Gökhan Okan 1 ✉ , Cuyan Demirkesen 2 1 Department of Dermatology, Aydin University, Istanbul, Turkey. 2 Department of Pathology, Acibadem University, Istanbul, Turkey. 157 2025;34:157-158 doi: 10.15570/actaapa.2025.28 Acta Dermatovenerologica Alpina, Pannonica et Adriatica Acta Dermatovenerol APA Cutaneous B-cell pseudolymphoma treated with imiquimod To the Editor, Cutaneous pseudolymphoma is a type of lymphocytic infiltrate with histopathological and/or clinical features resembling those of lymphoma (1). Cutaneous pseudolymphoma can be classified as B-cell (Spiegler–Fendt), T-cell (Jessner–Kanof) or mixed type. Some authors consider Jessner–Kanof T-cell pseudolymphoma a variant of cutaneous lupus erythematosus (CLE) tumidus (2). Pseudolymphoma type B may represent the cutaneous manifesta- tion of the second stage of Lyme disease (3). We describe a patient with cutaneous B-cell pseudolymphoma (CBPL) that responded well to imiquimod therapy. A 70-year-old man presented with a 6-month history of itchy infiltrating plaque between the second and third toe of the left foot (Fig. 1a). He denied a history of insect bites or exposure to any medication. His medical history was unremarkable. Labora- tory tests were within normal limits, including a negative result for Borrelia antibodies. Histopathological examination revealed dermal lymphoid infiltration, deeply burdened by squeezing ar- tifacts, forming lymphoid follicles and rich in eosinophils. The overlying epidermis displayed mild orthohyperkeratosis, pso- riasiform hyperplasia, and spongiosis (Figs. 2a, 2b). Immuno- histochemical examination revealed that the lymphoid follicles consisted of CD20-positive B cells, with retained CD21 + follicular dendritic cell meshwork and Bcl-6 + reactive germinal centers, with polarized proliferative activity, as demonstrated by Ki-67 (Figs. 2c–f). Clinical, histopathological, and immunohistochemi- cal findings confirmed the diagnosis of CBPL. Topical steroids, in- tralesional triamcinolone, and topical tacrolimus were employed without success. The patient declined cryotherapy and surgical intervention. Imiquimod 5% cream applied three times per week resulted in complete resolution of the lesion after 3 months (Fig. 1b). No recurrence was observed after 1 year of follow-up. Most CBPL cases are idiopathic, but they may develop as a response to contact dermatitis, arthropod reactions, tattoo dyes, vaccinations, drugs, or bacterial infections. Reported culprits include cytotoxins, anticonvulsants, antipsychotics, antihyper- tensives, antibiotics, and immunological therapies (4). Despite the absence of a history of insect or arthropod bites and negative Borrelia antibodies, the presence of eosinophil-rich lymphocytic infiltrates in the pathological results increased the likelihood of B-cell pseudolymphoma following arthropod or insect bites in our patient. There is a lack of standardized treatment for CBPL, but gen- erally accepted options include observation, antibiotics, topical, intralesional, and systemic corticosteroids, cryosurgery, photo- chemotherapy, local radiation therapy, and surgical excision (5). In our patient, imiquimod was administered with occlusion for enhanced penetration, three times a week for 3 months. Although Baumgartner-Nielsen and Lorenzen (6) reported the regression of pseudolymphoma lesions with imiquimod using a regimen of 5 days per week for 6 weeks, we decided to change the schedule of the treatment to 3 days per week over a period of 3 months to minimize the risk of irritation. The lesion disappeared at the end of the 3 months, and no relapse was observed during the follow- up period. Imiquimod is an immunomodulator that activates toll-like re- ceptor 7, thereby increasing the levels of proinflammatory T-help- er 1 cytokines, which activate cytotoxic T lymphocytes and natural killer cells (7). It stimulates the recruitment of dendritic cells and the production of interleukin-1, interleukin-6, tumor necrosis fac- tor, and interferon-alpha. Imiquimod has been successfully used for the management of cutaneous B-cell lymphomas refractory to conventional treatments (8). We believe that the regression of the pseudolymphoma lesion in our patient is due to the intensity of the inflammatory reaction induced by imiquimod. This case highlights the potential utility of topical imiquimod for the management of recalcitrant CBPL. Further studies are war- ranted to elucidate its role in treatment, mechanism of action in such patients, and the optimal dosing regimens. ✉ Corresponding author: gokhanokan@hotmail.com Keywords: pseudolymphoma, B-cell, imiquimod, eosinophil Received: 3 July 2025 | Returned for modification: 11 August 2025 | Accepted: 12 August 2025 Figure 1 | A) Before treatment; B) after imiquimod treatment. 158 Acta Dermatovenerol APA | 2025;34:157-158 G. Okan et al. References 1. Mitteldorf C, Kempf W. Cutaneous pseudolymphoma—a review on the spectrum and proposal for a new classification. J Cutan Pathol. 2020;47:76–97. 2. Pereira A, Ferrara G, Calamaro P, Cota C, Massone C, Boggio F, et al. The histo- pathological spectrum of pseudolymphomatous infiltrates in cutaneous lupus erythematosus. Am J Dermatopathol. 2018;40:247–53. 3. Maraspin V, Strle F. Borrelial lymphocytoma. Wien Klin Wochenschr. 2022. 4. Etesami I, Kalantari Y, Tavakolpour S, Mahmoudi H, Daneshpazhooh M. Drug- induced cutaneous pseudolymphoma: a systematic review of the literature. Australas J Dermatol. 2023;64:41–9. 5. Miguel D, Peckruhn M, Elsner P. Treatment of cutaneous pseudolymphoma: a systematic review. Acta Derm Venereol. 2018;98:310–7. 6. Baumgartner-Nielsen J, Lorenzen H. Imiquimod 5%: a successful treatment for pseudolymphoma. Acta Derm Venereol. 2014;94:469. 7. Hengge UR, Benninghoff B, Ruzicka T, Goos M. Topical immunomodulators— progress towards treating inflammation, infection and cancer. Lancet Infect Dis. 2001;1:189–98. 8. Hwang S, Johnson A, Fabbro S, Hastings J, Haverkos B, Chung C, et al. Topical imiquimod monotherapy for indolent primary cutaneous B-cell lymphomas: a single-institution experience. Br J Dermatol. 2020;183:386–7. Figure 2 | A,B) A dense infiltration rich in eosinophils surrounding blood vessels throughout the entire dermis (hematoxylin&eosin; ×20, ×100); C) most of the cells in lymphoid infiltration stained with CD20, the B-cell marker (×40); D) T lymphoid cells between the B lymphoid cells, highlighted by CD3 (×40); E) CD21 staining reveals a dendritic network within lymphoid follicles (×20); F) Ki-67 showed high proliferative activity in reactive lymph nodes (×40).