Langerhans cell histiocytosis: a review of the current recommendations of the Histiocyte Society

Abstract:  Langerhans cell histiocytosis is a rare proliferative disorder where pathologic Langerhans cells accumulate in a variety of organs. Historically, the nomenclature regarding this entity has been confusing because the disease had been subcategorized simply based upon the different clinical manifestations. In the following article, we summarize the current recommendation of the Histiocyte Society regarding the classification, evaluation, prognosis, and treatment of 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。     

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.     

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.     

Langerhans Cell Histiocytosis: A Case Report and Glimpses into Its Nomenclature

Class I Langerhans cell histiocytosis (LCH) is described in a two- and a half-year-old male. The initial expression of the disease was conspicuous by the presence of extensive pustular crusted rash and, later in its course, by purpura, diabetes insipidus, otitis media, enlargement of the liver and spleen, and infiltration into the lungs. The patient expired due to extensive hemorrhage over 24 hours.     

郎格罕细胞组织细胞增生症──韩－薛－柯病22例分析

报道２２例韩－薛－柯病，着重就该病典型的三联征（骨质缺损、突眼、尿崩症）和皮疹等进行了介绍和分析，并对郎格罕细胞组织细胞增生症的命名进行了历史回顾。此外还就该病病因、发病机理进行了探讨，指出该病可能系机体免疫功能失调性疾病。     

Case for diagnosis. Diffuse ulcerated nodular lesions

Langerhans cell histiocytosis is a rare clonal proliferative disease, characterized by the infiltration of one or multiple organs by histiocytes. Due to the diversity of signs and symptoms, the diagnosis of this disease is often late. The estimated incidence in adults is one to two cases per million, but the disease is probably underdiagnosed in this population. This report presents a case of disseminated Langerhans cell histiocytosis. The authors highlight the most characteristic aspects of this rare and heterogeneous disease, which usually presents as a challenging clinical diagnosis.     

Histiocytosis X

A patient with histiocytosis X had nonhealing mouth lesions. Evaluation revealed diabetes insipidus and numerous bony lesions. Electron microscopy of the mouth lesions and lymph nodes did not indicate Langerhans cells, which have frequently been described as occurring in histiocytosis X. A survey of 59 patients examined during a 20-year period at UCLA reported the presence of oral lesions in 42% of the cases and confirmed the occurrence of a wide range of clinical patterns and variations in the course of the disease.     

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.     

Vulvar ulcer as a presentation of systemic Langerhans cell histiocytosis

We report a 38-year-old housewife with systemic Langerhans cell histiocytosis (LCH) presenting as a chronic vulvar and peri-anal ulcer. She had systemic involvement in the form of diabetes insipidus and bone "hot-spots". She responded favorably to etoposide, 6-mercaptopurine, and systemic steroids, and has been in remission since 10 years. Chronic vulvar ulcers not responding to routine therapy should not be neglected and need to be biopsied repeatedly to come to a specific diagnosis. The vulvar ulcer in our case provided a vital clue to a systemic LCH, with a successful outcome.     

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 cell histiocytosis in monozygotic twins

Langerhans cells histiocytosis, one of a group of histiocytosis syndromes characterized by Langerhans cell infiltration, has many clinical manifestations. In the past 30 years, numerous cases of presumed Letterer-Siwe disease, the acute multiorgan variant, have been reported in twins and siblings. Only recently has the Histiocyte Society established a criterion for a "definitive diagnosis" of Langerhans cell histiocytosis--the presence of Birbeck granules within the cells of the histiocytic infiltrate. We report the fatal outcome of Langerhans cell histiocytosis in monozygotic twin infants. There is no satisfactory explanation why Langerhans cell histiocytosis occurs concurrently in twins. We suggest that cytokines may provide an endogenous signal that triggers the pathologic proliferation of Langerhans cells.     

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.     

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.     

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-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.     

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.     

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.     

Isolated Langerhans Cell Histiocytosis of the Vulva in an Infant

Abstract: Langerhans cell histiocytosis affecting only the vulva of a child is very rare. We report a 1‐year‐old female infant with isolated Langerhans cell histiocytosis presenting as pruritic papules confined to the vulva, confirmed by histopathology with immunohistochemical staining.     

Langerhans cell histiocytosis and multiple reticulohistiocytomas in a patient with TAR syndrome: An association not previously described

We describe a patient with thrombocytopenia‐absent radius (TAR) syndrome, multisystemic Langerhans cell histiocytosis and multiple reticulohistiocytomas. A mutational study by massive sequencing identified the Val600Glu (V600E) BRAF mutation in the Langerhans cell histiocytosis lesions, but no molecular alterations were found in the reticulohistiocytoma lesions. The concomitant presence in the same patient of more than one type of histiocytosis from two different groups recognized in the most recent Histiocyte Society classification is an extremely rare event. Our case is the first reported case of multisystemic Langerhans cell histiocytosis and multiple reticulohistiocytomas in a patient with TAR syndrome.