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Light Chain-Restricted Plasmacytoid Cells in Hyperplastic Germinal CentersA Clinicopathologic Investigation
Xuan J Wang1, Erika M Moore1,2, Steven H Swerdlow1,2
1Divisions of Hematopathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Insights
Follicular hyperplasias with light chain-restricted cells are usually benign, despite potential BCL2 expression and monoclonality. These findings may indicate autoimmunity or increased IgG4 cells, but lymphoma development is rare.
Area of Science:
- Hematopathology
- Immunohistochemistry
- Molecular Pathology
Background:
- Follicular hyperplasias (FHs) with light chain-restricted (LCR) plasmacytoid/plasma cells (PCs) in germinal centers (GCs) can be diagnostically challenging.
- Distinguishing these entities from lymphoid neoplasms is crucial for accurate patient management.
Purpose of the Study:
- To characterize FHs with LCR-positive GCs (LCRGCs) using immunohistochemistry (IHC)/in situ hybridization (ISH).
- To evaluate the clinical implications and potential association with lymphoma development.
Main Methods:
- Quantitative assessment of LCR expression in GCs of 17 FH cases.
- Staining for BCL2, CD10, BCL6, immunoglobulin heavy chains, IgG4, and Epstein-Barr encoding region.
- Polymerase chain reaction (PCR)-based clonality studies in 8 cases.
Main Results:
- All 17 cases showed FH, with 4 exhibiting progressively transformed GCs (PTGCs).
- LCRGCs constituted 0.8%–52% (median 21%) of GCs; 13/17 had both kappa (κ) and lambda (λ) LCRGCs.
- Prominent intrafollicular IgG4-positive cells were noted in 7/16 cases; B-cell monoclonality was found in 3/8 cases (post-microdissection).
- Seven patients had autoimmune disorders; three had a history of lymphoma, with one developing lymphoma and another lymphomatoid granulomatosis.
Conclusions:
- FHs with LCRGCs are typically not associated with lymphoma development, despite potential BCL2 expression and monoclonality.
- These findings may be linked to increased intrafollicular IgG4-positive cells, PTGCs, and autoimmunity.
- Accurate IHC/ISH interpretation is vital to avoid diagnostic errors in these challenging cases.
Objectives:
Follicular hyperplasias (FHs) with light chain-restricted (LCR) plasmacytoid/plasma cells (PCs) within germinal centers (GCs) based on immunohistochemistry (IHC)/in situ hybridization (ISH) can potentially lead to diagnostic error. This study aims to better characterize such cases, including their clinical implications.
Methods:
LC expression by IHC/ISH was quantitatively assessed in GCs of 17 FHs with LCRGCs. BCL2, CD10, BCL6, BCL2, immunoglobulin (Ig) heavy chains, IgG4, and Epstein-Barr encoding region stains were performed. In total, 8 cases had polymerase chain reaction (PCR)-based clonality studies.
Results:
All cases showed FH, including 4 with progressively transformed GCs (PTGCs); 0.8% to 52% (median, 21%) of the GCs were LCR; 13 of 17 had both κ- and λ-LCRGCs, and 4 of 17 had only κ-LCRGCs; 7 of 16 had prominent intrafollicular IgG4-positive cells. One case demonstrated BCL2-positive cells in focal LCRGCs but lacked BCL2 rearrangement. B-cell monoclonality was demonstrated in 3 of 8 cases (only after microdissection). Seven patients had autoimmune disorders, and 1 had had a transplant. Three patients had a history of lymphoma, 1 developed lymphoma, and 1 developed lymphomatoid granulomatosis subsequently.
Conclusions:
FHs with LCRGC by IHC/ISH are typically not associated with the development of lymphoma, even though they can express BCL2 and show monoclonality by PCR. They may be associated with increased intrafollicular IgG4-positive cells, PTGC, and autoimmunity.
