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Survey of Ophthalmology 2023An 8-year-old boy presented with acute visual loss in the right eye and nausea, vomiting, and diplopia. Imaging revealed a right orbital apex mass. Biopsy showed...
An 8-year-old boy presented with acute visual loss in the right eye and nausea, vomiting, and diplopia. Imaging revealed a right orbital apex mass. Biopsy showed Langerhans cell histiocytosis (LCH), and the patient was diagnosed with isolated orbital LCH causing an orbital apex syndrome. A 12-month cytarabine chemotherapy course was begun, during which the patient developed bilateral optic disc edema. He was diagnosed with cytarabine-induced intracranial hypertension, which was successfully treated with acetazolamide. The cytarabine course was completed with complete resolution of the LCH lesion. The ophthalmologic relevance of this rare disorder is discussed.
Topics: Male; Humans; Child; Histiocytosis, Langerhans-Cell; Orbital Diseases; Cytarabine; Diplopia; Papilledema
PubMed: 35970231
DOI: 10.1016/j.survophthal.2022.08.001 -
Clinics in Dermatology 2020Langerhans cell histiocytosis (LCH) is an uncommon but serious inflammatory neoplasia that affects many organs, including the skin. Though uncommon, it should remain... (Review)
Review
Langerhans cell histiocytosis (LCH) is an uncommon but serious inflammatory neoplasia that affects many organs, including the skin. Though uncommon, it should remain high on a clinician's differential diagnosis in treatment-resistant cases of conditions, such as seborrheic dermatitis, diaper dermatitis, arthropod bites, and many more. A thorough history nd physical examination for each patient can aid in the diagnosis; however, if clinically suspicious for LCH, a punch biopsy should be performed. Histologic evaluation of LCH is often enough to differentiate it from the many clinical mimickers. Characteristic findings include a histiocytic infiltrate with "coffee bean"-cleaved nuclei, rounded shape, and eosinophilic cytoplasm. Immunohistochemical stains, including CD1a, S100, and CD207 (langerin) are often needed for a definitive diagnosis. Electron microscopy also demonstrates the ultrastructural presence of Birbeck granules, but this is no longer needed due to immunohistochemical staining. Treatment is often necessary for LCH, if systemic involvement exists.
Topics: Antigens, CD; Antigens, CD1; Biomarkers; Biopsy, Needle; Diagnosis, Differential; Histiocytosis, Langerhans-Cell; Humans; Lectins, C-Type; Mannose-Binding Lectins; Microscopy, Electron; S100 Proteins; Skin; Skin Diseases
PubMed: 32513402
DOI: 10.1016/j.clindermatol.2019.10.007 -
Paediatric Drugs Jul 2023Histiocytic disorders are rare diseases defined by the clonal accumulation of a macrophage or dendritic cell origin. These disorders include Langerhans cell... (Review)
Review
Histiocytic disorders are rare diseases defined by the clonal accumulation of a macrophage or dendritic cell origin. These disorders include Langerhans cell histiocytosis, Erdheim-Chester disease, juvenile xanthogranuloma, malignant histiocytoses, and Rosai-Dorfman-Destombes disease. These histiocytic disorders are a diverse group of disorders with different presentations, management, and prognosis. This review focuses on these histiocytic disorders and the role of pathological ERK signaling due to somatic mutations in the mitogen--activated protein kinase (MAPK) pathway. Over the last decade, there has been growing awareness of the MAPK pathway being a key driver in many histiocytic disorders, which has led to successful treatment with targeted therapies, in particular, BRAF inhibitors and MEK inhibitors.
Topics: Humans; Erdheim-Chester Disease; Histiocytosis, Langerhans-Cell; Histiocytosis, Sinus; Mutation; Prognosis; Protein Kinase Inhibitors
PubMed: 37204611
DOI: 10.1007/s40272-023-00569-8 -
Pediatrics in Review Oct 2022Histiocytic disorders of childhood represent a wide spectrum of conditions that share the common histologic feature of activated or transformed "histiocytes." Langerhans...
Histiocytic disorders of childhood represent a wide spectrum of conditions that share the common histologic feature of activated or transformed "histiocytes." Langerhans cell histiocytosis (LCH) is the most common, with an incidence of approximately 5 per million children. LCH may be difficult to distinguish from more ubiquitous causes of skin rashes, bone pain, or fever. Current chemotherapy fails to cure more than 50% of children with multifocal disease, and treatment failure is associated with increased risks of long-term sequelae. Somatic activating mitogen-activated protein kinase (MAPK) pathway-activating mutations (most often BRAFV600E) have been identified in hematopoietic precursors in patients with LCH. Opportunities to improve outcomes with targeted therapies are under investigation. Juvenile xanthogranuloma (JXG) and Rosai-Dorfman disease (RDD) are less common than LCH and are distinguished by specific histologic and clinical features. Recurrent MAPK pathway gene mutations are also identified in JXG and RDD. In many cases, these conditions spontaneously resolve, but disseminated disease can be fatal. Although there has been historic debate regarding the nature of these conditions as inflammatory versus neoplastic, LCH, JXG, and RDD are now considered myeloid neoplastic disorders. In contrast, hemophagocytic lymphohistiocytosis (HLH) is clearly a disorder of immune dysregulation. HLH is characterized by extreme immune activation driven by hyperactivated T cells. HLH arises in approximately 1 child per million and is nearly universally fatal without prompt recognition and immune suppression. Outcomes of treated children are poor, with approximately 60% survival. Emapalumab, which targets interferon-γ signaling, was recently approved for patients with recurrent or refractory HLH, and additional cytokine-directed therapies are under investigation.
Topics: Child; Histiocytes; Histiocytosis, Langerhans-Cell; Histiocytosis, Sinus; Humans; Interferon-gamma; Mitogen-Activated Protein Kinases; Xanthogranuloma, Juvenile
PubMed: 36180546
DOI: 10.1542/pir.2021-005367 -
The Bone & Joint Journal Jun 2023The aim of this study was to report the long-term prognosis of patients with multiple Langerhans cell histiocytosis (LCH) involving the spine, and to analyze the risk...
AIMS
The aim of this study was to report the long-term prognosis of patients with multiple Langerhans cell histiocytosis (LCH) involving the spine, and to analyze the risk factors for progression-free survival (PFS).
METHODS
We included 28 patients with multiple LCH involving the spine treated between January 2009 and August 2021. Kaplan-Meier methods were applied to estimate overall survival (OS) and PFS. Univariate Cox regression analysis was used to identify variables associated with PFS.
RESULTS
Patients with multiple LCH involving the spine accounted for 15.4% (28/182 cases) of all cases of spinal LCH: their lesions primarily involved the thoracic and lumbar spines. The most common symptom was pain, followed by neurological dysfunction. All patients presented with osteolytic bone destruction, and 23 cases were accompanied by a paravertebral soft-tissue mass. The incidence of vertebra plana was low, whereas the oversleeve-like sign was a more common finding. The alkaline phosphatase was significantly higher in patients with single-system multifocal bone LCH than in patients with multisystem LCH. At final follow-up, one patient had been lost to follow-up, two patients had died, three patients had local recurrence, six patients had distant involvement, and 17 patients were alive with disease. The median PFS and OS were 50.5 months (interquartile range (IQR) 23.5 to 63.1) and 60.5 months (IQR 38.0 to 73.3), respectively. Stage (hazard ratio (HR) 4.324; p < 0.001) and chemotherapy (HR 0.203; p < 0.001) were prognostic factors for PFS.
CONCLUSION
Pain is primarily due to segmental instability of the spine from its destruction by LCH. Chemotherapy can significantly improve PFS, and radiotherapy has achieved good results in local control. The LCH lesions in some patients will continue to progress. It may initially appear as an isolated or single-system LCH, but will gradually involve multiple sites or systems. Therefore, long-term follow-up and timely intervention are important for patients with spinal LCH.
Topics: Humans; Retrospective Studies; Prognosis; Lumbar Vertebrae; Histiocytosis, Langerhans-Cell; Pain
PubMed: 37257861
DOI: 10.1302/0301-620X.105B6.BJJ-2022-1129.R1 -
Acta Paediatrica (Oslo, Norway : 1992) Nov 2021Langerhans cell histiocytosis (LCH) is caused by the expansion of CD1a+/CD207+ cells and is characterised by a wide spectrum of organ involvement and dysfunction,... (Review)
Review
Langerhans cell histiocytosis (LCH) is caused by the expansion of CD1a+/CD207+ cells and is characterised by a wide spectrum of organ involvement and dysfunction, affecting all ages. While almost all organs and systems can be affected, only the involvement and dysfunction of liver, spleen, and haematopoietic system influence survival. The LCH pathogenic cells are defined by universal activation of the mitogen-activated protein kinase (MAPK) signalling pathway. The most common alteration is a somatic BRAFV600E mutation, which is present in approximately two-thirds of the cases, followed by MAP2K1 mutations. Treatment of LCH is risk-adapted; patients with single lesions may respond well to local treatment, whereas patients with multi-system disease require systemic chemotherapy. While survival for patients without organ dysfunction is excellent, mortality rates for patients with organ dysfunction may reach 20%. Despite progress made in the treatment of LCH, disease reactivation rates remain above 30%, and standard second-line treatment has yet to be established. Long-term effects, including neuroendocrine dysfunction and neurodegeneration, represent a major challenge for survivors. Treatment with BRAF or MEK inhibitors results in immediate responses, but reactivations are very common after discontinuation. Their role as single agents and in combination with chemotherapy is being explored.
Topics: Histiocytosis, Langerhans-Cell; Humans; Mutation; Proto-Oncogene Proteins B-raf
PubMed: 34192374
DOI: 10.1111/apa.16014 -
Langerhans cell histiocytosis and associated malignancies: A retrospective analysis of 270 patients.European Journal of Cancer (Oxford,... Sep 2022The frequency of Langerhans cell histiocytosis (LCH) and associated malignancies (AM) is greater than statistically expected. Here, we analyze LCH-AM co-occurrence in... (Review)
Review
PURPOSE
The frequency of Langerhans cell histiocytosis (LCH) and associated malignancies (AM) is greater than statistically expected. Here, we analyze LCH-AM co-occurrence in both children and adults.
METHODS
Between 1991 and 2015, data were collected by regular questionnaires to members of the Histiocyte Society and searches in PubMed and Abstract Books. Patients were grouped by age at LCH diagnosis (≤ and >18 years), and types and timing of AM occurrence were plotted with respect to the LCH diagnosis. For the statistical analysis, only the first AM were considered.
RESULTS
A total of 285 LCH-AM in 270 patients were identified, 116 (43%) ≤ 18 years, and 154 (57%) >18 years. In childhood LCH-AM pairs, leukemias and myeloproliferative disorders (n = 58; 50.0%) prevailed over solid tumors (n = 43; 37.1%) and lymphoma (n = 15; 12.9%). In adults, solid tumors were reported in 61 patients (39.6%), lymphoma, and leukemias and myeloproliferative disorders in 56 (36.4%) and 37 (24.0%) patients, respectively. In most children, AM followed LCH (n = 69, 59.5%), whereas in adults, LCH and AM occurred concurrently in 69 patients (44.8%). In children, T-lineage acute lymphoblastic leukemia (ALL) and promyelocytic acute myeloid leukemia (AML) and retinoblastoma were over-represented and thyroid carcinoma in adults.
CONCLUSIONS
The largest collection of data on LCH-AM to date clearly indicates inherent relationships between specific types of AM and LCH, which may be due to therapy effects, clonal evolution, and germ-line predisposition, respectively. Prospective thorough genetic analysis is warranted and will hopefully shed light on the association of LCH and second neoplasms.
Topics: Adult; Child; Histiocytosis, Langerhans-Cell; Humans; Leukemia, Myeloid, Acute; Lymphoma; Prospective Studies; Retrospective Studies
PubMed: 35772351
DOI: 10.1016/j.ejca.2022.03.036 -
Der Radiologe Dec 2021The main granulomatous diseases of the musculoskeletal system are Langerhans cell histiocytosis, sarcoidosis, Erdheim-Chester disease (lipoidgranulomatosis) and... (Review)
Review
The main granulomatous diseases of the musculoskeletal system are Langerhans cell histiocytosis, sarcoidosis, Erdheim-Chester disease (lipoidgranulomatosis) and mastocytosis. In most cases the patients have only a few symptoms, and the disease is detected coincidentally. The diagnosis is usually made by a synopsis of topographical presentation, clinical appearance and the radiological pattern (destruction, reactive new bone formation).
Topics: Erdheim-Chester Disease; Histiocytosis, Langerhans-Cell; Humans; Musculoskeletal System; Radiography; Sarcoidosis
PubMed: 34889972
DOI: 10.1007/s00117-021-00938-9 -
Surgical Pathology Clinics Sep 2019Bone pathology can be challenging because the skeleton is a living tissue prone to developing a diverse array of inflammatory, metabolic, genetic, reactive, circulatory,... (Review)
Review
Bone pathology can be challenging because the skeleton is a living tissue prone to developing a diverse array of inflammatory, metabolic, genetic, reactive, circulatory, and neoplastic abnormalities. Several areas of bone pathology are particularly difficult or problematic for hematopathologists given the close resemblance of some hematologic entities to primary/metastatic bone lesions; examples include plasmacytic disorders versus osteoblastic tumors and lymphoma/leukemia versus round cell tumors of bone. This article provides a conceptual and practical overview of selective bone disorders commonly encountered in the differential diagnosis of hematologic diseases.
Topics: Bone Neoplasms; Chondrosarcoma, Mesenchymal; Diagnosis, Differential; Histiocytosis, Langerhans-Cell; Humans; Mastocytosis; Osteomyelitis; Osteosarcoma; Plasmacytoma; Prognosis
PubMed: 31352990
DOI: 10.1016/j.path.2019.03.007 -
The Pediatric Infectious Disease Journal Oct 2022
Topics: Diagnosis, Differential; Histiocytosis, Langerhans-Cell; Humans; Osteomyelitis
PubMed: 35830510
DOI: 10.1097/INF.0000000000003635