Gastrointestinal tract lymphoma
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Lymphoma of GIT, NHL, Lymphoreticular malignancy
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Gastrointestinal tract lymphoma
- 1. Gastrointestinal Tract Lymphoma Dr. Shad Salim Akhtar MBBS, MD, MRCP(UK), FRCP(Edin), FACP(USA), Member AUICC Fellows Consultant Medical Oncologist Medical Director Prince Faisal Oncology Center & KFSH Prof. of Clinical Medicine, Qassim Medical University Buraidah, Al-Qassim, KSA
- 2. Non Hodgkin's Lymphoma Heterogeneous collection of lympho-proliferative diseases Is it the same disease at all sites??? Major divisions Nodal Extra nodal Around 33-40% are extra nodal GIT is the commonest extra- nodal site Around 50% Henessey BT et al. Lancet Oncol 2004;5:341
- 3. Extra nodal NHL Clinically dominant (>75%) extra nodal component with No or Minor nodal involvement (25%) Tonsils / Waldeyer’s ring?? Zucca E et al: Ann Oncol 1997; 8:727
- 4. GI NHL-Definition Localized disease to the GIT Stage IE, IIE disease Lymphoma patients exhibiting GI symptoms or have a predominant lesion in GI Dawson IMP et al: Br. J Surg 1961; 49:80 Lewin KJ et al: Cancer 1978; 42:693 Haber DA et al: Semin Oncol 1988; 15:154
- 5. All patients who present with NHL that apparently originated at an extra nodal site even in the presence of disseminated disease, as long as the extra nodal component is dominant” GI NHL-Definition Krol ADG et al: Ann Oncol 2003; 14:131
- 6. NHL-Increasing incidence 1970 10.2/100,000 1990 18.5/100,000 81% increase or 3.6% per year Extra nodal NHL 3-6.9%/year Nodal NHL 1.7-2.5%/year Vose JM et al: Hematology 2002; 242 Ries LAG et al: National Cancer Institute 2002`
- 7. GI NHL-Sites of involvement Author Total Gastric Intest Koch P 371 277 70 Liang R 442 238 184 Radaszkiewicz T 307 264 59 Morton JE 175 78 95 Azab MB 106 55 43 Amer MH 185 94 91 El Foudeh M 215 185 66 Nakamura S 455 342 96 Ducreux M 78 42 13
- 8. GI NHL-Major symptoms Pain Nausea vomiting Bleeding Weight loss Diarrhea Acute abdomen
- 9. GI NHL-Symptoms versus site Stomach Small intestine Colorectal Pain Pain Pain Nausea & Vomiting Obstruction Bleeding Weight loss Weight loss Diarrhea Bleeding Malabsorption Crump M et al: Semin Oncol 1999; 26:324
- 10. GI NHL-Staging system TNM I Single nodal region Localized single extra lymphatic organ/site IE II 2 or more node regions same side of diaphragm Localized single extra lymphatic organ/site with its regional nodes+/- other nodes on the same side of diaphragm IIE III Node regions both sides of diaphragm+/- localized single extra lymphatic organ/site Spleen / Both IIIE IIIS IIIES IV Diffuse or multi focal involvement of extra lymphatic organs+/- regional nodes; isolated extra lymphatic organ and non regional lymph nodes Sobin LH et al: TNM Manual 6th Edition 2002; 238
- 11. GI NHL-Staging system Stage I Tumor confined to the GI tract Single primary site or multiple non contiguous lesions Stage II Tumor extending into abdomen from a primary GI site Nodal involvement II1 local (paragastric / paraintestinal) II2 distant (mesenteric, para-aortic, paracaval, pelvic, inguinal) Rohatiner A et al: Ann Oncol 1994; 5:397
- 12. Stage IIE Penetration of serosa to involve adjacent organs or tissues Stage IV Disseminated extra nodal involvement or GIT lesion with supradiaphragmatic nodal involvement GI NHL-Staging system Rohatiner A et al: Ann Oncol 1994; 5:397
- 13. ? X to denote the organ of origin X [stomach] II (gastric NHL with local nodes involved) X [stomach, colon] II Addition of IP index as in AJCC Cancer Staging Manual 6th Edition? GI NHL- Staging Suggested modifications Armitage JO; N Engl J Med 2005; 352:1250 Grothus-Pinke B et al: Ann Oncol 1996; 7:S126
- 14. GI NHL-Work up History & physical examination Weight loss not recorded as a B symptom Waldeyer’s ring assessment especially with limited GI involvement Routine bloods Endoscopic examination CT Barium studies Bone marrow examination!!! Endoscopic USG
- 15. GI NHL-Do they need laparotomy for diagnosis? In 30-50% of intestinal NHL who may present as an emergency Endoscopic biopsy from accessible lesions Diagnostic accuracy 62% to 98.5% First attempt diagnosis 80% of above May miss areas of transformation Al Akwaa AM et al: Worl J Gastroenterol 2004; 10:5
- 16. FNAC Laparoscopic biopsy Frozen section facility Bone marrow in the same sitting All tissues must be sent for Histological Immunohistochemistry Cytogenetic studies GI NHL-Diagnosis? Kaleem Z et al: Am J Clin Pathol 2001; 115:136 Koniaris LG et al: J Am Coll Surg 2003; 197:127
- 19. GI NHL-Histological types Diffuse B cell large cell Secondary DLBCL Extra nodal marginal zone lymphoma (MALT) Follicular lymphoma Mantle cell lymphoma Burkitt’s lymphoma Enteropathy type T cell lymphoma Peripheral T cell lymphoma NOS Majority of cases seen in KSA are DLBCL type
- 20. Risk of relapse from complete response according to the primary site of the lymphoma. GI, gastrointestinal. J Clin Oncol 23. © 2005Lo´ pez-Guillermo et al DOI: 10.1200/JCO.2005.07.155
- 21. Overall survival of 382 patients with diffuse large B-cell lymphoma according to the primary site of the lymphoma. GI, gastrointestinal. J Clin Oncol 23. © 2005 in pressLo´ pez-Guillermo et al DOI: 10.1200/JCO.2005.07.155
- 22. OS and EFS of nodal vs extra nodal lymphoma in 1168 patients including 216 GI lymphomas defined as per Krol ADG et al. Krol ADG et al: Ann Oncol 2003; 14:131
- 23. Extra nodal lymphomas-Why do these do better Gene expression of typical germinal center type B cell rather than activated circulating B cell. Former better prognosis Additionally bcl2 protein expression in the absence of t(14:18) translocation are susceptible to rituximab. ?? Significance in GI lymphomas Armitage JO: N Engl J Med 2004; 325:1250 J Clin Oncol 23. © 2005 in pressLo´ pez-Guillermo et al
- 24. Is surgical resection important for? Definitive diagnosis Improving survival (stage I & II) Preventing complications Gastric DBCLC NHL-Therapy questions?
- 25. Role of radiotherapy Role of chemotherapy Which chemotherapy Gastric DBCLC NHL-Therapy questions?
- 26. Gastrectomy – Points in favor Multiple studies Stage I surgical resection may be curative ? The number of MALT lymphomas in these series Patients undergoing radical excision have a superior outcome ? Inidicator of low burden disease Multimodality treatment better survival Small non randomized retrospective studies Data collected is of many years Crump M et al: Semin Oncol 1999; 26:324
- 27. Role of radiotherapy Multiple retrospective studies positive for multimodality therapy Has been used as the sole modality of therapy especially in MALT Post operative adjuvant 88% OS rate Problems of late toxicity Reserve for residual disease, elderly or inoperable patients Koniaris LG et al: J Am Coll Surg 2003; 197:127
- 28. Adjuvant RT in Early Stage NHL Miller TP et al NEJM 1998;339:21 Comp surg excision Complete response 5 yrs surv RFS 5 yrs surv OS Life threat toxic 58 104/243(73%) 64% 72% 40% 58 106/142(75%) 77% 82% 30% 0.03 0.02 0.06 CHOP 8 CHOP3+RT Stage I/II lymphoblastic NHL excluded
- 29. What therapy? Stage IPI Rx 5yr MSur Limited stage Proposed description I, IE 0 CHOP(3) + RT >90% Yes Very limited I, IE, II, IIE (non bulky) >=1 CHOP(3) + RT 70% Yes Limited Bulky II, IIE >=1 CHOP(8) 50% No Advanced Fisher RI et al: Hematology 2004; 221
- 30. German multi-center study Prospective non randomized Surgery left to the treating physician Post operative therapy standardized
- 31. 277 patients accrued and 185 analyzed IE 96; II1E 58; II2 E 31 High grade 101 pts (54.6%) 70% without low grade component Type Stage CT RT HG IE CHOP 4 EFRT (30G) + boost IIE COP 6 IFRT (40G) Gastric Lymphoma Therapy- German MC Study Koch P et al: J Clin Oncol 2001; 19:3874
- 32. Gastric Lymphoma Therapy- German MC Study Type Stage CT RT LG resected IE X EFRT IIE COP 6 EFRT LG unresec IE EFRT+boost IIE COP 6 EFRT+boost Koch P et al: J Clin Oncol 2001; 19:3874
- 33. Gastric Lymphoma Therapy- German MC Study High grade No surgery Surgery+CRT Number 54 47 EFS 69.6% 76.6% NS OS 77.9% 78.9% NS Low grade Number 52 32 EFS 87.6% 82.2% NS OS 90.2 87.2 NS Koch P et al: J Clin Oncol 2001; 19:3874
- 34. No Surgery Surgery Event free survival surgical intervention & conservative therapy only Koch Petal:JClinOncol 2001;19:3874
- 35. nonrandomized comparison; all histologic subtypes Koch P et al: J Clin Oncol 2001; 19:3874
- 36. EFS EFS of gastric lymphoma resected completely vs partial or incomplete resection Koch P et al: J Clin Oncol 2001; 19:3874
- 37. Gastrectomy present status Organ preservation is an important quality of life issue Resectabilty rates range from 60-80% Operative mortality and morbidity rates range from 3-25% Patient preference, tumor size, stage and resectability should be considered
- 38. Gastrectomy ideal approach “in between the extremes of never and always”
- 39. Which chemotherapy CHOP Variations Additional immunotherapy Gastric NHL-Chemotherapy
- 40. Binds CD20, which is present on normal and malignant pre- B and mature B cells; >90% of B-cell NHL express CD20 May induce antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity, based on in vitro data Also triggers apoptosis (programmed cell death) in vitro No apparent dependence on cell cycle for activity Rituximab
- 41. DLBCL Gastric origin Algorithm for therapy Localized (stage I, II) Advanced disease Complications Complete resectionPossible Not possible CHOP X 6-8 +Ritux CHOPX3+Ritux IFRT (avoid in young) Residual disease EFRT (avoid in young) Resection CR
- 42. GI NHL-Site of disease- Geographical Variation Site USA Ger Fra KSA NGui Nigeria Jord Gast 77 277 43 185 24 19 23 Small Intest 36 35 39 66* 55 62 59 Ileo- cecal 26 13 Colon 17 3 10 21 19 15 Rect 6 6 Panc 10 5 0 0 Diffu 5 24 16 10 0 2 Kniaris LG :J Am Coll Surg2003;197:127 Koch P :JCO 2001;19:3861
- 43. Intestinal DLBCL Surgical intervention is less controversial Acute presentation more common Completely resected patients do better Generally poorer prognosis as compared to gastric Survival Early stage disease better Surgery+CT+RT 50-70% Single modality 30-50% Koniaris LG et al: J Am Coll Surg 2003; 197:127 Daum S et al: J Clin Oncol 2003; 21:2740
- 44. Marginal Zone Mantle Zone Germinal Centre (Contains post germinal centre B cells, monocytoid B cells, plasma cells and centrocyte like cells) Normal MALT Rooney N et al: Curr Diag Pathol 2004; 10:69
- 45. Calam J etal. BMJ 2001;323:980 Relation of H pylori infection to UGI conditions
- 46. H pylori and Malt lymphoma ~90% have H pylori in gastric mucosa~90% have H pylori in gastric mucosa Case control studies confirm relationshipCase control studies confirm relationship between previous infection and lymphomabetween previous infection and lymphoma Clonal B cell detection in chronic gastritisClonal B cell detection in chronic gastritis which precedes lymphomawhich precedes lymphoma H pylori strain specific T cells promoteH pylori strain specific T cells promote lymphoma growth in culturelymphoma growth in culture Eradication of H pylori causes regression inEradication of H pylori causes regression in 75% of caces75% of caces
- 47. Gastric MALT lymphoma MALT reacts with the antigen present within the lumen An Pr Cells +H pyhlori antigen+CD4+ T cells stimulate peoliferation of B cells B cells synthesize immunoglobulins Immunoglobulins react with autoantigens Parsonnet J et al: N Engl J Med 2004; 350:213
- 48. Rooney N et al: Curr Diag Pathol 2004; 10:69
- 49. Rooney N et al: Curr Diag Pathol 2004; 10:69
- 50. Gastric MALT types A low grade classical <5% blasts and clusters of <10 cells B 10-20% transformed cells Clusters of >20 cells C high grade transformation with sheets of transformed cells D no MALT component is recognizable Isaacson PG: Hematology 2001; 241
- 51. MALT lymphoma management Careful imaging CT scan Endoscopic ultrasonography Sufficient tissue to Differentiate from Mantle cell lymphoma Follicular lymphoma Confirm presence of more transformed clone Immunohistochemical studies (bcl2 expression)
- 52. Gastric MALT management Antibiotic therapy Regression in approximately 75% cases Time to regression may be as long as 18 months Predictors of failure of antibiotic therapy t(14:18) do not respond to antibiotics Node positive disease Depth of invasion muscularis mucosa Lymphoma clone persists Therefore it becomes dormant rather than disappear Isaacson PG; Best Prac & Res 2005; 18:57 Cavalli F et al: Hematology 2001; 241
- 53. Surgical resection Antrectomy usually adequate Radiotherapy Chemotherapy Alone or in combinations 5 yr DFS >95% in IE 75% in IIE Gastric MALT management antibiotic failure or advanced Koniaris LG: J Am Coll Surg 2003; 197:127
- 54. IPSID MALT type B cell lymphoma Proximal small intestine involved Geographical distribution Mediterranean Middle East Africa Far East Children & young adults Monotypic truncated immunoglobulin α heavy chain Lecuit M et al: N Engl J Med 2004; 350:239
- 55. IPSID Campylobacter jejuni Small group of patients (4/6) FISH, PCR, DNA sequencing and immunohistochemistry Early stages respond to antibiotics Non responsive pts progress to lymphoma Lymphoplasmacytic & immunoblastic Locally invasive and metastatic Poor prognosis
Hinweis der Redaktion
- Unlike HD NHL is a group of more hetergenous collection of lymphoproliferative malignancies. With the passage of time we have come to recognize probably geneticall y different NHLs with different causes and prognosis. In spite of a similar HP picture the DBCL presenting in different areas is identified as a different subtype, like Pr. Med lymph, Pr. Eff lymphoma. In fact the question which is being asked is if Squamous cell carcinoma arising in different areas is treated as a different disease, why should NHL at any site be the same disease. Notwithstanding the major differences, traditionally, NHL has been classified as nodal and extra-nodal, the relative frequency of extra-nodal NHl varies in different series. Genreally around 33-40% are extranodal lymphomas. What is an extranodal lymphoma.
- Different criteria have been proposed. Generally a lymph can b considered extra nodal if after routine staging investigations there is either no or minor nodal component of the disease. A minor nodal component has been described as &lt;25% of the tumour and a major extra nodal component means if the latter constitutes &gt;75% of the NHL. However, this is not a widely accepted cut off proportion.
- Variously defined but the definition of Lewin is generally more acceptable. Dawson’s criteria were very stringent including only those patients who had GI lymphoma with normal CXray, no hepatosplenomegaly, no superficial or mediastinal lymphadenopathy, normal white cell count and predominant tumor mass in the bowel only with local lymphadenopathy.
- In a retrospective analysis looking at various definitions of extra nodal lymphoma, Krol an his collaegues from Netherland analysed 389 patients to compare the survival according to various definitions. Their conclusion was as above:
- Interesting observations of NHL incidence need to be stressed. The incidence of NHL has been increasing in USA at the above rate and the increase has been more so in the extra-nodal NHL. The increase has leveled off since 1990’s except among the black american females.
- The frequency of particular organ involvement varies in different geographical regions stomach being the commonest site of involvement in the west and the gulf region whileas intestinal involvement is more common in mediter middle east, africa and far east.
- The most commonly used staging system is the Ann Arbor classification with the Muschoff modification. The TNM manual incorporates the same staging system. In this system the suffix E denotes both invading growth as well as extra nodal origin, at the same time stage IV NHL originating at multiple sites cannot be compared with nodal lymphoma involving multiple non nodal or non GI organs. Hence this system needs further modification.
- In view of marked variation in reporting an International Workshop held in Lugano suggested the above staging system for GI NHL.
- Here E suffix is restricted to indicate invading growth
- It has been therefore suggested to use the Ann Arbor classification with modifications as laid down in Lugano Conference restricting E for direct invasion and adding X for extra nodal origin. Additionally recently the significance of the IPI in determinig the prognosis of high grade NHL has been recognised by its inclusion in the staging system of the AJCC and it might be soon generalized.
- Laparotomy is no longer needed in every patient, unless a patient presents with a surgical emergency diagnosis is established by endoscopic biopsy and the accuracy ranges from 62% in multi-institutional to 98% in single institutional studies.
- A high index of suspicion must be maintained especially in semi elective cases and FNAC or a mucosal biopsy must be considered to avoid delay in therapy that would result from concerns about wound healing associated with laparotomy. If tissue has not been obtained before, an intra operative frozen section should be obtained to plan for further management like in small bowel tumors where 20% may be lymphomas.
- Events in B cell development. The development and maturation process of B cells begins in the bone marrow. Here, the &quot;pre-B cell&quot; arises from the &quot;progenitor (Pro) B cell&quot; following rearrangement of the immunoglobulin heavy chain gene (symbolized with horizontal lines in black). Subsequently, rearrangement of the light chain genes occurs resulting in the expression of the whole immunoglobulin molecule on the cell surface, serving as an antigen receptor. With the production of this &quot;immature&quot; B cell, the initial phase of B-cell development is, thereby, completed. The &quot;immature&quot; B cell is so defined since it is unable to initiate an immune response following the presentation of a foreign antigen. The B-cell attains this ability only on leaving the bone marrow, passing through the blood stream and entering the peripheral lymphoid tissue. Here, the B cell migrates to the outer region of the lymph node in the &quot;primary&quot; follicles and, later, to the follicle mantles. This differentiation step is associated with the additional expression of IgD. These IgM+/IgD+ B cells are known as &quot;naive mature B-cells&quot;. When these cells come into contact with antigen (AG), which can bind to their immunoglobulin molecules, they transform into proliferating extrafollicular B blasts, from which short-lived plasma cells and &quot;antigen-induced&quot; or &quot;primed&quot; B cells are derived. These &quot;primed&quot; B cells initiate and maintain the germinal center reaction, during which they transform into rapidly proliferating centroblasts. During the mitotic proliferation and differentiation of the centroblasts into centrocytes, somatic mutations in the variable region of the immunoglobulin genes are inserted in a randomized manner (the mutations are represented by vertical lines). The centrocytes with advantageous mutations (i.e. those which lead to an increase in the affinity of the immunoglobulin receptor) differentiate further, passing out of the germinal centre into long-lived plasma cells or into &quot;memory&quot; B cells. The latter remain in the marginal zone. As a result of the differentiation phases of B-cells and of the somatic mutation process, 3 major different mature forms of B-cells can be identified: • Naive mature B-cells (recirculating and sessile subtypes) • Germinal center B-cells (centroblasts and centrocytes) • Post germinal center B-cells which include memory B cells and long-lived plasma cells From all of these different B-cell forms, malignant B-cell lymphomas arise, which distinguish themselves clinically and which are characterized in their biological behavior not only by the transformation event but also by the inherent characteristics of the cell of origin. Classical Hodgkin lymphomas, in which the phenotypical and clinical features are predominantly determined by the transformation event, are an exception to this rule. FDC, folicular dendritic cell; , apoptosis
- Figure 5. Model of B-cell non-Hodgkin&apos;s lymphoma (NHL) histogenesis and pathogenesis. A lymphoid follicle, constituted by the germinal center (GC) and the mantle zone (MZ), is represented together with the surrounding marginal zone (MargZ). Based on the absence or presence of IgV somatic mutations, B-cell NHL can be distinguished into two broad histogenetic categories: i) pre-GC derived NHL, lacking IgV mutations and including mantle cell lymphoma (MCL); ii) B-cell NHL derived from a cell that transited through the GC and harboring mutated IgV genes, exemplified in the figure by follicular lymphoma (FL), lymphoplasmacytic lymphoma (LPL), MALT lymphoma, diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL). In B-cell chronic lymphocytic leukemia/ small lymphocytic lymphoma (CLL/SLL), the presence of somatically mutated IgV genes in &gt;50% of the cases also suggests a derivation from a GC experienced B cell. For each category, the arrow indicating the histogenetic origin is flanked by the genetic lesion most frequently associated with the lymphoma. In CLL/SLL, as well as in a subset of DLBCL, the relevant cancer related gene has not been identified.
- Secondary diffuse large B cell meaning the one which has arisen on top of a MALT lymphoma
- In a multivariate analysis however, the site of disease did not maintain its prognostic value. Instead other factors like IPI and bulky disease and b2 microglobin became important.
- Bcl2 protein expression without t14:18 translocation respond better to immunotherapy.
- As already discussed the diagnosis can now be made endoscopically. The rate of complications is rather low and routine surgery to prevent complications is no longer indicated.
- Radiotherapy as an adjuvant as well as sole therapy has been found to be effective in treating GI lymphomas. However, as late toxicities are formidabel especially in younger patients who will be cured of their disease with multimodality therapy one should use radiotherapy only in special circumstances like in advanced disease after surgical resection, priamry therapy for older patients with small tumor burden or in patients with prohibitively high operative risk.
- A number of studies have shown the effectiveness of RT in treating localized lymphomas.
- Based on the updated SWOG data and that form Britic=sh Columbia Cancer Agency for limited disease NHL, we can conclude that the limited NHL actually can be further divided into various subgroups. While as CHOP3 +RT may be adequate therapy for a group as shown with an expected 5 yr surv &gt;90% others may need strategies as for advanced disease.
- High-grade NHL. Conservative treatment was unaffected by whether a resection had been performed or not. In stage IE, four cycles of CHOP (cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1.4 mg/m2 [maximum, 2 mg] each on day 1, plus prednisone 100 mg on days 1 to 5)22 were followed by EF Rx (30 Gy 10 Gy boost on tumor or residue). Patients in stage IIE received six cycles of CHOP and additional involved-field Rx (40 Gy).
- Low-grade lymphoma. After resection, patients in stages IE and IIE were treated by extended-field radiotherapy (EF Rx) with total abdominal irradiation (30 Gy) and, in case of residual tumor, by an additional boost (10 Gy). Without resection, patients in stages IE and IIE received EF Rx (30 Gy 10 Gy boost). In addition, in stage IIE, six cycles of COP (cyclophosphamide 500 mg/m2 on days 1 to 5; vincristine 1.4 mg/m2 [maximum, 2 mg] on day 1; prednisone 100 mg/m2 on days 1 to 5)21 preceded Rx for reduction of tumor load
- Fig 7. CSS of both treatment groups in stages IE and IIE (nonrandomized comparison; all histologic subtypes).
- EFS of gastric lymphoma resected completely vs partial or incomplete resection
- The intestinal lymphoma is relatively uncommon and incidence varies according to geographic location. The IPSID areas being Mediterranean middle east, Africa and Far east.
- Figure 1 Normal mucosa associated lymphoid tissue (MALT), top left haematoxylin and eosin, bottom left CD20 staining. The marginal zone contains post-germinal centre B-cells, including monocytoid B-cells, plasma cells and centrocyte-like cells, which infiltrate the epithelium. Most plasma cells are found in the superficial lamina propria.
- Relation of H pylori infection to upper gastrointestinal conditions. Various factors affect the outcome of HP infection. These include the host response, the extent and the severity of gastric inflammation and hence the amount of acid secreted. It can elevate the acid secretion in people who develop duodenal ulcer, decrease acid through gastric atrophy in those who develop gastric ulcers or cancer and leave acid secretion unchanged in those who do not develop these diseases. H pylori also impairs the bioavailability of vitamin c in these patients who may already have a poor intake. Eradication of H pylori increases secretion of vitamin C into gastric juice which might increase protection against gastric cancer.
- Marshall and Warren detected this organism in 1983. The spiral organisms between the junction of domes of the epithelial cells where it splits urea which leaks from the cell junction and ammonia is produced which increases the acidity.
- Figure. The Pathogenesis of Gastric MALT Lymphoma (Panel A) and Immunoproliferative Small Intestinal Disease (Panel B). In gastric MALT lymphoma, CD4+ T cells that encounter H. pylori antigens displayed by antigen-presenting cells stimulate the proliferation of neoplastic B cells. These B cells synthesize IgM, IgA, or IgG autoantibodies and differentiate to varying degrees into mature plasma cells. C. jejuni may play the same part in immunoproliferative small intestinal disease that H. pylori plays in gastric MALT lymphoma. However, in response to tissue autoantigens, the lymphoma cells synthesize defective a heavy chains. The autoantigenic stimulus is consequently uncontrolled, and the result is a continuous differentiation of lymphoma cells into atypical plasma cells. In both these conditions, the removal of the bacterial T-cell stimulus inhibits the proliferation of lymphomatous B cells.
- Figure 2 Early marginal zone lymphoma of MALT-type. Proliferation of marginal zone cells with crypt infiltration. Initially, proliferative drive is provided by HP reactive T-cells. Removal of HP may control the proliferation.
- Figure 3 Late marginal zone lymphoma of MALT-type. Mutations in the B-cells makes them independent of the T-cell drive and of the presence of H. pylori. Some cases progress to diffuse large B-cell lymphoma with aggregates of immunoblasts outside germinal centres.
- These four categories have different outcome