Gastrointestinal Tract Leiomyosarcoma

Definition

• Malignant smooth muscle neoplasm arising in the gastrointestinal tract

Diagnostic Criteria

• Fascicles of spindle cells
• Moderate to abundant eosinophilic cytoplasm
• Oval to moderately elongate nuclei
• Frequently blunt-ended
• Mild to marked cytologic atypia
• Mitotic rate >5/50 HPF appears to be the most important criterion
• Most cases have >50/50HPF mitotic figures
• Very few cases <26/50HPF
• Size is not a criterion for aggressive behavior
• Range 2-19 cm
• May form polypoid intraluminal masses
• Leiomyosarcomas rare at all GI sites
• CD117 and DOG1 negative
  • Any stromal neoplasm of the GI tract expressing CD117 or DOG1 should be considered a GIST

Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting/updates: 12/5/09, 11/27/09

Supplemental studies

Immunohistology

*one CD34 positive case reported

Genetic Studies

• All leiomyosarcomas tested show no evidence of mutation in KIT

Differential Diagnosis

GI Leiomyoma	GI Leiomyosarcoma
May be limited to muscularis mucosae	Nearly always arises in muscularis propria
Atypia if present is focal	Diffuse atypia
Mitotic rate ≤5/50HPF	Mitotic rate >5/50HPF
No coagulative tumor cell necrosis	May have coagulative tumor cell necrosis

GI Leiomyosarcoma	GIST (spindled, cytologically malignant)
Frequently markedly pleomorphic	Pleomorphism infrequent, even in malignant lesions
Frequently brightly eosinophilic cytoplasm	Usually indistinct cytoplasm
CD117, DOG1 negative	CD117 74-95%, DOG1 87-94%
Desmin variably positive	Desmin 1-2%

Clinical

• Mean age 50-60
• Local recurrences and metastases are common
• Behavior may be quite aggressive

Bibliography

• Bosman FT, Carneiro F, Hruban RH, Thiese ND (Eds). WHO Classifiication of Tumors of the Digestive System, IARC, Lyon 2010.
• Miettinen M, Kopczynski J, Makhlouf HR, Sarlomo-Rikala M, Gyorffy H, Burke A, Sobin LH, Lasota J. Gastrointestinal stromal tumors, intramural leiomyomas, and leiomyosarcomas in the duodenum: a clinicopathologic, immunohistochemical, and molecular genetic study of 167 cases. Am J Surg Pathol. 2003 May;27(5):625-41.
• Miettinen M, Furlong M, Sarlomo-Rikala M, Burke A, Sobin LH, Lasota J. Gastrointestinal stromal tumors, intramural leiomyomas, and leiomyosarcomas in the rectum and anus: a clinicopathologic, immunohistochemical, and molecular genetic study of 144 cases. Am J Surg Pathol. 2001 Sep;25(9):1121-33.
• Miettinen M, Sarlomo-Rikala M, Sobin LH, Lasota J. Esophageal stromal tumors: a clinicopathologic, immunohistochemical, and molecular genetic study of 17 cases and comparison with esophageal leiomyomas and leiomyosarcomas. Am J Surg Pathol. 2000 Feb;24(2):211-22.
• Miettinen M, Sarlomo-Rikala M, Sobin LH, Lasota J. Gastrointestinal stromal tumors and leiomyosarcomas in the colon: a clinicopathologic, immunohistochemical, and molecular genetic study of 44 cases. Am J Surg Pathol. 2000 Oct;24(10):1339-52.
• Miettinen M, Sarlomo-Rikala M, Sobin LH. Mesenchymal tumors of muscularis mucosae of colon and rectum are benign leiomyomas that should be separated from gastrointestinal stromal tumors—a clinicopathologic and immunohistochemical study of eighty-eight cases. Mod Pathol. 2001 Oct;14(10):950-6.
• Miettinen M, Sobin LH, Lasota J. True Smooth Muscle Tumors of the Small Intestine: A Clinicopathologic, Immunohistochemical, and Molecular Genetic Study of 25 Cases. Am J Surg Pathol. 2009 Mar;33(3):430-6