Gastrointestinal stromal tumour as a rare association with neurofibromatosis type 1

Gastrointestinal stromal tumour as a rare association with neurofibromatosis type 1 Gastrointestinal stromal tumours (GIST) are rare tumours of mesenchymal origin. These can be associated with neuro- fibromatosis type 1 (NF1), which is an autosomal dominant disorder. The prevalence of GIST in NF1 is estimated at 3.9–25%. This paper describes the presentation of a GIST arising from the jejenum in a 75-year-old lady with NF1, who presented with gastrointestinal bleeding. This was diagnosed by CT angiography. She was managed with laparotomy, with resection of small bowel, and an ischaemic segment of large bowel with two primary anastomoses. Pathology showed GIST of spindle cell type (Figs 3 and 4), 90 mm in size, with complete local excision. The patient was discharged on the eighth post-operative day and is currently undergoing regular clinic follow-up after multidisciplinary team meeting discussion. INTRODUCTION CASE REPORT A 75-year-old lady presented with melaena and per rectum bleed- This 75-year-old lady with a background of neurofibromatosis pre- ing and was found to have a gastrointestinal stromal tumour sented to the medical team with melaena and PR bleeding of both (GIST) of the small intestine, on a background of neurofibroma- altered and fresh blood, with intermittent generalized abdominal tosis type 1 (NF1). During the same admission, this was success- pain. She has previously had an upper GI bleed in 2013 with upper fully resected with two primary anastomoses. The patient was GI endoscopy which could not find a specificlesion, andaCT col- discharged home on the eighth post-operative day. onoscopy which showed no abnormality. Examination findings This is a rare presentation of GIST in association with NF1. revealed a soft abdomen with a palpable mass on the left-hand Although this is a known association, cases are still rare in the side. Per rectal examination revealed was soft stool only. literature. It is important to consider GIST in the differential She had an upper GI endoscopy which was unremarkable diagnosis in patients with known NF1 presenting with abdom- and subsequently she was referred to the surgical team. She inal symptoms including GI bleeding. had a CT angiogram and continued to have PR bleeding Received: December 1, 2017. Accepted: February 10, 2018 Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. © The Author(s) 2018. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com Downloaded from https://academic.oup.com/jscr/article-abstract/2018/2/rjy017/4885384 by Ed 'DeepDyve' Gillespie user on 16 March 2018 2 R.H. Hurley et al. requiring blood transfusion. She underwent surgery with an haemorrhage, with multiple further lesions in the duodenum. uneventful post-operative recovery and went home on the This was felt to be the source of the bleeding. Although the eighth post-operative day. tumour was identified in this case by CT angiography, a simple contrast enhanced CT would almost certainly have demonstrated this tumour adequately, given the typical CT appearance of GIST, Investigations with significant contrast enhancement and heterogeneity. Haemoglobin—88 g/l (106 g/l 2 months prior to admission) Pathology—GIST of spindle cell type (Figs 3 and 4), 90 mm in MCV—73.4 (fl) size, with complete local excision. Mitotic count—3 per 5 mm Haematocrit—0.278 l/l square. CD117 (Fig. 5) and DOG1 (Fig. 6) positive staining giving CRP—132 mg/l a prognostic group of moderate risk (Miettinen’s classification) WCC—20.2 × 10 /l of progressive disease. It is widely accepted that Interstitial Erect AP chest X-ray—reported as normal Cells of Cajal (ICC) are pace maker cells of the gut and probable Abdominal X-ray—reported as normal progenitor cells of GIST. Hyperplasia of ICC can be seen in cases Upper GI endoscopy–hiatus hernia only with NF1, however, in this case this could not be shown in the background bowel (Fig. 7). CT angiography (Figs 1 and 2)—large 9 cm exophytic cavitat- ing lesion arising from jejunum with no evidence of active Figure 3: Low power H&E for tumour in relation to bowel mucosa. Figure 1: Axial CT imaging. Large exophytic cavitating lesion arising from jejunum with no evidence of active haemorrhage. Figure 4: Higher power view showing the spindle appearance of tumour cells. Figure 2: Coronal CT imaging. Large exophytic cavitating lesion arising from jejunum with no evidence of active haemorrhage. Figure 5: Immunohistochemical positivity for CD117. Downloaded from https://academic.oup.com/jscr/article-abstract/2018/2/rjy017/4885384 by Ed 'DeepDyve' Gillespie user on 16 March 2018 Gastrointestinal stromal tumour as a rare association 3 treatment using tyrosine kinase inhibitors for advanced disease [1]. Patients with advanced GIST in the context of NF1 do not respond well to imatinib, since the NF1 mutation appears to be the key driver, rather than KIT mutations as most commonly observed. For this reason the consensus is to avoid giving adju- vant imatinib to patients with NF1 related GIST. Unless of course an imitinib sensitive mutation (e.g. KIT exon 11) is also present, which has very rarely been described [2]. NF1 is an autosomal dominant disorder. Features include café au lait spots and neurofibromata. Prevalence is 1 in 3000 people, with half of patients having a family history and half of cases arising spontaneously. There are several associated con- ditions including MEN2A, MEN2B, hereditary breast cancer and GIST [3]. There are various reports in the literature of GIST in Figure 6: Immunohistochemical positivity for DOG1. association with NF1, although little is known about the exact risk of developing GIST in NF1 patients. The prevalence of GIST in NF1 is estimated at 3.9–25%, with a median onset of 49 years, and multiple lesions can occur [1, 4]. An autopsy series has documented a GIST in one-third of NF1 patients [5], and a review paper noted that more than half of GISTs in NF1 were incidental findings compared to one in five in patients without NF1 [6]. Learning points/take home messages � GIST is a known association with NF type 1. � Presenting features may include abdominal pain, nausea, vomiting, change in bowel habit or GI bleeding so it is import- ant to consider GIST as a differential diagnosis in patients with symptomatic NF1. Figure 7: MNF staining the epithelium of the bowel while is negative in tumour � If OGD is normal in cases of GI bleeding; CT angiography cells. should be considered to further evaluate the source. � GIST should be discussed at a specialist MDT to allow for Differential diagnosis optimum surveillance according to grade of tumour. � GIST � Lymphoma ACKNOWLEDGEMENTS � Schwannoma Mr Dominique Byrne and Dr Margaret Balsitis. � Leiomyoma Treatment CONFLICT OF INTEREST STATEMENT 4 Units packed red cell transfusion. None declared. Laparatomy with resection of small bowel tumour and small bowel anastomosis and resection of ischaemic large bowel and large bowel anastomosis. Operative findings showed a large REFERENCES small bowel tumour to the left of the midline, with multiple 1. DYNAMED. https://www.dynamed.com/topics/dmp~AN~T21 hamartomatous lesions along the small bowel with a 6 cm 9072/Gastrointestinal-stromal-tumor-GIST. ischaemic segment of large bowel which had been adherent to 2. Judson I, Bulusu R, Seddon B, Dangoor A, Wong N, Mudan S. the tumour. Specimens were sent to pathology. UK clinical practice guidelines for the management of gastrointestinal stromal tumours (GIST). Clin Sarcoma Res Outcome and follow up 2017;7:6. 3. Wang SM, Chiang RA, Tzen CY, Cheng SP, Liu TP. This lady was discharged on the eighth post-operative day with Spontaneous rupture of recurrent gastrointestinal stromal follow-up in the outpatient clinic 6 weeks after discharge. Her tumour associated with neurofibromatosis type 1. J Chin Med case was discussed at the MDT which recommended moderate Assoc 2005;68:538–41. risk GIST follow-up, which will consist of regular clinic follow- 4. DYNAMED. https://www.dynamed.com/topics/dmp~AN~T11 up and imaging evaluation. 6711/Neurofibromatosis-type-1. 5. Miettinen M, Lasota J. Histopathology of gastrointestinal DISCUSSION stromal tumor. J Surg Oncol 2011;104:865–73. GIST are rare tumours of mesenchymal origin, most commonly 6. Caterino S, Lorenzon L, Petrucciani N, Lannicelli E, Pilozzi E, located in the stomach or small intestine. Symptoms may be Romiti A, et al. Gastrointestinal stromal tumors: correlation vague including abdominal pain, nausea, vomiting, alteration between symptoms at presentation, tumor location and in bowel habit or GI bleeding [1]. Treatment options include prognostic factors in 47 consecutive patients. World J Surg surgical resection for localized lesions and neoadjuvant Oncol 2011;9:article 13. Downloaded from https://academic.oup.com/jscr/article-abstract/2018/2/rjy017/4885384 by Ed 'DeepDyve' Gillespie user on 16 March 2018 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Surgical Case Reports Oxford University Press

Gastrointestinal stromal tumour as a rare association with neurofibromatosis type 1

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Abstract

Gastrointestinal stromal tumours (GIST) are rare tumours of mesenchymal origin. These can be associated with neuro- fibromatosis type 1 (NF1), which is an autosomal dominant disorder. The prevalence of GIST in NF1 is estimated at 3.9–25%. This paper describes the presentation of a GIST arising from the jejenum in a 75-year-old lady with NF1, who presented with gastrointestinal bleeding. This was diagnosed by CT angiography. She was managed with laparotomy, with resection of small bowel, and an ischaemic segment of large bowel with two primary anastomoses. Pathology showed GIST of spindle cell type (Figs 3 and 4), 90 mm in size, with complete local excision. The patient was discharged on the eighth post-operative day and is currently undergoing regular clinic follow-up after multidisciplinary team meeting discussion. INTRODUCTION CASE REPORT A 75-year-old lady presented with melaena and per rectum bleed- This 75-year-old lady with a background of neurofibromatosis pre- ing and was found to have a gastrointestinal stromal tumour sented to the medical team with melaena and PR bleeding of both (GIST) of the small intestine, on a background of neurofibroma- altered and fresh blood, with intermittent generalized abdominal tosis type 1 (NF1). During the same admission, this was success- pain. She has previously had an upper GI bleed in 2013 with upper fully resected with two primary anastomoses. The patient was GI endoscopy which could not find a specificlesion, andaCT col- discharged home on the eighth post-operative day. onoscopy which showed no abnormality. Examination findings This is a rare presentation of GIST in association with NF1. revealed a soft abdomen with a palpable mass on the left-hand Although this is a known association, cases are still rare in the side. Per rectal examination revealed was soft stool only. literature. It is important to consider GIST in the differential She had an upper GI endoscopy which was unremarkable diagnosis in patients with known NF1 presenting with abdom- and subsequently she was referred to the surgical team. She inal symptoms including GI bleeding. had a CT angiogram and continued to have PR bleeding Received: December 1, 2017. Accepted: February 10, 2018 Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. © The Author(s) 2018. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com Downloaded from https://academic.oup.com/jscr/article-abstract/2018/2/rjy017/4885384 by Ed 'DeepDyve' Gillespie user on 16 March 2018 2 R.H. Hurley et al. requiring blood transfusion. She underwent surgery with an haemorrhage, with multiple further lesions in the duodenum. uneventful post-operative recovery and went home on the This was felt to be the source of the bleeding. Although the eighth post-operative day. tumour was identified in this case by CT angiography, a simple contrast enhanced CT would almost certainly have demonstrated this tumour adequately, given the typical CT appearance of GIST, Investigations with significant contrast enhancement and heterogeneity. Haemoglobin—88 g/l (106 g/l 2 months prior to admission) Pathology—GIST of spindle cell type (Figs 3 and 4), 90 mm in MCV—73.4 (fl) size, with complete local excision. Mitotic count—3 per 5 mm Haematocrit—0.278 l/l square. CD117 (Fig. 5) and DOG1 (Fig. 6) positive staining giving CRP—132 mg/l a prognostic group of moderate risk (Miettinen’s classification) WCC—20.2 × 10 /l of progressive disease. It is widely accepted that Interstitial Erect AP chest X-ray—reported as normal Cells of Cajal (ICC) are pace maker cells of the gut and probable Abdominal X-ray—reported as normal progenitor cells of GIST. Hyperplasia of ICC can be seen in cases Upper GI endoscopy–hiatus hernia only with NF1, however, in this case this could not be shown in the background bowel (Fig. 7). CT angiography (Figs 1 and 2)—large 9 cm exophytic cavitat- ing lesion arising from jejunum with no evidence of active Figure 3: Low power H&E for tumour in relation to bowel mucosa. Figure 1: Axial CT imaging. Large exophytic cavitating lesion arising from jejunum with no evidence of active haemorrhage. Figure 4: Higher power view showing the spindle appearance of tumour cells. Figure 2: Coronal CT imaging. Large exophytic cavitating lesion arising from jejunum with no evidence of active haemorrhage. Figure 5: Immunohistochemical positivity for CD117. Downloaded from https://academic.oup.com/jscr/article-abstract/2018/2/rjy017/4885384 by Ed 'DeepDyve' Gillespie user on 16 March 2018 Gastrointestinal stromal tumour as a rare association 3 treatment using tyrosine kinase inhibitors for advanced disease [1]. Patients with advanced GIST in the context of NF1 do not respond well to imatinib, since the NF1 mutation appears to be the key driver, rather than KIT mutations as most commonly observed. For this reason the consensus is to avoid giving adju- vant imatinib to patients with NF1 related GIST. Unless of course an imitinib sensitive mutation (e.g. KIT exon 11) is also present, which has very rarely been described [2]. NF1 is an autosomal dominant disorder. Features include café au lait spots and neurofibromata. Prevalence is 1 in 3000 people, with half of patients having a family history and half of cases arising spontaneously. There are several associated con- ditions including MEN2A, MEN2B, hereditary breast cancer and GIST [3]. There are various reports in the literature of GIST in Figure 6: Immunohistochemical positivity for DOG1. association with NF1, although little is known about the exact risk of developing GIST in NF1 patients. The prevalence of GIST in NF1 is estimated at 3.9–25%, with a median onset of 49 years, and multiple lesions can occur [1, 4]. An autopsy series has documented a GIST in one-third of NF1 patients [5], and a review paper noted that more than half of GISTs in NF1 were incidental findings compared to one in five in patients without NF1 [6]. Learning points/take home messages � GIST is a known association with NF type 1. � Presenting features may include abdominal pain, nausea, vomiting, change in bowel habit or GI bleeding so it is import- ant to consider GIST as a differential diagnosis in patients with symptomatic NF1. Figure 7: MNF staining the epithelium of the bowel while is negative in tumour � If OGD is normal in cases of GI bleeding; CT angiography cells. should be considered to further evaluate the source. � GIST should be discussed at a specialist MDT to allow for Differential diagnosis optimum surveillance according to grade of tumour. � GIST � Lymphoma ACKNOWLEDGEMENTS � Schwannoma Mr Dominique Byrne and Dr Margaret Balsitis. � Leiomyoma Treatment CONFLICT OF INTEREST STATEMENT 4 Units packed red cell transfusion. None declared. Laparatomy with resection of small bowel tumour and small bowel anastomosis and resection of ischaemic large bowel and large bowel anastomosis. Operative findings showed a large REFERENCES small bowel tumour to the left of the midline, with multiple 1. DYNAMED. https://www.dynamed.com/topics/dmp~AN~T21 hamartomatous lesions along the small bowel with a 6 cm 9072/Gastrointestinal-stromal-tumor-GIST. ischaemic segment of large bowel which had been adherent to 2. Judson I, Bulusu R, Seddon B, Dangoor A, Wong N, Mudan S. the tumour. Specimens were sent to pathology. UK clinical practice guidelines for the management of gastrointestinal stromal tumours (GIST). Clin Sarcoma Res Outcome and follow up 2017;7:6. 3. Wang SM, Chiang RA, Tzen CY, Cheng SP, Liu TP. This lady was discharged on the eighth post-operative day with Spontaneous rupture of recurrent gastrointestinal stromal follow-up in the outpatient clinic 6 weeks after discharge. Her tumour associated with neurofibromatosis type 1. J Chin Med case was discussed at the MDT which recommended moderate Assoc 2005;68:538–41. risk GIST follow-up, which will consist of regular clinic follow- 4. DYNAMED. https://www.dynamed.com/topics/dmp~AN~T11 up and imaging evaluation. 6711/Neurofibromatosis-type-1. 5. Miettinen M, Lasota J. Histopathology of gastrointestinal DISCUSSION stromal tumor. J Surg Oncol 2011;104:865–73. GIST are rare tumours of mesenchymal origin, most commonly 6. Caterino S, Lorenzon L, Petrucciani N, Lannicelli E, Pilozzi E, located in the stomach or small intestine. Symptoms may be Romiti A, et al. Gastrointestinal stromal tumors: correlation vague including abdominal pain, nausea, vomiting, alteration between symptoms at presentation, tumor location and in bowel habit or GI bleeding [1]. Treatment options include prognostic factors in 47 consecutive patients. World J Surg surgical resection for localized lesions and neoadjuvant Oncol 2011;9:article 13. Downloaded from https://academic.oup.com/jscr/article-abstract/2018/2/rjy017/4885384 by Ed 'DeepDyve' Gillespie user on 16 March 2018

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Published: Feb 1, 2018

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