A Case of a Composite Adrenal Medullary Tumor of Pheochromocytoma and Ganglioneuroma Masquerading as Acute Pancreatitis
A 48-year-old male was referred to our endocrinologic clinic for the evaluation of an adrenal incidentaloma. Two months ago, he had been admitted to our gastroenterologic clinic at which time he complained of acute, severe intense abdominal discomfort. He claimed that the discomfort had a rapid onset reaching a maximum in 10 to 20 minutes. Further, he had band-like radiation on/to the back. He consumed small amounts of alcohol but had no significant medical and family history. Laboratory data revealed elevated serum pancreatic amylase and lipase levels (reference range shown parenthetically) of 98.8 U/L (8~53) and 603.4 U/L (0~60), respectively. A diagnosis of acute alcoholic pancreatitis was suggested. He was managed with conservative treatments including restriction of caloric intake. Ten days later, he was discharged with significant clinical improvements.\nHowever, seven days after he was discharged, the same symptoms and signs re-developed at which time he also described palpitation, facial flushing and resting hand tremor in the previous five months that were developed slightly, briefly and occasionally. On admission, the patient's body temperature was 36.6℃ while blood pressure was 110/70 mmHg. The pulse rate was 72 beats/minute and the respiratory rate was 19/minute. His height and body weight were 158 cm and 52 kg, respectively. The physical examination was unremarkable except for direct tenderness in the epigastric area. Laboratory data revealed normal blood cell counts, plasma glucose and serum electrolyte levels. The results of liver and renal function tests were also within the normal ranges. However, serum pancreatic amylase and lipase levels were elevated to 81.4 U/L (8~53) and 100.9 U/L (0~60), respectively. The serum calcium level was 2.22 mmol/L (2.15~2.50) and triglyceride level was 0.66 mmol/L (<2.83). The serum CPK-MB (creatinine phosphokinase-MB isoform) level was 1.8 µg/L (0.7~3.8) and the troponin-I level was 0.3 µg/L (0~0.5). The findings of a chest roentgenogram, electrocardiogram, and 24-hour holter monitor showed nothing signigficant. Echocardiographic findings were normal except for mild concentric left ventricular hypertrophy. An abdominal computed tomographic scan showed a mildly enlarged pancreatic change without abnormal fluid collection and necrosis. In addition, he showed a left adrenal mass, 3×3 cm in diameter, which was heterogeneously low attenuated and enhanced after intravenous contrast administration ().\nAbout one month after the second discharge, we performed medical tests for discriminating the functional status of the adrenal incidentaloma. The urinary metanephrine level was elevated to 24.7 µmol/24h (0.5~8.1) and the urinary VMA (vanillylmandelic acid) level was normal at 27.5 µmol/24h (7~33). The results of plasma catecholamines, baseline plasma ACTH and cortisol, urinary-free cortisol, uplight plasma renin activity and aldosterone and serum DHEA-S (dehydroepiandrosterone sulfate) levels were also within normal ranges. The results of 5-HIAA (5-hydroxyindoleacetic acid) and thyroid function tests were also normal. 131I-MIBG (Metaiodobenzyl guanidine) scintigraphy was performed for the confirmation of the provisional diagnosis and localization of additional extra-adrenal tumors. 131I-MIBG scintigraphic findings showed a marked uptake in a single location corresponding to the left adrenal mass (). Ultrasonographic findings of the neck were unremarkable and serum intact PTH and calcitonin levels were 14.39 pg/mL (15~65) and 1.4 ng/mL (0~10), respectively. Therefore, we could exclude pheochromocytoma from familial association of multiple endocrine neoplasia type II. An -adrenoceptor blocker (doxazocin mesylate 4mg qd for 11 days) was prescribed preoperatively to prevent an operative adrenal crisis. Then, the left adrenal gland was surgically removed trans-abdominally through a subcostal incision.\nOn pathologic examination, a composite adrenal medullary tumor of pheochromocytoma and ganglioneuroma was confirmed. On gross examination, a well-defined solid tumor measuring 2.8×2.5×2.5 cm was found within the adrenal gland and cut surface of the tumor was yellowish brown. The microscopic appearance of the tumor showed an abrupt transition of two different patterns of typical pheochromocytoma and a large area of ganglioneuroma (). In the pheochromocytoma area, organoid nests, called "Zellballen" pattern, of polygonal cells surrounded by fibrovascular stroma were observed. Each cell had granular basophilic or amphophilic cytoplasm and intracytoplasmic hyaline globules, positively stained by PAS (periodic acid-Schiff's reagent). Its round or oval nuclei had a prominent nucleoli which contained inclusion-like structures and showed moderate pleomorphism with hyperchromasia (). At the ganglioneuroma area, uncapsulated clusters of fully matured ganglion cells surrounded by fascicles of spindle (Schwann-like) cells were shown (). On immunohistochemical staining, it was weakly positive for NSE (neuron-specific enolase), chromogranin and synaptophysin, negative for HMB45 and CK in the pheochromocytoma component, and positive for S-100 protein in the ganglioneuroma component. The patient tolerated the operation well and had an smooth recovery. He was discharged on the 7th post-operative day. After surgery, there were no episodes of intense abdominal discomfort. Further, palpitation, facial flushing and hand tremor were resolved. Now, the patient has remained well and free of any symptoms for more than eight months.