• Tumor which differentiates along line of interstitial cell of Cajal, the gut's pacemaker cell

• Median age 67 years, usually > 50 years
• May occur in HIV+ children
• 30-50% are malignant with 5 year survival of 50%; malignant tumors metastasize to liver and peritoneum
• Note: don’t call GIST if CD117 negative without expert concurrence
• Types: spindle cell GIST (70%), epithelioid cell GIST (20%), mixed (10%)
• CD117- GIST: 5% predilection for stomach or omentum/peritoneum, exhibit epithelioid or mixed type
• Dedifferentiated GIST: rare, CD117- with marked anaplasia

• GI sites: stomach (60%), jejunum and ileum (30%), duodenum (5%) and colorectum (<5%, Mod Pathol 2003;16:366)

• Poor prognosis (malignant): over 5 cm, fresh tumor necrosis, extensive hemorrhage unrelated to surgery, hypercellular, marked atypia, 5+ mitotic figures/HPF, smaller cells
• High risk: > 1 cm and > 5 MF/50 HPF; also infiltrative border within muscularis propria
• Intermediate risk: 1-5 MF/50 HPF and > 1 cm
• Low risk: < 1 cm (often are serosal)

• 45 year old woman with mid-jejunal mass and malignant GIST (Case of the Week #237)
• 65 year old man with multiple intestinal and mesenteric nodules (Case of the Week #270)

• Gleevec (STI571) inhibits tyrosine kinases including CD117/KIT and Abl protein in CML

• Often large, well circumscribed, bulky, intramural masses
• Fish-flesh or tan-brown appearance, hemorrhage, necrosis, cystic softening

Case of Week #237 (pelvic mass was attached to the mid-jejunum)

• Usually histologically malignant, usually transmural, usually plump spindle cells with eosinophilic cytoplasm within variably hyalinized or edematous stroma
• Skenoid fibers (extracellular collagen globules) common
• Muscle infiltration is common but not predictive of behavior
• May have epithelioid morphology

Various images (H&E)

Low power jejunal GIST

Various immunostains

CD34

CD117

CD38

AE1-AE3

S100

Vimentin

• CD117 (Am J Surg Pathol 2003;27:625), CD34, vimentin
• Variable alpha smooth muscle actin, DOG1, Carbonic anhydrase II (Am J Surg Pathol 2009;33:1401)
• DOG1 and PKC8 can be used in the diagnosis of KIT negative GIST (Mod Pathol 2011;24:866)

• S100, desmin

• Long interdigitating cytoplasmic processes, intercellular junctions, dense core granules

• Activating mutations in KIT or platelet-derived growth factor receptor &alpha receptor tyrosine kinases (Arch Pathol Lab Med 2011;135:1298)

• Fibromatosis: may be CD117+ with some antibodies (Am J Surg Pathol 2000;24:947, Am J Surg Pathol 2001;25:549)
• Inflammatory fibroid polyp: spindle and stellate cells with onion skinning around blood vessels, eosinophils, lymphocytes and plasma cells; CD34+ spindle cells are KIT-, DOG1-)
• Leiomyoma-uterine type: attached to colon without wall involvement, resemble benign leiomyoma, actin+, desmin+, CD117-
• Leiomyosarcoma: atypical histology, smooth muscle actin OR desmin positive, CD117-, CD34-, no KIT mutations

• Median age 56 years (range 10-88 years)
• Associated with neurofibromatosis type 1 (often with multiple tumors)
• Often long period to recurrence or metastases

• >5 cm, > 5 mitoses/50 HPF
• Epithelioid pattern with mucosal invasion

• <2 cm and <5 mitoses/50 HPF
• Organoid pattern with low cellularity

• Small intramural or external nodules or large masses extending into retroperitoneum

• Usually spindle cell tumors, often with skenoid fibers

• CD117, CD34 (54%), smooth muscle actin (39%), S100 (20%)

• Desmin (trapped smooth muscle fibers are positive)

• KIT mutations in exon 11 (30%) and exon 9 (13%) are common

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