AUTHOR AND EDITOR INFORMATION

Section 1 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

INTRODUCTION

Section 2 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Background

Intestinal leiomyosarcomas are mesenchymal tumors of smooth muscle origin. In the past, gastrointestinal stromal tumors (GISTs) were misdiagnosed as leiomyosarcomas. GISTs, however, have recently been shown to lack characteristics of smooth muscle tumors on histologic examination. They are often CD34 immunoreactive and express tyrosine kinase c-kit (CD117) receptor activity, in contrast to leiomyosarcomas. Mutations in the c-kit receptor are linked to neoplastic development.

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

Pathophysiology

Leiomyosarcomas 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. With high-grade tumors, necrosis often is present.

When considering all 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, 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 lung occurs less frequently than spread to the liver and 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 2 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 larger, 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 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.

Frequency

United States

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

The Martin series, which was composed of 11,438 cases of GI tract tumors from 1944-1982, included only 280 patients with primary small intestine tumors. If ampullar lesions are excluded from this count, 217 cases of primary small intestine tumors, or 2.4%, were in the series.

In 1994, Disario reviewed the cases entered from 1966-1990 in the Utah Cancer Registry; only 328 cases of small intestine cancer were recorded. 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 with ampullar lesions excluded.

A 2004 study by Jun Zhan and colleagues determined that malignant tumors were the most common small intestinal disease. Of 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

Information on international frequency is unavailable.

Mortality/Morbidity

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

• 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 (1985) presented a 10-year series in which he followed the cases of 56 patients. Roughly 70% of these had high-grade tumors. 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 runs from 18-50%. 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 (Hill MA, 1998). The authors found that leiomyosarcomas of the small intestine and uterus had a somewhat better prognosis than those occurring in the retroperitoneum.

Sex

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.

Age

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

CLINICAL

Section 3 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

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 and were hemorrhagic in nature, 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 around 20%.
• Past medical history: One study performed by Hill in 1986 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.

Physical

• Unless the patient is bleeding or is acutely obstructed, physical findings usually are absent.
• A mass rarely is palpable.

Causes

Causes of leiomyosarcoma are unknown.

DIFFERENTIALS

Section 4 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Other Problems to be Considered

Lymphoma
Adenocarcinoma
Intestinal leiomyoma

WORKUP

Section 5 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Lab Studies

• Unless obstruction or perforation occurs, low hemoglobin caused by acute or chronic bleeding may be the only evidence of this tumor. 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 GI bleeding, sometimes massive.
• If findings on esophagogastroduodenoscopy (EGD) and colonoscopy are normal, always consider a focused contrast study of the small bowel followed by a CT scan in case the source of bleeding is not identified. Unfortunately, early detection of the tumor by CT scan depends on size and may not be helpful.
• A single report describes the use of preoperative endoscopic ultrasound in helping to plan resection (Ludwig DG, 1997). Ludwig postulated that this modality might be useful; further study is necessary.
• A 2004 study by Ping-Hong Zhou and colleagues evaluated the use of miniprobe ultrasonography during colonoscopy in diagnosing submucosal tumors of the large intestine. Leiomyosarcomas were identified as having inhomogeneous echoes and irregular borders. Zhou et al also concluded that this technique provided information about size and layer of origin. 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 these tumors are intramural in origin and tend to grow extraluminally, biopsy findings from the luminal wall obtained from over the tumor often will be reported as benign mucosa.
• If possible, endoscopic ultrasound with guided biopsy may be diagnostic.

Histologic Findings

These tumors are spindle cell in character, with high cellularity. 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.

TREATMENT

Section 6 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Medical Care

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 associated lymph nodes, but extended lymphadenectomy is not necessary because these tumors rarely metastasize to lymph nodes (see Pathophysiology).

Consultations

• A gastroenterologist probably will be involved in most of these cases because patients generally present with gastrointestinal bleeding.
• • Endoscopic ultrasound 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 and define the grade of the tumor.

MEDICATION

Section 7 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Imatinib mesylate (Gleevec), a 2-phenylaminopyridine that functions as a tyrosine kinase inhibitor, targets the c-kit domain expressed by some GIST tumors. 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.

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

Drug Category: Tyrosine kinase inhibitors

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

FOLLOW-UP

Section 8 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Further Outpatient Care

• Local and systemic recurrence is a real possibility, and even a probability, in many cases. 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.
• Certainly, regularly scheduled CT scans and, as appropriate, endoscopic examinations together with blood work (blood counts and liver profile) should be performed. 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.
• 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.

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 in 1998.
• 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 (Evans HL, 1985).
• A benign initial report on a resected tumor does not remove the patient from consequences because these tumors sometimes recur as malignancies—about 6% in one study (Ludwig, 1996).

MISCELLANEOUS

Section 9 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Medical/Legal Pitfalls

• Positive test results for occult blood in the stool of a patient demand a source. If colonoscopy and EGD results are negative, investigate the small bowel with a radio-opaque follow-through or further endoscopy.

ACKNOWLEDGMENTS

Section 10 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author, Jill Halonen, MD, to the development and writing of this article.

MULTIMEDIA

Section 11 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Media file 1:  Colonic mucosa with gastrointestinal stromal tumor (GIST) involving adjacent submucosa (hematoxylin and eosin [H&E] stain, medium power).
	View Full Size Image
Media type:  Photo

Media file 2:  Clusters of tumor cells separated by a hyaline and mucin-rich stroma (hematoxylin and eosin [H&E] stain, medium power).
	View Full Size Image
Media type:  Photo

Media file 3:  Oval- to spindle-shaped cells forming a fascicle (hematoxylin and eosin [H&E] stain, high power).
	View Full Size Image
Media type:  Photo

Media file 4:  CD-34 stain showing a tumor (medium power). CD-34 is a myeloid progenitor cell antigen.
	View Full Size Image
Media type:  Photo

Media file 5:  High-power magnification with CD-34 antigen immunohistochemical stain showing membrane positivity of tumor cells.
	View Full Size Image
Media type:  Photo

REFERENCES

Section 12 of 12

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

• Artigau Nieto E, Luna Aufroy A, Dalmau Portulas E, et al. Gastrointestinal stromal tumors: experience in 49 patients. Clin Transl Oncol. Aug 2006;8(8):594-8.
• 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. Oct 14 2006;368(9544):1329-38.
• Evans HL. Smooth muscle tumors of the gastrointestinal tract. A study of 56 cases followed for a minimum of 10 years. Cancer. Nov 1 1985;56(9):2242-50. [Medline].
• Hill MA, Mera R, Levine EA. Leiomyosarcoma: a 45-year review at Charity Hospital, New Orleans. Am Surg. Jan 1998;64(1):53-60; discussion 60-1. [Medline].
• Hines OJ, Nelson S, Quinones-Baldrich WJ, Eilber FR. Leiomyosarcoma of the inferior vena cava: prognosis and comparison with leiomyosarcoma of other anatomic sites. Cancer. Mar 1 1999;85(5):1077-83. [Medline].
• Ludwig DJ, Traverso LW. Gut stromal tumors and their clinical behavior. Am J Surg. May 1997;173(5):390-4. [Medline].
• Martin RG. Malignant tumors of the small intestine. Surg Clin North Am. Aug 1986;66(4):779-85. [Medline].
• Zhan J, Xia ZS, Zhong YQ, et al. Clinical analysis of primary small intestinal disease: A report of 309 cases. World J Gastroenterol. Sep 1 2004;10(17):2585-7. [Medline].
• 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 [in Chinese]. Zhonghua Wei Chang Wai Ke Za Zhi. Sep 2006;9(5):383-7.
• Zhou PH, Yao LQ, Zhong YS, et al. Role of endoscopic miniprobe ultrasonography in diagnosis of submucosal tumor of large intestine. World J Gastroenterol. Aug 15 2004;10(16):2444-6. [Medline].

Article Last Updated: Nov 9, 2006