Periampullary somatostatinoma and multiple gastrointestinal stromal tumors associated with von Recklinghausen?s disease

Abstract

VRD) with neurogenic malignancies, including neuroendocrine tumors, is well established, whereas its association with nonneurogenic malignancies is considered to be coincidental. We describe a rare case of periampullary somatostatinoma (neurogenic malignancy) and multiple gastrointestinal stromal tumors (GISTs, non-neurogenic malignancy) associated with VRD.A 62-year-old man with VRD was admitted to our hospital with a poor appetite and weight loss. Gastroduodenoscopy revealed a protuberant tumor with an irregular surface occupying half of the lumen in the second part of the duodenum. Contrast-enhanced computed tomography showed a tumor, 5 cm in diameter, extending from the second part of the duodenum to the head of the pancreas. Angiography showed a tumor stain with an increase in vascularity. Histological examination of a tumor biopsy specimen revealed that atypical small cells with low-grade growth had invaded the connective tissue of the duodenal mucosa, forming trabecular and tubular arrangements, suggesting a diagnosis of carcinoid. The tumor was positive for keratin, somatostatin ( Fig. 1b), synaptophysin (Fig. 1c), and chromogranin A (Fig. 1d) on immunohistochemical examination. The plasma somatostatin level was markedly elevated, but the plasma levels of glucagon, gastrin, serotonin, vasoactive intestinal peptide, and calcitonin were in the normal ranges. Under the diagnosis of somatostatinsecreting periampullary carcinoid, pancreatoduodenectomy was considered to be indicated for this patient with VRD.At the operation, the tumor was palpable from the inner and dorsal aspects of the duodenum to the head of the pancreas. There were four miliary white nodules on the surface of the liver. Histopathological examination of a frozen section taken from the nodule for rapid diagnosis during the operation showed atypical cells that formed a glandular structure, with stromal cell proliferation in normal hepatic tissues, indicating metastasis.As the tumor was considered to be unresectable because of the liver metastases, a gastrojejunal bypass was created. Immunohistochemical staining showed that atypical cells in the white nodules on the surface of the liver were positive for somatostatin, indicating that the nodules were metastases from a somatostatinoma (malignant endocrine tumor). A psammoma body was present in biopsy samples of liver (Fig. 1a). Several subserosal white nodules, 1 cm in diameter, were also found at operation, on the anterior wall of the stomach and small intestine. On histological examination, the nodules in the stomach and small intestine consisted of atypical cells of spindle shape showing a bundle pattern, and the cells were immunohistochemically positive for CD34 and C-KIT (Fig. 2a), but not for S-100 protein (Fig. 2b). Thus, we diagnosed these lesions as multiple GISTs.The neural tissues of patients with VRD contain high levels of a neuronotropic factor that stimulates DNA synthesis by neurofibroblasts. As a result, VRD is associated with neurogenic malignancies. Thus, in our current patien...

Somatostatin-Immunoreactive Pancreaticoduodenal Neuroendocrine Neoplasms: Twenty-Three Cases Evaluated according to the WHO 2010 Classification

“…To our knowledge, only 13 cases with the triad of GIST, dSOM and NF-1 have previously been reported [28,29,30,31,32,33,34,35,36,37,38,39,40,41]. …”

The Coexistence of Somatostatinoma and Gastrointestinal Stromal Tumor in the Duodenum of a Patient with Von Recklinghausen's Disease

“…The association of non-neurogenic malignancies with VRD has long been considered to be coincidental, however, recent observations reveal a consistent tendency for these malignancies to develop in patients with VRD (16). Although the association of NF-1 with neuroendocrine tumors has been established, it has rarely been described in association with a non-neurogenic malignancy, such as GIST (16).…”

“…Although the association of NF-1 with neuroendocrine tumors has been established, it has rarely been described in association with a non-neurogenic malignancy, such as GIST (16). Patients with NF1 may have an increased risk of developing non-neurogenic malignancies because the disease has been shown to arise from a mutation on the NF1 gene on the long arm of chromosome 17.…”

“…Pancreaticoduodenectomy was performed in 66.7% of the reported cases, whereas local resection was performed in the remaining cases (14)(15)(16)(17)(18)(19)(20)(21).…”

Gastrointestinal stromal tumours in patients with type 1 neurofibromatosis

“…Only 0.2 to 0.3% of all gastrointestin REVIEWS n n 250 n 2009 n Volume 3, Number 2 nal carcinoids are localised to this region, but a quarter of these is associated with von Recklinghausen's disease [26,33,34]. Concomitant occurrence of NF1-GIST -neuroendocrine tumour has been reported in 11 cases, almost exclusively in the periampullary region [11,16,18,24,[35][36][37][38][39]. Characteristically these tumours show functional inactivity, and they have a relatively good prognosis [35].…”