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Bleeding gastrointestinal stromal tumor in a patient with a history of leiomyoma of the ileum
Formosan Journal of Surgery (2013) 46, 23e25
Available online at www.sciencedirect.com
journal homepage: www.e-fjs.com
CASE REPORT
Bleeding gastrointestinal stromal tumor in a patient with a history of leiomyoma of the ileum Wei-Chen Lin a,c, Chen-Wang Chang a,c,*, Ching-Wei Chang a,c, Chung-Hsin Tsai b, Horng-Yuan Wang a,c a
Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan Department of General Surgery, Mackay Memorial Hospital, Taipei, Taiwan c Mackay Medicine, Nursing and Management College, Taipei, Taiwan b
Received 28 September 2011; received in revised form 23 January 2012; accepted 28 May 2012 Available online 4 February 2013
KEYWORDS gastrointestinal stromal tumor; leiomyoma; single-balloon enteroscopy
Summary Small intestine tumors, such as gastrointestinal stromal tumors (GISTs), are rare and difficult to be diagnosed. The most common GIST symptoms are abdominal pain and bleeding. A novel enteroscopy method is helpful in the localization and preoperative evaluation of small bowel tumors. We report a 77-year-old woman who had a history of leiomyoma in the ileum 20 years previously. She presented with intermittent bloody stool passage. Pathological examination showed a GIST in the ileum measuring 3.5 cm 2.5 cm 2.0 cm. The aim of this case report is to remind clinicians that GISTs should be considered if a patient with a history of leiomyoma in the small bowel has obscure, inexplicable gastrointestinal bleeding. Copyright ª 2012, Taiwan Surgical Association. Published by Elsevier Taiwan LLC. All rights reserved.
1. Introduction In the past, leiomyoma was an unascertained diagnosis. Since 1998, GIST was diagnosed by Hirota et al, according to mutations in the KIT gene.1 We now understand the molecular pathogenesis of GISTs and use a specific target
agent such as imatinib to block KIT and platelet-derived growth factor receptor-alpha (PDGFR alpha).2,3 Imatinib is indicated for treating unresectable or metastatic GISTs. We report a patient who intermittently passed bloody stools, which began years after she had had a complete resection of a localized leiomyoma in the ileum.
2. Case report * Corresponding author. Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Number 92, Section 2, Chung-Shan North Road, Taipei 104, Taiwan. E-mail address: [email protected] (C.-W. Chang).
A 77-year-old female had a history of leiomyoma in the ileum. The tumor was approximately 6 cm 5.5 cm 5 cm. It had caused intestinal obstruction and had been
1682-606X/$ - see front matter Copyright ª 2012, Taiwan Surgical Association. Published by Elsevier Taiwan LLC. All rights reserved. http://dx.doi.org/10.1016/j.fjs.2012.09.003
24 completely resected 20 years previously. She had been intermittently passing bloody stools since 2 years before her visit to our clinic. She had no recent fever, abdominal pain, or weight loss. Esophagogastroduodenoscopy, colonoscopy, a small bowel barium study, and a red blood cell (RBC) bleeding scan all failed to show the source of the active bleeding. An abdominal computed tomography (CT) study showed a soft tissue mass of approximately 3 cm in the distal ileum (Fig. 1). Single-balloon enteroscopy for preoperative marking revealed a submucosal tumor (Fig. 2) in the distal ileum, approximately 20e25 cm from the ileocecal valve. It measured approximately 3e4 cm and had linear ulceration. At surgery, after enterolysis for small bowel adhesion, a grayish friable tumor, measuring 3.5 cm 2.5 cm 2.0 cm, was found at the proximal ileum. The tumor cells microscopically exhibited prominent spindle cells in fascicles and in a focal storiform pattern (Fig. 3). The mitotic rate was less than 1 per 50 high power fields and the proliferation rate of Ki-67/MIB-1 was less than 1%.The tumor cells were extensively immunoreactive with CD117 and DOG-1; weakly immunoreactive with CD34; and had a negative immunoreactivity for desmin. She was diagnosed as having a GIST.
3. Discussion GISTs are the most common mesenchymal tumors of the intestinal tract. They may occur anywhere in the whole
Figure 1 Abdominal computed scan shows a soft tissue mass of approximately 3 cm in distal ileum at antimesenteric site (arrow).
W.-C. Lin et al.
Figure 2 Single-balloon enteroscopy shows a submucosal tumor with central deep ulceration (arrows).
gastrointestinal tract with 50e70% occurring in the stomach; 25e30% in the small intestine; 5e10% in the colonerectum; and less than 5% in the esophagus.2,4 Primary small intestine tumors are rare, and only 1e3% of all gastrointestinal malignancies and GISTs are composed of about 20% of these tumors.5 The infrequent location of the small intestine and nonspecific symptoms of GISTs in the small intestine may make diagnosis difficult. The rate of detecting small intestine GISTs may be increased with the development of new techniques such as capsule endoscopy or balloon-assisted endoscopy. Four percent to 53% of patients with a GIST are asymptomatic and 19% of the patients are diagnosed incidentally. The most common symptom of GISTs is abdominal pain (38%) and the second most common symptom is bleeding (30%).3 After the complete resection of the tumor, the typical sites of tumor recurrence are the liver and peritoneum. In a series by Dematteo et al,6 the median time to recurrence was 1.5e2 years. The recurrence-free survival at 1, 2, 5, and 10 years was 83%, 75%, 63%, and 60%, respectively. The recurrence rate of GISTs was related to the tumor location, size, and mitotic rate. For GISTs in the small intestine, a large tumor size of 10 cm or greater and a mitotic rate of more than 5 per 50 high power fields were associated with a markedly high recurrence rate. The leiomyoma in the ileum after resection proved to be a predictor of recurrence in our patient. Surgery and targeted molecular therapy are the two gold standards for GISTs. Surgery is the first choice if a complete resection is possible. Imatinib is indicated for treating patients with KIT-positive (i.e., CD117-positive) unresectable and/or metastatic GISTs. For KIT-mutant proteins, imatinib is the choice drug and the response rate is nearly 70%, even in advanced disease.3 In our patient, the leiomyoma specimen obtained 20 years before was not available and the recurrence rate in this type of GIST would decrease as time progresses. Recurrent GIST in our patient is thus an uncertified diagnosis. With prolonged follow-up, it appears that almost all GISTs presenting with
Bleeding gastrointestinal stromal tumor
25
Figure 3 (A) The tumor microscopically arises from the muscular layer of the intestinal wall extending to the mesentery [hematoxylin and eosin (H&E) stain, 40%]. (B)The tumor cells exhibit prominent spindle cells in fascicles and focal storiform pattern (H&E stain, 400%). (C) Immunohistochemistry stain shows that the tumor cells are extensively immunoreactive for c-kit (i.e., CD117). (D) Immunohistochemistry stain shows that the tumor cells are weakly immunoreactive for CD34.
clinical symptoms or signs leading to treatment have the potential to behave in a malignant fashion.4 Based on tumor size and mitotic count in a consensus approach to GISTs, our GIST case appears to have a low risk of malignancy. The role of adjuvant treatment with imatinib after the complete resection of primary GIST tumors is unknown. The American College of Surgeons Oncology Group (ACOSOG) Z9001 Trial7 showed that imatinib significantly reduces the recurrence risk of a primary GIST that measures at least 3 cm (3% recurrence on imatinib vs. 17% without therapy at 12 months). We are inclined to think that the adjuvant imatinib treatment should be prescribed for patients with a tumor measuring 3.5 cm 2.5 cm 2.0 cm, although the drug is not sponsored by the national health insurance in Taiwan. Our patient preferred long-term follow-up rather than taking medications. In conclusion, enteroscopy is useful in preoperatively evaluating small bowel tumors and obscure gastrointestinal bleeding. If a patient with a long-term previous history (e.g., 20 years) of leiomyoma in the ileum suffers from obscure bleeding, we should consider a GIST. Imatinib increases recurrence-free survival when administered soon after the complete resection of a primary GIST.
References 1. Hirota S, Isozaki K, Moriyama Y, et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science. 1998;279:577e580. 2. Abraham SC. Distinguishing gastrointestinal stromal tumors from their mimics: an update. Adv Anat Pathol. 2007;14:178e188. 3. Caterino S, Lorenzon L, Petrucciani N, et al. Gastrointestinal stromal tumors: correlation between symptoms at presentation, tumor location and prognostic factors in 47 consecutive patients. World J Surg Oncol. 2011;9:13. 4. DeMatteo RP, Lewis JJ, Leung D, et al. Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival. Ann Surg. 2000;231:51e58. 5. Partridge BJ, Tokar JL, Haluszka O, et al. Small bowel cancers diagnosed by device-assisted enteroscopy at a US referral center: a five-year experience. Dig Dis Sci. 2011;56:2701e2705. 6. Dematteo RP, Gold JS, Saran L, et al. Tumor mitotic rate, size, and location independently predict recurrence after resection of primary gastrointestinal stromal tumor (GIST). Cancer. 2008; 112:608e615. 7. American College of Surgeons Oncology Group (ACOSOG) Intergroup Adjuvant GIST Study Team. Adjuvant imatinib mesylate increases recurrence free survival (RFS) in patients with completely resected localized primary gastrointestinal stromal tumor (GIST): North American Intergroup Phase III Trial ACOSOG Z9001.
Available online at www.sciencedirect.com
journal homepage: www.e-fjs.com
CASE REPORT
Bleeding gastrointestinal stromal tumor in a patient with a history of leiomyoma of the ileum Wei-Chen Lin a,c, Chen-Wang Chang a,c,*, Ching-Wei Chang a,c, Chung-Hsin Tsai b, Horng-Yuan Wang a,c a
Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan Department of General Surgery, Mackay Memorial Hospital, Taipei, Taiwan c Mackay Medicine, Nursing and Management College, Taipei, Taiwan b
Received 28 September 2011; received in revised form 23 January 2012; accepted 28 May 2012 Available online 4 February 2013
KEYWORDS gastrointestinal stromal tumor; leiomyoma; single-balloon enteroscopy
Summary Small intestine tumors, such as gastrointestinal stromal tumors (GISTs), are rare and difficult to be diagnosed. The most common GIST symptoms are abdominal pain and bleeding. A novel enteroscopy method is helpful in the localization and preoperative evaluation of small bowel tumors. We report a 77-year-old woman who had a history of leiomyoma in the ileum 20 years previously. She presented with intermittent bloody stool passage. Pathological examination showed a GIST in the ileum measuring 3.5 cm 2.5 cm 2.0 cm. The aim of this case report is to remind clinicians that GISTs should be considered if a patient with a history of leiomyoma in the small bowel has obscure, inexplicable gastrointestinal bleeding. Copyright ª 2012, Taiwan Surgical Association. Published by Elsevier Taiwan LLC. All rights reserved.
1. Introduction In the past, leiomyoma was an unascertained diagnosis. Since 1998, GIST was diagnosed by Hirota et al, according to mutations in the KIT gene.1 We now understand the molecular pathogenesis of GISTs and use a specific target
agent such as imatinib to block KIT and platelet-derived growth factor receptor-alpha (PDGFR alpha).2,3 Imatinib is indicated for treating unresectable or metastatic GISTs. We report a patient who intermittently passed bloody stools, which began years after she had had a complete resection of a localized leiomyoma in the ileum.
2. Case report * Corresponding author. Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Number 92, Section 2, Chung-Shan North Road, Taipei 104, Taiwan. E-mail address: [email protected] (C.-W. Chang).
A 77-year-old female had a history of leiomyoma in the ileum. The tumor was approximately 6 cm 5.5 cm 5 cm. It had caused intestinal obstruction and had been
1682-606X/$ - see front matter Copyright ª 2012, Taiwan Surgical Association. Published by Elsevier Taiwan LLC. All rights reserved. http://dx.doi.org/10.1016/j.fjs.2012.09.003
24 completely resected 20 years previously. She had been intermittently passing bloody stools since 2 years before her visit to our clinic. She had no recent fever, abdominal pain, or weight loss. Esophagogastroduodenoscopy, colonoscopy, a small bowel barium study, and a red blood cell (RBC) bleeding scan all failed to show the source of the active bleeding. An abdominal computed tomography (CT) study showed a soft tissue mass of approximately 3 cm in the distal ileum (Fig. 1). Single-balloon enteroscopy for preoperative marking revealed a submucosal tumor (Fig. 2) in the distal ileum, approximately 20e25 cm from the ileocecal valve. It measured approximately 3e4 cm and had linear ulceration. At surgery, after enterolysis for small bowel adhesion, a grayish friable tumor, measuring 3.5 cm 2.5 cm 2.0 cm, was found at the proximal ileum. The tumor cells microscopically exhibited prominent spindle cells in fascicles and in a focal storiform pattern (Fig. 3). The mitotic rate was less than 1 per 50 high power fields and the proliferation rate of Ki-67/MIB-1 was less than 1%.The tumor cells were extensively immunoreactive with CD117 and DOG-1; weakly immunoreactive with CD34; and had a negative immunoreactivity for desmin. She was diagnosed as having a GIST.
3. Discussion GISTs are the most common mesenchymal tumors of the intestinal tract. They may occur anywhere in the whole
Figure 1 Abdominal computed scan shows a soft tissue mass of approximately 3 cm in distal ileum at antimesenteric site (arrow).
W.-C. Lin et al.
Figure 2 Single-balloon enteroscopy shows a submucosal tumor with central deep ulceration (arrows).
gastrointestinal tract with 50e70% occurring in the stomach; 25e30% in the small intestine; 5e10% in the colonerectum; and less than 5% in the esophagus.2,4 Primary small intestine tumors are rare, and only 1e3% of all gastrointestinal malignancies and GISTs are composed of about 20% of these tumors.5 The infrequent location of the small intestine and nonspecific symptoms of GISTs in the small intestine may make diagnosis difficult. The rate of detecting small intestine GISTs may be increased with the development of new techniques such as capsule endoscopy or balloon-assisted endoscopy. Four percent to 53% of patients with a GIST are asymptomatic and 19% of the patients are diagnosed incidentally. The most common symptom of GISTs is abdominal pain (38%) and the second most common symptom is bleeding (30%).3 After the complete resection of the tumor, the typical sites of tumor recurrence are the liver and peritoneum. In a series by Dematteo et al,6 the median time to recurrence was 1.5e2 years. The recurrence-free survival at 1, 2, 5, and 10 years was 83%, 75%, 63%, and 60%, respectively. The recurrence rate of GISTs was related to the tumor location, size, and mitotic rate. For GISTs in the small intestine, a large tumor size of 10 cm or greater and a mitotic rate of more than 5 per 50 high power fields were associated with a markedly high recurrence rate. The leiomyoma in the ileum after resection proved to be a predictor of recurrence in our patient. Surgery and targeted molecular therapy are the two gold standards for GISTs. Surgery is the first choice if a complete resection is possible. Imatinib is indicated for treating patients with KIT-positive (i.e., CD117-positive) unresectable and/or metastatic GISTs. For KIT-mutant proteins, imatinib is the choice drug and the response rate is nearly 70%, even in advanced disease.3 In our patient, the leiomyoma specimen obtained 20 years before was not available and the recurrence rate in this type of GIST would decrease as time progresses. Recurrent GIST in our patient is thus an uncertified diagnosis. With prolonged follow-up, it appears that almost all GISTs presenting with
Bleeding gastrointestinal stromal tumor
25
Figure 3 (A) The tumor microscopically arises from the muscular layer of the intestinal wall extending to the mesentery [hematoxylin and eosin (H&E) stain, 40%]. (B)The tumor cells exhibit prominent spindle cells in fascicles and focal storiform pattern (H&E stain, 400%). (C) Immunohistochemistry stain shows that the tumor cells are extensively immunoreactive for c-kit (i.e., CD117). (D) Immunohistochemistry stain shows that the tumor cells are weakly immunoreactive for CD34.
clinical symptoms or signs leading to treatment have the potential to behave in a malignant fashion.4 Based on tumor size and mitotic count in a consensus approach to GISTs, our GIST case appears to have a low risk of malignancy. The role of adjuvant treatment with imatinib after the complete resection of primary GIST tumors is unknown. The American College of Surgeons Oncology Group (ACOSOG) Z9001 Trial7 showed that imatinib significantly reduces the recurrence risk of a primary GIST that measures at least 3 cm (3% recurrence on imatinib vs. 17% without therapy at 12 months). We are inclined to think that the adjuvant imatinib treatment should be prescribed for patients with a tumor measuring 3.5 cm 2.5 cm 2.0 cm, although the drug is not sponsored by the national health insurance in Taiwan. Our patient preferred long-term follow-up rather than taking medications. In conclusion, enteroscopy is useful in preoperatively evaluating small bowel tumors and obscure gastrointestinal bleeding. If a patient with a long-term previous history (e.g., 20 years) of leiomyoma in the ileum suffers from obscure bleeding, we should consider a GIST. Imatinib increases recurrence-free survival when administered soon after the complete resection of a primary GIST.
References 1. Hirota S, Isozaki K, Moriyama Y, et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science. 1998;279:577e580. 2. Abraham SC. Distinguishing gastrointestinal stromal tumors from their mimics: an update. Adv Anat Pathol. 2007;14:178e188. 3. Caterino S, Lorenzon L, Petrucciani N, et al. Gastrointestinal stromal tumors: correlation between symptoms at presentation, tumor location and prognostic factors in 47 consecutive patients. World J Surg Oncol. 2011;9:13. 4. DeMatteo RP, Lewis JJ, Leung D, et al. Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival. Ann Surg. 2000;231:51e58. 5. Partridge BJ, Tokar JL, Haluszka O, et al. Small bowel cancers diagnosed by device-assisted enteroscopy at a US referral center: a five-year experience. Dig Dis Sci. 2011;56:2701e2705. 6. Dematteo RP, Gold JS, Saran L, et al. Tumor mitotic rate, size, and location independently predict recurrence after resection of primary gastrointestinal stromal tumor (GIST). Cancer. 2008; 112:608e615. 7. American College of Surgeons Oncology Group (ACOSOG) Intergroup Adjuvant GIST Study Team. Adjuvant imatinib mesylate increases recurrence free survival (RFS) in patients with completely resected localized primary gastrointestinal stromal tumor (GIST): North American Intergroup Phase III Trial ACOSOG Z9001.