PMC9043324_01
Unicentric Castleman Disease with an associated atypical spindle cell proliferation shows increased p53 protein expression and a PDGFRB p.Asn666Ser mutation. (A-C) Representative images of characteristic atretic follicle showing hyalinization of the germinal center with a penetrating vessel stained with hematoxylin and eosin (A), p53 (B) and SMA (C). (D-F) Representative images of spindle cell proliferation stained with H&E (D), p53 (E) and SMA (F). All images are presented at x400 magnification. (G) Graphic illustration of the PDGFRB p.Asn666Ser point mutation located within the 5q32 arm of chromosome 5.
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Due to the persistence of the mass and worsening clinical symptoms, the mass was excised, which revealed similar histomorphology as seen in the prior biopsy ( Figure 1 ). Interestingly, p53 overexpression by immunohistochemistry was noted in the spindle cell proliferation, rare FDCs and scattered spindle cells within the areas showing typical CD features ( Figure 1 ). Overall, p53 showed significant overexpression in 18 cases of UCD predominantly within an intrafollicular and paracortical distribution ( Figure 2 ) and appeared to colocalize with SMA positive single and grouped cells within the paracortex that were separate from vasculature ( Supplementary Figure 1 ).
p53 nuclear protein positive cell detection in Unicentric Castleman Disease. (A) Representative p53 immunohistochemical stain performed on additional UCD cases (magnification x100). (B) Post cell detection image from QuPath illustrating the presence of p53 nuclear protein overexpression[red] versus background negative cells [blue] (magnification x100). (C) Representative p53 immunohistochemical stain performed on an internal "control" case of reactive hyperplasia (magnification x200). (D) Post cell detection image from QuPath illustrating the presence of p53 nuclear protein overexpression[red] versus background negative cells [blue] (magnification x200). (E) Dot plot of p53 nuclear expression levels within UCD normalized to cases of reactive follicular hyperplasia. Of note, prospective clinical analysis showed that an additional 15 cases of reactive lymph nodes displayed a relative expression of 10 or less on p53 on staining (data not shown).
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Overall, p53 showed significant overexpression in 18 cases of UCD predominantly within an intrafollicular and paracortical distribution ( Figure 2 ) and appeared to colocalize with SMA positive single and grouped cells within the paracortex that were separate from vasculature ( Supplementary Figure 1 ).