Triple malignancy (NET, GIST and pheochromocytoma) as a first manifestation of neurofibromatosis type-1 in an adult patient

Abstract

Background Neurofibromatosis type-1 (NF1), also called von Recklinghausen disease, is a rare genetic disease which can lead to the development of benign or even malignant tumors. NF1 is mostly diagnosed in children or early adolescents who present with clinical symptoms. A curative therapy is still missing and the management of NF1 is based on careful surveillance. Concerning tumors which affect the gastrointestinal tract in patients with NF1, the most common is a gastrointestinal stromal tumor (GIST). Case presentation We present a case of a 58-year-old adult patient with dyspeptic symptoms who was incidentally diagnosed with triple malignancy (pheochromocytoma, multiple GISTs of small intestine and an ampullary NET) as a first manifestation of NF1. The patient underwent surgical treatment (adrenalectomy and pancreaticoduodenectomy) with no complications and after 2 years remains in oncological remission. Conclusion NF1 is a rare genetic disease which can cause various benign or malignant tumors. The coincidence of GIST and NET is almost pathognomonic for NF1 and should raise a suspicion of this rare disorder in clinical practice.

Pancreatic Gastrinoma, Gastrointestinal Stromal Tumor (GIST), Pheochromocytoma, and Hürthle Cell Neoplasm in a Patient with Neurofibromatosis Type 1: A Case Report and Literature Review

“…A review of patients with neuroendocrine tumors and NF1 found pheochromocytoma in 6/27 (22%), suggesting a possible link [ 41 ]. The co-existence of all 3 neoplasms (neuroendocrine tumor, pheochromocytoma, GIST) in NF1, such as in this report, is exceedingly rare, but has been reported previously [ 42 ]. Whether there is an underlying association or common mechanism between these malignancies is unknown; however, discovery of a neuroendocrine tumor in a patient with NF1 should prompt investigation of other potential neoplasms.…”

Neuroendocrine Tumor with Metachronous Gastrointestinal Stromal Tumor in a Patient: A Case Report

“…NET and GIST have been reported to be diagnosed simultaneously in the case of neurofibromatosis type 1, but it is known that they are extremely rare in patients with no genetic diseases, as in this case. 23,24 Of the previous reports regarding the simultaneous occurrence of GIST and NET in the gastrointestinal tract, we achieved to retrieve data only for four cases. Two cases were diagnosed in patients without complaints and the others were diagnosed in patients with symptoms such as melena or abdominal pain.…”

Synchronous Periampullary Tumors in a Patient With Pancreas Divisum and Neurofibromatosis Type 1

“…GIST, carcinoid tumors and other NETs are frequently reported in NF1 patients and they are considered part of the NF1 tumor spectrum, occurring in isolated manifestation or, in rare events, in synchronism with other tumors (Sørensen et al, 1986;Kim et al, 2014;Park et al, 2019). The co-occurrence of periampullary NET tumors and GIST has been proposed as highly suggestive or even pathognomonic of NF1 (Agaimy et al, 2012;Park et al, 2019;Poredska et al, 2019). LOH is a common event for the development of malignancies in NF1 patients, and has been considered by some as a prerequisite to cancer occurrence (Ruggieri and Packer, 2001).…”

“…In this report, the patient was diagnosed with multiple tumors (GIST, NET of the minor ampulla, and adenocarcinoma of the major ampulla), of which GIST and NET are likely related to NF1, a diagnosis confirmed by germline genetic testing. Among the tumors identified, GIST represents the most common gastrointestinal tumor in NF1 patients (Poredska et al, 2019), accounting for 5 to 25% of all NF1 neoplasms (Zöller et al, 1997;Miettinen et al, 2006). The last update of duodenal and periampullary tumors in NF1 patients indicates that most (60%) neoplasms arise in the duodenum, while 31% originate in the ampulla of Vater.…”