Co‐existence of Langerhans cell histiocytosis and reticulohistiocytosis with initial presentation of skull lesions: A case report

Langerhans cell histiocytosis (LCH) is a rare histiocytic disorder resulting from dysregulated clonal proliferation of Langerhans cells. Reticulohistiocytosis (RH) is another rare histiocytosis caused by the proliferation of histiocytes other than Langerhans cells. Co‐existence of LCH and RH in different organs and in the same skin area has not been reported. We present the case of a 20‐year‐old woman who initially had co‐existing bone LCH and cutaneous RH. After 1 year of chemotherapy with cytarabine, bone LCH significantly improved but cutaneous LCH developed in the same area where cutaneous RH was, resulting in hybrid LCH and RH of the skin. This unique history provides some evidence to support the theory that LCH and RH originate from the same stem cells and subsequently develop into hybrid LCH and RH of the skin in a cytokine environment influenced by chemotherapy. Repeat skin biopsies may be considered for adjusting treatment regimens in LCH patients whenever pre‐existing skin lesions progress.     

Langerhans cell histiocytosis of skin: a clinicopathologic analysis of five cases

BACKGROUND AND AIMS: Langerhans cell histiocytosis (LCH) is a rare proliferative disorder of histiocytes characterized by a proliferation of abnormal and clonal Langerhans cells. We retrospectively studied clinicopathologic features of this disorder in five cases. METHODS: Clinical and histopathological findings of five cases of cutaneous LCH were reviewed based on the hospital records. RESULTS: The age of patients ranged from 28 days to 5 years and M: F ratio was 1:1.5. Clinically, the diagnoses suggested were histiocytosis, varicella, transient neonatal pustular melanosis, keloid, sarcoidosis, seborrheic keratosis and LCH. The most common type of skin lesion was a generalized papular lesion. Histologically, all cases showed aggregates of large mononuclear histiocytes (Langerhans cells) with reniform, irregular, cleaved nuclei and abundant eosinophilic cytoplasm. There was multi-systemic involvement in two patients and single-system involvement in three patients. CONCLUSION: Cutaneous lesions may be the sole presenting feature of LCH. Diagnosis is based on demonstration of S-100 positive histiocytes.     

Adult Langerhans cell histiocytosis limited to the skin

BACKGROUND: The incidence of Langerhans cell histiocytosis (LCH) is 4-5 per million in children with only 30% of this number having an adult onset. While dermatological manifestations occur in as many as 50% of cases, disease limited to the skin is uncommon among reported cases of adult LCH. OBJECTIVES AND METHODS: To present 3 new cases of adult LCH and a review of the literature of isolated cutaneous LCH in adults. RESULTS: Three adults with scalp, vulvar and generalized LCH lesions had refractory responses to treatment. CONCLUSIONS: LCH may present with unusual cutaneous manifestations limited to the skin in adults. Optimal treatment has not yet been determined.     

Molluscum Contagiosum‐Like Presentation of Langerhans Cell Histiocytosis: A Case and Review

Langerhans cell histiocytosis (LCH) is a rare disorder characterized by clonal proliferation of Langerhans cells in the skin. A molluscum‐like presentation of cutaneous LCH is rare but important to consider for examination and management. We present an atypical molluscum‐like LCH case and review the literature for common features of this unusual presentation.     

Crusted Norwegian scabies in an adult with Langerhans cell histiocytosis: mishaps leading to systemic chemotherapy

BACKGROUND: Crusted Norwegian scabies is a rare hyperkeratotic variant of scabies infestation. We report herein a case of crusted scabies in a woman with underlying Langerhans cell histiocytosis (LCH). OBSERVATIONS: A 49-year-old woman with LCH was hospitalized owing to marked thrombocytopenia. Her hyperkeratotic skin eruption was thought to be secondary to LCH because several years earlier, she had positive biopsy findings and had been diagnosed as having LCH. After a 1-month hospital stay, her laboratory values improved despite worsening of her skin lesions. CONCLUSION: Analysis of skin scrapings confirmed the presence of scabies, and resolution was achieved with a 1-dose ivermectin treatment.     

Langerhans cell histiocytosis first presenting in the skin in adults: frequent association with a second haematological malignancy

Background Langerhans cell histiocytosis (LCH) in adults first presenting in the skin is rare. Guidelines for staging, treatment and follow‐up are lacking. Objectives To better define staging procedures, treatment results and clinical course in adult patients with LCH first presenting in the skin. Methods Eighteen adult patients with LCH first presenting in the skin were collected from five centres collaborating in the Dutch Cutaneous Lymphoma Group. Clinical records and (skin) biopsy specimens were reviewed and follow‐up data were obtained. A literature search on adult patients with LCH presenting in the skin was performed. Results Staging procedures showed extracutaneous disease in three of 16 patients who were adequately staged. One patient had a histologically confirmed lytic LCH bone lesion, while two patients had a myelodysplastic syndrome. During follow‐up two of 18 patients developed extracutaneous localizations of LCH. Five patients developed a second haematological malignancy, including (myelo)monocytic leukaemia (two cases), histiocytic sarcoma (one case), diffuse large B‐cell lymphoma (one case) and peripheral T‐cell lymphoma (one case). Review of the literature revealed six other adult patients with a second haematological malignancy preceding or following a diagnosis of LCH. Conclusions The results of the present study suggest an increased risk of a second haematological malignancy in adult patients with LCH presenting in the skin. Extensive staging at presentation and long‐term follow‐up are therefore warranted in such patients.     

Langerhans cell histiocytosis involving the skin of an elderly woman: a satisfactory remission with oral prednisolone alone

Langerhans cell histiocytosis (LCH) is a disorder characterized by neoplastic proliferation of Langerhans cells that rarely involves the skin in adults. A 74-year-old woman presented with a fourteen year history of eosinophilic granuloma and bone involvement caused by LCH. She had received three combination therapy courses of curettage and radiation since 1987 and had remained free of LCH signs for seven years, after which she started to notice brown nodules on her left leg. Biopsy specimens taken from the lesions showed massive proliferations of large histiocytic cells. Immunoperoxidase stainings for CD1a and S-100 protein were positive. Electron microscopy identified Birbeck granules in the cytoplasm of the atypical Langerhans cells. Treatment with oral prednisolone alone has resulted in the patient remaining in complete remission for 12 months.     

Narrowband Ultraviolet B Light in Langerhans Cell Histiocytosis: A Case Report

Langerhans cell histiocytosis (LCH) (previously called eosinophilic granuloma, Hand–Schüller–Christian syndrome, Letterer–Siwe disease, and Hashimoto–Pritzker disease) is a rare, heterogeneous disorder with highly variable presentation. LCH commonly affects the skin, as well as internal organs. Because the skin lesions appear benign, and LCH is unfamiliar to most physicians, diagnosis is often delayed. Treatment is controversial, with further clinical study needed. For persons with extensive, skin‐limited disease, the existing topical therapies are impractical. We present a child with cutaneous LCH lesions that responded to ultraviolet light phototherapy with minimal adverse effects or patient discomfort.     

CD30 positive anaplastic large‐cell lymphoma mimicking Langerhans cell histiocytosis

The presence of CD 1a+ dendritic cells (DC) has been well described in T‐cell lymphoproliferative disorders, and the presence of large numbers of DCs has rarely been reported as a mimicker of Langerhans cell histiocytsis (LCH). We present the case of a 56‐year‐old female with a solitary nodule on the chin whose case was referred to our institution for confirmation of the diagnosis of LCH. Skin biopsy showed an ulcerated nodule containing a wedge‐shaped infiltrate comprised of large atypical cells and cells with prominent grooved nuclei. The constellation of histologic and immunologic features favored a CD30 lymphoproliferative disorder of T‐cell lineage even though there were accompanying numerous dendritic histiocytes and CD1a positive Langerhans cells. The sheets of CD30 positive atypical lymphoid cells which express T‐cell markers were consistent with CD30 positive lymphoproliferative disease and favor CD30 positive anaplastic large‐cell lymphoma (ALCL) over Langerhans histiocytosis. The absence of Anaplastic Lymphoma Kinase (ALK) staining favored a primary cutaneous origin. This case signifies a CD 30+ ALCL of the skin which histopathologically mimics a LCH. Ezra N, Van Dyke GS, Binder SW. CD30 positive anaplastic large‐cell lymphoma (ALCL) mimicking Langerhans cell histiocytosis (LCH).     

A child with both Langerhans and non-Langerhans cell histiocytosis

The histiocytic syndromes consist of a group of disorders that share in common the proliferation of cells of the monocytic/macrophage lineage. It has been conventional to divide the histiocytoses into two separate groups: Langerhans cell histiocytosis (LCH) and non-LCH. We present a 2-year-old Hispanic boy who was referred to the dermatology clinic for evaluation of an asymptomatic cutaneous eruption of the head and upper trunk. In addition, he had a 3-week history of pain in his right leg and difficulty in walking. The patient's physical examination was normal, excluding the skin findings. On plain radiography, multiple lytic lesions in the skull, lumbar spine, and right tibia were seen. Histopathologic examination of a skin biopsy specimen revealed a predominantly histiocytic infiltrate in the dermis which was negative for S-100 and CD1a stains. A tibial biopsy specimen showed a monomorphous infiltrate of histiocytes that were S-100 and CD1a positive. This patient's concomitant findings of both LCH and non-LCH histiocytoses further support a potential overlap within the histiocytic syndromes, as has been suggested by others.     

Topical nitrogen mustard therapy in patients with Langerhans cell histiocytosis

Background Langerhans cell histiocytosis (LCH) is characterized by abnormal proliferation and infiltration of Langerhans cells in different organs. The skin is frequently involved either as unisystem or multisystem disease. Objectives To review the clinical response and side‐effects of nitrogen mustard therapy in LCH in children and adults with unisystem or multisystem disease. Patients and methods This retrospective study includes 10 children and four adults with LCH, treated with nitrogen mustard from 1975 to 2010. The median extent of skin involvement was 46% (range 5–100%). Results Overall, 13 patients had complete or partial response. Although eight patients achieved a complete response with a median time of 12·3 months (range 36 days to 1·9 years), six of these patients ultimately relapsed. One patient, who had unisystem disease limited to the skin, initially showed progression of her cutaneous lesions with nitrogen mustard treatment. Although subsequently the cutaneous lesions completely regressed, concomitant systemic involvement was noted. Four other patients similarly experienced improvement of their skin lesions with treatment, but also exhibited progression of the LCH systemically. The patients were treated with other therapies prior and adjunctive to nitrogen mustard. However, five patients had progression to other organs, despite regression of skin lesions, which supports that the treatment effect in the skin is related to topical nitrogen mustard. Six patients developed contact dermatitis to nitrogen mustard. Conclusions Topical nitrogen mustard can be an effective and safe therapy in both children and adults with cutaneous LCH, although relapses are common.     

Multisystem Langerhans cell histiocytosis in adult

Langerhans cell histiocytosis (LCH), is a rare disorder, clinically presents with heterogeneous manifestations, and has an unpredictable outcome. Commonly seen in infancy or early childhood, the disorder is characterized by proliferation of abnormal and clonal Langerhans cell in skin, bone, lymph nodes, lungs, liver, spleen, and bone marrow. Occurrence of LCH in adults is rare. Here, we report the case of an adult with acute onset of polymorphic eruptions all over the body, which on biopsy showed features of multisystem LCH, and was confirmed by immunohistochemistry. Although multisystem LCH has a poor prognosis, our patient responded well to chemotherapy.     

朗格汉斯细胞组织细胞增生症皮肤损害临床分析

目的:分析朗格汉斯细胞组织细胞增生症(LCH)的临床特点.方法:回顾性分析近10余年国内文献报道的918例诊断LCH的临床资料.结果:918例LCH中皮肤受累510例,占55.5%,以皮疹为首发症状的106例,占11.55%.临床上以湿疹样、脂溢性皮炎样或紫癜样皮疹多见.所有病例均合并其他系统损害,以发热(52.07%),肝肿大(52.29%)、脾肿大(48.26%)、骨损害(38.78%)、肺部损害(36.16%)最为常见.在918例LCH中,男593例,女317例,性别不详8例,最小出生4h,最大65岁,1岁以下占19.17%.皮肤活检151例.结论:皮肤是LCH常累及器官,对于1岁以下的小儿出现不典型湿疹样、脂溢性皮炎样或紫癜样皮疹应警惕LCH的可能,应进一步完善各项检查以明确诊断.     

Primary cutaneous Langerhans cell histiocytosis showing malignant phenotype in an elderly woman: report of a fatal case

BACKGROUND: Langerhans cell histiocytosis (LCH) is a proliferating disorder of Langerhans cells (LC) that are characterized by the presence of Birbeck granules. LCH has been considered to be a disease of childhood and there have been limited cases of adult LCH. We report here a fatal case of histiocytic tumor showing Langerhans cell phenotype, arising in the skin of a 74-year-old woman. METHOD: In addition to routine histological and immunohistological sections, electron microscopic examination and human androgen receptor gene (HUMARA) assays were performed. RESULTS: Histological examination revealed a dense dermal infiltrative proliferation of fairly large tumor cells with abundant ill-defined cytoplasms and oval or indented nuclei, in which numerous eosinophils were associated with the tumor nests. Tumor cells were positive with anti-S-100 and CD1a antibodies but negative with HMB-45 antibody or other epithelial or lymphocytic markers. Ultrastructural analysis showed typical Birbeck granules in the cytoplasm of the tumor cells. HUMARA assay of the tumor tissue revealed the nonrandom X inactivation pattern, indicating the clonal proliferation. CONCLUSIONS: We diagnosed this tumor as Langerhans cell histiocytosis with a clonal neoplastic phenotype originated in the skin. Although she demonstrated no recurrence nor metastases for 6 months after surgical resection of primary skin lesion and subsequent radiation therapy, the tumor recurred and extended multisystemically, and she died of multiple organ failure 14 months after initial diagnosis. Therefore, we would like to emphasize this case as LC "sarcoma" or "malignant" LCH.     

Xanthomas in a patient with Langerhans cell histiocytosis and liver cirrhosis

Skin involvement in acute forms of Langerhans cell histiocytosis (LCH) is in the form of erythematous papules, although rare forms of xanthomatous lesions have been described. We present the case of a boy with acute disseminated LCH who, at the age of 16 months, began to experience outbreaks of seborrheic dermatitis-like skin lesions and progressive hepatic dysfunction. The symptoms were complicated by partial central diabetes insipidus and specific pulmonary infiltration by Langerhans cells, which led to fibrosis. During the course of the disease, the patient developed liver cirrhosis, alterations in the lipid profile and disseminated xanthomatous skin lesions, concomitant with the lesions specific to the LCH. Despite successive cycles of chemotherapy, the outcome was the death of the patient after five years, due to his liver disease. Xanthomatous lesions in LCH are typical of the late stages of chronic progressive forms, such as Hand-Schüller-Christian disease. When they appear in acute disseminated forms, there is some controversy over whether they correspond to a progression of the disease towards more chronic forms, or whether they are associated independent lesions, such as in this case.     

Langerhans cell histiocytosis associated with breast carcinoma successfully treated with topical imiquimod

Langerhans cell histiocytosis (LCH) encompasses a group of disorders characterized by the proliferation and infiltration of Langerhans cells within internal organs and/or skin. There is often multiorgan involvement; isolated cutaneous LCH is less common. ¹ The aetiology of cutaneous LCH remains uncertain, and debate remains as to whether LCH represents a neoplastic condition or is simply reactive. We report a 53‐year‐old woman who developed isolated cutaneous LCH 15 months after being diagnosed with infiltrating ductal carcinoma of the left breast. The LCH was treated with topical imiquimod, resulting in clinical and histological resolution. Our case highlights the rare association between cutaneous LCH and breast carcinoma, and the clinical and histological response that can be achieved with topical imiquimod. After a diagnosis of LCH, patients require long‐term follow‐up, due to the risk of recurrence and/or development of a subsequent malignancy.     

Langerhans cell histiocytosis: a case report and summary of the current recommendations of the Histiocyte Society

Langerhans cell histiocytosis (LCH) is a rare proliferative disorder in which pathological Langerhans cells (LCs) accumulate in a variety of organs. Historically, the nomenclature regarding LCH has been confusing because the disease had been sub-categorized simply based upon different clinical manifestations. Herein, we report a child with the classic finding of disseminated LCH and summarize the current recommendation of the Histiocyte Society regarding the classification, evaluation, prognosis and treatment of LCH.     

Widespread skin-limited adult Langerhans cell histiocytosis: long-term follow-up with good response to interferon alpha

Langerhans cell histiocytosis (LCH) most frequently involves bone, but also involves the skin in 40% of cases; in 10% of patients it is limited to the skin. Cutaneous findings of skin-limited LCH are scaly papules, vesicles, nodules, tumours with erosion, ulceration, or crusting and/or purpura. We report a case of widespread adult-onset LCH confined to skin in which topical carmustine, photochemotherapy, systemic steroids, and 2-chlorodeoxyadenosine were only partially effective. However, longer remission was achieved by the use of subcutaneous interferon-alpha2b.     

Extensive nail changes in a toddler with multisystemic Langerhans cell histiocytosis

Langerhans cell histiocytosis (LCH) is a multisystem disorder involving various organs. Nail changes in LCH are extremely rare. We present this case report of extensive nail changes in an 18‐month‐old child with multisystem LCH.     

Treatment of adult Langerhans cell histiocytosis with etoposide.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a reactive disease in which abnormal Langerhans cells accumulate in various body sites and cause damage to affected organs. Adults often do not respond to conventional therapy with local or systemic steroids. OBJECTIVE: Our purpose was to investigate intravenous etoposide as monotherapy in the treatment of adult patients with severe or resistant LCH. METHODS: In an open study, three adult patients with LCH (one with single-system skin disease and two with multisystem disease) were treated with etoposide, 100 mg/m2/day, for 3 days. This was repeated every 3 or 4 weeks for three or four cycles. RESULTS: All patients achieved clinical remission that persisted during a 12- to 14-month follow-up. No serious side effects were noted. CONCLUSION: We recommend the use of etoposide monotherapy in severe or restricted LCH in adults.