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Gastric Lymphoma

Outline of Lymphoma Chapter

  1. Classification of Lymphomas
    • Hodgkin Lymphoma (HL)
      • Characteristics and subtypes
      • Typical clinical presentation
    • Non-Hodgkin Lymphoma (NHL)
      • Overview and classification (e.g., B-cell, T-cell lymphomas)
      • Specific GI-related lymphomas:
        • MALT lymphoma
        • Diffuse Large B-Cell Lymphoma (DLBCL)
        • Other rare types (e.g., Burkitt lymphoma, Mantle cell lymphoma)
  2. Epidemiology of Gastric Lymphomas
    • Incidence and prevalence
    • Risk factors
      • Helicobacter pylori infection
      • Autoimmune diseases (e.g., Sjögren’s syndrome)
      • Genetic predispositions and mutations
  3. Pathophysiology
    • Origin and development of lymphomas
    • Role of chronic inflammation and infection (e.g., H. pylori in MALT lymphoma)
    • Molecular genetics and translocations
      • t(11;18), t(1;14), and other relevant mutations
  4. Clinical Presentation
    • Symptoms and signs of gastric lymphoma
      • Common symptoms: epigastric pain, melena, anorexia, weight loss
      • Endoscopic findings
    • Diagnostic approach
      • Biopsy and histopathology
      • Imaging studies (e.g., CT, PET-CT)
      • Staging systems (e.g., Lugano classification)
  5. Staging and Prognosis
    • Lugano Classification for GI lymphomas
    • Prognostic factors
      • Clinical staging
      • Genetic markers
      • Response to H. pylori eradication (for MALT lymphoma)
  6. Management of Gastric Lymphomas
    • MALT Lymphoma
      • H. pylori eradication therapy
      • Role of radiotherapy and chemotherapy
      • Surgery in specific cases (e.g., complications, non-responsive cases)
    • Diffuse Large B-Cell Lymphoma (DLBCL)
      • Systemic chemotherapy (R-CHOP regimen)
      • Indications for surgery and radiotherapy
    • High-Grade Lymphomas
      • Aggressive treatment approaches (chemotherapy, stem cell transplant)
    • Surgical Indications and Management
      • Indications for surgery in lymphoma cases
      • Role in managing complications (e.g., perforation, bleeding)
  7. Follow-Up and Surveillance
    • Post-treatment monitoring strategies
    • Endoscopic surveillance
    • Management of recurrence
  8. Complications and Special Considerations
    • Treatment-related complications
    • Managing refractory disease
    • Role of emerging therapies and clinical trials

MCQ Callout: Characteristic Features of Lymphomas

Answer: A

Explanation:

  • Lymphoepithelial lesions are a hallmark of MALT lymphoma (Mucosa-Associated Lymphoid Tissue lymphoma). This feature involves the invasion and partial destruction of mucosal glands by malignant lymphocytes, which is a defining characteristic of MALT lymphomas, particularly in the stomach.
  • MALT lymphomas typically arise in the stomach, where chronic inflammation (often due to Helicobacter pylori infection) leads to the development of lymphoid tissue that can undergo malignant transformation into MALT lymphoma.
  • Histology: The lymphoepithelial lesions in MALT lymphomas are composed of intermediate-sized B cells with pale cytoplasm and slightly irregular nuclei, and they are particularly notable for their ability to invade and disrupt glandular structures in the gastric mucosa.

Summary Key Points:

  • MALToma (MALT lymphoma) is associated with lymphoepithelial lesions that involve the destruction of glandular structures by lymphocytes.
  • These lesions are significant in diagnosing MALT lymphoma and differentiating it from other lymphomas such as Burkitt lymphoma, Diffuse large B-cell lymphoma, and T-cell lymphoma.
  • The presence of Helicobacter pylori infection is strongly associated with the development of gastric MALT lymphoma.

Lugano Classification for Staging Non-Hodgkin's Lymphoma

Answer: D

Explanation:

  • The Lugano Classification, as shown in the provided image, does not include a Stage III. The staging system goes directly from Stage II to Stage IV, with Stage II being subdivided into stages II₁ and II₂.
  • Stage I: Confined to the GI tract, either as a single primary or noncontiguous lesions.
  • Stage II: Extends to abdominal lymph nodes.
    • Stage II₁: Involves local (paragastric) lymph nodes.
    • Stage II₂: Involves distant (mesenteric, paraaortic, paracaval, pelvic, inguinal) lymph nodes.
    • Stage IIₑ: Involves adjacent organs or tissues by direct infiltration.
  • Stage IV: Represents extranodal involvement or spread to extrabdominal lymph nodes, including noncontiguous involvement of separate GI sites or other organs, and potentially bone marrow involvement.

Since the Lugano Classification does not have a Stage III, the correct answer is D: None of the above.

Summary Key Points:

  • Lugano Classification for staging Non-Hodgkin's lymphoma does not include a Stage III. The classification jumps from Stage II (with subcategories II₁, II₂, IIₑ) directly to Stage IV.
  • Stage IV includes extensive involvement, such as extranodal spread, involvement of other organs, or noncontiguous GI tract involvement.

Management of Diffuse Large B-Cell Lymphoma (DLBCL) in the Stomach

Answer: A

Explanation:

  • Surgery Alone (Option A):
    • Not appropriate. Surgery alone is generally not sufficient for the treatment of Diffuse Large B-Cell Lymphoma (DLBCL) of the stomach. DLBCL is an aggressive type of non-Hodgkin's lymphoma, and the cornerstone of treatment is systemic chemotherapy, often combined with Rituximab (R-CHOP regimen). Surgery is rarely used as the sole treatment.
  • Surgery with Chemotherapy (Option B):
    • Appropriate. Surgery may be indicated in certain cases of gastric lymphoma, particularly for managing complications (e.g., perforation, bleeding). However, surgery is usually combined with chemotherapy to effectively manage the systemic nature of the disease.
  • Chemotherapy Alone (Option C):
    • Appropriate. Chemotherapy alone is often the primary treatment for gastric DLBCL, especially in the absence of complications requiring surgical intervention. The standard regimen includes Rituximab combined with CHOP (Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone).

Management Options of Gastric Lymphoma:

  1. Chemotherapy:
    • First-Line Therapy: For most cases of gastric lymphoma, particularly DLBCL, systemic chemotherapy is the primary treatment. The R-CHOP regimen (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone) is commonly used and is highly effective.
    • Chemotherapy alone is sufficient in many cases and is the mainstay of treatment unless complications arise.
  2. Surgery:
    • Limited Role: Surgery is not typically the primary treatment for gastric lymphoma but may be necessary in specific circumstances.
    • Indications for Surgery:
      • Complications: Surgery may be indicated for managing life-threatening complications such as perforation or massive bleeding that cannot be controlled with endoscopic or medical therapy.
      • Localized Disease: In rare cases where the disease is localized and confined to the stomach, surgery combined with chemotherapy might be considered.
      • Persistent Disease After Chemotherapy: If there is residual disease following chemotherapy, surgery may be considered to achieve complete remission.
  3. Combined Modality Therapy:
    • Surgery with Chemotherapy: In cases where surgery is performed for complications or localized disease, it is typically followed by chemotherapy to treat any residual microscopic disease and reduce the risk of recurrence.
  4. Radiotherapy:
    • Role of Radiotherapy: Radiotherapy may be used in specific cases, particularly for MALT lymphoma, but its role in DLBCL is less clear and typically reserved for localized disease or residual disease after chemotherapy.

Summary Key Points:

  • Chemotherapy (e.g., R-CHOP) is the mainstay of treatment for gastric DLBCL and is often sufficient alone.
  • Surgery alone is not an appropriate treatment option for DLBCL, as it does not address the systemic nature of the disease.
  • Indications for Surgery include managing complications like perforation or bleeding, localized disease, or persistent disease after chemotherapy.
  • Combined modality therapy involving surgery and chemotherapy may be necessary in certain cases, but chemotherapy should always be part of the treatment regimen.

MCQ Callout: Risk Factors for Recurrence After H. pylori Eradication in MALT Lymphoma

Answer: D

Explanation:

  • t(11;18) mutation (Option A): Associated with resistance to H. pylori eradication therapy and increased risk of recurrence in MALT lymphoma.
  • BCL-10 expression (Option B): Overexpression linked to poor response and recurrence risk.
  • Transmural involvement (Option C): Advanced disease with transmural involvement is less likely to respond to H. pylori eradication and more prone to recurrence.
  • t(1;14) mutation (Option D): While involving BCL-10, this mutation does not significantly impact response to H. pylori therapy and is not a major risk factor for recurrence.

Management of Low-Grade MALT Lymphoma:

  1. H. pylori Eradication Therapy:
    • First-Line Treatment: Effective in achieving remission in early-stage, low-grade MALT lymphomas confined to the gastric mucosa.
    • Therapy Regimen: Standard treatment involves a combination of a proton pump inhibitor (PPI) with antibiotics (clarithromycin and amoxicillin or metronidazole).
    • Follow-Up: Regular endoscopy and biopsy are required to monitor regression, with a significant proportion of patients achieving complete remission.
  2. When H. pylori Eradication Fails:
    • Radiotherapy: Used for localized disease, particularly effective for achieving local control.
    • Chemotherapy: Regimens such as R-CHOP may be used in cases unresponsive to H. pylori eradication or with more advanced disease.
    • Immunotherapy: Rituximab, an anti-CD20 monoclonal antibody, is an option in refractory cases.

Management of High-Grade MALT Lymphoma (e.g., Transformation to DLBCL):

  1. Systemic Chemotherapy:
    • First-Line Therapy: High-grade MALT lymphoma, particularly when it has transformed into Diffuse Large B-Cell Lymphoma (DLBCL), requires systemic chemotherapy.
    • R-CHOP Regimen: The most commonly used regimen, combining Rituximab with Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone. This regimen is effective in managing high-grade lymphomas and is typically used in multiple cycles.
  2. Surgery:
    • Limited Role: Surgery is generally reserved for managing complications such as perforation or bleeding but is not a primary treatment modality for high-grade MALT lymphoma.
  3. Radiotherapy:
    • Adjuvant Role: May be used in combination with chemotherapy for localized high-grade MALT lymphoma, especially to control residual disease or in cases where chemotherapy alone is insufficient.
  4. Management of Refractory Disease:
    • Alternative Chemotherapy Regimens: For patients who do not respond to initial R-CHOP therapy, alternative chemotherapy regimens may be considered.
    • Stem Cell Transplant: In some cases, particularly younger patients or those with refractory disease, an autologous stem cell transplant may be considered following chemotherapy.

H. pylori Therapy in MALT Lymphoma:

  • First-Line Treatment for Low-Grade MALT Lymphoma: Highly effective in early-stage disease confined to the gastric mucosa.
  • Monitoring: Close follow-up is essential to assess for regression and detect any residual or recurrent disease.

Significance of Different Translocations in MALT Lymphoma:

  1. t(11;18) (API2-MALT1):
    • Significance: Associated with resistance to H. pylori therapy and poorer prognosis, necessitating more aggressive treatment.
  2. t(1;14) (BCL-10):
    • Significance: Involves the BCL-10 gene but does not typically impact response to H. pylori eradication therapy.
  3. t(14;18) (IGH-MALT1):
    • Significance: Less common but linked to resistance to H. pylori therapy.
  4. t(3;14) (FOXP1):
    • Significance: Associated with aggressive disease and poor prognosis, requiring more intensive therapy.

Summary Key Points:

  • Low-Grade MALT Lymphoma Management:
    • H. pylori eradication is the first-line treatment for low-grade MALT lymphoma confined to the gastric mucosa, with a high success rate in inducing remission.
    • Follow-up is crucial to monitor remission.
    • Non-responsiveness to H. pylori eradication is often associated with specific genetic mutations or advanced disease characteristics.
      • t(11;18) mutation is a key predictor of resistance to H. pylori eradication therapy and is linked to a higher risk of recurrence.
      • Transmural involvement (deep infiltration of the gastric wall) reduces the likelihood of achieving remission with H. pylori eradication alone.
      • BCL-10 mutation contributes to the activation of pathways that promote lymphoma survival and may result in non-responsiveness to H. pylori therapy.
      • Nodal involvement indicates a more advanced stage of MALT lymphoma, often necessitating additional treatments beyond H. pylori eradication.
    • Additional therapies include radiotherapy, chemotherapy, and immunotherapy in cases resistant to H. pylori therapy.
  • High-Grade MALT Lymphoma Management:
    • combination of radiation therapy and/or chemotherapy, as they are less likely to respond to H. pylori eradication alone.
    • R-CHOP is the first-line chemotherapy regimen.
    • Surgery is reserved for complications.
    • Radiotherapy may be used as an adjuvant therapy.
  • Translocations:
    • t(11;18) is a key marker for resistance to H. pylori therapy.
    • Other translocations like t(1;14) are less predictive of recurrence after H. pylori eradication.

Summary Key Points for Low-Grade MALT Lymphoma:

  • Non-responsiveness to H. pylori eradication is often associated with specific genetic mutations or advanced disease characteristics.
  • t(11;18) mutation is a key predictor of resistance to H. pylori eradication therapy and is linked to a higher risk of recurrence.
  • Transmural involvement (deep infiltration of the gastric wall) reduces the likelihood of achieving remission with H. pylori eradication alone.
  • BCL-10 mutation contributes to the activation of pathways that promote lymphoma survival and may result in non-responsiveness to H. pylori therapy.
  • Nodal involvement indicates a more advanced stage of MALT lymphoma, often necessitating additional treatments beyond H. pylori eradication.
  • H. pylori eradication is the first-line treatment for low-grade MALT lymphoma confined to the gastric mucosa, with a high success rate in inducing remission.
  • High-grade tumors should be treated with a combination of radiation therapy and/or chemotherapy, as they are less likely to respond to H. pylori eradication alone.

Surveillance of MALT Lymphoma Patients Post-Treatment

Surveillance in MALT lymphoma patients is a critical component of managing the disease, particularly after H. pylori eradication therapy, as this determines the long-term outcomes and helps in the early detection of recurrence or progression. The approach to surveillance differs based on whether the patient achieves complete remission after H. pylori eradication or if there is persistent or refractory disease.

Surveillance in Patients with Complete Remission Post-H. pylori Eradication:

  1. Endoscopic Surveillance:
    • Frequency: Patients who achieve complete remission should undergo regular endoscopic follow-up. The typical schedule is:
      • 3-6 months after treatment to confirm remission. [ sabiston = redo endoscopy at 2 months ]
      • Every 6-12 months for the first 2-3 years.
      • Annually thereafter.
    • Purpose: The primary goal is to monitor for the recurrence of lymphoma, assess mucosal healing, and detect any new gastric lesions early.
  2. Biopsy:
    • Multiple Biopsies: During surveillance endoscopies, multiple biopsies should be taken from the previously involved sites and other suspicious areas of the stomach.
    • Histological Examination: This is crucial for detecting any residual or recurrent lymphoma, even in the absence of gross mucosal abnormalities.
  3. H. pylori Status Monitoring:
    • Reinfection: Periodic testing for H. pylori reinfection is recommended as reinfection can lead to recurrence of MALT lymphoma.
    • Non-Invasive Testing: Urea breath tests or stool antigen tests can be used for ongoing H. pylori monitoring.
  4. Clinical Monitoring:
    • Symptoms: Patients should be evaluated for any recurrence of symptoms such as epigastric pain, bleeding, or weight loss, which may indicate a recurrence of lymphoma.
    • Systemic Review: Regular clinical reviews focusing on general health and any new systemic symptoms are essential.

Surveillance in Patients with No Remission or Persistent Disease:

  1. Further Treatment:
    • Second-Line Therapy: Patients who do not achieve remission after H. pylori eradication may require further treatment such as:
      • Radiotherapy: Especially effective for localized residual disease.
      • Chemotherapy or Immunotherapy: For more advanced or resistant cases.
  2. Intensified Surveillance:
    • More Frequent Endoscopy: Patients with persistent disease may require more frequent endoscopic evaluations (every 3-6 months) until the disease is controlled.
    • Advanced Imaging: In cases where endoscopic findings are inconclusive, additional imaging such as endoscopic ultrasound (EUS) or PET scans may be warranted to assess the depth of invasion and detect any nodal or extranodal involvement.
  3. Re-Biopsy:
    • Targeted Biopsies: Re-biopsies are necessary during follow-up to evaluate the effectiveness of second-line therapies and to detect any progression to higher-grade lymphoma.
  4. Long-Term Surveillance:
    • Ongoing Monitoring: Even after achieving late remission, these patients require long-term surveillance due to the risk of late recurrences or transformation into more aggressive lymphoma types.
  5. Psychosocial Support:
    • Patient Counseling: Managing persistent disease can be stressful for patients. Regular counseling and support are important components of ongoing care.

Key Points in Surveillance:

  • Regular endoscopic surveillance with biopsies is essential for patients in remission to monitor for recurrence.
  • H. pylori status should be regularly checked to prevent reinfection and associated recurrence.
  • Persistent disease after H. pylori eradication requires more frequent and intensive monitoring, with additional treatment modalities considered based on disease progression.
  • Long-term follow-up is necessary for all MALT lymphoma patients due to the potential for late recurrences or transformation to aggressive forms of lymphoma.