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Case 10

Case 10. William G. Finn, M.D. New Frontiers in Pathology October 1, 2010. Case Presentation.

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Case 10

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  1. Case 10 William G. Finn, M.D. New Frontiers in Pathology October 1, 2010

  2. Case Presentation • A 67 year-old woman presented with chief complaints of swelling of her right upper eyelid and diplopia on extreme gaze. Physical examination revealed an apparent lacrimal gland mass. The slide is a section of an excisional biopsy of the lacrimal gland mass. A preliminary analysis of flow cytometricimmunophenotyping data was reported to show a polyclonal population of B-lymphocytes.

  3. Flow Cytometry Kappa:Lambda = 3.4 to 1

  4. Common Question: What kappa:lambda ratio by flow cytometry indicates clonality? • 10:1? 8:1? 4:1? • Wrong question • It isn’t just about ratios, it is about isolating an aberrant population • Skewed K:L ratio is not and end point • Skewed K:L ratio is a starting point for purification of an abnormal cell population based on broader immunophenotype • Analysis approach should be tailored based on case attributes

  5. Current Case • Differential diagnosis • Follicular lymphoid hyperplasia • Marginal zone lymphoma with background hyperplasic lymphoid follicles • For this case, flow cytometricclonality assessment can be based on separating GC vs non-GC B-cells based on immunophenotype

  6. Immuophenotype of Normal Germinal Center B-cell Maturation = Germinal center B cells = Non-germinal center B cells

  7. Our Patient’s Biopsy

  8. Flow cytometry interpretation: • Monoclonal B-cell population (CD5 negative, CD10 negative) admixed with a background polyclonal B-cell population • This pattern would support a histologic impression of extranodal marginal zone lymphoma in a setting of background follicular lymphoid hyperplasia

  9. Final Diagnosis: Extranodal marginal zone lymphoma of MALT type in a setting of background follicular lymphoid hyperplasia

  10. Follow-up • Staging CT scan revealed gastric wall thickening • Upper endoscopy revealed EMZL of stomach, H. pylori-negative • Local radiation to orbit and stomach • Follow-up stomach biopsy negative for lymphoma • Patient alive and well 7 months after diagnosis

  11. Extranodal Marginal Zone Lymphoma of MALT Type • Orbital MALT lymphoma usually localized • Stomach MALT lymphoma usually localized • But, MALT lymphomas may recur at distant MALT sites or involve distant MALT sites at diagnosis • H. pylori negative, and multifocal • Possibility of: • t(11;18)(q21;q21) – API2/MALT1 • t(14;18)(q32;q21) – IGH / MALT1 • t(1;14)(p22;q32) – BCL-10 / IGH • Not evaluated in this case

  12. Take Home Points • Current diagnostic flow cytometry is a dynamic, iterative process • Data, not dot-plots • Beware of static or unidirectional “gating” approaches • Interpretation is about isolating and defining immunophenotypic aberrancy not just “kappa:lambda ratio” • Slight skews in k:l ratio are starting points, not end points for discovery of aberrant populations

  13. Take Home Points • Interpretation of flow cytometry data requires knowledge of normal as well as abnormal • Normal cell subsets can be interpreted as aberrant if not routinely analyzed • Trust your histologic instincts

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