What does it mean if flow cytometry shows no definite monotypic B-cell or abnormal T-cell population identified, but uterine hysteroscopy and pathology reveal a lymphoplasmacytic infiltrate consistent with B cell lymphoproliferative neoplasm?

Discordance Between Flow Cytometry and Tissue Pathology in B-Cell Lymphoproliferative Disorder

The discrepancy between negative flow cytometry findings and positive histopathology with gene rearrangement studies indicates a B-cell lymphoproliferative neoplasm that was not detected by flow cytometry, likely due to technical limitations or sampling issues.

Understanding the Discrepancy

When flow cytometry shows no definite monotypic B-cell or abnormal T-cell population, but histopathology reveals a lymphoplasmacytic infiltrate with clonal gene rearrangements, this represents a diagnostic discordance that can occur for several reasons:

Reasons for False Negative Flow Cytometry Results:

1. Sampling issues:

   • The abnormal cells may be focally distributed or adherent to tissue stroma 1
   • Flow cytometry sample may not have captured the area with neoplastic cells

2. Technical limitations:

   • Plasma cell/lymphoplasmacytic neoplasms can be difficult to detect by flow cytometry
   • Neoplastic cells may have fragile membranes that don't survive processing 1
   • Some lymphoproliferative disorders have subtle immunophenotypic abnormalities

3. Tissue-based disease:

   • Some lymphoproliferative disorders are primarily tissue-based with minimal circulating disease

Clinical Significance

The histopathology findings are more definitive in this case because:

• Marked lymphoplasmacytic infiltrate in endometrial stroma is histologically consistent with B-cell lymphoproliferative neoplasm
• Demonstration of immunoglobulin heavy and light chain clonal gene rearrangements provides molecular confirmation of clonality 1
• Gene rearrangement studies are highly specific for confirming the presence of a clonal process

Diagnostic Approach to Resolve the Discrepancy

1. Review histopathology thoroughly:

   • Confirm morphologic features of lymphoplasmacytic infiltrate
   • Perform immunohistochemistry panel including CD20, CD79a, CD5, CD10, CD23, cyclin D1, kappa/lambda, and CD138 1

2. Additional molecular studies:

   • FISH for specific translocations (if not already performed)
   • Consider next-generation sequencing for mutations associated with specific lymphoma subtypes 1

3. Comprehensive staging:

   • Bone marrow biopsy to assess for marrow involvement
   • CT imaging to evaluate for additional sites of disease

Differential Diagnosis

Based on the lymphoplasmacytic infiltrate in the endometrium with clonal gene rearrangements, the differential diagnosis includes:

1. Extranodal marginal zone lymphoma of MALT type - Common in extranodal sites
2. Lymphoplasmacytic lymphoma/Waldenström macroglobulinemia - Characterized by lymphoplasmacytic infiltrate with clonal IgM 1
3. Small lymphocytic lymphoma - Usually CD5+ and CD23+ 1
4. Follicular lymphoma - Usually CD10+ and BCL2+ 1

Management Implications

The discrepancy between flow cytometry and histopathology should not delay appropriate management:

• The histopathology with molecular studies confirming clonality should guide diagnosis and treatment
• Flow cytometry can be repeated on additional specimens but should not override positive histopathologic findings
• Treatment should be based on the specific lymphoma subtype identified by comprehensive evaluation

Common Pitfalls to Avoid

1. Dismissing positive histopathology due to negative flow cytometry

   • Histopathology with molecular confirmation of clonality is more definitive

2. Inadequate immunophenotypic evaluation

   • Comprehensive immunohistochemistry panel is essential for lymphoma classification 1

3. Failure to integrate clinical findings

   • Clinical presentation and laboratory findings should be correlated with pathology

4. Overlooking sampling limitations

   • Consider repeat biopsy if diagnosis remains uncertain

In summary, when there is discordance between flow cytometry and histopathology with molecular studies, the tissue diagnosis with clonal gene rearrangements provides stronger evidence for a lymphoproliferative disorder. Further characterization and classification should be pursued to guide appropriate management.