Misleading ulcers: A rare case of lymphomatoid papulosis initially diagnosed as acquired reactive perforating collagenosis

Lymphomatoid papulosis (LyP) is a rare CD30+ lymphoproliferative disorder with low malignant potential and spontaneous remission. Herein, we present a unique case of LyP that primarily manifested as widespread ulceration, an atypical presentation that highlights the diverse clinical features of this condition. A 21-year-old female patient presented with an inflammatory papule on her inner thigh that enlarged and became painful following self-treatment with mupirocin. After the initial diagnosis of a cutaneous abscess, the lesion was treated with incision and drainage. However, red papules, nodules, and ulcers spread across the body, predominantly affecting the lower limbs. She was initially misdiagnosed with pyoderma gangrenosum and was treated with prednisone and hydroxychloroquine, which did not improve her condition. The patient's condition worsened 10 days before presenting to our hospital, with necrotic scabbing and no significant prior medical history except for polycystic ovary syndrome. Physical examination revealed scattered red papules on the neck, abdomen, back, and arms, and some pustules. Round ulcers with clear borders, bloody granulation tissue, scabs, and exudates were observed on the trunk and limbs (Figure 1A–D). Laboratory tests revealed an elevated white blood cell count (predominantly neutrophils) and increased interleukin-6 levels, whereas fungal and bacterial cultures were negative. The patient was initially diagnosed with acquired reactive perforating collagenosis (ARPC) and treated with prednisone, thalidomide, minocycline, topical antibiotics, and phototherapy. However, histopathological examination of an ulcer biopsy specimen from the left arm revealed acanthosis, central ulceration, and dense neutrophilic and lymphocytic infiltration, with atypical lymphoid cells resembling histiocytes (Figure 1E,F). Immunohistochemistry confirmed CD30+, CD4+, scattered CD8+, CD20−, CD56−, CD5+, CD7+, ALK−, mum-1−, and Ki-67 expression at 20%, leading to the diagnosis of LyP (Type A). Methotrexate was recommended for treatment; however, the patient declined due to concerns regarding side effects. Topical benzalkonium chloride, polymyxin B ointment, and a growth factor gel were prescribed. One week after discharge, the patient showed no new lesions on her limbs or trunk and the existing lesions began to resolve. During approximately 2 years of follow-up, she had no recurrence but was left with post-inflammatory hyperpigmentation and scarring. LyP was first described by Macaulay in 1968 and is characterized by chronic, recurrent, clinically benign, and histopathologically malignant skin lesions1 According to the 2018 World Health Organization-European Organization for Research and Treatment of Cancer classification of primary cutaneous lymphomas, they are categorized as cutaneous T-cell and NK-cell lymphomas. LyP is primarily defined by CD30+ expression, which is a feature of the disease. CD30, a member of the tumor necrosis factor receptor family, is expressed in activated lymphocytes. In LyP, this protein is found on large atypical T-cells, distinguishing it from other CD30 lymphoproliferative disorders.2 Although the etiology and pathogenesis remain unclear, some studies suggest viral infection as a potential trigger; however, the evidence is limited.3 LyP typically presents as papules, nodules, necrosis, and crusting, with recurrent cycles of flare-ups and healing. Lesions most commonly appear on the trunk and limbs, with rare cases affecting mucosal areas. Most patients reported mild pruritus or discomfort, although some experienced significant itching, pain, or fever.4 Although LyP is typically self-limiting, a subset of patients may develop another lymphoproliferative disorder, such as Hodgkin's lymphoma or primary cutaneous anaplastic large-cell lymphoma, making long-term follow-up essential. In contrast, ARPC is a distinct perforating disorder characterized by umbilical keratotic papules or nodules with intense itching, typically affecting the lower limbs, and is often associated with the Koebner phenomenon. ARPC is linked to various systemic diseases and malignancies; however, its pathogenesis remains unclear.5 Given the lack of awareness of this condition, it is frequently misdiagnosed. In this case, we observed an atypical LyP presentation characterized by widespread deep ulceration, a misleading clinical feature that led to repeated misdiagnosis. Previous reports have documented isolated or scattered ulcers,6, 7 but this case emphasizes the need to consider LyP in the differential diagnosis of widespread ulcerative lesions. Although there are no established guidelines for the treatment of LyP, commonly used therapies include topical corticosteroids, phototherapy, CD30 monoclonal antibodies (brentuximab), and low-dose methotrexate.4 Given the self-limiting nature of LyP and the low risk of lymphoma development, treatment decisions should balance therapeutic efficacy with potential adverse effects. Long-term monitoring is essential to prevent recurrence and manage malignant progression. Zhongyu Chen and Qiutian Lei: Conceptualization; investigation; writing original draft; and editing. Binbin Yang: Writing original draft. Danqi Deng: Writing original draft and editing; supervision. All the authors agree for the final version of the manuscript to be submitted for consideration of publication. The authors have nothing to report. The authors declare no conflicts of interest. Written consent has been obtained from the patient for the purpose of publication. The data used in this article are available from the corresponding author upon reasonable request.