Gastro 48 Lymphoma GIST

  1. The most common sites of extranodal lymphoma?
    • Skin
    • Stomach, and
    • Itestine

    • Lymphoma represents up to 10% of primary gastric neoplasms and is a common gastric malignancy second only to adenocarcinoma.
    • Gastric lymphomas tend to occur in the antrum or distal body.
  2. What are the types of gastric lymphoma?
    • Primary: when localized to stomach. 5% of gastric neoplasm
    • Secondary: stomach is involved secondary to generalized lymph node disease. This is more common than the primary lymphoma of stomach
  3. Most common site of Lymphoma?
    The stomach is the most common site of primary GI lymphoma, and over 95% are non-Hodgkin’s type.
  4. Etiology of NHL?
    • Familial and genetic influences
    • Immunosuppression - congenital syndromes, AIDS, or medication-induced immunosuppression.
    • Infections - T-lymphocyte virus-1, Epstein-Barr virus, hepatitis C virus, Helicobacter pylori
    • Environmental exposures, such as pesticides, insecticides, dust, hair dyes
  5. Clinical features of NHL of stomach?
    • Abdominal pain - most common symptom.
    • Nonspecific complains - dyspepsia, weight loss, abdominal pain, anorexia, change in bowel habits or even hemorrhage.
    • May present with signs and symptoms suggestive of gastric cancer—anemia, anorexia, asthenia
    • (3As)
    • May present with features of gastric outlet obstruction, i. e. sensation of fullness after meals
    • and vomiting
    • May present with lump in the abdomen
    • 30-50% of patients will present with an abdominal emergency
    • 25% of these cases will involve frank perforation.
    • Without systemic disease, constitutional “B symptoms,” such as fever, weight loss, and night sweats, are infrequent and occur in less than 12% of patients.
    • Abdominal tendernessis  and an abdominal mass
    • Because GI lymphomas are quite indolent, the diagnosis may be delayed for an extended time—months to years.

    Pel-Ebstein fever, the classic intermittent fever associated with Hodgkin disease, occurs at variable intervals of days to weeks and lasts for 1–2 weeks before resolving.
  6. Define lymphoma and classify it. Discuss about the advances in the diagnosis and management of gastrointestinal lymphoma.  [TU 2071]

    WHO classification of Non Hodgkins lymphoma?
    • Diffuse large B cell lymphoma (55%) - most common
    • Burkitt Lymphoma (3%)
    • Follicular Lymphoma (<1%)
    • Matle cell lymphoma (<1%)
    • Extranodal marginal zone lymphoma (MALT lymphoma) (40%) - second most common
    • [@ BB-F- Matl- Malt]
  7. Risk factors for development of diffuse large B Cell lymphoma
    • Immunodeficiency
    • H Pylori Infection
  8. What is the correlation between H. pylori infection and lymphoma?
    • „ Lymphocytes are usually not found in normal gastric mucosa but have been found in association with H. pylori infection
    • „ In some cases of early gastric lymphoma treatment for H. pylori eradication has caused regression of lymphomatous process thereby suggesting a strong correlation between H. pylori infection and primary gastric lymphoma
  9. Gastric MALT Lymphoma characterized by translocation of
    • t(1;14)
    • t(11;18)
  10. Classification systems of Lymphoma?
    • WHO
    • REAL
    • Working
    • Lukes-Collins
    • KLEL
    • Rappaport
  11. Ann-Arbor stages of Lymphoma?
    Stage I - located in a single region, usually one lymph node and the surrounding area.

    Stage II - cancer is located in two separate regions, an affected lymph node or organ and a second affected area, and that both affected areas are confined to one side of the diaphragm—that is, both are above the diaphragm, or both are below the diaphragm.

    Stage III - cancer has spread to both sides of the diaphragm, including one organ or area near the lymph nodes or the spleen.

    Stage IV - diffuse or disseminated involvement of one or more extralymphatic organs, including any involvement of the liver, bone marrow, or nodular involvement of the lungs
  12. Musshoff modifiction of Ann-Arbor staging for gastric lymphoma?
    • IE :Tumor Confined to GI Tract
    • IIE :Tumor with spread to regional LN Stage
    • IIIE: Tumor with spread beyond the regional lymph nodes (Para-aortic, iliac)
    • Stage IVE: Tumor with spread to other intra-abdominal organs(Liver, spleen) or beyond
    • abdomen (Chest, bone marrow).
  13. How to ascertain whether it is primary or secondary gastric lymphoma?
    Dawson’s criteria is used for labeling primary gastrointestinal lymphoma. The criteria are - 

    • No palpable superficial lymph nodes
    • Normal chest radiograph findings with no evidence of lymphadenopathy
    • Normal white blood cell (WBC) count
    • Predominant lesion within the GI tract, with lymph node involvement confined to the lymph node chain involved in drainage of that specific GI segment
    • No involvement of the liver or spleen
  14. Features of Burkitt Lymphoma?
    • Associated with Epstein Barr Virus
    • Very aggressive
    • Tends to affect younger patient
    • Found in the cardia or body of stomach as opposed to the antrum
  15. Treatment of Gastric Lymphoma?
    The initial step in treating gastric lymphoma is to determine the H. pylori status of the patient and to test the lymphoma itself for H. pylori. Almost all MALT lymphoma (especially low-grade histologic types) and some DLBCL may regress with conventional H. pylori treatment. 

    • The optimal treatment for lymphomas unresponsiveto initial H. pylori antibiotic treatment or those negativefor H. pylori still remains unclear84 and includes the conventionaloncologic therapies of chemotherapy, radiotherapy,surgical resection, and even immunotherapy, orcombinations of these.
    • Chemotherapy with CHOP regimen is found to be better than surgical excision or radiotherapy. 
    • CHOP regimen includes Cyclophosphamide, Hydroxydaunomycin (doxorubicin), Oncovin (Vincristine), and Prednisolone.
    • MOPP regimen Mechlorethamine, oncovin (vincristine), procarbazine and prednisolone.
    • Indication of surgery in gastric lymphoma - Massive bleeding, perforation and GOO. This may occur following initiation of chemotherapy.
    • Rituximab, a monoclonal antibody against the CD20 B-cell antigen, has also been used in combination with CHOP chemotherapy to improve remission rates and disease-free survival exhibiting the t(11;18) translocation.
    • Posttreatment surveillance - upper endoscopy every 3 months in the first 2 years, then every 6 months, and yearly after the fifth year.
  16. Predictors of failure of H. pylori eradication in MALT lymphoma?
    • Transmural tumor extension
    • Nodal involvement
    • Transformation into a large cell phenotype t(11:18)
    • Nuclear BCL -10 expression
  17. What is GIST?
    • Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the GIT arising from the cells of Cajal (intestinal pacemaker cell).
    • Positive for c-kit proto-oncogen (CD117) in 95% of cases and CD 34 positive in 70% of cases
  18. Familial syndromes associated with GIST?
    • GIST paraganglioma syndrome (Carney Triad)
    • Neurofibromatosis I
    • Hippel Lindau disease
  19. What is Carney’s triad?
    • This is a variety of familial GIST. Young women are usually affected and includes:
    • „ Functioning extraadrenal paraganglionomas
    • „ Pulmonary chondromas
    • „ Gastric GIST.
  20. Clinical features of GIST?
    • „ Asymptomatic
    • „ Microcytotic anemia due to slow hemorrhage.
    • „ Nonspecific symptoms like—anorexia, weight loss and anemia
    • „ Significant GI hemorrhage (hematemesis and melena) may occur in 25% of patients
    • „ Symptoms due to mass effect—nausea, vomiting, early satiety or abdominal distension.
  21. Diagnosis of GIST?
    • UGI endoscopy – smooth appearing, round submucosal tumor, occasionally containing area of central necrosis.
    • CECT scan of abdomen: Can assess the local extent of the tumor. Smaller tumors may appear as gut wall thickening.
    • Because of submucosal location, obtaining tissue with conventional endoscopic forcep has low yield. EUS assisted FNA – high yield.
    • Given the expense and specialized expertise involved in performing EUS-directed fine-needle aspiration, in addition to the fact that most submucosal GI tumors require surgical resection regardless of histology, some experts have argued that routine preoperative pathologic diagnosis is not needed for such tumors.
    • Some argue FNAC is not indicated in routine evaluation of GIST. GIST are usually fragile and may rupture if biopsied. These tumors are hypervascular and FNAC may cause intratumoral hemorrhage. The pathologist cannot diagnose GIST in fine needle aspirate.
  22. How will you assess malignant potential in GIST?
    • Benign: Size-<2 cm no more than 5 mitoses/ 50 hpf
    • Probably benign: >2 cm ≤5 cm, no more than 5 mitoses/50 HPF
    • Malignant: >5 cm but ≤10 cm, >5 mitoses/ 50 HPF. >10 cm, > 5 mitoses /50 HPF
  23. Treatment of GIST?
    The mainstay of treatment is complete surgical resection. R0 excision is the goal. 

    Tumors >2 cm - resection

    Tumors < 2 cm with high-risk features on endoscopy and EUS (irregular borders, ulceration, and heterogeneity) - resection

    Tumors <2cm with no high risk features -  observed with repeat endoscopy and EUS at 6- to 12-month intervals

    Depending on tumor size, resection can include wide local excision, enucleation, sleeve gastrectomy, or total gastrectomy, with or without en bloc resection of adjacent organs.

    Anatomic resection according to lymph node basins is not required, as lymph node metastases are rare. They usually spread by bloodstream to liver, lungs and bone.
  24. Adjuvent therapy in GIST?
    Imatinib mesylate (Gleevec) - first-line standard therapy for inoperable, metastatic, or recurrent GISTs. Selective tyrosine kinase inhibitor (TKI) of ABL, BCR-ABL, KIT, and PDGFR. Dose - 400 mg/day

    Sunitinib malate - second line therapy 

    Regorafenib - third line therapy
  25. Indications of neoadjuvant imatinib in GIST?
    • Unresectable or borderline resectable primary tumor
    • Potentially resectable tumor that requires extensive organ disruption
    • Local recurrence of locally advanced disease
    • Limited amount of potentially resectable metastatic disease.
  26. 1. How to classify gastrointestinal tumors (GIST)? Discuss the treatment of gastric GIST. 72/2
    • 2. Gastric lymphoma 70
    • 3. Gastric GIST 70, 68/2
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Gastro 48 Lymphoma GIST