Final Diagnosis -- Leiomyosarcoma, myxoid variant

FINAL DIAGNOSIS  

Leiomyosarcoma, myxoid variant

DISCUSSION

Primary leiomyosarcomas of the gastrointestinal tract are extremely rare. They generally occur in the older patient population (median age, 61, in one series). These tumors are most commonly found in the esophagus, colon, and rectum, although they can present anywhere within the GI tract. The tumors most frequently present as intraluminal polypoid lesions and may appear morphologically similar to gastrointestinal stromal tumors (GISTs), which are much more common overall in the GI tract. Histologically, leiomyosarcomas demonstrate intersecting fascicles of spindle cells and are usually quite cellular. Fibrosis or myxoid change may be seen. The nuclei are elongated with blunt ends, and nuclear pleomorphism is generally prominent, as are mitoses. However, both nuclear pleomorphism and mitoses may be focal or rare. The cytoplasm is typically eosinophilic with a fibrillar appearance, although it can be pale. Tumor necrosis and hyalinized, hypocellular areas may be seen in larger tumors. Immunohistochemically, leiomyosarcomas show smooth muscle differentiation and stain for smooth muscle actin, desmin, and/or caldesmon. They are always negative for CD117. Smooth muscle neoplasms of the GI tract are believed to arise from either the muscularis mucosae or the muscularis propria. A genetic abnormality is yet to be identified to aid in the diagnosis.

Colonic leiomyosarcomas are aggressive tumors with a high mortality rate. The majority of patients already have pulmonary metastases at the time of presentation. However, patients with polypoid tumors may have a better clinical outcome.

The differential diagnosis for leiomyosarcoma includes leiomyoma, GIST, schwannoma, and other neural tumors. Leiomyomas are most common in the esophagus and colorectum. Colorectal leiomyomas are small nodules arising from the muscularis mucosae that are typically incidental findings on colonoscopy. Microscopically, they consist of bland, spindle-shaped cells with eosinophilic cytoplasm. They can be differentiated from leiomyosarcomas by their lack of atypia, extremely low or non-existent mitotic activity, and absence of necrosis. GISTs of the colon are most often malignant and have a similar appearance to leiomyosarcomas. The spindle-shaped nuclei show significant pleomorphism with decreased cytoplasm compared to benign tumors. Many mitoses and tumor necrosis are usually present. GISTs have an immunohistochemical profile distinct from leiomyosarcomas and stain for C-KIT (CD117), CD34, and DOG-1. Schwannoma should also be considered, although it is rare in the gastrointestinal tract. The cells are spindle-shaped with wavy nuclei and low mitotic activity. Cellularity may vary within the tumor. Schwannomas stain for S100 and GFAP, but are negative for smooth muscle markers and C-KIT.

REFERENCES

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2. Aggarwal G, et al. Primary leiomyosarcomas of the gastrointestinal tract in the post-gastrointestinal stromal tumor era. Ann Diagn Pathol. 2012; 16(6):532-540.
3. Goldblum, John. "Mesenchymal Tumors of the GI Tract." Surgical Pathology of the GI Tract, Liver, Biliary Tract, and Pancreas. Robert D. Odze and John R. Goldblum, eds. 2nd ed. Philadelphia: Saunders/ Elsevier, 2009. 694-700.
4. Miettinen M, et al. Gastrointestinal stromal tumors and leiomyosarcomas in the colon: a clinicopathologic, immunohistochemical, and molecular genetic study of 44 cases. Am J Surg Pathol. 2000; 24(10):1339-1352.
5. World Health Organization. Smooth Muscle Tumours. Fletcher CDM, Unni KK, Mertens F, editors. Pathology and Genetics of Tumours of Soft Tissue and Bone. Lyon: IARC Press; 2002. pp. 130-134.

Contributed by Alicia Hunt, MD and Alyssa Krasinskas, MD