Liver Metastasis from GIST

Juan E Small, MD - Case Coordinator
Joshua L Rosebrook, MD - Radiology Discussion
Xuefei Hong, MD - Pathology Discussion
Kemal Tuncali, MD - Attending Radiologist
Steven E Seltzer, MD - Attending Radiologist
Pablo R Ros, MD, MPH - Attending Radiologist

August 11, 2003

Presentation

Imaging Findings

A PET scan shows a spherical area of uptake in the liver. The kidneys and bladder appear to be demonstrating normal excretion of tracer. Ultrasound images show a correlating round, heterogeneous (mostly hyperechoic) lesion in the left lobe. Doppler imaging illustrates blood flow around the mass, but very little within it. CT images with contrast (late phase) confirm a rounded, hypodense lesion in the left lobe. Given the patient's history, it is important to consider that this mass may be a metastatic lesion (e.g., gastric adenocarcinoma, GI stromal tumor). GI stromal tumor is somewhat less likely, because these masses are typically hypervascular. The degree of vascularity in this mass is unclear.

T2-weighted MR images indicate high fluid content, suggesting areas of necrosis. This finding favors a metastasis of GI stromal tumor. Other possible entities include a primary liver tumor (such as hepatocellular carcinoma) and gall bladder carcinoma.

Diagnosis

Discussion

The gross sample is the patient’s prior gastrectomy/splenectomy specimen. It contains a large (7 cm), fleshy mass with cystic changes and focal areas of hemorrhage and necrosis. Low power microscopy shows the submucosa and the solid component of the tumor. At higher power, sheets of spindle cells and focal myxoid changes are visible. The tumor cells have pale, pink eosinophilic cytoplasm and a high rate of mitotic activity (up to 52/50 HPF). Immunostains show the tumor is positive for CD34, focally positive for C-Kit, and negative for desmin, SMA and S100.

Radiology Discussion:

Gastrointestinal stromal tumors (GIST) represent 0.1-3% of all GI neoplasms and 5-6% of sarcomas. They affect men and women approximately equally, and tend to strike patients between the ages of 30 and 60 years. These tumors can arise anywhere in the GI tract, but most occur in the stomach (70%) or small bowel (20-30%). Once pathologically confused with leiomyomas and leiomyosarcomas, GIST were given a unique classification in 1983 based on their unique cell of origin: the interstitial cell of Cajal or its precursor.

The molecular biology of GIST is unique. The cells express the c-kit stem cell factor receptor, which causes them to stain positive with CD117. A gain of function mutation, found in 85-90% of GIST, leads to uncontrolled cell proliferation. NF1 and c-kit germ line mutations are associated with an increased risk of GIST.

Patients with GIST typically present with vague abdominal pain, obstruction, GI bleeding, and a palpable mass. The tumor is considered to be benign in 70-80% of cases; size and mitotic activity are the best predictors of malignant activity. A size greater than 2 cm, mitotic activity above 10%, and male gender increase the risk of malignancy. Metastases to the regional lymph nodes occur in approximately 15% of cases; other sites of spread include liver, peritoneum, and lungs. The five-year survival rate is 35% overall, increasing to 54% with complete resection.

CT is the modality of choice for evaluation, but (given the presenting symptoms), these are also seen on upper GI series, endoscopy, and MR. The tumors arise in muscularis propria, so GIST often have the appearance of a predominantly extraluminal soft tissue mass. On CT and MR, look for a heterogeneously enhancing mass with central hemorrhage, necrosis, and cyst formation. GIST are typically large; one study reported a mean of 10.8cm (64 cases). The differential diagnosis includes leimyoma, leiomyosarcoma, schwannoma, neurofibroma, adenocarcinoma, and neuroendocrine tumors (e.g., carcinoids).

Surgical resection is the preferred treatment, but there is a high rate of recurrence. Gleevec® (Novartis), an intracellular small molecule inhibitor that blocks the signal transduction pathways of GOF c-kit, is the treatment of choice for unresectable or malignant GIST. With effective treatment, GIST become entirely cystic. Upon reactivation, the cysts develop intracystic enhancing nodules.

References

Levy AD, et al. From the Archives of the AFIP: Gastrointestinal Stromal Tumors: Radiologic Features with Pathologic Correlation RadioGraphics 2003; 23: 283-304.

Chen M, Bechtold R, Savage P. Cystic Changes in Hepatic Metastases from Gastrointestinal Stromal Tumors (GISTs) Treated with Gleevec (Imatinib Mesylate) AJR 2002;179:1059-1062.

Nishida T, et al. Multidetector CT of High-Risk Patients with Occult Gastrointestinal Stromal Tumors. AJR 2003;180:185-189.

Weissleder R et al. Primer of Diagnostic Imaging, 2nd Ed. Mosby, St. Louis, 1997.

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