A 47-year-old female with past medical history of asthma, bicornuate uterus, and penicillin allergy initially presented in the summer of 2020 with a 1-cm painless solitary vaginal lesion near the upper third of the right labia majora, which appeared around a week before her clinic visit. A sexually transmitted infection (STI) panel demonstrated positive immunoglobulin G (IgG) for herpes simplex virus (HSV)-1, and positive IgG for HSV-2. Bacterial cultures demonstrated negative growth, and the patient was also negative for hepatitis C virus, human papillomavirus, human immunodeficiency virus, chlamydia, gonorrhoea and trichomonas. Despite treatment with penicillin G benzathine, valacyclovir, and doxycycline, the lesion persisted. A treponemal antibody test was negative. A biopsy of the lesion in late spring 2021 revealed granulation tissue and benign findings, negative for malignancy. An anaerobe culture from this visit was positive for diphtheroid. Over the next year, the patient was treated with doxylamine, valacyclovir, tramadol, and fluconazole. In the spring of 2024, the patient presented with a 2 cm ulcerated lesion and rolled-up borders expanding into the lower right labia majora, after being lost to follow-up for about a year. The patient denied any fever, chills, or weight loss. An excisional biopsy of the lesion (Figure 1) was done (Figure 2a,b). The excisional biopsy of the lesion reveals an ulcer with underlying sheets of large cells with pale eosinophilic cytoplasm and irregular nuclear contours in the dermis, surrounded by eosinophils. The immunohistochemical (IHC) stains demonstrated positive CD1a (Figure 3) and S100 cells (Figure 4), with a Ki-67 proliferative index of 50%–60%. The tumour demonstrated scattered positivity for CD68, confirming a diagnosis of Langerhans cell histiocytosis (LCH). Treponemal antibody testing was negative. Genetic sequencing demonstrated BRAF positivity, which is consistent with LCH. The patient underwent further workup and imaging to rule out systemic manifestations of the disease, with negative findings. The patient was diagnosed with isolated, solitary vulvar LCH. Very few isolated, solitary vulvar LCH lesions have been reported in the literature 1-3. LCH is a rare neoplasia of the myeloid cells in the bone marrow, with an incidence rate of 8.9 per million children below the age of 15 and 0.07 per million adults annually 4. Despite having a higher predominance in children, LCH is a rare condition in both age groups with a highly diverse initial cutaneous presentation, including granulation tissue, ulcers, blisters, or oedema 5. This will lead to a delay in LCH diagnosis, especially when it presents as a solitary cutaneous genital ulcer, which can easily be confused for primary syphilis, genital herpes, or chancroid. The differential diagnosis of vulvar LCH includes ulcerative lesions. Chancroid is a sexually transmitted disease caused by Haemophilus ducreyi 6. It presents as one or multiple painful genital ulcers with lymphadenitis 6. On histology, it demonstrates ulceration, granulation tissue, and lympho-plasmocytic infiltrates 6. Clinically, it is a diagnosis of exclusion, after syphilis and herpes are ruled out 6. Diagnosis is confirmed with PCR testing or cultures confirming H. ducreyi 6. Genital herpes is a sexually transmitted disease caused by herpes simplex virus (HSV) II. It presents with painful vesicles or ulcers with flu-like symptoms during primary infection 6. On histology, herpetic lesions classically present with large, atypical cells with nuclear moulding, margination, and multinucleation 6. Diagnosis is confirmed primarily through serologic testing, cultures, and Tzanck smears from lesions 6. Herpetic viral DNA detection is confirmed through PCR testing 6. Histologically, HSV immunostaining is also utilised to highlight virally infected cells and to confirm diagnosis when HSV is suspected 6. Primary syphilis is a sexually transmitted disease caused by Treponema pallidum 6. It usually presents as a round, solitary, painless ulcer, chancre, that typically resolves spontaneously within a few weeks 6. Serologic testing with non-treponemal cardiolipin testing (rapid plasma reagin and venereal disease research lab) followed by treponemal-specific antibodies detects syphilis infection 6. Histologically, syphilis infection demonstrates granulation tissue and plasmacytic infiltration similar to chancroid 6. Immunohistochemical staining with anti-treponemal antibodies is also used to highlight spirochaetes on histology 6. Although there is not a standard of care for vulvar LCH, topical steroids are the first line of treatment 7. Cases with skin involvement have also shown partial or complete response with the use of topical imiquimod 8, or nitrogen mustard (mechlorethamine) 9. Our patient was treated with clobetasol 0.05% ointment and nitrogen mustard with no response. She was then started on methotrexate 15 mg weekly for a few months. She experienced worsening of symptoms and developed a new peri-anal ulcer. The patient was referred to haematology & oncology again, and then the plan was for radiation therapy versus BRAF inhibitors. Farhanaz Panjshiri, Reed Gioe and Carole Bitar conceptualised the case report and contributed to the design, collected clinical data, including patient history, dermatological findings and pictures. All authors contributed to drafting the initial manuscript, reviewed and revised manuscript for accuracy, and scientific integrity. All authors have reviewed and approved the final version of the manuscript for submission and agree to be accountable for all aspects of the work. The authors received no specific funding for this work. The patient in this manuscript has given written informed consent forparticipation in the study, and use of their de-identified, anonymized aggregated data and their case details (including photographs) for publication. Ethical Approval: not applicable. The patient in this manuscript has given written informed consent for participation in the study, and use of their de-identified, anonymized aggregated data and their case details (including photographs) for publication. The authors declare no conflicts of interest. Data are available on request due to privacy restrictions.
Panjshiri et al. (Fri,) studied this question.