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CD21 Immunostaining Can Identify Dendritic Cell Network of Tertiary Lymphoid Tissue in Transplant Renal Biopsies and
Brandon D Metcalf1, Reenal Patel1, Dilip Samarapungavan2
1Department of Pathology, Corewell Health William Beaumont University Hospital, Royal Oak, MI, USA.
Objective:
Tertiary lymphoid tissue (TLT) has been described as germinal center-like lymphoid structures composed of a dendritic network, mixed lymphocytes, and high endothelial venules in internal organs. A recent study indicates that TLT can be seen in up to 19% of protocol renal transplant biopsies. We hypothesize that CD21 staining can identify dendritic cells in TLT so that borderline changes are not overdiagnosed.
Methods:
CD21 immunostaining was initially used for identifying TLT in multiple internal organs as a quality control. Subsequently, 34 transplant renal biopsies (TRB) with borderline changes were reviewed and stained for CD21 to reveal the incidence of overdiagnosed borderline changes in our database. The second study was to further explore the presence of CD21 immunostaining in a set of 10 renal transplant biopsies from patients with serum donor-derived cell-free DNA (ddcfDNA).
Results:
Routine hematoxylin and eosin (H.E.) staining showed TLT with isolated germinal center-like structures and smooth-rounded borders. CD21 staining highlighted wavy dendritic cells forming a lacy-like network within TLT in quality control cases. Of 34 TRB with borderline changes, five cases were retrospectively found to have TLT on routine sections and CD21 staining highlighted the dendritic cell network, thus confirming the presence of TLT in the biopsies, indicating an incidence of overdiagnosed borderline changes at 14.7% (5/34). The true borderline changes showed infiltrative lymphocytes (< 25%) with mild tubulitis, in the absence of TLT. In the second study, only one case (1/10) showed positive CD21 staining, confirming the presence of TLT, but ruling out borderline changes.
Conclusions:
TLT represents reactive changes that should not be considered as cellular rejection or borderline changes. Immunohistochemical staining of CD21 is a more reliable method than morphology to confirm TLT, thus helping to rule out TLT in uncertain aggregates of lymphocytes in TRB.
