What is the diagnosis and treatment approach for a round to spindle cell neoplasia of the stomach, likely a Gastrointestinal Stromal Tumor (GIST), in an adult patient over 50 years old presenting with a gastric mass?

Diagnosis and Management of Round to Spindle Cell Neoplasia of the Stomach (GIST)

A round to spindle cell neoplasm in the stomach should be presumed to be a gastrointestinal stromal tumor (GIST) until proven otherwise, given that the stomach accounts for 60% of all GISTs and spindle cell morphology represents 70% of cases. 1, 2

Diagnostic Confirmation

Immunohistochemical Algorithm

Perform KIT (CD117) immunostaining first without antigen retrieval, as 95% of GISTs are KIT-positive and this is the primary diagnostic marker. 1, 2

• If KIT is positive in a spindle cell tumor with compatible morphology, this strongly supports GIST diagnosis. 2
• If KIT is negative (5% of cases), immediately perform DOG1 staining, which will be positive in most KIT-negative GISTs. 1, 2
• CD34 staining provides supportive evidence (positive in 70% of GISTs) but is not diagnostic. 1

Exclusionary Testing

Check desmin and S-100 to rule out mimics:

• Desmin positivity indicates myogenic tumors (leiomyoma/leiomyosarcoma), not GIST. 1
• S-100 positivity suggests schwannoma. 1
• True gastric smooth muscle tumors would show both smooth muscle actin AND desmin positivity. 1

Molecular Confirmation

Perform mutation testing for KIT and PDGFRA genes, as nearly 80% and 10% of GISTs harbor these mutations respectively. 1, 2

• KIT exon 11 mutations are most common (65%), followed by exon 9 (8%). 1
• For gastric GISTs without KIT or PDGFRA mutations, perform SDHB immunostaining to identify SDH-deficient GISTs. 1, 2
• This testing is mandatory before initiating tyrosine kinase inhibitor therapy, as mutation status predicts imatinib sensitivity. 1

Critical Specimen Handling

Use only 4% buffered formalin fixation—never Bouin fixative, as Bouin impairs molecular analysis required for treatment planning. 1, 3

Risk Stratification

Document tumor size and mitotic count (expressed as mitoses per 5 mm², not per 50 HPF) for risk assessment. 1

High-risk features include:

• Size >5 cm 1
• Mitotic rate >5 per 5 mm² 1
• Tumor rupture or perforation 4
• Non-gastric location 1
• Irregular borders, internal heterogeneity, or ulceration 1

Treatment Algorithm

For Tumors <2 cm Without High-Risk Features

Perform annual endoscopic ultrasound (EUS) surveillance with initial follow-up at 6 months, then annually if stable. 1, 3

• Biopsy or excise only if growth occurs or symptoms develop. 1
• This conservative approach does not worsen prognosis for small gastric GISTs. 1

For Tumors ≥2 cm or Any Size with High-Risk Features

Obtain tissue diagnosis via EUS-guided fine needle aspiration or core needle biopsy before definitive surgery. 1, 3

• Pre-operative biopsy is safe when performed appropriately and does not compromise oncologic outcomes. 1
• For large tumors requiring extensive surgery (total gastrectomy, multi-visceral resection), pre-operative diagnosis is essential to enable neoadjuvant imatinib for tumor downstaging. 1

Surgical Management

Perform complete surgical resection with R0 (negative) margins:

• Wedge resection of the stomach is adequate for most gastric GISTs, preserving gastric function. 1, 4
• Avoid tumor rupture and capsule violation—use plastic bags for specimen removal to prevent peritoneal seeding. 4
• Lymph node dissection is unnecessary, as GISTs rarely metastasize to lymph nodes (except SDH-mutated subtypes). 1, 4
• Resect adherent organs en-bloc rather than risk capsular rupture. 1

Adjuvant Therapy

Administer adjuvant imatinib 400 mg daily for 3 years for high-risk features (size >5 cm, mitotic rate >5/5mm², rupture, or non-gastric location). 4, 5, 6

• For KIT exon 9 mutations, consider 800 mg daily due to relative imatinib resistance. 4
• For tumor rupture or perforation, consider lifelong imatinib due to very high peritoneal recurrence risk. 4
• The PDGFRA D842V mutation confers imatinib resistance—these patients require alternative strategies. 1, 6

Neoadjuvant Therapy

For marginally resectable tumors or those requiring extensive surgery, administer neoadjuvant imatinib to enable organ-sparing resection. 1, 6

• Confirm diagnosis and mutation status before starting therapy. 1
• Reassess resectability after tumor shrinkage. 1

Surveillance Protocol

For high-risk resected GISTs, perform contrast-enhanced CT abdomen/pelvis:

• Every 3-4 months for years 1-3 4, 3
• Every 6 months for years 4-5 4, 3
• Annually thereafter to 10 years 4, 3

For metastatic disease on imatinib, perform CT every 2-3 months to detect progression early. 3

Critical Pitfalls to Avoid

• Do not rely on KIT positivity alone—morphologic features must be compatible with GIST, as other tumors can show false-positive CD117 staining with antigen retrieval. 1
• Do not underestimate tumor rupture significance—it automatically places patients in very high-risk category requiring prolonged adjuvant therapy. 4
• Do not perform endoscopic resection—risk of positive margins, tumor spillage, and perforation make this investigational only. 1
• Do not omit mutation testing—it is mandatory for treatment planning and predicts imatinib response. 1
• Consult a sarcoma pathologist for equivocal cases, as diagnostic concordance among general pathologists is not always achievable. 1, 2