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.

COVID‐19 post‐vaccination lymphadenopathy: A review of the use of fine needle aspiration cytology

“…In the remaining two cases, lymph nodes were excised and diagnosed as reactive on histology. The authors of the present study believe these cases might match the case described by Patil et al 62 of atypical follicular hyperplasia with light chain-restricted germinal centres after a COVID-19 booster. It is conceivable that the immunological hyperstimulation or the hyperreactivity caused by RNA vaccines in certain patients might be responsible for the marked hyperplasia of germinal centres and pseudo-clonality, as is the case in some cases of autoimmune diseases.…”

“…The immunohistochemical phenotype (IHC) was reported in eight cases. 54,58,61,62,71 The results of flow cytometry were also reported in one case. 44 A case of atypical follicular hyperplasia with light chain-restricted germinal centres after a COVID-19 booster was described, 62 but the specific vaccine was not reported.…”

“…In our research, surgical excision or CNB of C19-LAP-or SLDI-enlarged lymph nodes have been performed in 55 cases. 20,22,23,35,39,[41][42][43]47,[49][50][51][52][53][54][55][56][57][58][59][60][61][62][63] The histological diagnoses were as follows: negative for neoplasia, reactive hyperplasia, and florid reactive hyperplasia (39 cases), 23,39,[50][51][52][53][54][55][56][57][58][59][60][61] progressive transformation of germinal centres (1 case), 54 atypical follicular hyperplasia with light chain-restricted germinal centres (1 case) 62 granulomatous reaction (2 cases), 50,63 metastases (4 cases), 20,22,50 Kikuchi-Fujimoto disease (KFD; 6 cases), [40][41]…”

“…Post-vaccine lymphadenopathy due to reactive changes is a wellknown phenomenon that may occur as a side effect of different vaccines, including bacillus Calmette-Guerin (BCG), hepatitis B, human papillomavirus, and tetanus vaccines, [4][5][6][7][8][9]12,14 sometimes simulating a lymphoma, 24,57,62 either clinically or pathologically. where it is translated into a protein, which is the target of the immune response.…”

“…Lymph node excision and core-needle biopsy (CNB) were the most frequently performed procedures for the pathological evaluation of COVID-19 post-vaccine lymphadenopathy. We retrieved 48 cases of C19-LAP with histological control (excision or CNB ) 22,23,39,43,48,49,51,53,56,57,61,62 and diagnosed as negative or reactive with or without follicular hyperplasia (37 cases). Two cases were reported as florid lymphoid hyperplasia 54,57 ; KFD was reported in four cases 37,39,49,56 (16.7%).…”