Adult Onset Langerhans Cell Histiocytosis Limited to the Skin.

Langerhans cell histiocytosis (LCH) is a proliferative disease commonly seen in the pediatric population but rarely encountered in the adult population. The exact etiology remains unclear. It has various clinical features and is very likely to be misdiagnosed. Histopathology and immunohistochemistry are very important for the diagnosis of LCH. Treatment protocols remain controversial. Herein, we report a rare adult onset LCH, which is confined to the skin. A 50-year-old Chinese man presented with a nodule with itchy rashes on the left lower leg, which gradually grew in size for the last 6 months. He also had multiple scattered rashes on the right lower leg. The skin biopsy demonstrated Langerhans cells infiltrating the superficial dermis, and the tumor cells were positive for CD1a and S-100 expression. The diagnosis was LCH based on the histopathological and immunohistochemistry results.

Introduction

Langerhans cell histiocytosis (LCH) is a rare group of disorders of unknown etiology characterized by abnormal proliferation and accumulation of Langerhans cells in various organs of the body.[1] Skin is the second most affected organ after bone. LCH confined to skin is rare in adult onset LCH.[2] We report a case of adult cutaneous LCH without extracutaneous involvement.

Case Report

A 50-year-old Chinese man presented with a nodule with itchy rashes on the left lower leg, which gradually grew in size for the last 6 months. With the progression of the disease, patient noticed multiple scattered rashes on the right leg. Prior to visiting our clinic, he had been treated as eczema for last 2 months at a local hospital with topical steroid and antihistamine without any appreciable improvement. On skin examination, we observed a dome-shaped crusted nodule measuring about 1.0 × 1.0 cm on the left lower limb and erythematous plaques with brownish silvery scales around the nodule [Figure 1a]. On palpation, nodule was single, round, firm, nontender, and immobile. There was mild infiltration of surrounding skin around the nodule. We also observed multiple scattered erythematous maculopapular rashes on right limb [Figure 1b]. Oral and genital mucous membranes were not involved. No lymphadenopathy was detected, especially in the inguinal areas. The patient denied any history of systemic symptoms such as fever, vomiting, diarrhea, cough, shortness of breath, bone pain, or polyuria. There was no history of weight loss or of any malignancy. The skin biopsy demonstrated a few large mononuclear cells infiltrated in superficial dermis. The mononuclear cells showed kidney-shaped nuclei and expressed S-100, CD1a, and langerin [Figure 2]. The diagnosis of LCH was confirmed by histopathological and immunohistochemical changes. Routine examinations including complete blood count, erythrocyte sedimentation rate, liver function, and renal function were within normal range. Electrocardiogram, abdominal ultrasound, and Positron emission tomography–computed tomography (PET-CT) showed no abnormalities. Unfortunately, the patient refused treatment. Further development could not be assessed due to no follow-up in our department.

Figure 1

(a) A dome-shaped nodule on the left lower limb and erythematous plaques with brownish silvery scales around, and (b) multiple erythematous maculopapular rashes on right lower limb

Figure 2

(a) A few large mononuclear cells infiltrating the superficial dermis (H and E, ×40). (b) The mononuclear cells showed kidney-shaped nuclei (H and E, ×400). Large mononuclear cells in the superficial dermis with (c) CD1a and (d) langerin expression (CD1a immunohistochemical staining, langerin immunohistochemical staining, ×100)

Discussion

LCH is a rare disease, which may occur at any age, and is commonly seen in children 1–4 years old. The incidence of LCH in the adult is 1–2 per million. Most LCH patients are male. The sex ratio (M:F) was 2:1.[3] Based on the number of organs involved and the number of sites present within systems that are affected, LCH is classified into single-system unifocal, single-system multifocal, and multisystem disease.[4] Several tissues may be involved simultaneously: bones, lungs, skin, oral–genital mucosa, and endocrine glands.[1] The prognosis of LCH is closely related to age of onset and number of involved organs. Adult LCH normally has a good prognosis. The prognosis is poor when there is involvement of LCH in the lung, liver, spleen, bone marrow, and a bad response to the early treatment, whereas prognosis is good when there is only involvement in skin and bone.[3] Patients with localized lesions have good prognosis, whereas patients having multiple system involvement and age (<2 years) have a high mortality rate, ranging up to 66%.[5] Isolated cutaneous LCH in the adult is very rare. Prevalence of skin-confined LCH ranged from 4.4% to 7.1% patients of LCH. In skin, it can present as single or generalized papules, plaques, nodules, or ulcers and most predominant sites include scalp, flexural and intertriginous area, external genitalia, perianal area, and glabrous skin.[2] The differential diagnosis of LCH includes eczema, seborrheic dermatitis, psoriasis, Candida infection, lichen planus, sepsis, malignant histiocytosis, and sarcoidosis.[46] The diagnosis of LCH depends on clinical manifestations, histopathology, and immunohistochemistry. The histopathological changes seen in LCH include dermal infiltration by characteristic Langerhans-like cells with “coffee bean” cleaved nuclei. CD1a is a marker for T cells and dendritic cells, whereas langerin (CD207) is a marker for Birbeck granules, which together identified the presence of Langerhans-type cells. Additionally, other histiocyte-related markers include S100 and CD68 protein, which can also be detected by immunostaining.[7] The laboratory tests should be performed for all patients independent of the affected organs, which include a complete blood count, blood chemistry, coagulation studies, thyroid function tests, and urine analysis. Others include abdominal ultrasound, a bone scan, skeletal and skull X-ray, and chest radiography (posteroanterior and lateral). Treatments are based on organ involvement and extension of the disease. There are several treatments for LCH limited to skin, such as phototherapy, thalidomide, azathioprine, and methotrexate. Surgical excision may be done for solitary lesions.[4]

Recently, a clinical study of 18 adult patients, with primary cutaneous LCH, showed that 5 of them developed secondary hematological malignancy during follow-up.[8] Herein, we reported a case of adult cutaneous LCH that could mimic a number of common dermatoses, which might represent the earliest sign of LCH, and could easily be misdiagnosed. So, if common dermatoses do not respond to conventional treatment, then LCH should be considered in the differential diagnosis. In addition, regular follow-up is also essential since there is a significant risk of multiorgan involvement and secondary malignancies, which may develop over time.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initial will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.