Cutaneous T-cell lymphoma (CTCL) exacerbation after viral vector COVID-19 vaccination

Introduction: We are living an ongoing global COVID-19 pandemic associated with a considerable number of fatal cases worldwide. Cancer patients seem to exhibit exacerbated conditions and higher mortality rates. Vaccines are a promising solution to minimize the problem amongst cancer patients but there are limitations to be considered. Case summary: Herein, we present two cutaneous T-cell lymphoma (CTCL) cases which were in long-term remission and experienced a flare after immunization with a viral vector COVID-19 vaccine (Vaxzevria, Oxford/AstraZeneca). The first case was a 60-year-old male with early-stage (T1a) folliculotropic mycosis fungoides (MF) clinically presented as alopecia areata-like lesions. The patient was in clinical remission during the last two years, maintaining a T1aN0M0 stage with only a single, stable alopecic patch on the scalp. Four weeks after the first COVID-19 vaccine dose, a minor lichenoid induration was observed in the periphery of the lesion, while a week after the second dose, small nodules surrounding the lesion were also noted. Histology confirmed the diagnosis of CD30+ Large cell transformation (LCT) of tumor-stage MF. The second case was a 73-year-old female with early-stage MF (T1a/IA) and Lymphomatoid papulosis (LyP). Clinically, she presented with pruritic erythematous patches and nodules on the trunk and upper legs. The patient was successfully treated with psoralen plus ultraviolet A (PUVA) phototherapy remaining in clinical remission for six years. After vaccination, she developed multiple erythematous papules and nodules on the trunk and limbs. A flare of LyP was confirmed from the pathology, which correlated to her clinical picture. Discussion: These cases raise the question of whether and via which pathways the vaccine might induce disease exacerbation of both MF and LyP. According to the literature, the education of T (CD4+ and CD8+) and B cells against SARS-CoV-2 spike protein appears to be the main strategy for COVID-19 vaccine production. Both cancers and viral infections can provide a chronic and persistent antigenic load, leading to up-regulated programmed cell death protein 1 (PD1) expression and ultimately T cell exhaustion. CD30 is known to be expressed in a small subset of activated T and B cells, as well as a variety of lymphoid neoplasms. Initial studies showed that CD30 expression on lymphocytes could be induced via in vitro antigenic stimulation by mitogens or viruses. CD30 expression also appears to be higher on CD4+ and CD8+ T cells producing a Th2-type cytokine profile. In our cases, the viral vector-based vaccines used do not contain a live virus but specific parts of the coronavirus attached to adenovirus, which can also stimulate an anti-viral immune response. Conclusion: The reported cases suggest that disease flare-ups may be associated with overproduction and exhaustion of CD4+/CD8+ T cells expressing CD30 after stimulation by the adenovirus. Expression of CD30, which can be a marker for disease progression, was high in biopsy samples of our patients.