Definition/General
Introduction:
Small intestinal GIST represents mesenchymal tumors arising from interstitial cells of Cajal or their precursors
It accounts for 20-30% of all GISTs
It is the second most common GIST location after stomach
It shows KIT or PDGFRA mutations in 85-90% cases.
Origin:
Originates from interstitial cells of Cajal (pacemaker cells) or their stem cell precursors
Myenteric plexus location common
Results from oncogenic mutations in KIT (75-80%) or PDGFRA (5-10%) genes
Wild-type GISTs (10-15%) lack these mutations.
Classification:
Classified by anatomical location: jejunum, ileum, duodenum
Risk stratification: very low, low, intermediate, high risk
Based on size, mitotic rate, location
Epithelioid variant (20%)
Spindle cell variant (70%)
Mixed variant (10%).
Epidemiology:
Accounts for 20-30% of all GISTs
Male predominance (slight)
Peak incidence: 50-70 years
Jejunum and ileum most common small bowel sites
Higher risk behavior compared to gastric GISTs.
Clinical Features
Presentation:
Abdominal pain (60-70% cases)
GI bleeding (melena, anemia)
Intestinal obstruction (30% cases)
Palpable mass
Perforation (10-15% cases)
Asymptomatic (incidental finding, 20%).
Symptoms:
Crampy abdominal pain
Iron deficiency anemia (chronic bleeding)
Melena or hematochezia
Small bowel obstruction symptoms
Early satiety
Fatigue and weakness.
Risk Factors:
Sporadic occurrence (95% cases)
Neurofibromatosis type 1 (2-3% risk)
Familial GIST syndromes (<1%)
Carney triad (GIST, paraganglioma, pulmonary chondroma)
Advanced age.
Screening:
CT abdomen/pelvis (hypervascular mass)
MRI (T2 hyperintense)
Endoscopy (submucosal mass)
EUS-guided biopsy
PET-CT (staging and follow-up)
Genetic testing (familial cases).
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Gross Description
Appearance:
Well-circumscribed mass
Bosselated surface
Tan-pink to gray cut surface
Fleshy consistency
Areas of hemorrhage and necrosis (large tumors)
Cystic degeneration possible.
Characteristics:
Intramural or subserosal location
Smooth, lobulated contour
Pseudocapsule present
Cut surface: whorled appearance
Hemorrhage common
Calcifications rare.
Size Location:
Jejunum (40-50%)
Ileum (30-40%)
Duodenum (10-20%)
Size range: 1-30 cm (average 5-8 cm)
Extraluminal growth pattern common.
Multifocality:
Usually solitary (90% cases)
Multiple GISTs in familial syndromes
Satellite nodules possible
Peritoneal implants (advanced cases)
Liver metastases (common metastatic site).
Microscopic Description
Histological Features:
Spindle cell morphology (70% cases)
Epithelioid morphology (20% cases)
Mixed morphology (10%)
Fascicular growth pattern
Storiform pattern
Perivascular arrangement.
Cellular Characteristics:
Spindle-shaped cells with elongated nuclei
Epithelioid cells with round nuclei
Eosinophilic cytoplasm
Nuclear atypia variable
Paranuclear vacuoles common
Skeinoid fibers (distinctive feature).
Architectural Patterns:
Fascicular arrangement of spindle cells
Storiform (cartwheel) pattern
Nested pattern (epithelioid type)
Syncytial growth
Myxoid stroma possible
Hyalinization and fibrosis.
Grading Criteria:
Mitotic count: key prognostic parameter
Low mitotic rate: ≤5 per 50 HPF
High mitotic rate: >5 per 50 HPF
Size criteria: ≤2 cm, 2-5 cm, 5-10 cm, >10 cm
Risk stratification based on size, mitoses, location.
Immunohistochemistry
Positive Markers:
CD117 (KIT) (95% cases)
DOG1 (95% cases)
CD34 (70% cases)
PKC-theta (80-90% cases)
Vimentin (positive)
Anoctamin 1 (DOG1, sensitive marker).
Negative Markers:
Desmin (negative, excludes smooth muscle)
S-100 (negative, excludes nerve sheath tumor)
SMA (usually negative)
Caldesmon (negative)
CD68 (negative).
Diagnostic Utility:
CD117 and DOG1: diagnostic markers for GIST
Distinguish from leiomyoma (desmin+, CD117-)
Distinguish from leiomyosarcoma (desmin+, caldesmon+)
Distinguish from schwannoma (S-100+).
Molecular Subtypes:
KIT-mutant GISTs (75-80%): exon 11, 9, 13, 17 mutations
PDGFRA-mutant GISTs (5-10%): exon 18, 12, 14 mutations
Wild-type GISTs (10-15%): SDH-deficient, NF1-associated.
Molecular/Genetic
Genetic Mutations:
KIT mutations (75-80%): exon 11 (60-70%), exon 9 (10-15%)
PDGFRA mutations (5-10%): exon 18 most common
SDH complex mutations (wild-type GISTs)
NF1 mutations (neurofibromatosis-associated)
BRAF mutations (rare).
Molecular Markers:
KIT protein overexpression
PDGFRA overexpression
Loss of SDHB expression (SDH-deficient GISTs)
p16 loss (progression marker)
p53 mutations (aggressive behavior).
Prognostic Significance:
Tumor size: >5 cm higher risk
Mitotic rate: >5/50 HPF higher risk
Small bowel location: higher risk than gastric
Tumor rupture: very high risk
KIT exon 11 deletions: higher risk.
Therapeutic Targets:
Imatinib (KIT/PDGFRA inhibitor): first-line therapy
Sunitinib: second-line (imatinib resistance)
Regorafenib: third-line therapy
Avapritinib: PDGFRA D842V mutants
Surgery: primary treatment.
Differential Diagnosis
Similar Entities:
Leiomyoma
Leiomyosarcoma
Schwannoma
Inflammatory myofibroblastic tumor
Dedifferentiated liposarcoma
Solitary fibrous tumor.
Distinguishing Features:
GIST: CD117+, DOG1+
Leiomyoma: desmin+, caldesmon+, CD117-
Leiomyosarcoma: desmin+, high mitoses
Schwannoma: S-100+, CD117-
IMT: ALK+ (50%), inflammatory cells.
Diagnostic Challenges:
Distinguishing low-grade GIST from leiomyoma
Identifying epithelioid variant
CD117-negative GISTs (5%)
Risk stratification accuracy
Differentiating from metastatic disease.
Rare Variants:
Pediatric GIST (SDH-deficient)
Familial GIST (germline KIT mutations)
NF1-associated GIST
Carney triad
Inflammatory GIST.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
Small bowel resection with tumor, measuring [size] cm
Diagnosis
Gastrointestinal stromal tumor (GIST) of small intestine
Classification
Histological type: [spindle cell/epithelioid/mixed]
Histological Features
[Spindle/epithelioid] cell tumor with [fascicular/storiform] growth pattern
Size and Mitoses
Tumor size: [X] cm, mitotic count: [X] per 50 HPF
Margins
Resection margins: [involved/uninvolved]
Special Studies
CD117: [positive/negative], DOG1: [positive/negative], CD34: [result]
Mutation analysis: [recommended/performed]: [result]
[other study]: [result]
Risk Assessment
Risk category: [very low/low/intermediate/high] risk of aggressive behavior
Final Diagnosis
Small intestinal GIST, [size] cm, [mitotic rate], [risk category]