Summary
Gastrointestinal lymphomas are a diverse group of extranodal non-Hodgkin lymphomas that most commonly affect the stomach, small intestine, and colon. Diagnosis is challenging because these tumors often manifest with nonspecific symptoms such as abdominal pain, weight loss, and/or GI bleeding. Histological subtypes vary; mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma are the most common. Diagnostic studies include endoscopy with biopsy and cross-sectional imaging. Management depends on the subtype, and may consists of chemotherapy, immunotherapy, and occasionally surgery.
MALT lymphoma is discussed in a separate article.
Overview
| Overview of primary gastrointestinal lymphomas | ||||
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| Etiology | Histopathology | Immunophenotype | Management | |
| Diffuse large B-cell lymphoma of the GI tract [1][2] |
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| Burkitt lymphoma of the GI tract[1][2][3] |
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| Enteropathy-associated T-cell lymphoma [1][4] |
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| Monomorphic epitheliotropic intestinal T-cell lymphoma [1][4] |
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| Mantle cell lymphoma (MCL)[1][2] |
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Diffuse large B-cell lymphoma of the GI tract
Epidemiology [1][2]
- Diffuse large B-cell lymphoma of the GI tract (DLBCL) accounts for 70% of all gastric lymphomas. [1]
- Peak incidence: 50 years [2]
- ♂ > ♀
Etiology [1][2]
-
DLBCL may manifest as:
- De novo tumor
- Transformation of a low-grade B-cell lymphoma, most commonly MALT lymphoma
- May occur in patients with immunocompromise (e.g., due to HIV infection, posttransplant)
Clinical features [1]
- Features are nonspecific and may include:
- Abdominal pain
- Dyspepsia
- Nausea and vomiting
- Diarrhea
- Palpable abdominal mass
Diagnosis
Endoscopic assessment with biopsy and histopathology analysis is required for diagnostic confirmation.
Endoscopy [1]
Findings are nonspecific and may include:
- Erythematous mucosa
- Mucosal ulceration or erosions
- Enlarged and thickened gastric folds
Biopsy [1][2]
-
Histopathology
- Diffuse cell proliferation infiltrating the gastric glands and the lamina propria
- Neoplastic cells are medium to large, with markedly enlarged nuclei and scant pale or eosinophilic cytoplasm.
- Immunohistochemistry [2]
Differential diagnoses [1]
- Nonneoplastic conditions
- Reactive gastropathy and gastritis
- Reactive germinal centers within MALT lymphoma
- Malignancies
- Gastric adenocarcinoma
- Other gastrointestinal lymphomas (e.g., MALT lymphoma, mantle cell lymphoma, follicular lymphoma)
Management
- Management depends on tumor stage.
- First-line therapy consists of chemoimmunotherapy (i.e., R-CHOP and dose–adjusted EPOCH-R).
- Second-line therapy
Burkitt lymphoma of the GI tract
Classification of Burkitt lymphoma [1][2][3]
Burkitt lymphoma is classified into three variants, each with different epidemiological and clinical characteristics.
-
Sporadic variant
- Affects all age groups
- Variant in which GI tract involvement is most common.
- May be associated with EBV infection, especially in older adults
-
Endemic variant
- Mostly affects children and adolescents
- 95–100% of patients have EBV infection; infection with Plasmodium spp. is also common. [3]
-
Immunodeficiency-associated variant
- Mostly affects adults
- Commonly associated with HIV infection, may be associated with EBV infection
Epidemiology [1][2][3]
- Burkitt lymphoma accounts for ∼ 5% of all primary non-Hodgkin lymphomas of the GI tract. [1]
- The sporadic and endemic variants most commonly affect children and adolescents; the immunodeficiency-associated variant typically affects adults.
- The endemic variant occurs in equatorial Africa and Papua New Guinea. [3]
Etiology [1][2]
- Derived from germinal center B cells
- t(8;14) leads to overactivation of the C-MYC gene and transcription.
Clinical features [1][2][3]
Presentation is typically dramatic, with a rapidly growing mass that spreads systemically.
-
GI tract involvement (most common in the sporadic form)
- Rapidly growing large masses, commonly in the ileocecal region
- Bowel obstruction
- Other organs may be affected, e.g.:
- Peritoneum
- Thyroid
- Breasts
- Kidney
- Ovaries, testicles
- CNS (most common in the immunodeficiency-associated variant)
- Tumor lysis syndrome
Differential diagnoses
- Diffuse large B-cell lymphoma
- Other high-grade B-cell lymphomas with MYC translocations, e.g.:
- Mantle cell lymphoma
- Precursor B-cell lymphoblastic lymphoma
Diagnosis
General principles [3]
- Obtain initial laboratory studies (e.g., CBC, LDH, viral serologies).
- Staging of non-Hodgkin lymphomas is required for all patients.
- Diagnosis is confirmed with histopathological studies.
- See "Diagnosis of non-Hodgkin lymphoma" for more information.
Histopathology [3] [1][2]
A large-bore core needle or surgical biopsy is required; findings are similar across the three variants of Burkitt lymphoma.
- Diffuse infiltrate of monomorphic, medium-sized B cells
- Round nuclei with vesicular chromatin and multiple basophilic nucleoli
- Basophilic cytoplasm
- Ki-67 index ∼ 100% [1][3]
- Multiple tingible body macrophages ("starry sky" pattern)
Immunohistochemistry [1][2][3]
- Positive markers
-
Negative markers
- BCL-2
- CD5
- CD23
Cytogenetics
- MYC t (8;14) in ∼ 75% of tumors [1][3]
- May not be detected with standard fluorescence in situ hybridization
Management [3]
Emergency management is required to avoid complications.
- Systemic chemoimmunotherapy: combination regimens (e.g., cyclophosphamide, rituximab, methotrexate), based on patient risk
- CNS prophylaxis: in patients with features of high-risk tumors (e.g., patients with ECOG PS ≥ 2, ↑ LDH, tumor size ≥ 7 cm)
- See also "Treatment of non-Hodgkin lymphoma."
Burkitt lymphoma can be cured in ∼ 90% of children and adolescents. [3]
Complications [2]
- Hemorrhage
- Necrosis
- Tumor lysis syndrome
- Intestinal perforation
Enteropathy-associated T-cell lymphoma
Epidemiology [4]
- Prevalence is highest in Europe (∼ 9%) and among individuals of northern European descent. [4]
- Peak incidence: 60–70 years [4]
- ♂ ≈ ♀
Etiology [4]
- EATL occurs in the context of celiac disease (patients may be undiagnosed).
- HLA-DQA1*0501, HLA-DQB*0201 may be present.
- Patients with refractory celiac disease are at the highest risk for EATL.
- De novo tumor: in patients without complicated celiac disease
- Secondary to refractory celiac disease
Clinical features [1][4]
- Symptoms are nonspecific and may mimic celiac disease, e.g.:
- Constitutional symptoms
- Abdominal pain
- Diarrhea
- Clinical features of bowel obstruction (e.g., vomiting)
- GI bleeding
- Intestinal perforation (in 25–50% of patients) [4]
- Refractory celiac disease features may be present.
- Hemophagocytic syndrome (in 16–40% of patients) [4]
- Involvement of extraintestinal organs (e.g., bone marrow, lung, skin)
Diagnosis [1][4]
Endoscopy with biopsy, and histopathology and immunohistochemistry analysis are required for diagnosis.
-
Histopathology
- Diffuse proliferation of pleomorphic, medium to large atypical lymphocytes
- Cells have a round or irregular nucleus, with abundant eosinophilic or pale cytoplasm
- Concomitant polymorphic inflammatory infiltrate (e.g., eosinophils, neutrophils, plasma cells)
- Vascular invasion and extensive necrosis are common.
- Adjacent mucosa may show features of celiac disease (e.g., villous atrophy, crypt hyperplasia).
- Immunohistochemistry
Differential diagnoses [4]
- Monomorphic epitheliotropic intestinal T-cell lymphoma
- Intestinal T-cell lymphoma, not otherwise specified
- Indolent T-cell lymphoproliferative disorder of the GI tract
- NK-cell enteropathy
- Inflammatory GI disorders (e.g., celiac disease, inflammatory bowel disease)
Management [4]
EATL has a poor response to available treatment options. [4]
- Chemotherapy (e.g., CHOP regimen)
- Autologous stem cell transplant postchemotherapy may improve survival rates.
- Tumor reduction surgery may reduce the risk of chemotherapy-associated complications (e.g., tumor necrosis, peritonitis, GI bleeding).
EATL is often refractory to chemotherapy; the 5-year survival rate is ∼ 10–20%. [4]
Monomorphic epitheliotropic intestinal T-cell lymphoma
Epidemiology [1][4]
Etiology [1][4]
- Etiology is unknown
- No association with celiac disease (formerly known as EATL type II)
Clinical features [1][4]
Symptoms are often nonspecific, e.g.:
- Abdominal pain
- Diarrhea
- Weight loss
- GI bleeding
- Intestinal obstruction or perforation (most commonly in the jejunum)
Diagnosis [1][4]
Endoscopy with biopsy and histopathology and immunohistochemistry analysis are required for diagnosis.
Differential diagnoses [4]
- Enteropathy-associated T-cell lymphoma
- Anaplastic large cell lymphoma
- Indolent T-cell lymphoproliferative disorder of the GI tract
- NK-cell enteropathy
- Chronic active EBV infection of the GI tract
- Inflammatory disorders (e.g., celiac disease, inflammatory bowel disease)
Management [4]
MEITL has a very poor response to available treatment options. [4]
- Chemotherapy: CHOP regimen
- Autologous stem cell transplant after chemotherapy may improve survival rate.
- CNS prophylaxis may be considered. [4]
One third of tumors are advanced upon diagnosis; the survival rate at 5 years is ∼ 30%. [4]
Mantle cell lymphoma of the GI tract
Epidemiology [1][2]
- Primary GI mantle cell lymphomas (MCL) are rare.
- GI involvement in systemic MCL occurs in up to 90% of patients. [2]
Clinical features [1]
Patients may be asymptomatic or present nonspecific features, e.g.:
- Lymphadenopathy
- Constitutional symptoms
- Multiple intestinal polyposis
Diagnosis [1][2]
- Endoscopy: multiple intestinal polyps, ulcerations, mucosal protrusion
-
Histopathology
- Diffuse infiltration of monomorphic small-sized to medium-sized cells arranged in a nodular or mantle-zone pattern
- Cells have irregular nuclear borders, small nucleoli, and scant cytoplasm.
- Immunohistochemistry
- Cytogenetics: t(11;14)(q13;q32) is present in > 95% of patients. [1]
Differential diagnoses [1]
Management [2]
Tumors are aggressive, with poor response to treatment.
- Chemotherapy (e.g., combination regimens containing cytarabine, R-CHOP).
- Autologous hematopoietic stem cell transplant and/or rituximab may be offered as consolidation therapy.