pressure signs Erlangen, Germany). The tumor in (Fig. 2C). On diffusion-weighted throughout the splenic and renal the adrenal gland showed low-signal ­imaging (DWI), the lesion was hyper- vessels, all caused by the mass. intensity on T1-weighted MRI intense compared to the adjacent There was no evidence of surround-

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10-3 mm2/s), and it was suggested that the higher cellurarity of malignant ­lesions restricted free diffusibility of water molecules; thus, increased ­cellurarity and dense tissues have a relatively low ADC (9). In our case, the ADC value of lesion was 1.65 × 10-3 mm2/s, similar to the value in Gahr’s study. Kim et al. (8) recently reported DWI findings of an intracra- nial GN that showed relatively low ADC values (mean ADC, 0.72 × 10-3 mm2/s). The difference between Kim’s cases and our case may be due to the different tumor histopa- thologies. Although they concluded that differentiation was not yet clear, they found that all had lower ADC values than did GNs Fig. 3. — A microscopic view of the adrenal GN. The tumor and ganglioneuroblastomas. was composed of mature ganglion cells and Schwann cells with The differential diagnosis among abundant fibrous stroma (Hematoxylin and Eosin staining, original adrenal incidentalomas, adrenal car- magnification × 400). cinomas and need detailed evaluation is a crucial point before surgery. Preoperative ing tissue infiltration, regional lymph related symptoms and may be pharmacologic preparation is indicat- node enlargement, or intra-abdomi- ­hormonally active, secreting cate- ed for all patients with - nal fluid. cholamine or its metabolites (1-3). secreting neoplasms. Resecting a Because the tumor was large, 13 × Unlike noradrenaline/adrenaline- pheochromocytoma is a high-risk 23 × 25 cm, an open transabdominal secreting pheochromocytomas/ surgical procedure and an experi- adrenalectomy with complete tumor para­gangliomas, dopamine-secret- enced surgeon/anesthesiologist excision was performed. The cut sur- ing tumors lack a classical presenta- team is required. Cardiovascular and face of the tumor was grayish-white tion, are extra-adrenal, and have a hemodynamic variables must be with extensive mucoid degeneration higher malignant potential (4). Mea- monitored closely. Controlling hyper­ and calcification. Histopathological surement of urinary dopamine may tension (including preventing a examination revealed that the adre- be very useful in detecting this rare ­hypertensive crisis during surgery) nal tissue was replaced by tumor tumor with selective dopamine and volume expansion is mandato- composed of low cellular density ­hypersecretion, because plasma ry. As stated in the article, preopera- consisted of mature ganglion cells metanephrine fractions are not ­direct tively, the patient was administered and Schwann cells surrounded by metabolites of dopamine and may 2 mg doxazosin daily (alpha adrener- more stroma. No evidence of malig- be normal in the setting of a dopa- gic blockade) and hydrated ade- nancy or pheochromocytoma-relat- mine-secreting tumor (5). quately. Unlike ganglioneuromas, ed findings indicated that the tumor On CT, adrenal GNs appear as adrenocortical carcinomas are rare was a pure GN (Fig. 3). The immuno- well-circumscribed, homogeneous and aggressive tumors. Complete histochemical staining was per- masses that demonstrate mild en- surgical resection is the only poten- formed using antibodies for S 100, hancement. Calcifications appear in tially curative treatment for those tu- for Schwann cells, approximately 2.4–50% of the cas- mors. Resection of pheochromocy- and neuron specific enolase (NSE) es (1-3). Calcification was seen in our tomas has the risks of hypertensive positive staining for ganglion cells. case. Accurate diagnosis of adrenal crisis, malignant arrhythmia, and During the postoperative follow- GN before surgery is usually diffi- multiple organ failure (10). On the up, the clinical and laboratory find- cult; Qing reported a 64.7% rate of other hand, resection of adrenocorti- ings were normal. Two years after misdiagnosis of adrenal GN with CT cal carcinomas, with respect to the operation, the clinical course of and MRI (3). On MRI, GN shows ho- choosing between open and laparo- the patient was uneventful, and CT mogeneously low or intermediate scopic procedures, is critical in the showed no residual tissue or tumor signal intensity on T1-weighted im- cases where invasion of periadrenal recurrence. ages; and heterogeneous slightly tissue is suspected. On DWI, the ADC high-signal intensity on T2-weighted value of our case was consistent Discussion images. The heterogeneity on T2- with a benign lesion, but because the weighted images depends on the tumor size was measured to be GN is a slow-growing tumor in the amount of myxoid stroma, collagen 25 cm and elevated hormone levels group of neurogenic tumors that fibers, and cellular components in were coherent for pheochromocyto- originates in the ganglion cells, like the tumor (6-8). Gahr et al. studied ma endocrinologically, an open ganglioblastoma and neuroblasto- the differences between GN, gan- transabdominal adrenalectomy with ma, but the main difference is that glioneuroblastoma, and neuroblas- complete tumor excision was per- GN consists of mature and differenti- toma by evaluating their ADC values formed. ated cells. GNs are rare, mostly on MRI. In their study, the mean ADC Macroscopically, GNs are large ­asymptomatic, and hormonally non- of the 4 GNs and 2 ganglioneuro- encapsulated firm masses with homo- functioning; however, occasionally blastomas was 1.60 × 10-3 mm2/s (SD geneous, grayish-white cut surface. they may cause nonspecific mass- 0.34 × 10-3 mm2/s; range, 1.13-1.99 × On immunohistochemical staining,

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they are characterized with S-100, in this case. However, DWI was able 5. Eisenhofer G., Goldstein D.S., Sullivan NSE, and synaptophysin positivi- to contribute the diagnosis of lesion P., et al.: Biochemical and clinical ty (1, 3). The histology of adrenal GN as benign with obtaining high ADC manifestations of dopamine-produc- has been reported to be overlap with value. ing paragangliomas: utility of plasma that of cortical adenoma/pheochro- methoxytyramine. J Clin Endocrinol Metab, 2005, 90: 2068. macytoma, and myelolipoma (1). 6. Ichikawa T., Ohtomo K., Araki T., et The present case showed histological References al.: Ganglioneuroma: computed to- findings specific for GN, and despite mography and magnetic resonance elevated hormone levels, the patient 1. Linos D., Tsirlis T., Kapralou A., features. Br J Radiol, 1996, 69: 114-121. symptoms were clinically silent. ­Kiriakopoulos A., Tsakayannis D., 7. Zhang Y., Nishimura H., Kato S., et al.: Prognosis of mature GN is excel- ­Papaioannou D.: Adrenal ganglioneu- MRI of ganglioneuroma: histologic lent when resected completely. In romas: incidentalomas with mislead- correlation study. J Comput Assist our case, two years after complete ing clinical and imaging features. Tomogr, 2001, 25: 617-623. resection, the patient was evaluated ­Surgery, 2011, 149: 99-105. 8. Kim S.K., Jeong M.Y., Kang H.K., 2. Rondeau G., Nolet S., Latour M., et Yoon W.: Diffusion-weighted magnet- endocrinologically and with CT and al.: Clinical and biochemical features ic resonance imaging findings in a no sign of recurrence was observed. of seven adult adrenal ganglioneuro- patient with trigeminal ganglioneuro- In conclusion, GNs are rare be- mas. J Clin Endocrinol Metab, 2010, ma. Korean J Radiol, 2013, 14: 118- nign tumors and have a favorable 95: 3118-3125. 121. prognosis when completely resect- 3. Qing Y., Bin X., Jian W., et al.: Adrenal 9. Gahr N., Darge K., Hahn G., Kreher ed. However, their mixed histopath- ganglioneuromas: a 10-year experi- B.W., von Buiren M., Uhl M.: Diffu- ological pattern, variability in hor- ence in a Chinese population. Sur- sion-weighted MRI for differentiation monal activity, and possible gery, 2010, 147: 854-860. of and ganglioneuro- suspicious imaging characteristics of 4. Foo S.H., Chan S.P., Ananda V., blastoma/ganglioneuroma. Eur J Ra- ­Rajasingam V.: Dopamine-secreting diol, 2011, 79: 443-446. adrenal masses occasionally make phaeochromocytomas and paragan- 10. Lo C.Y., Lam K.Y., Wat M.S., Lam K.S.: accurate preoperative diagnosis dif- gliomas: clinical features and man- Adrenal pheochromocytoma remains ficult. Suspicious malignant imaging agement. Singapore Med J, 2010, 51: a frequently overlooked diagnosis. findings were size and calcifications e89-93. Am J Surg, 2000, 179: 212-215.

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