Atypical follicular hyperplasia with light chain-restricted germinal centers after COVID-19 booster: a diagnostic pitfall

Abstract

There has been a surge in COVID-19 vaccine-associated lymphadenopathy (LAD), including after the booster dose of vaccine. This can create diagnostic dilemmas in oncology patients as the relatively sudden LAD can mimic metastasis or cancer recurrence, at a risk of leading to additional but unnecessary anti-neoplastic therapy. Here we report the histopathologic features in a case of persistent LAD occurring in a patient with history of breast invasive ductal carcinoma which followed a COVID-19 vaccine booster. A needle core and then excisional biopsy showed atypical follicular hyperplasia with features that histologically and phenotypically could mimic follicular lymphoma, but the findings were ultimately interpreted to be reactive in nature and related temporally to COVID-19 vaccine. To our knowledge, this is the first case of an atypical lymphoproliferative lesion with features potentially mimicking lymphoma associated with COVID-19 vaccine.

Keywords: COVID-19; COVID-19 vaccine; COVID-19-related lymphadenopathy; Mimicker of lymphoma.

Fig. 1

18F-FDG PET/CT. Imaging shows bilateral enlarged axillary lymph nodes, right external iliac lymph nodes and left inguinal lymph nodes

Fig. 2

Core needle biopsy of axillary lymph node. Histologic sections show a small and fragmented biopsy of lymph node containing few prominent and atypical-appearing germinal centers (A, hematoxylin and eosin stain, 100 × magnification). The atypical follicles have ill-defined borders, lack mantle zones and germinal center polarization, and contain a relatively monotonous population of medium- to large-sized centrocytic and centroblastic lymphoid cells with decreased apoptotic bodies and no tingible body macrophages (B, hematoxylin and eosin stain, 500 × magnification). Follicular B cells express CD10 (C) and BCL6 (D) and are negative for BCL2 (E) by immunohistochemistry. For comparison, BCL2 immunostain in normal germinal centers of reactive tonsil is included in the inset of panel E. Compared to normal tonsil, the atypical follicles in the patient biopsy are irregular in shape and lack mantle zones. The Ki-67 proliferative rate is high, ~ 80%, without polarization although the entire germinal centers are not present in the biopsy and markedly hyperplastic germinal centers do not necessarily show polarization (F)

Fig. 3

Excisional lymph node biopsy. Histologic section of right axillary lymph node shows intact nodal architecture with most secondary follicles showing normal shapes and distribution with well-defined mantle zones and polarized germinal centers containing tingible body macrophages (A, hematoxylin and eosin stain, 20 × magnification; inset hematoxylin and eosin stain, 200 × magnification). Occasional large atypical-appearing follicles have non-polarized germinal centers containing a relatively monotonous population of cells with variable plasmacytic morphologic features (B, hematoxylin and eosin stain, 100 × magnification; C, hematoxylin and eosin stain, 500 × magnification). The atypical follicles with increased plasmacytic cells show stronger expression of CD79a (D, arrow) and dim coexpression of BCL2 (E, arrow) and have an atypical low Ki67 proliferative rate (F, arrow) compared to adjacent normal follicles. IRF4/MUM1 is strongly expressed in the atypical follicles (G) and some show kappa restriction (H, arrow) while others show lambda restriction (I, arrow). Panels H and I depict kappa and lambda ultrasensitive RNA in situ hybridization assays