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Helicobacter pylori - Associated Lesions and Pathogenesis

MD Pathology Exam - Comprehensive Notes

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1. The Organism

First bacterium declared a Class I (definite) human carcinogen by the WHO/IARC in 1994.

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2. Virulence Factors and Mechanism of Survival

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3. H. pylori-Associated Lesions

3.1 Chronic Active Gastritis (Most Common; Universal in Infection)

• Organisms visible in gastric mucus and adherent to the apical surface of foveolar cells on H&E; highlighted by Giemsa, Warthin-Starry silver stain, or immunohistochemistry (IHC) - the most sensitive method
• Superficial gastritis pattern - inflammation concentrated in the upper mucosa
• Lamina propria - heavy lymphoplasmacytic (chronic) infiltrate
• Active component - neutrophils in the epithelium ("cryptitis"); neutrophilic infiltration into gastric pits forms pit abscesses
• Lymphoid follicles (MALT - mucosa-associated lymphoid tissue) in the lamina propria - physiologically absent from normal gastric mucosa; their presence is pathognomonic of H. pylori infection
• Distribution: Antrum >> Body; if both affected = pangastritis

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3.2 Peptic Ulcer Disease (PUD)

1. H. pylori antral gastritis → ↓ somatostatin from D-cells → ↑ gastrin from G-cells → ↑ acid secretion (hypersecretion)
2. Acid load in duodenum → gastric metaplasia in the duodenal cap (duodenal mucosa acquires gastric-type epithelium)
3. H. pylori colonises this metaplastic epithelium → active duodenitis → ulceration
4. CagA+ strains also express a duodenal ulcer-promoting gene (dupA)

1. H. pylori infection causes mucosal injury directly via ammonia, cytotoxins (VacA), and inflammatory mediators (IL-8, TNF-α)
2. ↓ prostaglandin synthesis (disrupted by inflammation) → impaired mucus/bicarbonate barrier
3. Normal or low acid (vs. duodenal ulcer which has high acid) - injury is primarily mucosal defence failure rather than acid excess

• Punched-out ulcer with clean base (benign), heaped edges
• Base shows necrotic slough, granulation tissue, fibrosis, endarteritis obliterans of vessels at the ulcer margin
• Adjacent mucosa shows chronic active gastritis with H. pylori organisms

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3.3 Atrophic Gastritis and Intestinal Metaplasia

• Loss of native gastric glands (oxyntic glands in the body, antral glands in the antrum)
• Replacement by intestinal metaplasia (IM) - goblet cells, absorptive cells, Paneth cells appear in the gastric mucosa

• Type I (complete/small-intestinal): Mucin-secreting goblet cells with brush border; sialomucins; lower malignant potential
• Type II/III (incomplete/colonic type): Goblet cells with sulphomucins; no brush border; higher malignant potential

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3.4 Gastric Adenocarcinoma - The Correa Cascade

Normal Gastric Mucosa
        ↓  (H. pylori infection)
Chronic Active Gastritis
        ↓  (years–decades)
Multifocal Atrophic Gastritis
        ↓
Intestinal Metaplasia (complete → incomplete)
        ↓
Low-Grade Dysplasia
        ↓
High-Grade Dysplasia (Carcinoma in situ)
        ↓
INVASIVE INTESTINAL-TYPE GASTRIC ADENOCARCINOMA

1. CagA oncoprotein - directly injected into epithelial cells via T4SS; activates SHP-2 tyrosine phosphatase, ERK/MAPK, Wnt/β-catenin pathways; promotes proliferation, inhibits apoptosis
2. NF-κB activation - by CagA, VacA, and lipopolysaccharide → ↑ IL-8, IL-1β, TNF-α → sustained mutagenic inflammation
3. Reactive oxygen species (ROS) - generated by activated neutrophils and macrophages → DNA strand breaks, TP53 mutations
4. Epigenetic silencing - H. pylori-induced promoter methylation of tumour suppressor genes (CDH1/E-cadherin, RUNX3, MLH1)
5. Microsatellite instability (MSI) - epigenetic silencing of MMR gene MLH1
6. ↑ cell proliferation / ↓ apoptosis - VacA disrupts apoptosis pathways; CagA disrupts cell polarity

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3.5 Gastric MALT Lymphoma (MALToma)

1. Normal gastric mucosa contains no lymphoid tissue
2. H. pylori infection induces acquired MALT (lymphoid follicles in lamina propria - the reactive lymphocytes seen in gastritis)
3. Chronic antigenic stimulation by H. pylori → T-cell-driven B-cell proliferation
4. Initially polyclonal; with accumulating genetic mutations → monoclonal B-cell proliferation
5. Monoclonal expansion = low-grade MALT lymphoma (also called marginal zone B-cell lymphoma of MALT type; formerly called "pseudolymphoma" in early descriptions)
6. Further mutations (e.g., t(11;18)(q21;q21) - BIRC3-MALT1 translocation) → progression to high-grade diffuse large B-cell lymphoma (DLBCL)

• Histology: lymphoepithelial lesions (infiltration of gastric gland epithelium by lymphoid cells, causing gland destruction) - this is the defining histological feature
• Cells are centrocyte-like (monocytoid) B-cells in the marginal zone
• Reactive germinal centres are invaded by the neoplastic B cells
• IHC: CD20+, CD79a+, CD5-, CD10- (marginal zone phenotype)

• Low-grade MALT lymphoma dependent on T-cell stimulation by H. pylori antigen
• H. pylori eradication → tumour regression in ~75-80% of cases (gastric MALToma is essentially the only cancer known to regress with antibiotic therapy)
• Cases with t(11;18) translocation are typically H. pylori-independent and do NOT regress with eradication

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4. Summary Table - H. pylori Associated Lesions

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5. Histological Diagnosis

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6. H. pylori and the Sydney Classification of Gastritis

• H. pylori density (0-3+)
• Chronic inflammation (mononuclear cells)
• Activity (neutrophil infiltration)
• Glandular atrophy
• Intestinal metaplasia

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7. Key Exam Points (Quick Recall)

1. H. pylori is exclusively extracellular and does not invade mucosa
2. It colonises the gastric-type epithelium only (not intestinal metaplastic foci, except with PPI use when deeper gland colonisation occurs)
3. Lewis-b antigen is the main mucosal receptor (blood group O → slightly higher risk)
4. CagA strains are more virulent and more strongly associated with carcinoma and ulcers
5. The lymphoid follicle in the gastric mucosa is pathognomonic of H. pylori infection
6. Correa cascade is the accepted model; it is potentially reversible with eradication at early stages
7. MALT lymphoma is the only neoplasm that can regress with antibiotic therapy
8. H. pylori is classified as a Group 1 carcinogen (IARC)
9. Duodenal ulcer = high acid; Gastric ulcer = normal/low acid - this distinction traces back to H. pylori affecting gastrin/somatostatin balance
10. VacA causes vacuolization; CagA causes cytoskeletal changes and oncogenic signalling - remember both are delivered by Type IV Secretion System

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Helicobacter pylori - Associated Lesions and Pathogenesis

MD Pathology Exam - Comprehensive Notes (Robbins + Multitext)

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1. The Organism

"First bacterium classified as a definite (Group I) carcinogen" - WHO/IARC 1994, and the first bacterium declared a carcinogen.

• Robbins, Cotran & Kumar Pathologic Basis of Disease

"H. pylori now has acquired the dubious distinction of being the first bacterium classified as a carcinogen... implicated in the genesis of both gastric adenocarcinoma and gastric lymphomas."

• Robbins & Kumar Basic Pathology

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2. Virulence Factors - Robbins' Four Key Features

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3. Pathogenesis - The Two Disease Patterns (Robbins PBD)

H. pylori infection
        |
        +---> Predominantly ANTRAL gastritis (most common)
        |         - Inflammation stimulates G cells → ↑ gastrin
        |         - ↑ parietal cell expansion in body → ↑ acid secretion
        |         - OUTCOME: Peptic ulcer disease (gastric or duodenal)
        |
        +---> PANGASTRITIS (body + antrum, long-standing infection)
                  - Progressive atrophy of parietal cell mass
                  - ↓ acid secretion
                  - Intestinal metaplasia
                  - OUTCOME: Gastric adenocarcinoma
                  - (Inverse relationship: atrophy/carcinoma vs. ulcer)

• Robbins, Cotran & Kumar Pathologic Basis of Disease

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4. H. pylori-Associated Lesions

4.1 Chronic Active Gastritis (Universal in Infection)

• H. pylori organisms colonise the antral mucosa; the bacteria and associated inflammation stimulate G cells → gastrin release → hyperacidity and increased risk of PUD
• Released CagA (and other cytotoxins) trigger IL-8 secretion from epithelial cells → neutrophil recruitment
• Sustained chronic inflammation produces the histological picture below

"The organism is concentrated within the superficial mucus overlying epithelial cells in the surface and neck regions. The distribution can be irregular, with areas of heavy colonization adjacent to those with few organisms."

• H. pylori organisms visible in gastric mucus and on apical surface of foveolar cells on H&E or Giemsa; most reliably identified by IHC or Warthin-Starry silver stain
• Large numbers of plasma cells, often in clusters or sheets in the superficial lamina propria - this is a hallmark feature
• Increased lymphocytes, macrophages and neutrophils in lamina propria
• Neutrophils cross the basement membrane into the epithelium, and accumulate in gland lumens = pit abscesses
• Lymphoid aggregates with germinal centers (submucosal) = induced MALT - normally absent from the stomach; their presence = pathognomonic of H. pylori infection; potential for lymphomatous transformation
• Intestinal metaplasia (goblet cells + columnar absorptive cells) in longstanding disease = risk factor for adenocarcinoma
• Thickened rugal folds with intense inflammation (mimics infiltrative malignancy endoscopically)
• Hyperplastic/inflammatory polyps may develop due to regenerative changes from mucosal damage

"Submucosal lymphoid aggregates, some with germinal centers, are frequently present and represent an induced form of mucosa-associated lymphoid tissue (MALT) that has the potential to transform into lymphoma."

• Robbins & Kumar Basic Pathology

• The organism shows tropism for gastric foveolar epithelium
• Not found in areas of intestinal metaplasia, acid-producing oxyntic mucosa of the gastric body, or duodenal epithelium
• Therefore antral biopsy is the preferred site for H. pylori evaluation (unless on PPIs - then organisms may be seen deeper in body mucosa)

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4.2 Peptic Ulcer Disease

1. Antral H. pylori gastritis → inflammation inhibits D-cells (↓ somatostatin) → G cells release ↑ gastrin
2. ↑ Gastrin → parietal cell hyperplasia and expansion in the body → hypersecretion of acid
3. Acid load delivered to duodenum → gastric metaplasia of duodenal mucosa
4. H. pylori colonises this metaplastic epithelium → active duodenitis → ulceration
5. CagA+ strains additionally express dupA (duodenal ulcer-promoting gene)

1. Direct mucosal cytotoxicity (ammonia, VacA, CagA-mediated IL-8/cytokine release)
2. ↓ Prostaglandin synthesis → impaired mucus-bicarbonate barrier
3. Acid level normal or low (cf. duodenal ulcer - high acid)
4. Primarily a failure of mucosal defence rather than acid excess

• Active phase: base shows necrotic slough + granulation tissue
• Healing: fibrosis in base; endarteritis obliterans of vessels at the ulcer margin
• Adjacent mucosa invariably shows H. pylori chronic active gastritis
• Benign ulcer: punched-out, regular margins, perpendicular walls, smooth base
• Malignant ulcer (contrast): irregular heaped-up margins, irregular base

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4.3 Atrophic Gastritis and Intestinal Metaplasia

• Loss of oxyntic glands in the body; loss of antral glands in the antrum
• Replacement by intestinal metaplasia (goblet cells, absorptive enterocytes, Paneth cells)
• Not associated with autoantibodies (unlike autoimmune/Type A gastritis) and is patchy
• Reduced acid secretion → mild ↑ gastrin (but not to the extreme degree of autoimmune gastritis where all parietal cells are lost)

• Complete (Type I): Sialomucins; brush border; lower risk
• Incomplete (Type II/III): Sulphomucins; no brush border; higher malignant risk

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4.4 Gastric Adenocarcinoma - The Correa Cascade

"The proposed scenario for the development of gastric adenocarcinoma in the setting of H. pylori infection involves increased epithelial cell proliferation in a background of chronic inflammation, which may generate genotoxic agents such as reactive oxygen species. The H. pylori genome also contains genes directly implicated in oncogenesis. Strains associated with gastric adenocarcinoma have a 'pathogenicity island' that contains the cytotoxin-associated gene A (CagA). Although H. pylori is noninvasive, released CagA can penetrate gastric epithelial cells, where it has a variety of effects including the initiation of a signaling cascade that mimics growth factor stimulation."

• Robbins & Kumar Basic Pathology

"Persistent infection first leads to development of chronic gastritis, followed by gastric atrophy, intestinal metaplasia of the lining cells, dysplasia, and cancer. This sequence takes decades to complete and occurs in less than 5% of infected individuals."

Normal Gastric Mucosa
     ↓ H. pylori infection (CagA+ strain)
Chronic Active Gastritis (antrum)
     ↓ progression to body/fundus (pangastritis)
Multifocal Atrophic Gastritis
     ↓ (years-decades)
Intestinal Metaplasia (incomplete/Type III is high risk)
     ↓
Low-grade Dysplasia
     ↓
High-grade Dysplasia
     ↓
INTESTINAL-TYPE GASTRIC ADENOCARCINOMA (distal/non-cardia)

1. CagA (injected by T4SS) → mimics growth factor stimulation → activates SHP-2, ERK/MAPK, Wnt/β-catenin → proliferation, inhibited apoptosis
2. NF-κB activation → ↑ pro-inflammatory cytokines (IL-8, IL-1β, TNF-α) → sustained mutagenic inflammation
3. Reactive oxygen species (ROS) generated by neutrophils/macrophages → DNA strand breaks, TP53 mutations
4. Epigenetic silencing of tumour suppressor genes (CDH1/E-cadherin, RUNX3, MLH1) via CpG promoter methylation
5. Host cytokine polymorphisms - IL-1β and TNF promoter polymorphisms (Robbins PBD emphasis) → amplified inflammatory response → greater mucosal injury and carcinogenesis risk

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4.5 Gastric MALT Lymphoma (MALToma)

1. Normal stomach has no MALT (lymphoid tissue is not present)
2. H. pylori infection induces appearance of H. pylori-reactive T cells
3. These T cells stimulate a polyclonal B-cell proliferation (the MALT seen in chronic gastritis)
4. In chronic infections, mutations accumulate giving certain B-cell clones a growth advantage
5. These cells grow out as a monoclonal lymphoma that still remains dependent on T-cell stimulation of NF-κB
6. At this stage the tumour is localized to the stomach → H. pylori eradication "cures" the lymphoma by removing the antigenic stimulus
7. With persistent disease, additional mutations cause constitutive NF-κB activation (e.g., t(11;18)(q21;q21) BIRC3-MALT1 translocation) → tumour no longer requires bacterial antigen → does not regress with eradication → spreads beyond the stomach

"At this stage, the B-cell proliferation remains localized to the stomach and eradication of H. pylori by antibiotic therapy 'cures' the lymphoma by removing the antigenic stimulus for T cells."

• Robbins & Kumar Basic Pathology

• Dense lymphocytic infiltrate in the lamina propria
• Lymphoepithelial lesions = neoplastic lymphocytes infiltrating and destroying gastric glands - the defining histological feature
• Reactive-appearing B-cell follicles may be present
• ~40% of tumours show plasmacytic differentiation

• CD19+, CD20+ (B-cell markers)
• CD5-, CD10- (marginal zone phenotype - not CLL or follicular lymphoma)
• CD43+ in ~25% (unusual feature, diagnostically helpful)
• Monoclonality confirmed by: restricted κ or λ light chain expression, or clonal IgH rearrangement by molecular analysis

• Associated with p53 and p16 tumour suppressor gene inactivation (Robbins PBD)
• Histology: sheets of large, transformed B cells - diffuse large B-cell lymphoma (DLBCL)

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5. Robbins Key Concepts Summary (exam-ready, direct from text)

• Most common cause of chronic gastritis = H. pylori infection
• H. pylori gastritis: antrum predominantly, associated with increased gastric acid production
• Later involvement of body → atrophy → reduced acid → risk of adenocarcinoma
• H. pylori gastritis induces MALT that can give rise to B-cell lymphomas (MALTomas)
• Intestinal metaplasia develops in all forms of chronic gastritis and is a risk factor for gastric adenocarcinoma
• Peptic ulcer disease: secondary to H. pylori-induced gastritis and resulting hyperchlorhydria

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6. Diagnostic Methods for Exam (Robbins + Jawetz)

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7. Master Summary Table

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Helicobacter pylori - Associated Lesions and Pathogenesis

MD Pathology Exam - Master Answer

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1. The Organism

"H. pylori has acquired the dubious distinction of being the first bacterium classified as a carcinogen - implicated in the genesis of both gastric adenocarcinoma and gastric lymphomas."

• Robbins & Kumar Basic Pathology

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2. Virulence Factors

• CagA is injected directly into gastric epithelial cells via a Type IV Secretion System (T4SS) encoded by the cag Pathogenicity Island (CagPAI) - a ~40 kb genomic insert. Inside the cell, CagA reorganises the actin cytoskeleton, activates SHP-2 phosphatase, ERK/MAPK, Wnt/β-catenin, and NF-κB, mimicking growth-factor stimulation and promoting malignant transformation
• VacA (vacuolating cytotoxin A) - also delivered by the T4SS; causes vacuolization of the endosomal compartment, mitochondrial damage, apoptosis, and T-cell suppression
• NH₃ from urease is directly cytotoxic to the mucosa and disrupts tight junctions
• Urease expression is pH-regulated; it is upregulated when gastric pH rises (e.g., after a meal), allowing the organism to fine-tune its acid protection

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3. Pathogenesis - The Dual-Pathway Model (Robbins PBD)

H. pylori infection acquired in childhood
              |
    ┌─────────┴──────────┐
    ↓                    ↓
ANTRAL-PREDOMINANT    PANGASTRITIS
   GASTRITIS         (body + antrum)
(most common)      (longstanding disease)
    |                    |
↑ G-cell gastrin    Parietal cell
↑ Acid secretion      atrophy
    |                ↓ Acid secretion
    ↓                    |
 PEPTIC ULCER       INTESTINAL
  DISEASE           METAPLASIA
(gastric +              |
duodenal)               ↓
                GASTRIC ADENOCARCINOMA

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4. Associated Lesions - Individual Discussion

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4.1 Chronic Active Gastritis

• H. pylori colonises antral mucosa → organisms + inflammation stimulate G cells → ↑ gastrin → ↑ acid → increased PUD risk
• CagA/VacA/urease → IL-8 secretion by epithelial cells → neutrophil infiltration
• T-cell-driven B-cell accumulation → lymphoid follicle formation (MALT)
• With time, infection may spread to involve body and fundus → atrophic change

• H. pylori organisms in surface mucus and on foveolar cell apices - visible on H&E/Giemsa; best shown by IHC or Warthin-Starry silver stain
• Large numbers of plasma cells, often in clusters or sheets in the superficial lamina propria (hallmark)
• Increased lymphocytes and macrophages in the lamina propria
• Neutrophils crossing the basement membrane into the epithelium
• Neutrophils accumulating in gland lumens = pit abscesses (pathognomonic of active gastritis)
• Submucosal lymphoid aggregates with germinal centres = induced MALT; absent in normal stomach; potential to transform into lymphoma (Robbins Basic + PBD)
• Intestinal metaplasia (goblet cells + columnar absorptive cells) in longstanding disease - risk factor for adenocarcinoma
• Thickened rugal folds with intense inflammation - can mimic infiltrative malignancy endoscopically
• Hyperplastic polyps (elongated foveolar glands with inflamed stroma) from regenerative repair

"Submucosal lymphoid aggregates, some with germinal centers, are frequently present and represent an induced form of MALT that has the potential to transform into lymphoma. Thus, risk of lymphoma, as well as adenocarcinoma, is increased in chronic H. pylori gastritis." - Robbins & Kumar Basic Pathology

• Shows tropism for gastric-type foveolar epithelium only
• Not found in areas of intestinal metaplasia, oxyntic (acid-secreting) mucosa of the body (unless patient is on PPIs), or duodenal epithelium
• Therefore antral biopsy is the preferred site for H. pylori evaluation

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4.2 Peptic Ulcer Disease

"Peptic ulcer disease is usually secondary to chronic H. pylori-induced gastritis and the resulting hyperchlorhydria." - Robbins PBD Key Concepts

H. pylori antral gastritis
    ↓
Inflammation → ↓ D-cell somatostatin
    ↓
Disinhibition of G cells → ↑ Gastrin secretion
    ↓
↑ Parietal cell mass (body) → HYPERSECRETION OF ACID
    ↓
Excess acid delivered to duodenal bulb
    ↓
Gastric metaplasia of duodenal mucosa
(duodenum acquires gastric-type foveolar epithelium)
    ↓
H. pylori colonises this metaplastic epithelium
    ↓
Active duodenitis → Duodenal ulceration

• Direct mucosal cytotoxicity: ammonia (urease), VacA, CagA-mediated IL-8/cytokine release
• ↓ Prostaglandin E₂ synthesis (disrupted by inflammation) → impaired mucus/bicarbonate barrier
• Acid level is normal or low (cf. duodenal ulcer with high acid) - primary mechanism is mucosal defence failure
• Sites: Lesser curve of antrum/incisura most common (watershed area with poor blood supply)

• Active phase: necrotic slough (zone 1) + granulation tissue (zone 2) + fibrosis (zone 3) + endarteritis obliterans (zone 4) at ulcer margin
• Adjacent mucosa: invariably shows H. pylori chronic active gastritis with organisms
• Benign features: punched-out margins, perpendicular walls, smooth base (vs. malignant ulcer with heaped-up irregular margins)

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4.3 Atrophic Gastritis and Intestinal Metaplasia

"Changes seen in atrophic H. pylori gastritis are sometimes referred to as environmental metaplastic atrophic gastritis, to distinguish it from autoimmune metaplastic atrophic gastritis." - Robbins PBD

• Loss of oxyntic glands (body) and antral glands → glandular atrophy (patchy, unlike autoimmune gastritis which is diffuse and body-only)
• No autoantibodies against parietal cells or intrinsic factor (distinguishes from autoimmune/Type A)
• Replaced by intestinal metaplasia: goblet cells, absorptive enterocytes, Paneth cells appear in gastric mucosa

• Type I (Complete/small intestinal): Sialomucins, brush border, complete absorptive cell differentiation; lower risk
• Type II/III (Incomplete/colonic): Sulphomucins, no brush border; higher malignant risk

"Intestinal metaplasia develops in all forms of chronic gastritis and is a risk factor for gastric adenocarcinoma." - Robbins PBD Key Concepts

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4.4 Gastric Adenocarcinoma - The Correa Cascade

Normal Gastric Mucosa
    ↓  H. pylori infection (especially CagA+ strain)
Chronic Active Gastritis (antral-predominant)
    ↓  spread to body, decades of inflammation
Multifocal Atrophic Gastritis
    ↓
Intestinal Metaplasia
(Complete → Incomplete/Type III - higher risk)
    ↓
Low-Grade Dysplasia
    ↓
High-Grade Dysplasia (Carcinoma in situ)
    ↓
INVASIVE INTESTINAL-TYPE GASTRIC ADENOCARCINOMA
(distal/non-cardia stomach)

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4.5 Gastric MALT Lymphoma (MALToma)

"H. pylori gastritis induces MALT that can give rise to B-cell lymphomas (MALTomas)." - Robbins PBD Key Concepts

H. pylori chronic gastritis
    ↓
H. pylori-reactive T cells appear
    ↓
T cells stimulate POLYCLONAL B-cell proliferation
(the lymphoid follicles/MALT of chronic gastritis)
    ↓
Accumulation of mutations → individual B-cell clones
gain growth advantage
    ↓
MONOCLONAL B-cell lymphoma
(still NF-κB dependent; still T-cell stimulated)
    ↓ ERADICATION WORKS HERE (75-80% regression)
    ↓ further mutations (e.g., t(11;18)(q21;q21) BIRC3-MALT1)
CONSTITUTIVE NF-κB ACTIVATION
(tumour is now antigen-independent)
    ↓ eradication no longer effective
Spread beyond stomach
    ↓
Additional mutations (p53, p16 inactivation)
HIGH-GRADE DLBCL TRANSFORMATION

• Dense lymphocytic infiltrate in the lamina propria
• Lymphoepithelial lesions = neoplastic centrocyte-like B-cells infiltrating and destroying gastric gland epithelium - THE defining histological feature
• Reactive B-cell follicles may be present
• ~40% show plasmacytic differentiation

• CD19+, CD20+, CD79a+ (B-cell)
• CD5-, CD10- (marginal zone phenotype; not CLL, not follicular lymphoma)
• CD43+ in ~25% (diagnostically helpful unusual feature - Robbins PBD)
• Monoclonality confirmed by: restricted κ or λ light chain expression OR clonal IgH rearrangement by molecular methods

"At this stage, the B-cell proliferation remains localized to the stomach and eradication of H. pylori by antibiotic therapy 'cures' the lymphoma by removing the antigenic stimulus for T cells."

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5. Histological Identification Methods

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6. Master Comparison: Type A vs Type B Gastritis

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7. All H. pylori-Associated Lesions - Summary Table

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8. High-Yield Quick Recall for Exam

1. H. pylori = extracellular only; does not invade tissue
2. Four virulence factors (Robbins): Flagella, Urease, Adhesins, Toxins (CagA/CagE)
3. CagA is delivered by Type IV Secretion System encoded by cag Pathogenicity Island
4. Lewis-b antigen is the main mucosal receptor; blood group O individuals have higher risk
5. Organisms show tropism for gastric foveolar epithelium only - not intestinal metaplastic foci (unless on PPIs)
6. Lymphoid follicle in gastric mucosa = pathognomonic of H. pylori (normally absent)
7. Pit abscesses = neutrophils in gastric pit lumens = hallmark of ACTIVE gastritis
8. Plasma cells in sheets in superficial lamina propria = characteristic of H. pylori gastritis
9. Duodenal ulcer = high acid (↑ gastrin pathway); Gastric ulcer = normal/low acid (defence failure)
10. Correa Cascade = normal → gastritis → atrophy → intestinal metaplasia → dysplasia → intestinal-type carcinoma
11. Sequence takes decades; occurs in <5% of infected individuals (Robbins Basic)
12. MALToma = only neoplasm that regresses with antibiotics (if NF-κB not constitutively active)
13. t(11;18) = BIRC3-MALT1 translocation = H. pylori-independent; does NOT regress with eradication
14. IL-1β and TNF polymorphisms (host genetics) determine whether antral-only disease or pangastritis/carcinoma develops (Robbins PBD)
15. H. pylori = WHO/IARC Group I carcinogen since 1994 = first bacterium so classified

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