Cutaneous Lymphomas and Lymphoproliferative Disorders Associated With SARS-CoV-2 Vaccination: A Systematic Review

Cutaneous lymphomas (CLs) are rare neoplastic skin disorders, primarily of T-cell origin. Since the widespread rollout of SARS-CoV-2 vaccines, several cases of CLs and non-neoplastic lymphoproliferative disorders (nn-LPDs) temporally associated with vaccination have been reported, raising concerns about a potential immunologic link.

To systematically review the literature on cases of CLs and related nn-LPDs occurring after COVID-19 vaccination, focusing on clinical features, subtype distribution, latency to onset, and proposed pathophysiological mechanisms.

A systematic review was conducted according to PRISMA guidelines. Case reports and series describing new-onset or relapsed CLs or nn-LPDs temporally following SARS-CoV-2 vaccination were included. Demographic, clinical, histological, therapeutic and temporal data were extracted and analysed.

Fifteen manuscripts encompassing 35 cases met the inclusion criteria. Eighteen (51.4%) were histologically confirmed CLs, most commonly lymphomatoid papulosis (n = 9), followed by Sézary syndrome (n = 3) and mycosis fungoides (n = 2). The remaining 17 cases (48.6%) were classified as nn-LPDs, including cutaneous lymphoid hyperplasia, lymphomatoid reactions and CD4+ small/medium T-cell lymphoproliferative disorders. CD30 positivity was noted in 76.2% of the cases with available immunophenotyping. Most patients (80%) received the BNT162b2 (Pfizer-BioNTech) vaccine. In the 17 new-onset CLs, time to onset ranged from 3 to 42 days, with most cases clustering within 14 days.

Most of the cases were low-grade T-cell CLs and nn-LPDs. Although a causal relationship cannot be established, the short latency observed in many new-onset cases raises the possibility that some patients may have harboured an undiagnosed disease, with vaccination acting as a trigger for clinical manifestation or for raised awareness. These findings support indeed the need for continued pharmacovigilance among clinicians, especially in patients with prior or latent lymphoproliferative conditions. Nevertheless, these extremely rare and indolent events should not alter the overall favourable risk-benefit profile of COVID-19 vaccination.