Gastrointestinal Stromal Tumors Associated with Neurofibromatosis 1: A Single Centre Experience and Systematic Review of the Literature Including 252 Cases
Aims. The objectives of this study were (a) to report our experience regarding the association between neurofibromatosis type 1 (NF1) and gastrointestinal stromal tumors (GISTs); (b) to provide a systematic review of the literature in this field; and (c) to compare the features of NF1-associated GISTs with those reported in sporadic GISTs. Methods. We reported two cases of NF1-associated GISTs. Moreover we reviewed 23 case reports/series including 252 GISTs detected in 126 NF1 patients; the data obtained from different studies were analyzed and compared to those of the sporadic GISTs undergone surgical treatment at our centre. Results. NF1 patients presenting with GISTs had a homogeneous M/F ratio with a mean age of 52.8 years. NF1-associated GISTs were often reported as multiple tumors, mainly incidental, localized at the jejunum, with a mean diameter of 3.8？cm, a mean mitotic count of 3.0/50 HPF, and KIT/PDGFRα wild type. We reported a statistical difference comparing the age and the symptoms at presentation, the tumors’ diameters and localizations, and the risk criteria of the NF1-associated GISTs comparing to those documented in sporadic GISTs. Conclusions. NF1-associated GISTs seem to have a distinct phenotype, specifically younger age, distal localization, small diameter, and absence of KIT/PDGRFα mutations. 1. Introduction Neurofibromatosis type 1 (NF1, von Recklinghausen’s disease) is an autosomal-dominant disorder occurring in 1 out of 3,000 births that is caused by the inactivation of the NF1 gene. NF1 is a tumor suppressor that encodes for the neurofibromin protein, a member of the Ras family. The inactivation might be a familial condition with an autosomal-dominant inheritance pattern; otherwise it might be sporadic [1, 2]. The disease is characterized by cutaneous neurofibromas, café au lait macules, axillary and inguinal freckling, and Lisch nodules. NF1 is also associated with several tumors, including tumors of the nervous system (central and peripheral) and of the gastrointestinal (GI) tract, with the gastrointestinal stromal tumors (GISTs) indicated as the most common GI NF1-associated tumors [3]. GISTs are mesenchymal and usually kit positive tumors, originating from the interstitial cell of Cajal or their related stem cells [4, 5]. The incidence of the GISTs has been reported in 10–20 new cases per million/year [6]. GISTs represent 80% of mesenchymal GI tumors and 0.1–3% of all GI malignancies [7–10]. GIST’s pathogenesis is related to kit and platelet-derived growth factor receptor alpha (PDGFRa) mutation. Kit and PDGFRa encode for
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