Adult-onset Langerhans cell histiocytosis in an elderly female with cutaneous and nodal involvement: A case report

Dear Editor, Langerhans cell histiocytosis (LCH) is a rare clonal proliferative disorder of CD1a+/CD207+ dendritic cells derived from myeloid precursors that infiltrate tissues and cause organ dysfunction that may be limited to a single site or affect multiple systems.[1] LCH predominantly affects children, with an estimated incidence of 5–10 cases per million annually, while adult cases are less common, at approximately 1–2 cases per million.[2] We report a rare case of LCH in an elderly patient presenting with cutaneous and nodal involvement. An 86-year-old woman presented with a 2-month history of pruritic erythematous eruptions and a 6-month history of a gradually enlarging, nontender neck mass. Her medical history included dyslipidemia, glaucoma, and gastroesophageal reflux disease. Cutaneous findings revealed multiple infiltrative erythematous to purpuric plaques and nodules on the face, neck, and bilateral extremities, particularly on extensor surfaces [Figure 1]. Several fainter plaques were observed on the chest and abdomen. Physical examination revealed bilateral submental and cervical lymphadenopathy, with nodes measuring up to 3 cm × 2 cm. Initial laboratory investigations demonstrated peripheral eosinophilia (29.5%), metamyelocytes (0.8%), and atypical lymphocytes (1.6%), with a normal total white blood cell count (5.77 × 109/L). Inflammatory markers were within normal limits.Figure 1: Multiple infiltrative erythematous to purpuric plaques and nodules involving the (a and b) bilateral upper and (c) lower extremities, with a (d) predominance on extensor surfaces. Lesions over the knees appeared more violaceous in color.Because of persistent lymphadenopathy, a computed tomography (CT) imaging of the head and neck was arranged after 3 months, during which the patient also experienced a gradual progression of pruritic skin eruptions. CT scan revealed multiple enlarged lymph nodes in the submental, bilateral supraclavicular, right level IV, and left axillary regions. An excisional biopsy of a submental lymph node was performed. Histopathological examination revealed aggregates of histiocytes with irregular nuclei and abundant cytoplasm. Immunohistochemical staining showed strong positivity for CD1a and S100, and negativity for CD68 and CD163, confirming the diagnosis of LCH. BRAF V600E mutation testing was negative. Based on the presence of infiltrative erythematous plaques and lymphadenopathy, differential diagnoses included cutaneous lymphoma, other histiocytic disorders, infectious etiologies, drug reaction with eosinophilia and systemic symptoms, and eczema. She was referred to our dermatology department for further evaluation. A skin biopsy from the arm showed atypical cells with irregular, grooved nuclei and fine chromatin, which were CD1a and S100 positive and CD163 negative [Supplementary Figure 1], consistent with cutaneous LCH.Supplementary Figure 1: Histopathological findings from a skin biopsy of the arm, demonstrating (a and b) atypical Langerhans cells with irregular, grooved nuclei and fine chromatin. Immunohistochemical staining shows positivity for (c) CD1a and (d) S100, and (e) negativity for CD163, consistent with cutaneous Langerhans cell histiocytosis.Further imaging with abdominal and pelvic CT, brain magnetic resonance imaging (MRI), and positron emission tomography scan showed no evidence of central nervous system, abdominal, or pelvic involvement. Given the patient’s advanced age and preference, a bone marrow biopsy was suggested but declined. Treatment was initiated with high-dose systemic corticosteroids (prednisolone 10–50 mg per day), hydroxyurea (500–1000 mg per day), and low-dose methotrexate (7.5–10 mg weekly). During the initial 3 weeks of follow-up, the patient exhibited significant improvement in both cutaneous lesions and lymphadenopathy, without the emergence of new systemic symptoms. Serial imaging was planned to monitor disease progression over the subsequent 3 months. LCH can affect various organs, including skin, bones, lymph nodes, or visceral organs such as the lungs, liver, and spleen, and the central nervous system, with the skull and pituitary gland being frequent sites in pediatric cases.[3] In adults, LCH most often presents after age 40 and is usually multisystemic at diagnosis. Orbital involvement is more frequent in children, whereas mandibular and mucocutaneous lesions are more commonly seen in adults. Adults also show higher rates of disease reactivation and mortality, although overall 10-year survival is comparable between the two groups.[4] Cutaneous manifestations may include localized nodules, plaques, or generalized seborrheic dermatitis-like eruptions, frequently involving the trunk, scalp, folds, and genital or perianal regions.[5] LCH is histologically characterized by the presence of oval-to-round histiocytes with nuclear grooves, often forming eosinophilic granulomas accompanied by eosinophils, macrophages, T cells, and multinucleated giant cells. Immunohistochemically, cells express CD1a/CD207 and S100.[6] Once histologic confirmation is obtained, systemic imaging using CT or MRI is recommended to assess the extent of organ involvement. LCH is classified based on extent and organ involvement into high-risk, multisystem; low-risk, multisystem LCH, and a low-risk, single lesion.[7] Management in LCH varies by the disease classification. In cases of multifocal and multisystem LCH, require thorough evaluation for critical organ involvement–such as the brain, liver, or lungs–and signs of end-organ dysfunction. Adult treatment guidelines remain undefined due to the rarity of the condition and absence of prospective clinical trials. The majority of adults with unifocal disease can be effectively treated with localized therapies. Locally extensive cutaneous LCH typically exhibits limited responsiveness to topical or systemic corticosteroids but shows a favorable response to systemic agents such as hydroxyurea or low-dose methotrexate. In addition, systemic therapy is commonly required for multisystem involvement, with agents such as cladribine, cytarabine, and, more recently, BRAF or MEK inhibitors for mutation-positive cases.[8] In summary, this case underscores the importance of considering LCH in elderly patients presenting with persistent pruritic rash and lymphadenopathy. Early biopsy and histopathologic confirmation are essential for timely diagnosis. The favorable response to immunosuppressive therapy may guide treatment in similar adult-onset cases. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. Data availability statement The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.