Congenital Langerhans cell histiocytosis presenting in a 27‐week‐gestation neonate

Langerhans cell histiocytosis is exceedingly rare in premature infants, and the few cases reported suggest a poor prognosis with systemic involvement. We present a case of Langerhans cell histiocytosis limited to a single cutaneous lesion, presenting in a 27‐week‐gestation infant, which is the youngest gestational age of reported Langerhans cell histiocytosis cases. The lesion showed spontaneous resolution by 41 weeks corrected gestational age, and systemic involvement was absent, demonstrating a mild course of skin‐only Langerhans cell histiocytosis in a premature infant.     

Langerhans-Zell-Histiozytose

Langerhans cell histiocytosis is the general term for all clinical entities characterized by a proliferation of dendritic cells that are phenotypically identical to the Langerhans cells of the skin. As dendritic cells are present in nearly every tissue of the body, Langerhans cell histiocytosis shows a broad spectrum of clinical manifestations, mostly in the bone (approximately 80%) and skin (approximately 60%). Langerhans cell histiocytosis is basically a disease of the childhood and early youth, but can rarely occur in the elderly. Here, we report on a 70-year-old man presenting with a single facial lesion of Langerhans cell histiocytosis and summarize the most important clinical aspects as well as current therapeutic concepts.     

Satisfactory Remission Achieved by PUVA Therapy in Langerhans Cell Hisiocytosis in an Elderly Patient

Langerhans cell histiocytosis is currently regarded as a reactive proliferative process of Langerhans cells rather than a malignancy. The disease is characterized by Langerhans cell infiltration of skin, lung, bone and other organs. We report a 74-year-old man with Langerhans cell histiocytosis who had generalized hemorrhagic and crusted papules. He also had diabetes insipidus. Because he did not have any severe constitutional symptoms or failure of vital organs, we applied topical PUVA treatment to his skin lesions, which responded well to the therapy. Diabetes insipidus, however, remained, in spite of X ray radiotherapy for the pituiary lesion.     

Monosystemische, oligoläsionale Langerhans-Zell-Histiozytose der Haut

A five-day-old female infant presented with congenital red-livid papules and nodules on the head, chest, back and left arm. The nodule on the chest was ulcerated at birth. The pregnancy and delivery were uneventful. There was no history of birth trauma to account for the ulcerated lesion. The parents and the three older siblings were healthy without similar skin lesions. The skin biopsy showed in the deep layer of the dermis a multinodular, granulomatous histiocytic infiltrate. The histiocytic cells expressed S-100 and CD1a. There were additionally many eosinophils. The suspected diagnosis Langerhans cell histiocytosis was confirmed by the histologic results. The patient was referred to pediatric hematology-oncology where evaluation showed no evidence of systemic involvement. The clinical, radiological, sonographic and histological results led to the diagnosis of a congenital, monosystemic, oligolesional Langerhans cell histiocytosis of the skin. In addition to the case presentation, we review the current stand of knowledge of the pathogenesis, the clinical classification and the therapy of the Langerhans cell histiocytosis.     

Cutaneous Langerhans cell histiocytosis presenting with hypopigmented lesions: Report of two cases and review of literature

Langerhans cell histiocytosis is a rare group of disorders that results from the abnormal proliferation and accumulation of dendritic‐derived cells in various organs of the body, such as the skin and bones. Hypopigmented macules are a rare cutaneous presentation of Langerhans cell histiocytosis that may pose a diagnostic dilemma when no other findings of Langerhans cell histiocytosis are present at the time of examination. We present 2 cases of the hypopigmented variant of Langerhans cell histiocytosis, including a case with histopathologic features of regression, and a review of the literature. These cases highlight the importance of including Langerhans cell histiocytosis in the differential diagnosis of an infant with hypopigmented macules and papules.     

朗格汉斯细胞组织细胞增生症

报告1例朗格汉斯细胞组织细胞增生症.患儿男,10个月.躯干部出现丘疹2个月,经组织病理及免疫组化检查证实为朗格汉斯细胞组织细胞增生症.     

Extracellular signal‐regulated kinase activation of self‐healing Langerhans cell histiocytosis: A case report

A 3‐month‐old boy developed small papules on his trunk. After the papules increased in number, the patient was diagnosed with Langerhans cell histiocytosis based on the pathological findings. He was referred to our department for further examination. Upon initial examination, the papules and nodules were scattered on his back, abdomen and lumbar region. Because he did not present with any organ involvement except the skin, he was diagnosed with single‐system and skin‐limited Langerhans cell histiocytosis. Skin rashes were treated with a topical steroid and started regressing 3 months after onset. All papules disappeared 6 months after onset. In this boy, the Langerhans cell histiocytosis tumor cells expressed phosphorylated extracellular signal‐regulated kinases. In Langerhans cell histiocytosis, BRAF V600E and other genes are known to mutate to act as driver mutations in stem cells of the myeloid dendritic cell lineage. Consequently, extracellular signal‐regulated kinases are continuously activated, which contributes to Langerhans cell histiocytosis carcinogenesis.     

黄色肉芽肿样单发型朗格汉斯细胞组织细胞增生症一例

朗格汉斯细胞组织细胞增生症（Langerhans cell histiocytosis, LCH）是一种少见的病因不明的疾病，表现为单发型皮损的朗格汉斯细胞组织细胞增生症更是罕见,本文报道一例。该患儿7个月，表现为右侧肩部单发黄红色结节2个月，皮损与黄色肉芽肿非常相似，极易误诊为黄色肉芽肿。     

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.     

Langerhans Cell Histiocytosis (Histiocytosis X) with Morphologic Expression of Desmosomes and Microvillous Structures

An unusual case of Langerhans cell histiocytosis in a 7-year-old female is presented. She had ultrastructural evidence of desmosomal biogenesis and formation of gland-like structures by lesional cells; their apical plasma membranes were folded into large numbers of microvilli. Despite the presence of these structures characteristic of epithelial cells, an infiltrated plaque on the abdominal skin of this patient was interpreted as cutaneous involvement of multiple system Langerhans cell histiocytosis because the immunohistochemical staining of the lesional cells for CD1a, S100, PNA, CD4, EN-4, and HLA-DR was positive, and numerous Birbeck granules were ultrastructurally identified in some lesional cells. Other clinical data included the presence of scaly erythematous skin lesions on the forehead and lytic osseous lesions in the maxilla, which were also histologically diagnosed as Langerhans cell histiocytosis. The absence of any internal malignancy in this patient readily ruled out the other diagnostic possibility of a metastatic adenocarcinoma showing glandular differentiation with brush border morphogenesis. The possibility that the desmosome-linked lesional epithelioid cells were actually cells of sweat glands entrapped in the histiocytic proliferation was also ruled out. The functional significance of the desmosomes and microvillous structures in the present case of Langerhans cell histiocytosis remains to be clarified. Awareness of this variant of Langerhans cell histiocytosis will be important for averting potential misdiagnosis in favor of epithelial tumors, especially metastatic adenocarcinomas.     

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.     

Langerhans cell histiocytosis and juvenile xanthogranuloma. Two case reports

BACKGROUND: Histiocytoses represent a large, puzzling group of diseases which may involve the skin and other organs. At present, juvenile xanthogranuloma is the disorder most often confused with Langerhans cell histiocytosis. A complex overlap exists between juvenile xanthogranuloma and Langerhans cell histiocytosis, with lesions showing clinical and/or pathological features of both disorders. OBSERVATIONS: We report 2 patients affected by Langerhans cell histiocytosis who, during chemotherapy, presented cutaneous lesions with clinical and histological features of juvenile xanthogranuloma. During the therapy, in both cases, histological examination of new biopsies revealed the presence of Touton giant cells in the dermis with a few histiocytic cells; immunohistochemical staining was negative for CD1a, and no Birbeck granules were seen by ultrastructural examination. RESULTS AND CONCLUSION: A possible explanation for the link between Langerhans cell histiocytosis and juvenile xanthogranuloma regards the lineage development and the relationships of histiocytes. We suggest that chemotherapy can modify the production of cytokines by influencing the conversion or 'maturation' of pathological cells into macrophages or xanthomatous cells and fusing them to form multinucleated giant Touton cells. In our opinion, the modification of the cutaneous lesions during chemotherapy in Langerhans cell histiocytosis patients, as observed in our cases, could be a favorable prognostic factor.     

Value of correlated immunofluorescence and immunoperoxidase study of monoclonal markers in 2 adult cases of histiocytosis X

Two cases of adult histiocytosis X have been studied using monoclonal antibodies on skin sections by two techniques: indirect immunofluorescence and immunoperoxidase. This study confirm: --that histiocytosis X express two specific antigens Ia and T6, --the relations between Langerhans cell and histiocytosis X. Especially, it suggests that histiocytosis X cell would be a dedifferentiated cell with receptors OKT4 and OKT10.     

Congenital solitary reticulohistiocytosis (Hashimoto - Pritzker)

Congenital and self-healing Hashimoto-Pritzker reticulohistiocytosis is the benign variant of the Langerhans cell histiocytosis (LCH) group. It is characterized by multiple skin lesions (congenital or appearing during the first days after birth), without systemic manifestations and spontaneous resolution in days to months. The authors report the case of a boy with a single congenital leg skin lesion, a rare disease variant. Through histopathology, a dense skin infiltration of S100 protein-, CD1a-, CD207-immunomarked cells was found. KI67 index was high (62%). A complete spontaneous resolution occurred 07 days after the biopsy (25 days after birth). Monolesional disease, distal limb lesion, absence of lesions in the mucous membrane or seborrheic area, and less than 25 percent of LCs with Birbeck granules were said to be possible clues for a favorable prognosis in LCs histiocytosis. But, as a precautionary measure, the child will be followed up until at least 2 years of age.     

Congenital self-healing histiocytosis presenting as blueberry muffin baby: a case report and literature review

Congenital self-healing Langerhans cell histiocytosis (CSHLCH), also called as Hashimoto-Pritzker disease, is a rare, benign variant of histiocytosis. Despite the initial dramatic clinical presentation, affected infants are otherwise healthy and skin lesions disappear spontaneously within several weeks to months. We present a case of CSHLCH presenting as blueberry muffin baby. The lesions appeared in the first week of life and lasted 6 months. The follow-up period was 24 months, without any signs of relapse. At the pediatric dermatology unit of our clinic, during the last 20 years, we had 10 children with Langerhans cell histiocytosis and among them only one with CSHLCH. In the literature, we found only 5 newborns with Langerhans cell histiocytosis presenting as blueberry muffin baby, among them only 4 with self-healing CSHLCH. The early recognition of CSHLCH may spare children from redundant and potentially toxic systemic treatment.     

Acquired Bilateral Agminated Spitz Nevi in a Child with Langerhans Cell Histiocytosis

Abstract: Multiple Spitz nevi are rare and may occur in agminated, widespread, or dermatomal distributions. Agminated Spitz nevi usually arise in children, presenting on grossly normal, hyperpigmented, or most rarely, hypopigmented skin. We present a child with Langerhans cell histiocytosis who developed bilateral agminated Spitz nevi in the inguinal area. Unusual features included the multifocal distribution, bilateral inguinal location, and co‐occurrence with Langerhans cell histiocytosis.     

朗格汉斯细胞组织细胞增多症126例临床分析

目的 分析朗格汉斯细胞组织细胞增多症患儿的临床特点。 方法 对2006—2011年我院126例朗格汉斯细胞组织细胞增多症进行临床回顾性分析。 结果　126例患者中年龄最小为2个月,最大9岁,男女比例是2.5 ∶ 1。皮肤病变呈湿疹样、脂溢性、出血性斑丘疹样、黄色结节样和白色斑疹样。在3种传统临床分型中,Letterer-Siwe病所占比例最高,患者年龄最小,受累器官最多,多伴有肝脾肿大、X线胸片异常、造血功能损伤、多部位骨受累,临床分级主要是Ⅲ级和Ⅳ级。Hand-Schüller-Christian病的患儿临床分级各级均有分布,以Ⅱ级最多。骨嗜酸细胞肉芽肿患者年龄最大,除骨骼以外未发现其他器官受累,临床分级大部分为Ⅰ级。治疗采用外科手术或联合化疗。结论　朗格汉斯细胞组织细胞增多症皮损表现有特征性,临床表现多样,病理有诊断意义,治疗和疗效取决于疾病程度和受累器官。     

儿童朗格罕细胞组织细胞增生症50例临床分析

目的探讨朗格罕细胞组织细胞增生症(Langerhans cell histocytosis,LCH)的临床表现、分型、分级、实验室检查和治疗情况及预后随访。方法对本院(2002～2010)年收治的50例住院LCH患儿临床资料进行回顾性分析及随访。结果临床分型LS 20例,LSC 2例,EG 18例,中间型10例。分级I级16例,II级15例,III 9例,IV 10例。本组50例中,31例均进行了手术或联合化疗治疗,其中10例EG病例单纯手术,8例EG行手术切除+化疗。结论 LCH是一种反应性非肿瘤性增殖性疾病,病因不明,儿童多见,临床表现多样性,易误诊、漏诊,X线是其重要的辅助检查,皮损、软组织肿块、溶骨性病灶、肿大的淋巴结、肝脾等进行活组织病理检查是确诊本病的依据,如有可疑皮疹,需及时完善皮疹印片及皮肤活检以协助诊断。本病是一组异质性疾病,个体化治疗极为重要,患者的年龄、病变的范围及损害的部位是选择治疗的依据,目前尚无特异有效的治疗方法。     

Solitary congenital self-healing reticulohistiocytosis in monozygotic twins

We report monozygotic twins with congenital self-healing reticulohistiocytosis, whose lesions initially presented as hemorrhagic bullae at birth with rapid progression into crusted papules the following day. Physical examination disclosed crusted papules on the right side of the neck of twin 1 and a similar solitary lesion on the lateral side of the right thumb of twin 2. Excisional biopsy specimen findings of the neck and thumb lesions were consistent with Langerhans cell histiocytosis, which was further confirmed by positive CD1a staining. The lesions resolved completely by 2 months with no evidence of recurrence or systemic involvement. Congenital self-healing reticulohistiocytosis is a rare, self-limited form of Langerhans cell histiocytosis. Although familial clustering in Langerhans cell histiocytosis was previously reported, to the best of our knowledge there is no report suggesting familial clustering in congenital self-healing reticulohistiocytosis. Our patients are interesting in terms of raising the question of whether the presence of congenital self-healing reticulohistiocytosis in monozygotic twins is implicative of a genetic role in its pathogenesis.     

Mixed histiocytosis: A case report and published work review

Histiocytoses are a group of heterogeneous diseases that encompass Langerhans cell histiocytosis and non‐Langerhans cell histiocytosis. Cutaneous plane xanthoma is a non‐Langerhans cell histiocytic disorder characterized by the presence of yellow‐orange plaques on the face, neck, upper trunk and extremities. It can appear in association with several systemic diseases (including dyslipidemias, paraproteinemias, cardiovascular diseases and lymphoproliferative disorders), but is rarely connected with Langerhans cell histiocytoses. Eosinophilic granuloma is one of the clinical entities of Langerhans cell histiocytoses, characterized by skeletal lesions and occurring prominently in children. Mixed histiocytosis, the concomitant occurrence of Langerhans cell histiocytosis and non‐Langerhans cell histiocytosis in a single patient, is exceptional. We herein report a case of eosinophilic granuloma in an adult Chinese man who also developed plane xanthoma on his scalp and face, and we also include a published work review of the comorbid cases of eosinophilic granuloma and non‐Langerhans cell histiocytosis. To the best of our knowledge, this is the first report on the mixed histiocytosis of cutaneous plane xanthoma and eosinophilic granuloma in China.