Gastrointestinal autonomic nerve tumor secreting catecholamines

Abstract

Dear Editors: Gastrointestinal autonomic nerve tumors (GANTs) form a subset of gastrointestinal stromal tumors (GISTs) [4]. In contrast to classical GISTs, GANTs have ultrastructurally a distinct neuroendocrine phenotype [1,4]. The nature of these ultrastructural neuroendocrine granules remains enigmatic. With the exception of a single GANT, which was described as secreting vascular endothelial growth factor and endostatin [3], there are no published reports that these tumors secrete polypeptide hormones, growth factors, or biogenic amines.In the present paper, we report a GANT found to secrete catecholamines. We are submitting this case for publication to indicate that GANTs can be functionally active.A 49-year-old man visited his primary care physician complaining of lower quadrant pain that began following a minor work-related injury of the abdomen. During the initial examination, an abdominal mass was palpated, and a subsequent computerized tomographic examination revealed a 15-cm lower abdominal mass. He was obese and had been treated for elevated blood pressure, which fluctuated between 150/105 and 163/93 mm Hg, even though he was taking antihypertensive drugs. Because of the suspicion that the tumor might be secreting catecholamines, several laboratory tests were performed, and the following abnormalities were found: urinary 5-hydroxyindolacetic acid (5-HIAA) was elevated 13.7 mg/24 h (normal, <6 mg/24 h), homovalinic acid 10.7 mg/24 (normal, <8 mg/24 h), fractionated metanephrine 281 μg/24 h (normal,<180 μg/24 h; hypertensive range, >400 μg/24 h), normetanephrine 610 μg/24 h (normal, 451 μg/24 h), and total metanephrines 891 μg/24 h (normal, 680 μg/24 h). The tumor was located in the mesentery of the small intestine and was resected in toto with a segment of the small intestine. The patient recovered completely.The tumor was multilobular and solid and measured 15×14×13 cm (Fig. 1a). Histologically, it was composed of elongated spindle cells showing moderate nuclear pleomorphism and hyperchomasia (Fig. 1b). There was an average of eight mitotic figures per ten high-power fields. Immunohistochemical stains showed that the tumor was positive for CD117, CD 34, and vimentin (Fig. 1c). Other immunohistochemical tests, including the staining with antibodies to S100, smooth muscle actin, desmin, cytokeratins, chromogranin, and synaptophysin gave negative results. Electron microscopy revealed that many cells have elongated or rounded-up filopodia-like processes containing neurosecretory granules (Fig. 1d). There were also prominent interdigitating cytoplasmic processes and rudimentary intercellular junctions. There was no evidence of smooth muscle or Schwann cell differentiation. On the basis of these morphologic data, the diagnosis of a malignant GANT was rendered. On the basis of the size (more than 10 cm in diameter) and the number of mitoses, the tumor was designated as high risk, as defined at the National Institutes of Health Consensus Conference [2]. The patient was treated with Gleevac, which he tolerated ...

Gastrointestinal Autonomic Nerve Tumors: a Clinical Review

“…24 -26 GANT secreting catecholamines with its associated symptoms of flushing, fluctuating hypertension, and raised urinary 5-hydroxyindoleacetic acid was also reported. 27 GANTs may also arise in the setting of other medical conditions such as von Recklinghausens disease (neurofibromatosis type 1), 23 , 24 Crohn's disease, 6 Meckel's diverticulum, 28 c o l o r e c t a l a d e n o m a o r c a r c i n o m a , 1 0 a d r e n a l ganglioneuroma, 29 , 30 Carney's triad, 31 , 32 and renal cell carcinoma. 33 Multiple familial GANTs in association with small intestinal neuronal dysplasia have also been reported.…”