Definition/General
Introduction:
Small intestinal lymphoma represents primary lymphoid malignancies arising in the small bowel
It accounts for 1-2% of all lymphomas and 20-30% of small bowel malignancies
Non-Hodgkin lymphomas predominate (95%)
It includes MALT lymphoma, DLBCL, and T-cell lymphomas.
Origin:
Arises from mucosa-associated lymphoid tissue (MALT) or acquired lymphoid aggregates
Most common types: B-cell lymphomas (70-80%)
T-cell lymphomas (20-30%) including enteropathy-associated T-cell lymphoma (EATL)
Associated with chronic inflammation, celiac disease, and immunosuppression.
Classification:
WHO Classification 2017: Extranodal marginal zone lymphoma (MALT)
Diffuse large B-cell lymphoma (DLBCL)
Enteropathy-associated T-cell lymphoma (EATL)
Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL)
Burkitt lymphoma
Mantle cell lymphoma.
Epidemiology:
Rare tumors (1-2% of all lymphomas)
Male predominance (2:1 ratio)
Peak incidence: 50-70 years
Geographic variation: EATL higher in Northern Europeans
Celiac disease association (EATL)
Higher incidence in immunocompromised patients.
Clinical Features
Presentation:
Abdominal pain (most common, 80% cases)
Diarrhea and malabsorption
Intestinal obstruction (40% cases)
Perforation (20% cases)
GI bleeding
Weight loss and fatigue
B-symptoms (fever, night sweats, weight loss).
Symptoms:
Crampy abdominal pain
Chronic diarrhea and steatorrhea
Intestinal obstruction symptoms
Perforation with peritonitis
Iron deficiency anemia
Protein-losing enteropathy
Constitutional symptoms.
Risk Factors:
Celiac disease (50-100x increased risk for EATL)
Immunosuppression: HIV, transplant recipients
Inflammatory bowel disease
H
pylori infection (gastric MALT)
Autoimmune disorders
Prior chemotherapy or radiation.
Screening:
CT abdomen/pelvis (wall thickening, lymphadenopathy)
Small bowel follow-through
Capsule endoscopy
Double-balloon enteroscopy
PET-CT scan (staging)
Bone marrow biopsy.
Master Intestinal Lymphoma Pathology with RxDx
Access 100+ pathology videos and expert guidance with the RxDx app
Gross Description
Appearance:
Polypoid or ulcerative masses
Circumferential wall thickening
Multiple nodules or plaques
Surface ulceration common
Bowel wall rigidity
Perforation may be present (20% cases).
Characteristics:
Firm, gray-white masses
Mucosal ulceration and irregularity
Transmural involvement common
Luminal narrowing
Serosal surface may show nodules
Cut surface: homogeneous, flesh-like.
Size Location:
Jejunum most common site (40-50%)
Ileum involvement (30-40%)
Duodenum less common (10-20%)
Multiple sites possible (30% cases)
Size: 2-15 cm (average 5-8 cm).
Multifocality:
Multifocal involvement in 30% cases
Skip lesions characteristic of EATL
Diffuse involvement possible
Concurrent nodal involvement
Systemic disease at presentation (40% cases).
Microscopic Description
Histological Features:
Dense lymphoid infiltrate
Mucosal destruction and ulceration
Lymphoepithelial lesions (MALT lymphoma)
Transmural involvement
Vascular invasion common
Necrosis and inflammatory infiltrate.
Cellular Characteristics:
Monomorphic lymphoid cells
Large cells (DLBCL): pleomorphic nuclei, prominent nucleoli
Small to medium cells (MALT): irregular nuclei
T-cell lymphomas: pleomorphic, often large cells
Mitotic activity variable.
Architectural Patterns:
Diffuse growth pattern (DLBCL)
Marginal zone pattern (MALT lymphoma)
Epitheliotropism (T-cell lymphomas)
Angioinvasion common
Villous atrophy and crypt destruction
Granulomatous response possible.
Grading Criteria:
WHO Classification based on cell morphology and immunophenotype
Low-grade: MALT lymphoma
Intermediate-grade: DLBCL
High-grade: Burkitt lymphoma, EATL
Ki-67 proliferation index variable.
Immunohistochemistry
Positive Markers:
CD20 (B-cell lymphomas)
CD3 (T-cell lymphomas)
CD5 (mantle cell lymphoma)
CD10 (Burkitt lymphoma, some DLBCL)
BCL-2 (MALT lymphoma)
Cyclin D1 (mantle cell lymphoma)
MUM1 (activated B-cells).
Negative Markers:
CD5 (MALT lymphoma)
CD10 (MALT lymphoma)
CD23 (mantle cell lymphoma)
Cyclin D1 (most B-cell lymphomas)
TdT (mature lymphomas).
Diagnostic Utility:
Confirms lymphoid nature of infiltrate
Distinguishes B-cell from T-cell lymphomas
Identifies specific lymphoma subtypes
Clonality assessment (light chains for B-cells)
Excludes reactive lymphoid proliferation.
Molecular Subtypes:
MALT lymphoma: CD20+, BCL-2+, CD5-, CD10-
DLBCL: CD20+, CD79a+, variable CD10
EATL: CD3+, CD7+, CD103+
Burkitt lymphoma: CD20+, CD10+, BCL-6+, MYC+.
Molecular/Genetic
Genetic Mutations:
t(11;18)(q21;q21): API2-MALT1 fusion (MALT lymphoma)
t(14;18)(q32;q21): BCL-2 rearrangement
t(8;14)(q24;q32): MYC-IGH fusion (Burkitt)
TP53 mutations (aggressive lymphomas)
MYD88 mutations.
Molecular Markers:
Clonal immunoglobulin rearrangements (B-cell lymphomas)
T-cell receptor rearrangements (T-cell lymphomas)
MYC overexpression (Burkitt lymphoma)
BCL-2 overexpression (MALT lymphoma)
p53 overexpression.
Prognostic Significance:
Stage at presentation: most important prognostic factor
Histological subtype: MALT lymphoma best prognosis
Perforation: poor prognostic factor
High Ki-67: worse prognosis
T-cell lymphomas: generally worse prognosis.
Therapeutic Targets:
Rituximab (CD20+ B-cell lymphomas)
Chemotherapy: CHOP, R-CHOP
Radiation therapy (localized MALT)
H
pylori eradication (gastric MALT)
Gluten-free diet (celiac-associated)
Stem cell transplant (high-grade).
Differential Diagnosis
Similar Entities:
Adenocarcinoma
Gastrointestinal stromal tumor (GIST)
Carcinoid tumor
Reactive lymphoid hyperplasia
Inflammatory bowel disease
Infectious enteritis.
Distinguishing Features:
Lymphoma: monoclonal lymphoid infiltrate, specific immunophenotype
Adenocarcinoma: epithelial markers positive, glandular architecture
GIST: CD117+, DOG1+
Carcinoid: chromogranin A+, synaptophysin+
Reactive: polyclonal population.
Diagnostic Challenges:
Distinguishing reactive from neoplastic
Identifying specific lymphoma subtype
Adequate tissue sampling
Assessing clonality
Excluding secondary involvement
Correlation with imaging.
Rare Variants:
Primary intestinal T-cell lymphoma NOS
NK/T-cell lymphoma
Plasmablastic lymphoma
Primary effusion lymphoma
Intravascular large B-cell lymphoma.
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 from [jejunum/ileum], measuring [size] cm
Diagnosis
[Lymphoma subtype] of small intestine
Classification
WHO Classification: [specific subtype and grade]
Histological Features
Dense [lymphoid cell type] infiltrate with mucosal destruction and transmural involvement
Size and Extent
Tumor size: [X] cm, extent: [mucosal/transmural], perforation: [present/absent]
Margins
Resection margins: [involved/uninvolved]
Lymph Nodes
Lymph nodes: [X] positive out of [X] examined
Special Studies
Immunohistochemistry: [CD20/CD3]: [result], [other markers]: [results]
Flow cytometry/PCR: [clonality result]
[other study]: [result]
Staging
Pathologic stage: [stage], based on extent of disease
Final Diagnosis
[Lymphoma subtype] of small intestine, [stage], [prognostic factors]