Definition/General
Introduction:
Small intestinal adenocarcinoma is a rare malignant epithelial tumor of the small bowel
It represents less than 3% of all GI malignancies
Duodenum is most common location (50-60%)
Has poor prognosis due to late presentation.
Origin:
Arises from intestinal epithelium through adenoma-carcinoma sequence
May develop from pre-existing adenomas
Crohn disease increases risk
Celiac disease predisposes to jejunal tumors.
Classification:
Intestinal-type adenocarcinoma (most common)
Diffuse/signet ring type
Mucinous adenocarcinoma
Poorly differentiated variants
Graded as well, moderately, or poorly differentiated.
Epidemiology:
Peak incidence in 6th-7th decades
Male predominance (1.5:1)
Higher incidence in Crohn disease patients
Duodenal tumors more common than jejunal/ileal
Increasing incidence in developed countries.
Clinical Features
Presentation:
Abdominal pain (70-80%)
Weight loss (50-60%)
Nausea and vomiting (40-50%)
GI bleeding (30-40%)
Bowel obstruction (20-30%)
Jaundice (periampullary tumors)
Perforation (rare).
Symptoms:
Cramping abdominal pain
Progressive weight loss
Iron deficiency anemia
Steatorrhea (malabsorption)
Early satiety
Constitutional symptoms (fatigue, weakness).
Risk Factors:
Crohn disease (increased risk 60-fold)
Celiac disease
Familial adenomatous polyposis
Hereditary nonpolyposis colorectal cancer
Peutz-Jeghers syndrome
Age >50 years
Male gender.
Screening:
No routine screening protocols
CT enterography for suspected cases
Upper endoscopy for duodenal lesions
Capsule endoscopy for small bowel evaluation
Push enteroscopy for tissue diagnosis
Surveillance in high-risk patients.
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Gross Description
Appearance:
Polypoid or ulcerative mass
Gray-white cut surface
Firm consistency
Central ulceration common
Circumferential growth causing obstruction
Serosal involvement in advanced cases.
Characteristics:
Irregular borders with infiltration
Areas of necrosis
Desmoplastic reaction
Mucinous component in some cases
Direct extension to adjacent organs.
Size Location:
Duodenum (50-60%, especially periampullary)
Jejunum (20-30%)
Ileum (15-20%)
Size at presentation typically 2-5 cm
Multifocal disease in 5-10% cases.
Multifocality:
Usually solitary at presentation
Multiple tumors in FAP and HNPCC
Synchronous adenomas possible
Lymph node metastases common (60-70%)
Distant metastases to liver and peritoneum.
Microscopic Description
Histological Features:
Invasive glandular epithelium with varying differentiation
Well-differentiated: Well-formed glands
Moderately differentiated: Irregular glands
Poorly differentiated: Solid sheets, signet ring cells
Desmoplastic stroma.
Cellular Characteristics:
Columnar epithelial cells with nuclear atypia
Loss of polarity
Increased nuclear-cytoplasmic ratio
Prominent nucleoli
Mitotic activity variable
Mucin production in glandular areas.
Architectural Patterns:
Glandular architecture with invasion
Cribriform pattern
Solid growth in poorly differentiated areas
Single cell infiltration
Perineural invasion (40-50%)
Lymphovascular invasion (50-60%).
Grading Criteria:
WHO grading system: Grade 1 (well-differentiated, >95% glandular)
Grade 2 (moderately differentiated, 50-95% glandular)
Grade 3 (poorly differentiated, <50% glandular)
Based on glandular formation percentage.
Immunohistochemistry
Positive Markers:
CK20 (80-90% positive)
CDX2 (70-80% positive)
CK7 (variable, 30-50%)
CEA (60-70% positive)
EMA (positive)
Villin (intestinal differentiation).
Negative Markers:
TTF-1 (negative)
PSA (negative)
Hepatocyte marker (negative)
WT1 (negative)
Inhibin (negative).
Diagnostic Utility:
CK20 and CDX2 support intestinal origin
CK7/CK20 profile helps determine primary site
MMR proteins (MLH1, MSH2, MSH6, PMS2) for Lynch syndrome screening
p53 expression in dysplasia.
Molecular Subtypes:
Microsatellite stable (majority)
Microsatellite unstable (Lynch syndrome, sporadic)
CpG island methylator phenotype
Chromosomal instability pathway.
Molecular/Genetic
Genetic Mutations:
APC mutations (adenoma-carcinoma sequence)
KRAS mutations (40-50%)
TP53 mutations (50-60%)
PIK3CA mutations (20-30%)
SMAD4 mutations
MMR gene defects in Lynch syndrome.
Molecular Markers:
p53 overexpression (40-50%)
β-catenin nuclear accumulation
Loss of SMAD4 (advanced tumors)
High microsatellite instability (10-15%)
BRAF mutations (rare).
Prognostic Significance:
Stage at presentation most important factor
Grade correlates with survival
Lymph node involvement indicates poor prognosis
MSI status may predict immunotherapy response
KRAS mutations predict anti-EGFR resistance.
Therapeutic Targets:
Surgical resection primary treatment
5-fluorouracil-based chemotherapy
Oxaliplatin combinations
Targeted therapy (anti-EGFR, anti-VEGF)
Immunotherapy for MSI-high tumors.
Differential Diagnosis
Similar Entities:
Metastatic adenocarcinoma (pancreatic, colorectal)
Carcinoid tumor
GIST
Lymphoma
Adenoma with high-grade dysplasia
Inflammatory conditions (Crohn disease).
Distinguishing Features:
Primary SI adenocarcinoma: CK20+/CDX2+
Pancreatic metastases: CK7+/CK20+
Colorectal metastases: CK20+/CDX2+ (clinical correlation needed)
Carcinoid: Chromogranin+/Synaptophysin+
GIST: KIT+/DOG1+.
Diagnostic Challenges:
Distinguishing primary vs metastatic adenocarcinoma
Separating from high-grade dysplasia in adenomas
Identifying early invasion
Sampling adequacy in small biopsies.
Rare Variants:
Mucinous adenocarcinoma
Signet ring cell carcinoma
Adenosquamous carcinoma
Undifferentiated carcinoma
Medullary carcinoma (MSI-associated).
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
[resection type], [size] cm
Diagnosis
Adenocarcinoma, [grade]
Grade
WHO Grade [1/2/3] ([well/moderately/poorly] differentiated)
Size and Extent
Size: [X] cm, T stage: [T1-T4]
Lymph Nodes
[X] positive out of [X] examined, N stage: [N0-N2]
Margins
Proximal: [X] cm, Distal: [X] cm, Radial: [X] mm
TNM Stage
pT[X]N[X]M[X], Stage [I-IV]
Final Diagnosis
Small intestinal adenocarcinoma, Grade [X], pT[X]N[X]M[X], Stage [X]