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Nature Reviews. Disease Primers Oct 2021The historic term 'histiocytosis' meaning 'tissue cell' is used as a unifying concept for diseases characterized by pathogenic myeloid cells that share histological... (Review)
Review
The historic term 'histiocytosis' meaning 'tissue cell' is used as a unifying concept for diseases characterized by pathogenic myeloid cells that share histological features with macrophages or dendritic cells. These cells may arise from the embryonic yolk sac, fetal liver or postnatal bone marrow. Prior classification schemes align disease designation with terminal phenotype: for example, Langerhans cell histiocytosis (LCH) shares CD207 antigen with physiological epidermal Langerhans cells. LCH, Erdheim-Chester disease (ECD), juvenile xanthogranuloma (JXG) and Rosai-Dorfman disease (RDD) are all characterized by pathological ERK activation driven by activating somatic mutations in MAPK pathway genes. The title of this Primer (Histiocytic disorders) was chosen to differentiate the above diseases from Langerhans cell sarcoma and malignant histiocytosis, which are hyperproliferative lesions typical of cancer. By comparison LCH, ECD, RDD and JXG share some features of malignant cells including activating MAPK pathway mutations, but are not hyperproliferative. 'Inflammatory myeloproliferative neoplasm' may be a more precise nomenclature. By contrast, haemophagocytic lymphohistiocytosis is associated with macrophage activation and extreme inflammation, and represents a syndrome of immune dysregulation. These diseases affect children and adults in varying proportions depending on which of the entities is involved.
Topics: Erdheim-Chester Disease; Histiocytosis, Langerhans-Cell; Histiocytosis, Sinus; Humans; Inflammation; Xanthogranuloma, Juvenile
PubMed: 34620874
DOI: 10.1038/s41572-021-00307-9 -
Journal of Clinical and Experimental... 2012In this review, representative types of granulomatous lymphadenitis (GLA) are described. GLA can be classified as noninfectious GLA and infectious GLA. Noninfectious GLA... (Review)
Review
In this review, representative types of granulomatous lymphadenitis (GLA) are described. GLA can be classified as noninfectious GLA and infectious GLA. Noninfectious GLA includes sarcoidosis and sarcoid-like reaction. The cause of sarcoidosis remains unknown, but it has good prognosis. Sarcoid-like reaction, which is considered to be a biological defense mechanism, is observed in regional lymph nodes with many underlying diseases. Infectious GLA can be classified as suppurative lymphadenitis (LA) and nonsuppurative LA. Suppurative LA generally shows follicular hyperplasia and sinus histiocytosis in the early phase. In tularemia and cat scratch disease, monocytoid B lymphocytes (MBLs) with T cells and macrophages contribute to the formation of granuloma. However, none of the epithelioid cell granulomas of Yersinia LA contains MBLs like in cat scratch disease. In addition, almost all have a central abscess in granulomas induced by Gram-negative bacteria. In terms of the lymph nodes, tularemia and cat scratch disease are apt to affect the axillary and cervical regions while Yersinia LA affects the mesenteric lymph node. Nonsuppurative LA includes tuberculosis and BCG-histiocytosis. These are induced by delayed allergic reaction of M. tuberculosis. Tuberculosis LA mainly appears in the cervical lymph node. Organisms are histologically detected by Ziehl-Neelsen staining in the necrotic area. Toxoplasmosis is also a nonsuppurative protozoan infection (Toxoplasma gondii). In toxoplasma LA, MBLs can also be seen, but round and organized, well-formed granulomas are not found in this disease. Furthermore, necrosis is not induced and there are no accompanying neutrophils, eosinophils and fibrosis. GLA described above is associated with characteristic histological findings. An accurate pathological diagnosis using the above findings can lead to precise treatment.
Topics: Animals; Cat-Scratch Disease; Gram-Negative Bacterial Infections; Granuloma; Humans; Lymph Nodes; Sarcoidosis
PubMed: 22706525
DOI: 10.3960/jslrt.52.1 -
Blood Jun 2018Rosai-Dorfman-Destombes disease (RDD) is a rare non-Langerhans cell histiocytosis characterized by accumulation of activated histiocytes within affected tissues. RDD,... (Review)
Review
Rosai-Dorfman-Destombes disease (RDD) is a rare non-Langerhans cell histiocytosis characterized by accumulation of activated histiocytes within affected tissues. RDD, which now belongs to the R group of the 2016 revised histiocytosis classification, is a widely heterogeneous entity with a range of clinical phenotypes occurring in isolation or in association with autoimmune or malignant diseases. Recent studies have found , , , and mutations in lesional tissues, raising the possibility of a clonal origin in some forms of RDD. More than 1000 reports have been published in the English literature; however, there is a lack of consensus regarding approach for the clinical management of RDD. Although in most cases RDD can be observed or treated with local therapies, some patients with refractory or multifocal disease experience morbidity and mortality. Here we provide the first consensus multidisciplinary recommendations for the diagnosis and management of RDD. These recommendations were discussed at the 32nd Histiocyte Society Meeting by an international group of academic clinicians and pathologists with expertise in RDD. We include guidelines for clinical, laboratory, pathologic, and radiographic evaluation of patients with RDD together with treatment recommendations based on clinical experience and review of the literature.
Topics: Adrenal Cortex Hormones; Biopsy; Disease Management; Genetic Predisposition to Disease; Histiocytes; Histiocytosis, Sinus; Humans; Immunotherapy; Mutation; Practice Guidelines as Topic; Prognosis; Radiotherapy
PubMed: 29720485
DOI: 10.1182/blood-2018-03-839753 -
Cancers Oct 2022Rosai-Dorfman disease (RDD) is a rare myeloproliferative disorder of histiocytes with a broad spectrum of clinical manifestations and peculiar morphologic features... (Review)
Review
Rosai-Dorfman disease (RDD) is a rare myeloproliferative disorder of histiocytes with a broad spectrum of clinical manifestations and peculiar morphologic features (accumulation of histiocytes with emperipolesis). Typically, the patient with RDD shows bilateral painless, massive cervical lymphadenopathy associated with B symptoms. Approximately 43% of patients presented with extranodal involvement. According to the 2016 revised histiocytosis classification, RDD belongs to the R group, including familial and sporadic form (classical nodal, extranodal, unclassified, or RDD associated with neoplasia or immune disease). Sporadic RDD is often self-limited. Most RDD needs only local therapies. Nevertheless, a small subpopulation of patients may be refractory to conventional therapy and die of the disease. Recent studies consider RDD a clonal neoplastic process, as approximately 1/3 of these patients harbor gene mutations involving the MAPK/ERK pathway, e.g., , , , and, rarely, the mutation. In addition to typical histiocytic markers (S100/fascin/CD68/CD163, etc.), recent studies show that the histiocytes in RDD also express BCL-1 and OCT2, which might be important in pathogenesis. Additionally, the heterozygous germline mutation involving the FAS gene is identified in some RDD patients with an autoimmune lymphoproliferative syndrome type Ia. germline mutation is associated with familial or Faisalabad histiocytosis and H syndrome.
PubMed: 36358690
DOI: 10.3390/cancers14215271 -
Neuro-oncology Sep 2021Histiocytoses are heterogeneous hematopoietic diseases characterized by the accumulation of CD68(+) cells with various admixed inflammatory infiltrates. The... (Review)
Review
Histiocytoses are heterogeneous hematopoietic diseases characterized by the accumulation of CD68(+) cells with various admixed inflammatory infiltrates. The identification of the pivotal role of the mitogen-activated protein kinase (MAPK) pathway has opened new avenues of research and therapeutic approaches. We review the neurologic manifestations of 3 histiocytic disorders with frequent involvement of the brain and spine: Langerhans cell histiocytosis (LCH), Erdheim-Chester disease (ECD), and Rosai-Dorfman-Destombes disease (RDD). Central nervous system (CNS) manifestations occur in 10%-25% of LCH cases, with both tumorous or neurodegenerative forms. These subtypes differ by clinical and radiological presentation, pathogenesis, and prognosis. Tumorous or degenerative neurologic involvement occurs in 30%-40% of ECD patients and affects the hypothalamic-pituitary axis, meninges, and brain parenchyma. RDD lesions are typically tumorous with meningeal or parenchymal masses with strong contrast enhancement. Unlike LCH and ECD, neurodegenerative lesions or syndromes have not been described with RDD. Familiarity with principles of evaluation and treatment both shared among and distinct to each of these 3 diseases is critical for effective management. Refractory or disabling neurohistiocytic involvement should prompt the consideration for use of targeted kinase inhibitor therapies.
Topics: Central Nervous System; Erdheim-Chester Disease; Histiocytosis, Langerhans-Cell; Histiocytosis, Sinus; Humans; Prognosis
PubMed: 33993305
DOI: 10.1093/neuonc/noab107 -
Clinical Lymphoma, Myeloma & Leukemia Jan 2021Histiocytic disorders are an exceptionally rare group of diseases with diverse manifestations and a paucity of approved treatments, thereby leading to various challenges... (Review)
Review
Highlights of the Management of Adult Histiocytic Disorders: Langerhans Cell Histiocytosis, Erdheim-Chester Disease, Rosai-Dorfman Disease, and Hemophagocytic Lymphohistiocytosis.
Histiocytic disorders are an exceptionally rare group of diseases with diverse manifestations and a paucity of approved treatments, thereby leading to various challenges in their diagnosis and management. With the discovery of novel molecular targets and the incorporation of targeted agents in the management of various adult histiocytic disorders, their management has become increasingly complex. In an attempt to improve the understanding of the clinical features and management of common adult histiocytic disorders (Langerhans cell histiocytosis, Erdheim-Chester disease, Rosai-Dorfman disease, and hemophagocytic lymphohistiocytosis), we created this document based on existing literature and expert opinion.
Topics: Adult; Drug Therapy, Combination; Erdheim-Chester Disease; Histiocytosis, Langerhans-Cell; Histiocytosis, Sinus; Humans; Lymphohistiocytosis, Hemophagocytic; Treatment Outcome
PubMed: 32943371
DOI: 10.1016/j.clml.2020.08.007 -
Singapore Medical Journal Oct 2010Sinus histiocytosis with massive lymphadenopathy, also known as Rosai-Dorfman disease, is a rare histiocytic proliferative disorder of unknown aetiology. The classic...
Sinus histiocytosis with massive lymphadenopathy, also known as Rosai-Dorfman disease, is a rare histiocytic proliferative disorder of unknown aetiology. The classic presentation of Rosai-Dorfman disease is massive, bilateral, painless cervical lymphadenopathy. Extranodal disease is also common, often with a particular predilection for the head and neck regions. We report a rare case of Rosai-Dorfman disease with nodal and multiple extranodal manifestations in a 13-year-old girl. The patient had cervical and mediastinal lymphadenopathy, multiple soft tissue swellings of the scalp, bilateral proptosis and goitre due to thyroid gland involvement. She responded to steroids, with remission of the swellings and symptoms. This case is being reported for its rarity, multiple extranodal manifestations and thyroid gland involvement. Thyroid gland involvement in Rosai-Dorfman disease has rarely been reported in the literature.
Topics: Adolescent; Biopsy, Fine-Needle; Female; Goiter; Histiocytosis, Sinus; Humans; Lymphatic Diseases; Lymphocytes; Radiography, Thoracic; Thyroid Gland
PubMed: 21103807
DOI: No ID Found -
Journal of the European Academy of... Aug 2020Reticulohistiocytoses (RH) are rare and clinically heterogeneous histiocytic disorders of dermatological interest. Three clinical entities with superimposable... (Review)
Review
Reticulohistiocytoses (RH) are rare and clinically heterogeneous histiocytic disorders of dermatological interest. Three clinical entities with superimposable histopathological features are currently considered, namely solitary reticulohistiocytoma, diffuse/generalized reticulohistiocytosis and multicentric reticulohistiocytosis. Although in the last decade, RH studies have only minimally progressed, histiocytosis research has advanced considerably: the prognostic and therapeutic importance of the clinical subclassification of histiocytosis patients as well as of the detection of genetic alterations in the genes of the ERK pathway has been highlighted. According to these insights, we previously reported the presence of molecular alteration RH and described a subset of patients with disseminated multisystem involvement lacking arthritis. In the present review, we aim to update and revise the knowledge regarding RH. We first reviewed their histopathological, immunophenotypical and ultrastructural features, discussed their histopathological differential diagnosis with other conditions characterized by infiltrates made of oncocytic or epithelioid cells (with special regard to Destombes-Rosai-Dorfman disease) and finally summarized the molecular landscape of RH. We therefore tried to adjust the clinical subclassification of Langerhans cell histiocytosis to the clinical phenotypes of RH, outlining five clinically different groups of patients. Finally, we reconsidered the clinical workflow to the evaluation of RH patients, in light of the 5 different clinical groups and discussed the different therapeutic approaches and the possible role of target inhibitors.
Topics: Diagnosis, Differential; Epithelioid Cells; Histiocytosis, Langerhans-Cell; Histiocytosis, Non-Langerhans-Cell; Histiocytosis, Sinus; Humans
PubMed: 31955466
DOI: 10.1111/jdv.16214 -
Arquivos de Neuro-psiquiatria Jul 2014Histiocytosis is a systemic disease that usually affects the central nervous system. The aim of this study is to discuss the neuroimaging characteristics of Langerhans... (Review)
Review
OBJECTIVE
Histiocytosis is a systemic disease that usually affects the central nervous system. The aim of this study is to discuss the neuroimaging characteristics of Langerhans cell histiocytosis (LCH), the most common of these diseases; and the non-Langerhans cells histiocytosis (NLCH), which includes entities such as hemophagocytic syndrome, Erdheim-Chester and Rosai-Dorfman diseases.
METHOD
Literature review and illustrative cases with pathologic confirmation.
RESULTS
In LCH, the most common findings are 1) osseous lesions in the craniofacial bones and/or skull base; 2) intracranial, extra-axial changes; 3) intra-axial parenchymal changes (white and gray matter); 4) atrophy. Among the NLCH, diagnosis usually requires correlation with clinical and laboratory criteria. The spectrum of presentation includes intraparenchymal involvement, meningeal lesions, orbits and paranasal sinus involvement.
CONCLUSION
It is important the recognition of the most common imaging patterns, in order to include LCH and NLCH in the differential diagnosis, whenever pertinent.
Topics: Diagnosis, Differential; Female; Histiocytosis, Langerhans-Cell; Histiocytosis, Non-Langerhans-Cell; Humans; Magnetic Resonance Imaging; Male; Neuroimaging
PubMed: 25054989
DOI: 10.1590/0004-282x20140063 -
Blood Advances Aug 2023Erdheim-Chester disease (ECD) and Rosai-Dorfman disease (RDD) are rare non-Langerhans cell histiocytoses (non-LCHs), for which therapeutic options are limited. MAPK...
Erdheim-Chester disease (ECD) and Rosai-Dorfman disease (RDD) are rare non-Langerhans cell histiocytoses (non-LCHs), for which therapeutic options are limited. MAPK pathway activation through BRAFV600E mutation or other genomic alterations is a histiocytosis hallmark and correlates with a favorable response to BRAF inhibitors and the MEK inhibitor cobimetinib. However, there has been no systematic evaluation of alternative MEK inhibitors. To assess the efficacy and safety of the MEK inhibitor trametinib, we retrospectively analyzed the outcomes of 26 adult patients (17 with ECD, 5 with ECD/RDD, 3 with RDD, and 1 with ECD/LCH) treated with orally administered trametinib at 4 major US care centers. The most common treatment-related toxicity was rash (27% of patients). In most patients, the disease was effectively managed at low doses (0.5-1.0 mg trametinib daily). The response rate of the 17 evaluable patients was 71% (73% [8/11] without a detectable BRAFV600E achieving response). At a median follow-up of 23 months, treatment effects were durable, with a median time-to-treatment failure of 37 months, whereas the median progression-free and overall survival were not reached (at 3 years, 90.1% of patients were alive). Most patients harbored mutations in BRAF (either classic BRAFV600E or other BRAF alterations) or alterations in other genes involved in the MAPK pathway, eg, MAP2K, NF1, GNAS, or RAS. Most patients required lower than standard doses of trametinib but were responsive to lower doses. Our data suggest that the MEK inhibitor trametinib is an effective treatment for ECD and RDD, including those without the BRAFV600E mutation.
Topics: Adult; Humans; Proto-Oncogene Proteins B-raf; Retrospective Studies; Erdheim-Chester Disease; Histiocytosis, Sinus; Protein Kinase Inhibitors; Mitogen-Activated Protein Kinase Kinases
PubMed: 36857436
DOI: 10.1182/bloodadvances.2022009013