Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Japan
Submission:December 31, 2019; Published: January 07, 2020
*Corresponding author:Shigenaga Matsui, Department of Gastroenterology and Hepatology, Kindai University Faculty of medicine, Osaka, Japan
How to cite this article: Shigenaga Matsui, Hiroshi Kashida, Kenji Nomura, Yoriaki Komeda and Masatoshi Kudo. Multiple Gastrointestinal Stromal
Tumors of the Duodenum Associated with Neurofibromatosis Type. Adv Res Gastroentero Hepatol, 2020;14(3): 555889.
A 69-year-old woman patient, with known neurofibromatosis type 1(NF1), was admitted to our hospital for melena. Gastrointestinal endoscopy revealed several submucosal tumors with ulcer in the second of the duodenum. The patient underwent subtotal stomach-preserving pancreaticoduodenectomy (SSPPD). Those tumors were diagnosed gastrointestinal stromal tumors (GISTs) in the duodenum with NF1-related.
Keywords: Neurofibromatosis type 1; Von Recklinghausen’s disease; Gastrointestinal stromal tumors; Duodenumr
Abbreviations: NF1: Neurofibromatosis Type 1; VRD: Von Recklinghausen’s Disease; GISTs: Gastrointestinal Stromal Tumors; CT: Computed Tomography; EUS: Endoscopic Ultrasound; SSPPD: Subtotal Stomach-Preserving Pancreaticoduodenectomy; PDGFRA: Platelet-Derive Growth Factor Receptor A polypeptide
Neurofibromatosis Type 1(NF1), also known as Von Recklinghausen’s Disease (VRD), is a hereditary autosomal dominant disease with an incidence rate of from 1/2,000 to 1/5,000 in most population base studies . NF1 is a dominantly inheritable disease with abnormality at chromosome 17q11.2,
which leads to a loss of neurofibromin, a tumor suppressor protein [1,2]. Therefore, patients with NF1 have a higher risk of developing various malignant neoplasms, with Gastrointestinal Stromal Tumors (GISTs) developing in approximately 5-25% of patients with NF1 . We report a case of the multiple GISTs of the duodenum associated with NF1.
A 69-year-old woman patient, with known NF1, was admitted
to our hospital for melena the physical examination revealed
diffuse cutaneous multiple neurofibromas on the skin (Figure
1a). Abdominal Computed Tomography (CT) revealed tumors
with contrast effect in the second of the duodenum (Figure 1b).
Gastrointestinal endoscopy revealed several submucosal tumors
with ulcer in the second of the duodenum (Figure 1c). Endoscopic
Ultrasound (EUS) revealed multiple low echoic masses with clear
boundary derived from the muscle layer (Figure 1d), suggesting
the diagnosis of GISTs. The patient subsequently underwent
Subtotal Stomach-Preserving Pancreaticoduodenectomy (SSPPD).
Pathological examination (Hematoxylin and Eosin staining)
of the tumors revealed the fascicular proliferation of spindleshaped
cells, predominantly in the muscle layer (Figure. 2a).
Immunohistochemical staining revealed that the tumor cells were
positive for c-kit and CD34(Figure. 2b & 2c), but the cells were
negative for S-100 and desmin (Figure. 2d). Thus, those tumors
were confirmed GISTs in the duodenum with NF1.
NF1 should be suspected in the presence of multiple cutaneous
neurofibromas, café au lait spots, axillary or inguinal freckling
. It is a dominantly inheritable disease with abnormality at
chromosome 17q11.2 [1,2]. This gene encodes a GTPase activating
protein which can regulate the activity of the p21 product of
the ras oncogene, and which seems to play an important role
in controlling cellular proliferation and differentiation in a
wide range of tissues. Different gene mutations are involved in
the development of the various clinical manifestations of NF1,
including malignant tumors, with GISTs . Therefore, GISTs is
reported developing in approximately 5-25% of patients with NF1
GISTs are the most common mesenchymal neoplasms of
the gastrointestinal tract, originating from the progenitors of
intestinal cells of Cajal, which regulate digestive tract motility
. Sporadic GIST has been considered to involve specific KIT
(CD117) or Platelet-Derive Growth Factor Receptor α Polypeptide
(PDGFRA) signaling - driven tumors, KIT and PDGFRA activating
mutations are the oncogenic mechanisms in most sporadic GISTs.
In NF1-related GIST, mutation in KIT and PDGFRA are rarely found
[7-9]. Sporadic GIST can occur within the entire gastrointestinal
tract, in which it accounts for the largest proportion of 60-70%
in the stomach, 25-30% in the ileum to jejunum, 5-15% in the
colorectum, and 5% in the duodenum . By contrast, NF1-
related GISTs are located in the small intestine usually in the
jejunum and characterized by their tendency for multiplicity .
In the present case, the clinical manifestations corresponded to
typical NF1-related GISTs.
Duodenal GISTs are rare neoplasms which may be associated
with NF1. The clinician should be aware of this entity in patients
with known NF1 disease presenting with gastrointestinal
symptoms or intra-abdominal mass.