Cutaneous Langerhans Cell Histiocytosis Responsive to Topical Nitrogen Mustard

August 2020 | Volume 19 | Issue 8 | Case Reports | 803 | Copyright © August 2020

Published online July 31, 2020

Ai-Tram N. Bui , Ashleigh Eberly Puleo , Alvaro Laga Canales , Eric D. Jacobsen , Nicole R. LeBoeuf

aHarvard Medical School, Boston, MA bCenter for Cutaneous Oncology, Department of Dermatology, Dana-Farber/Brigham and Women’s Cancer Center, Boston, MA cDepartment of Pathology, Brigham and Women’s Hospital, Boston, MA dDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA eDepartment of Dermatology, Brigham and Women’s Hospital, Boston, MA

Langerhans cell histiocytosis (LCH) limited to the skin is rare in adult patients. Given the challenges of prospective clinical trials for this rare disease, there is paucity in data to guide the management of cutaneous LCH. Topical nitrogen mustard is a possible treatment for cutaneous LCH with positive responses in five known adult cases in the literature. In this report, we present two adult patients with recalcitrant cutaneous LCH and no evidence of systemic involvement who had rapid and complete response on topical nitrogen mustard therapy. We provide support for topical nitrogen mustard as a treatment option for primary cutaneous LCH which may spare patients from requiring systemic immunosuppressive treatments.

J Drugs Dermatol. 2020;19(8):803-805. doi:10.36849/JDD.2020.4943


Langerhans cell histiocytosis (LCH) is a rare clonal proliferation of pathologic langerhans cells that accumulate in organs including skin, bone, liver, or spleen.1 LCH that is limited to the skin is rare in adult patients;1 larger studies estimate that up to 11% of LCH is limited to the skin.2 While cutaneous LCH has better prognosis than multisystem LCH, response to skin-directed therapies remains variable particularly for recalcitrant disease.1

There are a lack of guidelines and consensus in the management of cutaneous LCH.3 Current reported therapies include topical corticosteroids, topical imiquimod, radiation therapy, methotrexate, hydroxyurea, phototherapy, thalidomide, or vinblastine.1,4-7 Topical nitrogen mustard therapy, or mechlorethamine, is a treatment with positive responses in six known pediatric cases5 and five known adult cases of cutaneous LCH without systemic involvement.5,8-11 It has also shown positive response in larger pediatric cohort studies of multisystem LCH.5,6 We present two adults with skin-limited LCH with complete response after treatment with topical nitrogen mustard.

Report of Cases
Case 1
A 75-year-old woman presented in dermatologic consultation with a painful, pruritic eruption of 8 years’ duration. Physical examination showed scattered, red-brown crusted papules without ulcerations in her inguinal folds and vulva, extending onto the perineum and labia. There were also scattered papules on a background of macular erythema on the bilateral inframammary folds (Figure 1). The patient did not have systemic symptoms at diagnosis but was diagnosed at subsequent follow-up with chronic myelomonocytic leukemia (CMML) and immune thrombocytopenic purpura.

A punch biopsy from her vulvar area found focal parakeratosis overlying a superficial dermal proliferation of medium-sized discohesive cells, positive for CD1a, langerin, S100, and cyclin D1, and negative for CD123 (Figure 2). She was positive for the BRAFV600E mutation. Positron emission tomography, pituitary MRI, and bone survey did not show multisystem involvement. The final diagnosis was of LCH, limited to cutaneous involvement.