GI Stromal Tumor

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A previously healthy 26-year-old woman was hospitalized for melena. She denied prior episodes of GI bleeding, fatigue, or dyspnea.

The patient was pale. Heart rate was 102 beats per minute, and blood pressure was 100/50 mm Hg. Hemoglobin level was 5 g/dL. Esophagogastroduodenoscopy showed 2 large submucosal tumors in antrum with central umbilication, 1 with active bleeding (A). The bleeding lesion was treated with an injection of epinephrine and normal saline (1:10,000) and placement of a ligating clip (B). Examination of biopsy specimens from the nonbleeding lesion revealed a spindle cell tumor that showed CD117 and CD34 expression, consistent with a GI stromal tumor (GIST).

Despite endoscopic therapy, severe bleeding recurred. The patient subsequently underwent hemigastrectomy. The resected stomach revealed 2 tumors between 2 and 2.5 cm, tumor-free margins, and no metastases. Results of histopathological studies confirmed the diagnosis and showed no predictors of malignancy. At 12-month follow-up, there was no evidence of recurrence.

GISTs are mesenchymal tumors that arise from the GI wall, mesentery, omentum, or retroperitoneum.¹ They differ from true leiomyomas, leiomyosarcomas, and other mesenchymal tumors of the GI tract by the expression of the c-kit proto-oncogene protein, a cell membrane receptor with tyrosine kinase activity, also known as CD117.¹ In addition, GISTs frequently co-express CD34, a transmembrane glycoprotein found in mesenchymal cells. Therefore, immunohistochemical staining for CD34 and CD117 has become crucial for accurate diagnosis.

GISTs are most often found in patients in their 60s; however, cases in younger persons have been reported. Most GISTs are located in the stomach (60% to 70%) or are confined to the small intestine (20% to 30%); up to 30% of GISTs are malignant.² Standard histopathological features that confirm malignant behavior are lacking. Malignancy is defined by metastasis to omentum, mesentery, or peritoneal adjacent organs; recurrence after surgical resection; or metastasis to extra-intestinal organs (liver, lungs) or the abdominal wall.

In tumors that present without metastasis, pathological factors that have been used to determine malignancy include mitotic activity, nuclear pleomorphism, degree of cellularity, nuclear to cytoplasmic ratio, tumor size, mucosal invasion, ulceration, and tumor necrosis. Of these, both mitotic activity and tumor size are the most useful morphologic features in predicting malignant behavior.^1,2

Tumor resection remains the primary treatment of all symptomatic GISTs and those suspected of being malignant or potentially malignant. Standard chemotherapy and radiotherapy have not been effective for patients with metastatic or unresectable GIST. The use of imatinib mesylate may be effective for some patients with malignant GIST.¹

References:

REFERENCES:
1. Davila RE, Faigel DO. GI stromal tumors. Gastrointest Endosc. 2003;58:80-88.
2. Miettinen M, Sarlomo-Rikala M, Lasota J. Gastrointestinal stromal tumors: recent advances in understanding of their biology. Hum Pathol. 1999;30:1213-1220.