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Anales de Pediatria Aug 2022Langerhans cell histiocytosis (LCH) is a type of myeloid neoplasia that can affect different organs or tissues and exhibits substantial variability in its clinical...
Langerhans cell histiocytosis (LCH) is a type of myeloid neoplasia that can affect different organs or tissues and exhibits substantial variability in its clinical presentation and biological behaviour, so it may mimic different diseases. Performance of different clinical assessments and laboratory and imaging tests is recommended to determine the extent of involvement, which may be of a single location or multisystemic, and the presence or absence of dysfunction in risk organs, such as the haematopoietic system, liver and spleen. The diagnosis must be confirmed by histological examination of a biopsy sample. Molecular tests have identified mutations in the mitogen-activated protein kinase (MAPK) pathway, which has expanded treatment options. The diagnosis is complex and there is controversy regarding the management of certain cases. Treatment recommendations depend on the location of the lesions and the extent of involvement. International collaborative studies have demonstrated the effectiveness of prolonged combination therapies such as vinblastine and prednisone in severe or multisystemic forms, and anti-inflammatory drugs such as indomethacin and other cytostatic combinations have proven beneficial. Langerhans cell histiocytosis is a good example of the importance of precision medicine and the benefit of identifying molecular targets, common to different neoplasms, to develop new therapies. MAPK pathway inhibitors offer an alternative treatment option in refractory cases and neurodegenerative forms of LCH. Molecular testing can contribute to the prognosis, treatment and follow-up of LCH, especially in severe forms of disease.
Topics: Combined Modality Therapy; Histiocytosis, Langerhans-Cell; Humans; Mutation; Neoplasms; Prognosis
PubMed: 35869015
DOI: 10.1016/j.anpede.2022.05.005 -
Archives of Pathology & Laboratory... Oct 2015Langerhans cell histiocytosis (LCH) comprises a wide spectrum of clinical disorders that have in common a proliferation of Langerhans-type cells with characteristic... (Review)
Review
Langerhans cell histiocytosis (LCH) comprises a wide spectrum of clinical disorders that have in common a proliferation of Langerhans-type cells with characteristic morphologic, immunophenotypic, and ultrastructural features. In part because of the diverse clinical manifestations of LCH, there has long been controversy over whether LCH is best considered a reactive process or a neoplasm. Herein, we discuss the clinical and pathologic features of LCH, including recent advances in the understanding of the molecular pathogenesis of this disease that support its categorization as a neoplasm. We also review the implications that these recently described molecular characteristics may have on risk stratification and treatment of LCH.
Topics: Antigens, CD1; Biomarkers, Tumor; Diagnosis, Differential; Histiocytosis, Langerhans-Cell; Humans; Langerhans Cells; MAP Kinase Kinase 1; Mutation; Proto-Oncogene Proteins B-raf; S100 Proteins
PubMed: 26414464
DOI: 10.5858/arpa.2015-0199-RA -
Journal of Clinical and Experimental... 2016Langerhans cell (LC) histiocytosis (LCH) and LC sarcoma (LCS) are proliferative processes consisting of cells having morphologic and phenotypic features of Langerhans... (Review)
Review
Langerhans cell (LC) histiocytosis (LCH) and LC sarcoma (LCS) are proliferative processes consisting of cells having morphologic and phenotypic features of Langerhans cells (LCs), although the latter may have lost some of these features. Because neoplastic nature of LCH as well as LCS is more likely by recent studies, a category of LC hyperplasia can be better characterized. LCH and LCS are rarely seen in daily pathology practice, but it is important to accurately characterize these lesions. For this purpose, an outline covering proliferations of LC and related cells was constructed. The scheme of this outline is based especially on evaluating borderline lesions, neoplastic trans-differentiation, and degree of similarity with the normal counter-parts. In addition, the organization and update of the current classification scheme for histiocytic and dendritic-cell proliferations is presented.
Topics: Diagnosis, Differential; Histiocytosis, Langerhans-Cell; Humans; Langerhans Cell Sarcoma
PubMed: 27980300
DOI: 10.3960/jslrt.56.109 -
The Indian Journal of Medical Research Sep 2018
Topics: Antidiuretic Agents; Antineoplastic Agents; Biopsy; Child, Preschool; Deamino Arginine Vasopressin; Diabetes Insipidus, Neurogenic; Female; Histiocytosis, Langerhans-Cell; Humans; Magnetic Resonance Imaging; Mercaptopurine; Pituitary Gland; Prednisolone; Skin; Treatment Outcome; Vinblastine
PubMed: 30425231
DOI: 10.4103/ijmr.IJMR_1988_16 -
Journal of Feline Medicine and Surgery Apr 2020The aim of this study was to report the clinical, radiographic and pathological features of pulmonary Langerhans cell histiocytosis in four cats, and carry out a... (Review)
Review
OBJECTIVES
The aim of this study was to report the clinical, radiographic and pathological features of pulmonary Langerhans cell histiocytosis in four cats, and carry out a literature review of feline histiocytic diseases.
METHODS
Necropsy reports archived at the Department of Veterinary Pathology of the Federal University of Rio Grande do Sul were reviewed. The clinical information was then obtained from the clinical records at the Veterinary Hospital. Routine samples had been collected during necropsy, fixed in 10% formalin, routinely processed for histology, and stained with hematoxylin and eosin. Samples of lung were submitted for bacterial and fungal culture. Tissue sections of lung underwent immunohistochemical testing for vimentin, pancytokeratin, CD18, CD3, CD79αcy, E-cadherin and Iba1.
RESULTS
This disease affected mixed breed cats aged 7-14 years. Clinical signs consisted of severe mixed inspiratory and expiratory restrictive dyspnea, lethargy and anorexia. Thoracic radiographs revealed different lesion profiles, predominantly of an interstitial and alveolar pattern. Grossly, the lungs were diffusely firm and did not collapse. The pleural surface was bright and irregular due to multifocal-to-coalescent, well-demarcated, white, firm nodules that also extended into and obliterated the pulmonary parenchyma. Histological changes were characterized by poorly demarcated infiltration with histiocytic cells arranged in cohesive groups within the alveolar, bronchiolar and bronchial spaces. Histiocytic cells had intense cytoplasmic immunolabeling for vimentin and Iba1, and robust membrane immunolabeling with CD18 and E-cadherin; these cells were negative for CD3, CD79αcy and pancytokeratin in all cases.
CONCLUSIONS AND RELEVANCE
This article confirms that pulmonary Langerhans cell histiocytosis is a rare disease that occurs in middle-aged to older cats and causes widespread involvement of the pulmonary parenchyma, inducing acute or chronic, progressive respiratory disease characterized by mixed restrictive dyspnea that eventually leads to death. While a definitive clinical diagnosis is challenging, the nodular appearance of the pulmonary changes, together with the histological and immunohistochemistry findings, suffice for diagnostic confirmation of pulmonary Langerhans cell histiocytosis.
Topics: Animals; Cat Diseases; Cats; Histiocytosis, Langerhans-Cell
PubMed: 30977699
DOI: 10.1177/1098612X19842384 -
Biomedica : Revista Del Instituto... Sep 2020Langerhans cell histiocytosis is a rare pathology with different clinical manifestations in the neonatal period ranging from isolated bone lesions to systemic... (Review)
Review
Langerhans cell histiocytosis is a rare pathology with different clinical manifestations in the neonatal period ranging from isolated bone lesions to systemic compromise. We report a case of Langerhans cell histiocytosis including a literature review focused on the clinical manifestations, diagnosis, and treatment. A one-month-old patient was brought to medical consultation with lymphadenopathy and skin lesions, which were initially managed as an infectious pathology. The disease continued its progression without improvement with the treatment until the patient died due to respiratory failure. The lymph node and skin biopsies revealed infiltration of atypical cells with positive immunohistochemistry for S100, CD1, and CD68 confirming Langerhans cell histiocytosis. This disorder represents a great challenge and, therefore, it is important to alert and sensitize medical teams about it for timely diagnosis and management.
Topics: Biopsy; Cytomegalovirus Infections; Diagnosis, Differential; Disease Progression; Fatal Outcome; Histiocytosis, Langerhans-Cell; Humans; Infant; Lymphadenopathy; Male; Skin; Skin Diseases; Skin Diseases, Viral
PubMed: 33030824
DOI: 10.7705/biomedica.5150 -
Haematologica Sep 2023Langerhans cell histiocytosis (LCH) is a potentially life-threatening inflammatory myeloid neoplasia linked to pediatric neurodegeneration, whereby transformed LCH cells...
Langerhans cell histiocytosis (LCH) is a potentially life-threatening inflammatory myeloid neoplasia linked to pediatric neurodegeneration, whereby transformed LCH cells form agglomerated lesions in various organs. Although MAP-kinase pathway mutations have been identified in LCH cells, the functional consequences of these mutations and the mechanisms that cause the pathogenic behavior of LCH cells are not well understood. In our study, we used an in vitro differentiation system and RNA-sequencing to compare monocyte-derived dendritic cells from LCH patients to those derived from healthy controls or patients with Crohn's disease, a non-histiocytic inflammatory disease. We observed that interferon-γ treatment exacerbated intrinsic differences between LCH patient and control cells, including strikingly increased endo- and exocytosis gene activity in LCH patients. We validated these transcriptional patterns in lesions and functionally confirmed that LCH cells exhibited increased endo- and exocytosis. Furthermore, RNA-sequencing of extracellular vesicles revealed the enrichment of pathological transcripts involved in cell adhesion, MAP-kinase pathway, vesicle trafficking and T-cell activation in LCH patients. Thus, we tested the effect of the LCH secretome on lymphocyte activity and found significant activation of NK cells. These findings implicate extracellular vesicles in the pathology of LCH for the first time, in line with their established roles in the formation of various other tumor niches. Thus, we describe novel traits of LCH patient cells and suggest a pathogenic mechanism of potential therapeutic and diagnostic importance.
Topics: Humans; Child; Secretome; Histiocytosis, Langerhans-Cell; Myeloid Cells; Killer Cells, Natural; Neoplasms
PubMed: 36924254
DOI: 10.3324/haematol.2022.282638 -
Immunology and Allergy Clinics of North... May 2023Cysts and cavities in the lung are commonly encountered on chest imaging. It is necessary to distinguish thin-walled lung cysts (≤2 mm) from cavities and characterize... (Review)
Review
Cysts and cavities in the lung are commonly encountered on chest imaging. It is necessary to distinguish thin-walled lung cysts (≤2 mm) from cavities and characterize their distribution as focal or multifocal versus diffuse. Focal cavitary lesions are often caused by inflammatory, infectious, or neoplastic processes in contrast to diffuse cystic lung diseases. An algorithmic approach to diffuse cystic lung disease can help narrow the differential diagnosis, and additional testing such as skin biopsy, serum biomarkers, and genetic testing can be confirmatory. An accurate diagnosis is essential for the management and disease surveillance of extrapulmonary complications.
Topics: Humans; Lymphangioleiomyomatosis; Histiocytosis, Langerhans-Cell; Birt-Hogg-Dube Syndrome; Tomography, X-Ray Computed; Lung Diseases; Lung; Cysts; Diagnosis, Differential
PubMed: 37055093
DOI: 10.1016/j.iac.2023.01.003 -
Medicina Oral, Patologia Oral Y Cirugia... May 2009Langerhans cell histiocytosis (LCH) is a rare disease, of unknown pathogenesis, characterized by intense and abnormal proliferation of bone marrow-derived histiocytes... (Review)
Review
Langerhans cell histiocytosis (LCH) is a rare disease, of unknown pathogenesis, characterized by intense and abnormal proliferation of bone marrow-derived histiocytes (Langerhans cells). It can present both local and systemic manifestations involving bone, skin and mucosal tissue, and internal organs. Three basic clinical forms develop: Letterer-Siwe disease (subacute or acute disseminated form), Hand-Schüller-Christian disease (disseminated chronic form) and eosinophilic granuloma (localized chronic form). LCH may manifest orally with single or multiple lesions of the alveolar or basal bone, ulcerated mucosal lesions accompanied by adenopathies and/or periodontal lesions, presenting gingival inflammation, bleeding, recession, necrosis, odontalgia, dental hypermobility and premature loss of teeth. The principal differential diagnoses include advanced periodontal disease or a periapical process of dental or periodontal origin. The odontologist plays a vital role in the diagnosis and multidisciplinary treatment of such patients, by performing routine examinations for periodic follow-up of the disease and its possible oral manifestations, bearing in mind that these may be the first or only signs of LCH.
Topics: Histiocytosis, Langerhans-Cell; Humans; Mouth Diseases; Prognosis
PubMed: 19218906
DOI: No ID Found -
Orphanet Journal of Rare Diseases Mar 2012Pulmonary Langerhans Cell Histiocytosis (PLCH) is a relatively uncommon lung disease that generally, but not invariably, occurs in cigarette smokers. The pathologic... (Review)
Review
Pulmonary Langerhans Cell Histiocytosis (PLCH) is a relatively uncommon lung disease that generally, but not invariably, occurs in cigarette smokers. The pathologic hallmark of PLCH is the accumulation of Langerhans and other inflammatory cells in small airways, resulting in the formation of nodular inflammatory lesions. While the overwhelming majority of patients are smokers, mechanisms by which smoking induces this disease are not known, but likely involve a combination of events resulting in enhanced recruitment and activation of Langerhans cells in small airways. Bronchiolar inflammation may be accompanied by variable lung interstitial and vascular involvement. While cellular inflammation is prominent in early disease, more advanced stages are characterized by cystic lung destruction, cicatricial scarring of airways, and pulmonary vascular remodeling. Pulmonary function is frequently abnormal at presentation. Imaging of the chest with high resolution chest CT scanning may show characteristic nodular and cystic abnormalities. Lung biopsy is necessary for a definitive diagnosis, although may not be required in instances were imaging findings are highly characteristic. There is no general consensus regarding the role of immunosuppressive therapy in smokers with PLCH. All smokers must be counseled on the importance of smoking cessation, which may result in regression of disease and obviate the need for systemic immunosuppressive therapy. The prognosis for most patients is relatively good, particularly if longitudinal lung function testing shows stability. Complications like pneumothoraces and secondary pulmonary hypertension may shorten life expectancy. Patients with progressive disease may require lung transplantation.
Topics: Adult; Child, Preschool; Female; Histiocytosis, Langerhans-Cell; Humans; Hypertension, Pulmonary; Infant; Langerhans Cells; Lung Diseases; Male; Pneumothorax; Prognosis; Respiratory Function Tests; Smoking; Young Adult
PubMed: 22429393
DOI: 10.1186/1750-1172-7-16