Intestinal Leiomyosarcoma

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Background

Primary gastrointestinal (GI) sarcomas in general are a very rare entity, accounting for 1%-2% of GI malignancies. Of this uncommon group of highly malignant neoplasms, the leiomyosarcoma is the most common histiotype.[1] Intestinal leiomyosarcomas are mesenchymal tumors of smooth muscle origin. They occur mainly in the fifth and sixth decades of life, and abdominal pain and GI bleeding have been reported to be the most common clinical signs at presentation.

In the past, GI stromal tumors (GISTs) were misdiagnosed as leiomyosarcomas. GISTs, however, have been shown to lack characteristics of smooth muscle tumors on histologic examination.[2] They are often CD34 immunoreactive and express tyrosine kinase c-kit (CD117) receptor activity, in contrast to leiomyosarcomas.[3] Mutations in the c-kit receptor are linked to the neoplastic development. (See image below.)



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Colonic mucosa with gastrointestinal stromal tumor (GIST) involving the adjacent submucosa (hematoxylin and eosin [H&E] stain, medium power).

Approximately 1%-2% of solid tumors are soft-tissue sarcomas, and leiomyosarcomas comprise roughly 2%-9% of these sarcomas. Of the leiomyosarcomas, 20% are found in the GI tract, with sites of occurrence evenly divided between the stomach and the small intestine.

Pathophysiology

The causes of leiomyosarcoma are unknown.

These lesions apparently arise between the muscularis propria and muscularis mucosa layers of the bowel wall, though the exact histological source is in question. The tumors generally are made up of spindle-shaped cells and have a high cellularity. (See the following image.) With high-grade tumors, necrosis often is present.



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Oval- to spindle-shaped cells forming a fascicle (hematoxylin and eosin [H&E] stain, high power).

When considering all the primary malignancies of the small bowel, adenocarcinomas tend to occur more proximally, whereas carcinoids, lymphomas, and leiomyosarcomas occur more distally. Depending on the study reviewed, the primary sites of occurrence of leiomyosarcomas are divided equally between the stomach and the small intestine. As many as 50% of the leiomyosarcomas occurring in the small intestine are found in the ileum. Relatively few leiomyosarcomas have been found in the esophagus, colon, or rectum.

The natural history of this tumor involves local growth initially, with much of its growth being extraluminal; thus, bowel obstruction occurs late. Multiple primary sites are unusual. Often, as the size of the leiomyosarcoma increases, necrosis and bleeding follow. This leads to the most common presenting feature in symptomatic patients, bleeding, which often is massive.

Metastasis is primarily hematologic. Lymph node metastasis is rare, occurring in 0%-15% of cases, depending on the series. Leiomyosarcomas spread to the liver and peritoneum first. Spread to the lungs occurs less frequently than spread to the liver and the peritoneum. This is in contrast to other soft tissue sarcomas in which the lung is the most common site of metastasis. About 20%-40% of patients have metastasis at the initial laparotomy.

The two factors that are recurrent themes in any discussion of leiomyosarcomas are size and grade. These features largely determine the survivability of a patient with this disease. The impact of size is debatable. Logically, resection, which is the only hope for a cure, appears to be more difficult with larger tumors.

If a tumor is large, metastasis is more likely to have occurred. Because these tumors are extraluminal, they can grow quite large before they become symptomatic. They can range from 4-5 cm in diameter to as large as 19 cm.

The grade of malignancy is judged microscopically and is accepted universally as a prognostic indicator. Generally, high-grade change is considered greater than 5 mitotic figures per 10 high-powered fields.

Recurrence occurs in the peritoneum and/or the retroperitoneum. As many as 55% of patients with recurrence have metastatic lesions to the liver at the time that their recurrence is discovered. If a low-grade tumor recurs, it often does so with a new, more aggressive grade of histology.

Epidemiology

United States statistics

Intestinal leiomyosarcomas are fairly rare, with a frequency of around 1.4 cases per 100,000 patients.

The Martin series, which comprised 11,438 cases of gastrointestinal (GI) tract tumors from 1944 to 1982, included only 280 patients with primary small intestine tumors.[4] If ampullary lesions are excluded from this count, 217 cases of primary small intestine tumors, or 2.4%, were included in the series.

In 1994, DiSario reviewed the cases entered from 1966 to 1990 in the Utah Cancer Registry; only 328 cases of small intestine cancer were recorded.[5] Of these cases, 41% were carcinoid, 24% were adenocarcinomas, and 11% were sarcomas (1% was not clearly identified).

Carcinoid and adenocarcinomas are far more common, even when ampullary lesions are excluded.

A study by Jun Zhan and colleagues determined that malignant tumors were the most common small intestinal neoplasia.[6] Of the 125 patients with malignant tumors, 11% had leiomyosarcoma, 11% had adenocarcinoma, and 9% had small intestinal lymphoma. Patients with primary small intestinal disease most commonly presented with periumbilical pain.

International data

Information on international frequency is unavailable.

Sex- and age-related demographics

Depending on the study, the male-to-female ratio ranges from 1:1 to 2:1. No study was found in which sex was a prognostic indicator.

Leiomyosarcomas primarily are a disease of middle-aged persons, with the average age on presentation falling between the fifth and seventh decades of life.

Prognosis

With curative resection, the 5-year survival rate for patients with leiomyosarcoma of the small intestine is 40%-50%, according to Hill's review.[7]

In cases in which the grade of the tumor was documented, the median survival for patients with high-grade tumors was 25 months in one study, whereas the median survival for patients with low-grade tumors was approximately 98 months.[8]

A benign initial report on a resected tumor does not remove the patient from serious consequences because these tumors sometimes recur as malignancies—about 6% in one study.[9]

In a report on the characteristics of duodenal gastrointestinal stromal tumors (GISTs), Miki et al compared the clinicopathologic findings in and recurrence-free survival of 7 patients with these lesions with the same data for 34 patients with GISTs of the stomach or elsewhere and determined that the rates for symptomatic lesions were 86% in the duodenum, 32% in the stomach, and 56% elsewhere, with melena and anemia being the most common symptoms associated with duodenal GISTs.[10]  The rates of 2-year recurrence-free survival among patients were 51.4% for duodenal GISTs, 78.4% for stomach GISTs, and 100% for other GISTs. Using multivariate Cox analysis, the authors concluded that in terms of GIST recurrence, significant prognostic factors included symptoms, mitotic index, and tumor location.[10, 11, 12]

 

Morbiditymortality

The prognosis ranges from universally fatal to poor. Size and grade are determinants of prognosis, depending on the case series. Histology consisting of high-grade malignancy and a large tumor size portends a poor prognosis.

With curative resection, the 5-year survival rate of patients with a gastric leiomyosarcoma is 68%-90%, whereas small intestine tumors are associated with a survival rate of 40%-50%. Distant metastasis decreases the survival rate to around 30%.

Evans presented a 10-year series in which he followed the outcomes of 56 patients and found that approximately 70% of them had high-grade tumors.[8]  Patients with high-grade tumors had a median survival of 25 months. Patients with a low-grade tumor survived much longer, with a median survival of 98 months. In fact, 2 patients (15%) survived the study. Overall, the 5-year survival rate ranges from 18% to 50%. This range largely is a factor of patient selection.

In a study published in 1998, all leiomyosarcomas occurring over the span of 45 years at Charity Hospital in New Orleans were reviewed.[7]  The authors found that leiomyosarcomas of the small intestine and uterus had a somewhat better prognosis than those occurring in the retroperitoneum.

History

Symptoms are usually lacking; if present, they are nonspecific. Vague complaints, such as malaise, fatigue, and nonfocal abdominal pain, are often described.

The sign most often cited is bleeding. These tumors sometimes necrose and bleed into the bowel. In one study, 59% of patients with leiomyosarcomas were symptomatic. For 70% of these patients, bleeding was the primary symptom. Of those who bled, 69% bled acutely, and 82% of the acute bleeders required transfusions. Of those who bled acutely, 45% required emergent laparotomy. Duodenal tumors bled most often. Of the duodenal tumors, 75% bled, requiring an average replacement of 11.5 units of blood.

Complaints of malaise and fatigue likely are due to anemia, which often is present in patients who bleed chronically.

Weight loss is reported as a late feature, with an incidence of around 20%.

Past medical history: One study reported a possible relationship between leiomyosarcomas and Crohn disease. In this series, which reviewed more than 11,000 cases, 6% of the patients with leiomyosarcomas also had a history of Crohn disease.[7]

Physical

Unless the patient is bleeding or is acutely obstructed, physical findings usually are absent.

A mass rarely is palpable.

Patients with malignancy may present with the findings of obstruction, such as distention, borborygmi, a palpable mass, and diffuse mild-to-moderate abdominal tenderness.

Other patients present with jaundice secondary to either biliary obstruction or hepatic replacement by metastases.

Cachexia, hepatomegaly, and ascites may be present in patients with advanced metastatic disease.

Laboratory Studies

Unless obstruction or perforation occurs, low hemoglobin caused by acute or chronic bleeding may be the only laboratory evidence of leiomyosarcoma. If the bleeding is chronic, the appropriate indices will be affected.

Imaging Studies

Notably, as many as 40% of these tumors are discovered incidentally. With this in mind, the principle symptom or sign of leiomyosarcomas is gastrointestinal (GI) bleeding, sometimes massive.

Positive test results for occult blood in the stool of a patient demand a source. If colonoscopy and esophagogastroduodenoscopy (EGD) results are normal, always consider a focused contrast study of the small bowel followed by a computed tomography (CT) scan. In case the source of bleeding is not identified, consider CT enterography, magnetic resonance (MR) enterography or video-capsule endoscopy (VCE). Unfortunately, early detection of the tumor with CT scanning depends on the tumor size and may not be helpful.

In a study that evaluated 562 patients who underwent VCE from August 2001 to November 2003 for a variety of indications, 443 (79%) of the 562 had evidence of occult GI bleeding.[13] A diagnosis was made by VCE in 277 patients (49.3%). Of the 562 patients studied, 50 (8.9%) were found to have a small intestinal tumor, 48% of which were malignant.[13]

A single report describes the use of preoperative endoscopic ultrasonography in helping to plan resection.[9] Ludwig postulated that this modality might be useful; further study is necessary.

A study by Ping-Hong Zhou and colleagues that evaluated the use of miniprobe ultrasonography during colonoscopy in diagnosing submucosal tumors of the large intestine identified leiomyosarcoma as having inhomogeneous echoes and irregular borders.[ref10} Zhou et al also concluded that this technique provided information about the size and layer of origin of the tumors. As leiomyosarcoma account for only 0.1% of colonic malignancies, miniprobe ultrasonography is more useful in other submucosal tumors, such as lipomas and leiomyomas.

Procedures

Because leiomyosarcomas are intramural in origin and tend to grow extraluminally, biopsy tissue obtained from the luminal side from the lining over the tumor often will be reported as benign mucosa.

Computed Tomography (CT)-guided biopsy may be helpful in certain cases.

If possible, endoscopic ultrasonography with guided biopsy may be diagnostic.[14]

Histologic Findings

Leiomyosarcomas are malignant mesenchymal non-gastrointestinal stromal tumors (GISTs) with a high proliferation rate and positivity for desmin, alpha-MSA (alpha–muscle-specific actin), and vimentin. These tumors are spindle cell in character, with high cellularity. Leiomyomas arise from the smooth muscle cells in the muscularis propria or muscularis mucosa, can be intraluminal or extraluminal, and account for about 40% of benign intestinal neoplasms. Leiomyomas with more than 2 mitoses per high-power field are reclassified as leiomyosarcomas. The mitotic figure count is of supreme importance. A count of more than 5 mitotic figures per 10 high-powered fields places a tumor into the high-grade category. Necrosis often occurs with high-grade tumors. (See the images below.)



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Colonic mucosa with gastrointestinal stromal tumor (GIST) involving the adjacent submucosa (hematoxylin and eosin [H&E] stain, medium power).



View Image

Clusters of tumor cells separated by a hyaline and mucin-rich stroma (hematoxylin and eosin [H&E] stain, medium power).



View Image

Oval- to spindle-shaped cells forming a fascicle (hematoxylin and eosin [H&E] stain, high power).



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CD-34 stain showing a tumor (medium power). CD-34 is a myeloid progenitor cell antigen.



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High-power magnification with CD-34 antigen immunohistochemical stain showing membrane positivity of the tumor cells.

Medical Care

The National Comprehensive Cancer Network (NCCN) workup for intra-abdominal sarcomas includes evaluation and management, prior to initiation of therapy, by a multidisciplinary team with expertise and experience in sarcoma. A pretreatment chest/abdominal/pelvic computed tomography (CT) scan with contrast, with or without magnetic resonance imaging (MRI), is also indicated.

Preresection biopsy is not necessarily required, based on the degree of suspicion of other malignancies. Biopsy is required for patients receiving preoperative radiation therapy (RT) or chemotherapy. For resectable disease, surgery with or without intraoperative RT or preoperative therapy with RT and chemotherapy are options.

Chemotherapy and radiation have shown only limited benefit in the treatment of leiomyosarcomas. Response rates to various chemotherapeutic regiments generally have been below 40%.

Surgical Care

Resection of the tumor is the only hope for cure. Remove the associated lymph nodes, but extended lymphadenectomy is not necessary because these tumors rarely metastasize to lymph nodes (see Pathophysiology).[15]

Per the National Comprehensive Cancer Network (NCCN), for resectable disease, surgery with or without intraoperative radiation therapy (RT) or preoperative therapy with RT and chemotherapy are options. For unresectable disease, attempt downstaging of the tumor with chemotherapy or RT and then resect. If it is still unresectable or progressive disease, consider palliative chemotherapy, palliative RT, palliative surgery for symptom control, observation if asymptomatic, and always consider resection of resectable metastatic disease if the primary tumor can be controlled.

Postoperative treatment with RT or reresection, if technically feasible, may be options depending on the surgical outcomes. With R0 disease (negative margins), consider postoperative RT in highly selected patients. With R1 disease (positive margins), consider postoperative RT if no preoperative RT was given or consider a boost (10-16 Gy) if preoperative RT was given. For R2 disease (macroscopic incomplete resection), consider reresection if technically feasible or follow the course for unresectable disease as described above.

Consultations

A gastroenterologist will likely be involved in most cases of leiomyosarcoma, because affected patients generally present with gastrointestinal (GI) bleeding. Endoscopic ultrasonography may be of some benefit for diagnosing the more proximal tumors. Also, if ulceration occurs, performing a biopsy may be possible.

A surgeon must be involved to provide the definitive treatment.

A hematologist/oncologist may be able to provide insights into the prognosis, define the grade of the tumor and offer possible chemotherapy.

A radiation oncologist may be able to provide insight into possible preoperative, intraoperative, and/or postoperative RT.

Long-Term Monitoring

Local and systemic recurrence is a real possibility, and even a probability, in many cases of leiomyosarcoma. Closely monitor the patient for such a recurrence, but specific guidelines for follow-up are lacking because of the relatively rare nature of this tumor.

Perform regularly scheduled computed tomography (CT) scans and, as appropriate, endoscopic examinations together with blood work (blood counts and liver profile). The authors suggest a follow-up CT scan of the abdomen and endoscopy, if possible, at 3 and 6 months after surgery. This is followed with yearly screening.

The National Comprehensive Cancer Network (NCCN) recommends physical examination with imaging (abdomen/pelvic CT) every 3-6 months for 2-3 years, then every 6 months for the next 2 years, and then annually.

Stool should be screened for occult blood with the same frequency.

Any abdominal complaint should be evaluated aggressively.

A chest radiograph should be performed with each screening, together with a blood count.

Medication Summary

Imatinib mesylate (Gleevec), a 2-phenylaminopyridine that functions as a tyrosine kinase inhibitor, targets the c-kit domain expressed by some GISTs.[16] It has been shown to improve disease-free intervals in patients after resection of the tumor. A similar compound, sunitinib (Sutent), has been shown to be effective in patients with mutant GIST cells that are resistant to imatinib mesylate.[17]

Clinical trials are currently investigating agents, such as AP13573 and ET743 (trabectedin), in patients with advanced leiomyosarcomas, liposarcomas, or osteosarcomas.

Trabectedin (Yondelis) was approved in November 2015 in the United States for unresectable or metastatic liposarcoma or leiomyosarcoma in patients who have received a prior anthracycline-containing regimen.[18, 19] It is an alkylating drug that binds guanine residues in the minor groove of DNA. Approval was based on a phase 3 trial (n = 518) that showed a statistically significant improvement in progression-free survival compared with dacarbazine (4.2 mo vs 1.5 mo; P < 0.0001). No improvement in overall survival was observed.[18, 19]

Imatinib mesylate (Gleevec)

Clinical Context:  Specifically designed to inhibit tyrosine kinase activity of bcr-abl kinase in GISTs. GISTs are characterized by expression of the product of the proto-oncogene c-kit and often harbor gain-of-function kit mutations, leading to ligand-independent kinase activation. Imatinib inhibits abl, kit, and platelet-derived growth factor receptor (PDGFR) tyrosine kinase.

Sunitinib (Sutent)

Clinical Context:  Mulitkinase inhibitor that targets several tyrosine kinase inhibitors implicated in tumor growth, pathologic angiogenesis, and metastatic progression. Inhibits PDGFRs (ie, PDGFR-alpha, PDGFR-beta), vascular endothelial growth factor receptors (ie, VEGFR1, VEGFR2, VEGFR3), stem cell factor receptor (kit), Fms-like tyrosine kinase-3 (FLT3), colony-stimulating factor receptor type 1 (CSF-1R), and the glial cell-line–derived neurotrophic factor receptor (RET). Indicated for persons with GISTs whose disease has progressed or who are unable to tolerate treatment with imatinib mesylate (Gleevec). Delays median time to tumor progression.

Class Summary

These agents inhibit the signal transduction pathway regulated by receptor tyrosine kinase.

Trabectedin (Yondelis)

Clinical Context:  An alkylating drug that binds guanine residues in the minor groove of DNA. It is indicated for unresectable or metastatic liposarcoma or leiomyosarcoma in patients who have received a prior anthracycline-containing regimen.

Class Summary

Treatment with trabectedin may be considered in patients who have already received an anthracycline.

Author

Jaspreet K Ghumman, DO, Fellow, Department of Internal Medicine, Section of Gastroenterology, Providence Hospital

Disclosure: Nothing to disclose.

Coauthor(s)

Bradley J Warren, DO, FACG, FACOI, Consulting Staff, Digestive Health Associates, PLC

Disclosure: Nothing to disclose.

Janice M Fields, MD, FACG, FACP, Assistant Professor of Internal Medicine, Oakland University William Beaumont School of Medicine; Consulting Staff, Department of Internal Medicine, Section of Gastroenterology, Providence Hospital, St John Macomb-Oakland Hosptial

Disclosure: Nothing to disclose.

Michael H Piper, MD, Clinical Assistant Professor, Department of Internal Medicine, Division of Gastroenterology, Wayne State University School of Medicine; Consulting Staff, Digestive Health Associates, PLC

Disclosure: Nothing to disclose.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

BS Anand, MD, Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Rajeev Vasudeva, MD, Clinical Professor of Medicine, Consultants in Gastroenterology, University of South Carolina School of Medicine

Disclosure: Received honoraria from Pricara for speaking and teaching; Received consulting fee from UCB for consulting.

Acknowledgements

George Brasinikas, MD Staff Physician, Gallup Indian Medical Center

George Brasinikas, MD is a member of the following medical societies: American Medical Association, College of American Pathologists, and Medical Association of the State of Alabama

Disclosure: Nothing to disclose.

Jill Halonen, MD Staff Physician, Department of Surgery, St Agnes Medical Center

Disclosure: Nothing to disclose.

Richard K Spence, MD Senior Vice President for Clinical Affairs, Infonale

Disclosure: Nothing to disclose.

References

  1. McGrath PC, Neifeld JP, Lawrence W Jr, Kay S, Horsley JS 3rd, Parker GA. Gastrointestinal sarcomas. Analysis of prognostic factors. Ann Surg. 1987 Dec. 206(6):706-10. [View Abstract]
  2. Kosela-Paterczyk H, Rutkowski P. Dermatofibrosarcoma protuberans and gastrointestinal stromal tumor as models for targeted therapy in soft tissue sarcomas. Expert Rev Anticancer Ther. 2017 Dec. 17(12):1107-16. [View Abstract]
  3. Aggarwal G, Sharma S, Zheng M, et al. Primary leiomyosarcomas of the gastrointestinal tract in the post-gastrointestinal stromal tumor era. Ann Diagn Pathol. 2012 Dec. 16(6):532-40. [View Abstract]
  4. Martin RG. Malignant tumors of the small intestine. Surg Clin North Am. 1986 Aug. 66(4):779-85. [View Abstract]
  5. DiSario JA, Burt RW, Vargas H, McWhorter WP. Small bowel cancer: epidemiological and clinical characteristics from a population-based registry. Am J Gastroenterol. 1994 May. 89(5):699-701. [View Abstract]
  6. Zhan J, Xia ZS, Zhong YQ, et al. Clinical analysis of primary small intestinal disease: A report of 309 cases. World J Gastroenterol. 2004 Sep 1. 10(17):2585-7. [View Abstract]
  7. Hill MA, Mera R, Levine EA. Leiomyosarcoma: a 45-year review at Charity Hospital, New Orleans. Am Surg. 1998 Jan. 64(1):53-60; discussion 60-1. [View Abstract]
  8. Evans HL. Smooth muscle tumors of the gastrointestinal tract. A study of 56 cases followed for a minimum of 10 years. Cancer. 1985 Nov 1. 56(9):2242-50. [View Abstract]
  9. Ludwig DJ, Traverso LW. Gut stromal tumors and their clinical behavior. Am J Surg. 1997 May. 173(5):390-4. [View Abstract]
  10. Miki Y, Kurokawa Y, Hirao M, et al. Survival analysis of patients with duodenal gastrointestinal stromal tumors. J Clin Gastroenterol. 2010 Feb. 44(2):97-101. [View Abstract]
  11. Raut CP, Espat NJ, Maki RG, et al. Efficacy and tolerability of 5-year adjuvant imatinib treatment for patients with resected intermediate- or high-risk primary gastrointestinal stromal tumor: The PERSIST-5 clinical trial. JAMA Oncol. 2018 Dec 1. 4(12):e184060. [View Abstract]
  12. Segawa K, Sugita S, Aoyama T, et al. Detection of specific gene rearrangements by fluorescence in situ hybridization in 16 cases of clear cell sarcoma of soft tissue and 6 cases of clear cell sarcoma-like gastrointestinal tumor. Diagn Pathol. 2018 Sep 15. 13(1):73. [View Abstract]
  13. Cobrin GM, Pittman RH, Lewis BS. Increased diagnostic yield of small bowel tumors with capsule endoscopy. Cancer. 2006 Jul 1. 107(1):22-7. [View Abstract]
  14. Yoshida S, Yamashita K, Yokozawa M, et al. Diagnostic findings of ultrasound-guided fine-needle aspiration cytology for gastrointestinal stromal tumors: proposal of a combined cytology with newly defined features and histology diagnosis. Pathol Int. 2009 Oct. 59(10):712-9. [View Abstract]
  15. Tien YW, Lee CY, Huang CC, Hu RH, Lee PH. Surgery for gastrointestinal stromal tumors of the duodenum. Ann Surg Oncol. 2010 Jan. 17(1):109-14. [View Abstract]
  16. D'Adamo D. Advances in the treatment of gastrointestinal stromal tumor. Adv Ther. 2009 Sep. 26(9):826-37. [View Abstract]
  17. Guo T, Hajdu M, Agaram NP, et al. Mechanisms of sunitinib resistance in gastrointestinal stromal tumors harboring KITAY502-3ins mutation: an in vitro mutagenesis screen for drug resistance. Clin Cancer Res. 2009 Nov 15. 15(22):6862-70. [View Abstract]
  18. US Food and Drug Administration. FDA approves new therapy for certain types of advanced soft tissue sarcoma [news release]. October 23, 2015. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm468832.htm. Accessed: January 11, 2016.
  19. Demetri GD, von Mehren M, Jones RL, et al. A randomized phase III study of trabectedin (T) or dacarbazine (D) for the treatment of patients (pts) with advanced liposarcoma (LPS) or leiomyosarcoma (LMS). Presented at 2015 Annual Meeting of the American Society of Clinical Oncology; Chicago, Illinois; May 29, 2015. J Clin Oncol. 2015. 33 (suppl):abstr 10503.
  20. Zhou PH, Yao LQ, Zhong YS, et al. Role of endoscopic miniprobe ultrasonography in diagnosis of submucosal tumor of large intestine. World J Gastroenterol. 2004 Aug 15. 10(16):2444-6. [View Abstract]
  21. Artigau Nieto E, Luna Aufroy A, Dalmau Portulas E, et al. Gastrointestinal stromal tumors: experience in 49 patients. Clin Transl Oncol. 2006 Aug. 8(8):594-8. [View Abstract]
  22. Demetri GD, van Oosterom AT, Garrett CR, et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet. 2006 Oct 14. 368(9544):1329-38. [View Abstract]
  23. Yang WL, Yu JR, Wu YJ, et al. Duodenal gastrointestinal stromal tumor: clinical, pathologic, immunohistochemical characteristics, and surgical prognosis. J Surg Oncol. 2009 Dec 1. 100(7):606-10. [View Abstract]
  24. Zhan WH, Wang PZ, Shao YF, et al. [Efficacy and safety of adjuvant post-surgical therapy with imatinib in gastrointestinal stromal tumor patients with high risk of recurrence: interim analysis from a multicenter prospective clinical trial] [Chinese]. Zhonghua Wei Chang Wai Ke Za Zhi. 2006 Sep. 9(5):383-7. [View Abstract]
  25. Fragulidis GP, Vezakis A, Chondrogiannis K, Mellou A, Melemeni A, Polydorou A. Clinical presentation and management of gastro-intestinal and pancreatic secondary metastatic tumors. J BUON. 2015 Jul-Aug. 20(4):1009-14. [View Abstract]

Colonic mucosa with gastrointestinal stromal tumor (GIST) involving the adjacent submucosa (hematoxylin and eosin [H&E] stain, medium power).

Oval- to spindle-shaped cells forming a fascicle (hematoxylin and eosin [H&E] stain, high power).

Colonic mucosa with gastrointestinal stromal tumor (GIST) involving the adjacent submucosa (hematoxylin and eosin [H&E] stain, medium power).

Clusters of tumor cells separated by a hyaline and mucin-rich stroma (hematoxylin and eosin [H&E] stain, medium power).

Oval- to spindle-shaped cells forming a fascicle (hematoxylin and eosin [H&E] stain, high power).

CD-34 stain showing a tumor (medium power). CD-34 is a myeloid progenitor cell antigen.

High-power magnification with CD-34 antigen immunohistochemical stain showing membrane positivity of the tumor cells.

Colonic mucosa with gastrointestinal stromal tumor (GIST) involving the adjacent submucosa (hematoxylin and eosin [H&E] stain, medium power).

Clusters of tumor cells separated by a hyaline and mucin-rich stroma (hematoxylin and eosin [H&E] stain, medium power).

Oval- to spindle-shaped cells forming a fascicle (hematoxylin and eosin [H&E] stain, high power).

CD-34 stain showing a tumor (medium power). CD-34 is a myeloid progenitor cell antigen.

High-power magnification with CD-34 antigen immunohistochemical stain showing membrane positivity of the tumor cells.