Wotherspoon criteria combined with B cell clonality analysis by advanced polymerase chain reaction technology discriminates covert gastric marginal zone lymphoma from chronic gastritis

Gut. 2006 Jun;55(6):782-7. doi: 10.1136/gut.2005.080523. Epub 2006 Jan 19.


Background and aims: Gastric mucosa associated lymphoid tissue lymphoma is a well defined B cell lymphoma yet often impossible to distinguish from severe chronic gastritis on morphological grounds alone. Therefore, it was suggested to use the clonality of the immunoglobulin (Ig) heavy chain (H) genes, as detected by polymerase chain reaction (PCR), as a decisive criterion. However, there is controversy as to whether B cell clonality also exists in chronic gastritis, hence rendering this approach futile at present.

Methods: An expert panel re-examined the histology and immunohistochemistry of a total of 97 cases of gastric biopsies, including clearcut marginal zone lymphoma, chronic gastritis, and ambiguous cases, applying the Wotherspoon criteria on the basis of haematoxylin-eosin and CD20 immunostainings. In addition, a new and advanced PCR system for detection of clonal IgH gene rearrangements was independently applied in two institutions in each case.

Results: The overall IgH clonality assessments of both institutions were in total agreement. Overt lymphoma (Wotherspoon score 5) was clonal in 24/26 cases. Chronic gastritis (Wotherspoon scores 1 and 2) was not clonal in 52/53 cases; the clonal case being Wotherspoon score 2. Of 18 cases with ambiguous histology (Wotherspoon scores 3 and 4) four were clonal.

Conclusions: Using advanced PCR technology, clonal gastritis is extremely rare, if it exists at all. Thus B cell clonality in Wotherspoon 3 and 4 cases is regarded as suitable for definitively diagnosing gastric marginal zone lymphoma.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Algorithms
  • Antigens, CD20 / metabolism
  • Biomarkers, Tumor / metabolism
  • Chronic Disease
  • Clone Cells / pathology
  • Diagnosis, Differential
  • Gastritis / diagnosis*
  • Gastritis / pathology
  • Gene Rearrangement, B-Lymphocyte, Heavy Chain
  • Genes, Immunoglobulin
  • Humans
  • Immunoglobulin Heavy Chains / genetics
  • Lymphoma, B-Cell, Marginal Zone / diagnosis*
  • Lymphoma, B-Cell, Marginal Zone / pathology
  • Neoplastic Stem Cells / pathology
  • Pilot Projects
  • Polymerase Chain Reaction / methods
  • Reproducibility of Results
  • Stomach Neoplasms / diagnosis*
  • Stomach Neoplasms / pathology


  • Antigens, CD20
  • Biomarkers, Tumor
  • Immunoglobulin Heavy Chains