CL Corless

DR Stewart

Esam Aboutaleb

I Besana-Ciani

KA Behranwala

M Miettinen

Manish Kothari

MJ Frost

Osama Damrah

RK Yantiss

Roben Canelo

RP DeMatteo

S Teramoto

Y Takazawa

English

PubMed

Springer - Publisher Connector

c-KIT positive Gastrointestinal Stromal Tumor presenting with acute bleeding in a patient with neurofibromatosis type 1: a case report

BioMed Central
International Seminars in Surgical 
Oncology
ssOpen AcceCase report
c-KIT positive Gastrointestinal Stromal Tumor presenting with 
acute bleeding in a patient with neurofibromatosis type 1: a case 
report
Esam Aboutaleb*, Manish Kothari, Osama Damrah and Roben Canelo
Address: Imperial College Healthcare Trust, Hammersmith Hospital, Department of Hepatopancreatic and Biliary Surgery, Du Cane Road, 
London, W12 0HS, UK
Email: Esam Aboutaleb* - esam.aboutaleb@imperial.nhs.uk; Manish Kothari - m.kothari@doctors.org.uk; 
Osama Damrah - osama.damrah@imperial.ac.uk; Roben Canelo - Ruben.canelo@imperial.nhs.uk
* Corresponding author    
Abstract
Background: Gastrointestinal stromal tumours are rare (GIST). However, the incidence of GIST
among neurofibromatosis type 1 (NF-1) patients is approximately 3.9-25%. GIST can present
clinically in different ways such as abdominal pain, gastrointestinal bleeding and obstruction.
Case report: We present 51 year female patient admitted with Background of neurofibromatosis
type 1 admitted with melena. OGD has been done and showed duodenitis with large volume fresh
blood in distal duodenum but no obvious bleeding point. Exploratory laparotomy revealed smooth
nodular masses on the serosal surface of jejunum. Small bowel resection and side-to-side
anastomosis were performed. Histopathoogical examination revealed small bowel gasrointestinal
stromal tumour with low risk malignant potential.
Conclusion: The incidence of GIST among neurofibromatosis type 1 (NF-1) patients is not
uncommon and we should pay attention to gastrointestinal manifestation in such patients.
Introduction
Neurofibromatosis is an autosomal dominant disorder
that affects all 3 germinal layers; thereby affecting any
organ system. The National Institutes of Health (NIH)
Consensus Development Conference has defined 2 dis-
tinct types: the commoner of the two, neurofibromatosis
type 1 (NF1) affecting 85% of patients; and neurofi-
bromatosis type 2 (NF2) [1]. NF1diagognsis made if 2 or
more of following criteria found: Six or more café au lait
macules larger than 5 mm, two or more neurofibromas,
multiple freckles, A distinctive osseous lesion, optic gli-
oma, two or more iris hamartomas, a first-degree relative
with NF1. Rarely, the neurofibromatosis may become
cancerous (3-5%). Gastrointestinal stromal tumours
(GIST) are generally rare however; the incidence of GIST
among NF-1 patients is approximately 5-25% [2]. GISTs
are usually located in the stomach and small intestine and
can present in a variety of different ways ranging from
vague symptoms to major G.I. bleeding. The first line
treatment is surgical resection for operable GIST and 5-
year survival ranges from 21% to 88% depending on risk
grading and completeness of surgical resection [3,4]. The
second line of treatment is Imatinib mesylate, a tyrosine
kinase inhibitor, which provides an option for treating
high risk GISTs.
Published: 23 October 2009
International Seminars in Surgical Oncology 2009, 6:17 doi:10.1186/1477-7800-6-17
Received: 25 June 2009
Accepted: 23 October 2009
This article is available from: http://www.issoonline.com/content/6/1/17
© 2009 Aboutaleb et al; licensee BioMed Central Ltd. 
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), 
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Page 1 of 3
(page number not for citation purposes)
International Seminars in Surgical Oncology 2009, 6:17 http://www.issoonline.com/content/6/1/17We report the case of a 51 year female patient with NF-1
who presented with lower GI bleeding caused by a jejunal
GIST.
Case report
A 51 year old lady with NF-1 as she has multiple neurofi-
bromas and seven café au lait macules larger than 5 mm.
Presented to A&E with a 24 hour history of malena. She
was on warfarin for aortic root and valve replacement sur-
gery she had in the previous year. Although she remained
haemodynamically stable, her haemoglobin levels gradu-
ally dropped 4 units over the next 36 hours. Along with
correction of her clotting function, investigations were ini-
tiated that included an upper GI endoscopy which
revealed blood in the second part of duodenum. Due to a
rapid deterioration in her haemodynamic status colonos-
copy was cancelled and a mesenteric angiogram was done
that suggested bleeding from the region between the 4th
part of duodenum and upper jejunum from intestinal
mass. She was subjected to emergency laparotomy. At sur-
gery, smooth nodular masses were found on the serosal
surface of the first 50 cm of jejunum; these were 3-4 cm
and projected into the lumen having eroded the mucosal
surface. Resection of the affected segment and end to end
anastomosis was performed. The rest of the bowel
appeared free of any masses and after concluding surgery
the patient was transferred to ITU postoperatively. She
made an uncomplicated recovery and was discharged 7
days after operation. A subsequent CT scan did not reveal
any other masses.
Histopathology revealed an 8 cm length of jejunum
involved with tumour nodules, smallest 3.4 cm and larg-
est 4.4 cm, composed of spindle and polygonal cells. The
tumour involved the full thickness of the bowel wall and
there was no spread of disease to lymph nodes. Immuno-
histochemistry demonstrated positive staining for CD117
(cKit) (Figure 1), and negative staining for broad range
cytokeratins; MNF 116, CD34, desmin, S-100 and chrom-
ogranin. On the basis of mitotic count (2/50 HPF) and
tumour size it was classified as a GIST of intermediate
malignant potential. Proliferation index detected by Ki67
was very low (less than 1-2%).
Gastro-intestinal stromal tumour (GIST) in small bowel, aris-ing from the submucosa (haematoxylin and eosin; original m gnifica ion × 40)Fi u e 1
Gastro-intestinal stromal tumour (GIST) in small 
bowel, arising from the submucosa (haematoxylin 
and eosin; original magnification × 40).
The tumour is composed of spindle cells with plump nuclei and abundant eosinophilic cytoplasm with f brovascular stroma (haemat xylin and eosin; original magnification × 100)Figure 2
The tumour is composed of spindle cells with plump 
nuclei and abundant eosinophilic cytoplasm with 
fibrovascular stroma (haematoxylin and eosin; origi-
nal magnification × 100).
Immunohistochemical staining for CD117 (A) and S100 pro-tein (B)Figure 3
Immunohistochemical staining for CD117 (A) and 
S100 protein (B). The tumour cells show strong diffuse 
membranous and cytoplasmic expression for CD117 and 
negative expression for S100 protein.Page 2 of 3
(page number not for citation purposes)
International Seminars in Surgical Oncology 2009, 6:17 http://www.issoonline.com/content/6/1/17Discussion
Abdominal involvement in NF-1 has been described
before. This includes GISTs [5], pheochromocytomas [6]
and ampullary tumours [7]. 78% of sporadic GISTs show
c-KIT mutations [8]. However, this typical mutation is
rarely seen in NF-1 associated GISTs [5,9] leading to
authors proposing an alternative pathogenesis of GISTs in
NF-1 patients [10]. This has potential implications for
Imatinib therapy when required as this is likely to be inef-
fective in c-KIT negative ones as in NF-1 [11].
Figure 1- Gastro-intestinal stromal tumour (GIST) in
small bowel, arising from the submucosa (haematoxylin
and eosin; original magnification × 40)
Figure 2- The tumour is composed of spindle cells with
plump nuclei and abundant eosinophilic cytoplasm with
fibrovascular stroma (haematoxylin and eosin; original
magnification × 100)
Figure 3 and Figure 4. Immunohistochemical staining for
CD117 (A) and S100 protein (B). The tumour cells show
strong diffuse membranous and cytoplasmic expression
for CD117 and negative expression for S100 protein
Our patient possessed the known c-KIT mutation that
does not appear typical of NF-1 associated GISTs from
review of literature. It may be that our patient developed
a GIST by co-incidence rather than as an association with
NF-1. However the finding of a low malignant potential
GIST in our patient based on mitotic count is consistent
with other NF-1 associated GISTs reported, along with
other features like young age and female preponderance
[5].
Consent
Written informed consent was obtained from the patient
for publication of this case report and accompanying
images. A copy of the written consent is available for
review by the Editor-in-Chief of this journal.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
EA participated in the sequence alignment and drafted the
manuscript. MK participated in the sequence alignment.
OD participated in the design of the study. RC conceived
of the study, and participated in its design and coordina-
tion. All authors have read and approved the manuscript.
Acknowledgements
To R Ahmed who provides us with histopathology slides
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Immunohistochemical staining for CD117 (A) and S100 pro-tein (B)Figure 4
Immunohistochemical staining for CD117 (A) and 
S100 protein (B). The tumour cells show strong diffuse 
membranous and cytoplasmic expression for CD117 and 
negative expression for S100 protein.Page 3 of 3
(page number not for citation purposes)


Crossref

Antonescu CR: Multiple gastrointestinal stromal tumors in type I neurofibromatosis: a pathologic and molecular study. Mod Pathol

Biology of gastrointestinal stromal tumors.

Conference statement.

DG: Mitotic recombination as evidence of alternative pathogenesis of gastrointestinal stromal tumours in neurofibromatosis type 1. J Med Genet

Fukayama M: Gastrointestinal stromal tumors of neurofibromatosis type I (von Recklinghausen's disease). Am J Surg Pathol

Gastrointestinal stromal tumors in patients with neurofibromatosis 1: a clinicopathologic and molecular genetic study of 45 cases.

LK: Juxtamembrane mutant V560GKit is more sensitive to Imatinib (STI571) compared with wild-type c- kit whereas the kinase domain mutant D816VKit is resistant. Mol Cancer Ther

MF: Two hundred gastro-intestinal stromal tumors: recurrence patterns and prognostic factors for survival. Ann Surg

Outcome and long-term results of surgical resection for gastrointestinal stromal tumors (GIST).

Small bowel gastrointestinal stromal tumours and ampullary cancer in Type 1 neurofibromatosis. World J Surg Oncol

Two von Recklinghausen's disease cases with pheochromocytomas and gastrointestinal stromal tumors (GIST) in combination.

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c-KIT positive Gastrointestinal Stromal Tumor presenting with acute bleeding in a patient with neurofibromatosis type 1: a case report

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