New Diagnosis of B-cell Follicular Lymphoma Temporally Associated With Routine Vaccination: A Report of Two Cases

Follicular lymphoma (FL) is an indolent B-cell non-Hodgkin lymphoma with potential for transformation into diffuse large B-cell lymphoma (DLBCL). While transient lymphadenopathy is a known response to vaccination, particularly with mRNA COVID-19 vaccines, recent case reports suggest that immune activation may potentially unmask previously undocumented subclinical lymphoproliferative disorders. We report two cases of newly diagnosed FL following routine adult vaccinations. Case 1 involves a 69-year-old male with no prior history of malignancy or immunosuppression, who developed bilateral axillary lymphadenopathy four weeks after receiving the Moderna COVID-19 vaccine, influenza, and pneumococcal vaccines. Excisional biopsy revealed Grade 1-2 FL with a t(14;18)(q32;q21) translocation, and he achieved complete remission following mosunetuzumab therapy. Case 2 describes a 70-year-old male with no prior history of malignancy or immunosuppression, who developed mild, nonspecific symptoms approximately four weeks after completing a two-dose Pfizer COVID-19 vaccine series, with subsequent progression to symptomatic lymphadenopathy. He was diagnosed with FL that had undergone histologic transformation to Stage IV DLBCL and was successfully treated with R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, prednisone) protocol and radiation. These reports illustrate the ability of immune stimulation by vaccination to unmask existing but asymptomatic lymphoid malignancies. While vaccination is not implicated as an oncogenic driver, the resulting inflammatory response may serve as a diagnostic "stress test" for the lymphoid system, revealing underlying pathology.