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Case Presentation - Spring, 2006

Gastrointestinal Stromal Tumor (GIST)

ThinPrep® Non-gyn Cytology

NOTE: The diagnosis and analysis for this case study were provided by an independent physician. All conclusions and opinions are those of the physician and not Hologic, Inc.

History: 73 year old male

Specimen type: Gastric Endoscopic Ultrasound FNA

Case provided by: Rhode Island Hospital, Providence, Rhode Island

ThinPrep® Cytology:

Discussion
The Gastrointestinal stromal tumor (GIST) is a well-known, but relatively uncommon neoplasm of the GI tract. Until a few years ago, most GISTs were diagnosed as leiomyosarcomas. It was originally thought that some GISTs originate in the muscle layer of the GI tract while others originate in nerve cells. More recently, these cancers are no longer identified as muscle or nerve tumors, yet are thought to arise in cells of the GI tract called the interstitial cells of Cajal (ICCs). ICCs are part of the autonomic nerve system, which send signals to the GI tract. ICCs are also referred to as the "pacemakers" of the GI tract, regulating the movement of the gut.

GISTs may be benign or malignant. Although GISTs can occur anywhere in the GI tract, they are found most commonly in the stomach (60%-70%) and less commonly in the small intestine (20%-30%). These tumors may also originate in the large intestine, rectum, anus and esophagus. GISTs occur in people between 40-80 years of age and are more common in men.

Symptoms of GISTs include abdominal discomfort or pain, and intestinal bleeding. Tumors may also grow into the intestine causing intestinal blockage. In patients with intestinal obstruction, severe abdominal pain and vomiting may occur. Patients with smaller tumors may be asymptomatic.

Gastric cytology in combination with endoscopic biopsy increases the accuracy of both tests. Gastrointestinal stromal tumors are very difficult to sample because they originate in the mucosal layer of the GI tract.

Cytology
Cells of GISTs may range in appearance from bland, benign appearing cells to very pleomorphic cells. Cells can be spindled or epithelioid. The spindled varieties present as elongated, bland appearing cells with blunted nuclei and evenly distributed chromatin with indistinct nucleoli. Cells may be arranged in cohesive fascicles, loose clusters, fragments or singly. Stripped nuclei and perinuclear vacuoles may be seen. Those with an epithelioid presentation have polygonal or round cells with round to oval hyperchromatic nuclei. Tumors with a significant epithelioid component are typically associated with more aggressive behavior. In malignant tumors necrosis and mitoses may be seen. Metastases to the liver are common.

Typically cells of GISTs stain positive for CD34 and CD117 (C-kit protein) by immunohistochemistry. The absence of staining with actin, desmin helps to exclude a smooth muscle neoplasm. Similarly, the absence of S100 staining lessens the consideration of a Schwannoma.

Treatment and Prognosis
Surgery is the most common treatment for patients with small tumors. Larger tumors and tumors that have metastasized do not respond well to surgery. Tumors may recur after surgery and chemotherapy and radiation may be used as adjunctive treatments. Due to the reduced effectiveness of these treatments, researchers are looking into other drugs for the treatment of GISTs. Gleevec, a tyrosine kinase inhibitor, is a treatment option because of its ability to block critical enzyme that supports the growth of tumor cells. This treatment is given as a single dose or with surgery although it is most effective for tumors that can not be removed by surgery, have metastasized or have returned after original treatment. In spite of other treatment options, surgery is still the preferred treatment choice for GISTs.

Staging of this disease is very important in predicting the prognosis. Prognostic factors include size of tumor, location and whether the cancer has metastasized. Histologic grading is another way to evaluate the prognosis of GISTs. In histiologic grading, the pathologist counts the number of mitoses and this can be used to predict whether the GIST is benign or malignant. Further separation of patients into categories such as those more likely to be cured (low risk), and those less likely to be cured (intermediate and high risk) may also be established from these counts.

Newly introduced treatment options for GISTs that have recurred or spread have made the survival rates harder to predict. Past survival rates for those categorized as low risk (tumor smaller than 1-2 inches with few mitoses) indicate 100% survival. Patients with intermediate risk (tumors smaller than 1.2 inches but with more mitoses) had a 75% 5 year survival rate and high risk patients had a 25% 5 year survival rate.

References
  1. American Cancer Society. Gastrointestinal Stromal Tumors. Atlanta, GA: American Cancer Society Inc; 2004. www.cancer.org
  2. Gray, Winifred and McKee, Grace. Diagnostic Pathology 2nd edition. 2003: 403-404.
  3. Ramzy, Ibrahim MD. Clinical Cytopathology and Aspiration Biopsy 2nd edition. 2001: 289-290.
  4. www.peoplelivingwithcancer.org Cancer Type: Gastrointestinal Stromal Tumor.
  5. www.gistsupport.org GIST Support International.