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Regressed GCs: Grade 1
Plasmacytosis: Grade 1
FDC prominence: Grade 0
Vascularity: Grade 0
Hyperplastic GCs: Grade 1

Part of the GCs are hyperplastic (Grade 1) and only sporadic GCs show signs of regression (Grade 1). There is no prominent FDC prominence (Grade 0), nor increased vascularity (Grade 0). The interfollicular area shows a normal amount of plasma cells (Grade 1). The CD20 immunostain illustrates the B-cell compartment.

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Abbreviations

GCs, germinal centres; FDC, follicular dendritic cell.

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Regressed GCs: Grade 2
Plasmacytosis: Grade 1
FDC prominence: Grade 2
Vascularity: Grade 2
Hyperplastic GCs: Grade 1

This lymph node is characterised by a very prominent regression of GCs (Grade 2). The GCs contain very little residual centrocytes and centroblasts, giving rise to prominence of FDCs (Grade 2). There is only mild vascularity inside the GCs, with only sporadic penetrating vessels. However there is a prominent vascular expansion in the paracortex (Grade 2). Some plasmacytosis is present (Grade 1).

With this histopathological picture iMCD can be considered, but a chronic viral infection (HIV, EBV), auto-inflammatory disorder, and angioimmunoblastic T-cell lymphoma, should be ruled out. Additional stains that are necessary to perform in this context are: CD21, CD4, PD1, ICOS, HHV-8, EBER in situ hybridization. TCR PCR can be performed to rule out T-cell clonality.

The following images are provided, CD21 shows no increased FDC networks surrounding the high endothelial venules in the paracortical area, as one should expect in AITL; CD20 shows the lack of centrocytes and centroblasts in the GCs, corresponding to the small amount of BCL2-negative cells.

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Abbreviations

AITL, angioimmunoblastic; EBV, Epstein-Barr virus; GCs, germinal centres; FDC, follicular dendritic cell; HHV-8, human herpesvirus-8; HIV, human immunodeficiency virus; iMCD, idiopathic Multicentric Castleman Disease.

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Regressed GCs: Grade 1
Plasmacytosis: Grade 3
FDC prominence: Grade 1
Vascularity: Grade 2
Hyperplastic GCs: Grade 3

This H&E section shows prominent secondary B-cell follicles (Grade 3) with only few regressed GCs (Grade 1). The GCs contain a mixture of centroblasts and centrocytes, follicular T-helper cells, and some tingible body macrophages. The follicular dendritic cells (FDCs) are present in the GCs but show no proliferation (Grade 1). Only a few of the GCs contain identifiable small vessels, there is moderate interfollicular proliferation (Grade 2).

These histopathological features from this stain are consistent with the plasma cell variant of iMCD, but IgG4-related lymphadenitis, auto-inflammatory disorders, infectious diseases (e.g., syphilis, viral infection) need to be excluded before iMCD can be diagnosed. Additional stains that are necessary to perform are: kappa/lambda, HHV-8, IgG4, Warthin-Starry. The following immunostains are provided: IgG4 shows no increase in IgG4+ plasma cells; There is no nuclear positivity for HHV-8/LANA; CD21 shows the FDC networks in the reactive GCs.

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Abbreviations

CD21, cluster of differentiation 21; FDCs, follicular dendritic cells; GCs, germinal centres; HHV-8, human herpesvirus-8; H&E, hematoxylin and eosin; IgG4, immunoglobulin G4; iMCD, idiopathic Multicentric Castleman Disease; LANA, latency-associated nuclear antigen.