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Year : 2016  |  Volume : 59  |  Issue : 3  |  Page : 359-361
Combined presence of multiple gastrointestinal stromal tumors along with duodenal submucosal somatostatinoma in a patient with neurofibromatosis type 1

1 Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
2 Department of Gastrointestinal Surgery, All India Institute of Medical Sciences, New Delhi, India
3 Department of Radiology, All India Institute of Medical Sciences, New Delhi, India

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Date of Web Publication10-Aug-2016


Neurofibromatosis type-1 (NF-1) is an autosomal dominant disorder, with increased risk of developing benign and malignant tumors of the gastrointestinal tract (GIT). However, the synchronous presence of multiple GIT stromal tumors and duodenal submucosal somatostatinoma, like in this 50-year-old female NF-1 patient, is very rare. She presented with hematemesis, malena, along with multiple neurofibromas all over the body. Thorough radiological and peroperative work-up revealed multiple ulcerated submucosal and serosal nodules in the proximal small intestine. Histological work-up revealed diagnosis of a duodenal submucosal somatostatinoma with multifocal serosal gastrointestinal stromal tumors. This case is being reported to highlight the rare coincidence of multiple GIT tumors in an NF-1 patient.

Keywords: Multiple gastrointestinal stromal tumors, neurofibromatosis type 1, periampullary somatostatinoma

How to cite this article:
Kumar T, Gupta B, Das P, Jain D, Jain HA, Madhusudhan KS, Dash NR, Gupta SD. Combined presence of multiple gastrointestinal stromal tumors along with duodenal submucosal somatostatinoma in a patient with neurofibromatosis type 1. Indian J Pathol Microbiol 2016;59:359-61

How to cite this URL:
Kumar T, Gupta B, Das P, Jain D, Jain HA, Madhusudhan KS, Dash NR, Gupta SD. Combined presence of multiple gastrointestinal stromal tumors along with duodenal submucosal somatostatinoma in a patient with neurofibromatosis type 1. Indian J Pathol Microbiol [serial online] 2016 [cited 2022 Jan 26];59:359-61. Available from: https://www.ijpmonline.org/text.asp?2016/59/3/359/188123

   Introduction Top

Neurofibromatosis type 1 (NF-1) is a genetic disorder with nearly 100% penetrance. It has a prevalence of one case per 3000 population/year in the Western population with an approximate disease burden of >3 lacs patients in India.[1] They are at 180-folds increased risk (incidences of 3.9–25%) for developing gastrointestinal stromal tumors (GIST), as compared to the general population; 60% of which are multifocal.[2] On the other hand, the overall incidence of NF-1 in patients with GIST is around 6%.[2] Though, various other intra-abdominal tumors have been reported with NF-1, especially the periampullary neuroendocrine (NE) tumors, such as somatostatinomas, adrenal pheochromocytomas (1–3% association) and nerve sheath tumors, synchronous multifocal GIST and periampullary somatostatinoma are rare. There has been a report of only around ten such cases reports in English literature.[3],[4] Herein, we have described one of such rare case of NF1 with multiple synchronous tumors.

   Case Report Top

A 50-year-old female, known case of rheumatoid arthritis with clinical features of NF-1 presented to the surgical casualty with history of malena since 12 days, associated with and history of six episodes of hematemesis for the since last 7 days. She also gave a history of dull aching epigastric pain of same duration and postural hypotension. No associated fever, cough, jaundice, or history of preceding drug intake was present. On clinical examination, she was found to have multiple subcutaneous nodules all over the body [Figure 1]d, with pallor and vague fullness in the epigastric region. Laboratory investigation documented severe anemia of 8.3 g%. Upper gastrointestinal endoscopy showed an elevated nodular lesion with the central depression at D2, with blood clot and ooze; however, biopsy was not taken. Double balloon enteroscopy showed similar findings. Computer tomogram of the abdomen showed multiple well-circumscribed masses arising from the serosal surfaces of duodenum and jejunum, the largest one measuring 2 cm × 1.5 cm [Figure 1]a, [Figure 1]b, [Figure 1]c. A pylorus-preserving pancreaticoduodenectomy was performed. Intraoperatively, multiple tumor masses were identified on the serosal aspect. Gross examination also showed well circumscribed multiple serosal nodules, varying from 0.5 to 2.5 cm in diameter. In addition, on cutting open the specimen, a submucosal 0.4 cm × 0.4 cm × 0.3 cm nodule was identified near the duodenal ampulla [Figure 1]e. Histological examination from the serosal nodules showed features of well-circumscribed fasciculated spindle cell tumors with focal skeinoid fibers. No atypical mitosis or necrosis was identified [Figure 2]a. The tumor cells were immunopositive for CD117 (Spring Bioscience, CA, USA, dilution 1:50), smooth muscle actin (Thermo Scientific, USA, dilution 1:400), with focal expression of S-100 (Dako, USA, dilution 1:800), and CD34 (Spring bioscience, CA, USA, dilution 1:200) stains. Based on the overall features, diagnosis of multiple GISTs was made. Adjoining smooth muscle in the intestine wall was unremarkable; however, focal hypertrophy of the myenteric ganglia was noted. Sections from the duodenal submucosal nodule showed a gland forming tumor. Tumor cells had abundant eosinophilic granular cytoplasm with monomorphic nuclei and foci of intraglandular calcific bodies [Figure 2]b. No atypical mitosis or metastasis was noted. Duodenal mucosa overlying the ampullary nodule was ulcerated. Below the lesion, deeper neural and muscular structures were unremarkable. Immunohistochemically, these cells were strongly immunopositive for synaptophysin (Spring Bioscience, CA, USA, dilution 1:20) [Figure 2]c, and somatostatin (Thermo Scientific, CA, USA, dilution 1:200) [Figure 2]d. Hence, a final diagnosis of an ampullary somatostatinoma was given. Rest of the intra-abdominal organs was unremarkable. On the postoperative day 5, the patient again had a bout of severe upper gastrointestinal tract bleed, pulmonary edema, and subsequently had a multiorgan failure. Her condition deteriorated in spite of all necessary life-saving measures and the patient died on the 10th postoperative day, due to the development of sepsis and multiorgan failure. No hormone-related symptom was observed preoperatively, and hence, serum somatostatin level was not investigated. After pathological diagnosis, the patient died soon after, and hence, serum somatostatin level could not be corroborated.
Figure 1: Axial contrast computed tomography scan images show enhancing masses arising from the duodenum (arrow in a) and jejunum (arrow in b), located on their serosal surfaces. Oblique coronal contrast-enhanced computed tomography image showing both the masses (arrows in c). Peroperative photograph taken shows multiple skin nodules (d). Gross specimen shows a periampullary submucosal nodule (arrow) (e)

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Figure 2: Photomicrograph taken from sections from serosal nodules shows a spindle cell tumor (a: H and E, ×40). Sections from the periampullary tumor show a gland forming tumor, with monomorphic cell nuclei, abundant granular eosinophilic cytoplasm, and focally identifiable intraluminal calcific bodies (arrows) (b: H and E, ×20). These tumor cells showed synaptophysin (c: ×40) and somatostatin (d: ×40) positivity

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   Discussion Top

Gastrointestinal manifestations in NF-1 patients vary from 12% to 60%, mostly present during midlife amongst these manifestations, which include hyperplasia of the submucosal or myenteric neural plexuses, GIST, and periampullary NE tumors are common.[5],[6],[7] Majority of these patients, with these complications remain asymptomatic, or may sometimes present with abdominal pain, bowel obstruction, upper GI bleed, or perforation. Isolated GIST and ampullary NE tumors, including the somatostatinoma have been described, while the coincidence of these tumors have been described as a disease-defining feature of NF-1.[8] In NF-1 patients, while periampullary somatostatinomas are common (43%), intrapancreatic counterparts are seen only in 4–5% cases. In the present case, radiological and peroperative identification of the serosal nodules, akin to the GISTs were not explainable finding for the severe hematemesis the patient presented with. Upper GI endoscopy though detected the ulcerated duodenal nodule, it was overlooked and biopsy was not taken. Interestingly, it should be noted that most of the ampullary lesions in NF-1 patients are nonfunctional. Hence, depending solely on the biochemical or clinical findings may be misleading.[9] It should also be highlighted that any periampullary tumor in NF-1 is not a somatostatinoma; and gastrinomas, insulinomas, and gangliocytic paraganglioma in this location have been described.[10] Hence, to achieve a correct diagnosis, awareness, thorough histological examination and judicious use of immunohistochemical stains are necessary, even if the patient is asymptomatic.

   Conclusion Top

Though intra-abdominal tumors in NF-1 are common, the synchronous presence of multifocal GISTs and ampullary somatostatinoma is rare. As these periampullary NE tumors can be nonfunctional, biochemical investigation is often not diagnostic.


We express our thanks to Prof MCS for assisting in immunohistochemical staining.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

Statistics by Country For Neurofibromatosis-1. Available from: http://www.rightdiagnosis.com/n/neurofibromatosis_1/stats.htm#extrapwarning [Last accessed on 2015 Jun 10].  Back to cited text no. 1
Suzuki S, Sato K, Katada E, Kuno Y, Mizoquchi N, Tokuda H, et al. Periampullary somatostatinoma and multiple gastrointestinal stromal tumors associated with von Recklinghausen disease. J Gastroenterol 2004;39:1011-39.  Back to cited text no. 2
Miettinen M, Fetsch JF, Sobin LH, Lasota J. Gastrointestinal stromal tumors in patients with neurofibromatosis 1: A clinicopathologic and molecular genetic study of 45 cases. Am J Surg Pathol 2006;30:90-6.  Back to cited text no. 3
Tanaka S, Yamasaki S, Matsushita H, Ozawa Y, Kurosaki A, Takeuchi K, et al. Duodenal somatostatinoma: A case report and review of 31 cases with special reference to the relationship between tumor size and metastasis. Pathol Int 2000;50:146-52.  Back to cited text no. 4
Agaimy A, Vassos N, Croner RS. Gastrointestinal manifestations of neurofibromatosis type 1 (Recklinghausen's disease): Clinicopathological spectrum with pathogenetic considerations. Int J Clin Exp Pathol 2012;5:852-62.  Back to cited text no. 5
Fuller CE, Williams GT. Gastrointestinal manifestations of type 1 neurofibromatosis (von Recklinghausen's disease). Histopathology 1991;19:1-11.  Back to cited text no. 6
Giuly JA, Picand R, Giuly D, Monges B, Nguyen-Cat R. Von Recklinghausen disease and gastrointestinal stromal tumors. Am J Surg 2003;185:86-7.  Back to cited text no. 7
Mullan MH, Gauger PG, Thompson NW. Endocrine tumours of the pancreas: Review and recent advances. ANZ J Surg 2001;71:475-82.  Back to cited text no. 8
Garbrecht N, Anlauf M, Schmitt A, Henopp T, Sipos B, Raffel A, et al. Somatostatin-producing neuroendocrine tumors of the duodenum and pancreas: Incidence, types, biological behavior, association with inherited syndromes, and functional activity. Endocr Relat Cancer 2008;15:229-41.  Back to cited text no. 9
Relles D, Baek J, Witkiewicz A, Yeo CJ. Periampullary and duodenal neoplasms in neurofibromatosis type 1: Two cases and an updated 20-year review of the literature yielding 76 cases. J Gastrointest Surg 2010;14:1052-61.  Back to cited text no. 10

Correspondence Address:
Dr. Prasenjit Das
Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi - 110 029
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.188123

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