Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019621 (Langerhans cell histiocytosis)
 3,250 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Disseminated dermal tumors in a 71-year-old male represented the first clinical manifestation of a chronic myelomonocytic leukemia. The dermal infiltrate in one of the nodules consisted predominantly of closely packed pleomorphic Langerhans' cells (LC) with typical Birbeck granules and a strong reactivity for S-100 protein. The simultaneous presence of immature myeloid cells led to the suspicion of an underlying myeloproliferative disorder. The diagnosis of chronic myelomonocytic leukemia was subsequently confirmed by bone marrow histology and blood picture. Although some peritrabecular foci of histiocytic cells were detected in bone marrow, no LC could be identified by electron microscopy and histochemical methods. Tumorous aggregates of LC in myeloproliferative disorders have not been described in the literature. Histiocytosis X and related diseases could be definitely excluded in the present case. This case obviously suggests an interrelation between the myeloproliferative disease and the focal accumulation of LC in the dermis. In animal studies by Katz et al. LC have been shown to originate in the bone marrow, whereas the origin of LC in man is still a matter of discussion. The present case supports the hypothesis that LC in man are also of myeloid origin. The neoplastic blood monocytes could be the precursors of the dermal LC. This differentiation did not take place in the bone marrow but only in the dermis where LC occur under nonneoplastic conditions ("homing").
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PMID:Dermal Langerhans' cell tumor in chronic myelomonocytic leukemia. 316 10

The liver can be involved directly, by infiltration, and indirectly--by remote effects--in the histiocytoses of childhood. Langerhans cell disease, the most well recognized of these, infiltrates the liver directly but has a remarkable selectivity for the bile ducts. Early involvement is by Langerhans cell histiocytosis (LCH) infiltration leading to a sclerosing cholangitis and, eventually, biliary cirrhosis. Gamma glutamyl transpeptidase is a sensitive indicator of liver infiltration in a child with LCH. The indirect effects on the liver of LCH elsewhere in the body are mediated through an accompanying macrophage activation syndrome that is most likely responsible for hepatomegaly and hypoalbuminemia but without direct infiltration. These indirect effects are completely reversible. Juvenile xanthogranuloma/xanthoma disseminatum, a related dendritic cell disorder that can have systemic manifestations, has a strikingly different pattern, with a predominantly portal infiltrate spilling over into the adjacent lobule but sparing the biliary tree. The biology of the liver lesions is not clear but regression has been documented. Myeloproliferative disorders and myeloid leukemias can express CD1a and/or S100 protein, mimicking LCH but distinguished by their sinusoidal pattern. The primary macrophage histiocytoses such as the familial hemophagocytic syndromes can lead to severe liver damage. Although a portal lymphohistiocytic infiltrate is most characteristic, it is probably cytokine-mediated hepatocellular damage that can cause substantial functional impairment or even hepatic failure as a presenting feature. Liver involvement in other, more unusual histiocytic disorders, is also illustrated.
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PMID:Liver involvement in the histiocytic disorders of childhood. 1502 67

Congenital neutropenia predisposes to the development of haematopoetic malignancies. We present a 3,5-year child, diagnosed with congenital neutropenia at the age of I month. The diagnosis was based on peripheral blood and bone marrow aspirate analyses, performed after the treatment of multiple axillar abscesses. Recurrent infections were treated with broad-spectrum antibiotics and leukocyte colony stimulating factors. At the age of 19 months during routine check-up the child presented with gingival hypertrophy, fragility and bleeding. The histopathological analysis of gingival biopsy was consisted with the diagnosis of Langerhans cell histiocytosis. The child was treated according to LCH protocol for therapeutic group C. After 12 months of such chemotherapy, the follow-up histopathological analysis of gingival biopsy revealed the presence of Langerhans cells, which was the indication for chemotherapy prolongation (6 additional VP courses). Chemotherapy was completed after 6 additional courses and the disease remission was confirmed by histopathological analysis of gingival biopsy. Congenital neutropenia predisposes to myeloproliferative disorders, particularly to childhood myeloblastic leukemia. Based on the presented case report we would like to emphasize the possibility of other hematological syndromes development.
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PMID:[Langerhans cell histiocytosis in a child with congenital neutropenia]. 1530 29

Neither accurate incidence nor survival data for pediatric patients with hematological malignancies (HM) have been available in Japan to date. Incidence of patients under 20 years of age, who were diagnosed with HM from 2006 to 2010, and their two-year survival rate (2y-OS) were obtained from disease registry data maintained by the Japan Society of Pediatric Hematology (JSPH). A total of 5,287 cases of HM were identified during this period. Acute lymphoblastic leukemia (ALL, 46.6%) showed the highest incidence, followed by acute myeloid leukemia (AML, 16.7%), non-Hodgkin lymphoma (NHL, 11.9%), and histiocytosis (11.8%). ALL, AML and histiocytosis were common in younger patients aged 1-4, while NHL tended to occur more frequently in older patients aged 5-14. The 2y-OS of HM was 91.6%, with that for the most common B-precursor ALL rising to 96.2%. The 2y-OS for M3 AML, lymphoblastic-B-precursor or diffuse large B cell NHL, Hodgkin lymphoma, myeloproliferative disorders, and Langerhans cell histiocytosis was >95%. There were no gender differences in prognosis, while infants (88.0%) and adolescents aged 15-19 (90.6%) tended toward a poorer prognosis. This is the first report to describe incidence and survival times from the nationwide JSPH disease registry. More precise data with longer follow-up is needed.
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PMID:Incidence and survival rates of hematological malignancies in Japanese children and adolescents (2006-2010): based on registry data from the Japanese Society of Pediatric Hematology. 2370 13

Langerhans cell histiocytosis (LCH) is a rare histiocytic neoplasm characterized by clonal proliferation of Langerhans cells in multi-organ systems including skin, bone, pituitary gland, liver and spleen. Skin-limited involvement of LCH usually indicates an indolent clinical course; however, in rare cases, LCH is accompanied by other myeloproliferative disorders, which may determine the prognosis. An 82-year old Japanese man presented with numerous asymptomatic facial papules clinically simulating rhinophyma. Although findings of histopathology and general examination including bone marrow biopsy led to the diagnosis of cutaneous LCH, he died from chronic myelomonocytic leukemia, which emerged 10 months after the initial diagnosis of LCH. The previously reported cases of LCH concomitant with other hematological disorders are also summarized and described compared with the present case.
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PMID:Cutaneous Langerhans cell histiocytosis in elderly with chronic myelomonocytic leukemia. 2462 74

Langerhans cell histiocytosis (LCH) is a myeloproliferative disorder characterized by lesions composed of pathological CD207(+) dendritic cells with an inflammatory infiltrate. BRAFV600E remains the only recurrent mutation reported in LCH. In order to evaluate the spectrum of somatic mutations in LCH, whole exome sequencing was performed on matched LCH and normal tissue samples obtained from 41 patients. Lesions from other histiocytic disorders, juvenile xanthogranuloma, Erdheim-Chester disease, and Rosai-Dorfman disease were also evaluated. All of the lesions from histiocytic disorders were characterized by an extremely low overall rate of somatic mutations. Notably, 33% (7/21) of LCH cases with wild-type BRAF and none (0/20) with BRAFV600E harbored somatic mutations in MAP2K1 (6 in-frame deletions and 1 missense mutation) that induced extracellular signal-regulated kinase (ERK) phosphorylation in vitro. Single cases of somatic mutations of the mitogen-activated protein kinase (MAPK) pathway genes ARAF and ERBB3 were also detected. The ability of MAPK pathway inhibitors to suppress MAPK kinase and ERK phosphorylation in cell culture and primary tumor models was dependent on the specific LCH mutation. The findings of this study support a model in which ERK activation is a universal end point in LCH arising from pathological activation of upstream signaling proteins.
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PMID:Mutually exclusive recurrent somatic mutations in MAP2K1 and BRAF support a central role for ERK activation in LCH pathogenesis. 2537 60

The case of a 10-year old female child is described with a history of myeloproliferative disorder having skin, bone and visceral involvement. Bone marrow biopsy revealed histiocytosis X. During chemotherapy necrotizing fasciitis of the lower abdominal wall was diagnosed. Multiple microbiological cultures taken from the wound base revealed Pseudomonas aeruginosa infection. Surgical necrectomy and application of negative pressure wound therapy (NPWT) was started together with intensive care treatment for sepsis. As both wound and general condition of the patient improved, autologous split thickness skin grafting was carried out in two sitting under continuing NPWT application. The applied skin grafts showed excellent take, the perilesional subcutaneous recesses resolved and complete healing was achieved after 28 days of NPWT treatment. Proper dermatological diagnosis and immediate escharectomy complemented with application of NPWT can be life-saving in the treatment of necrotizing fasciitis.
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PMID:Excessive pediatric fasciitis necrotisans due to Pseudomonas aeruginosa infection successfully treated with negative pressure wound therapy. 2603 96

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis that most commonly affects adults and is driven by a high frequency of mutations in BRAF, MAP2K1, and kinases promoting MAPK signaling. Because of the relative rarity of ECD, key clinical features of the disease may not be well defined. Across a multi-institutional cohort of 189 patients with ECD and ECD overlapping with Langerhans cell histiocytosis (so-called mixed histiocytosis [MH]), we identified an unexpected and heretofore undescribed frequent occurrence of myeloid neoplasms among patients with ECD and MH. Some 10.1% (19/189) of patients with ECD have an overlapping myeloid neoplasm, most commonly occurring as a myeloproliferative neoplasm (MPN), myelodysplastic syndrome (MDS), or mixed MDS/MPN overlap syndrome (including chronic myelomonocytic leukemia). Consistent with this, molecular analysis frequently detected hallmark driver mutations of myeloid neoplasms (such as JAK2V617F and CALR mutations) coexisting with those characteristic of histiocytosis (such as BRAFV600E and MAP2K1 mutations). Histiocytosis patients diagnosed with a concomitant myeloid malignancy were significantly older at diagnosis and more commonly presented with MH than those without a myeloid malignancy. In some cases, the presence of distinct kinase mutations in the histiocytosis and myeloid neoplasm resulted in discordant and adverse responses to kinase-directed targeted therapies. These data highlight the clinical importance of evaluating adults with histiocytosis for a concomitant myeloid neoplasm.
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PMID:High prevalence of myeloid neoplasms in adults with non-Langerhans cell histiocytosis. 2867 34

Langerhans cell histiocytosis (LCH) may clinically manifest in a variety of ways due to its ability to involve nearly every organ system. LCH may present as a single bone lesion, skin rash, or as invasive disseminated disease and occurs typically in the pediatric and adolescent population, affecting both males and females. Independent of its clinical presentation and severity, LCH lesions share the common histology of CD1a+/CD207+ dendritic cells along with an inflammatory infiltrate, and, based upon improved scientific understanding, is now classified as a myeloproliferative neoplasm. We present a case report of an adult diagnosed with LCH of the pelvis.
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PMID:Langerhans cell histiocytosis of bone in an adult: A case report. 2990 62

Langerhans cell histiocytosis (LCH) is a myeloproliferative disorder that is characterized by the inflammatory lesions with pathogenic CD1a+CD207+ dendritic cells (DCs). BRAFV600E and other somatic activating MAPK gene mutations have been identified in differentiating bone marrow and blood myeloid cells, but the origin of the LCH lesion CD1a+CD207+ DCs and mechanisms of lesion formation remain incompletely defined. To identify candidate LCH CD1a+CD207+ DC precursor populations, gene-expression profiles of LCH lesion CD1a+CD207+ DCs were first compared with established gene signatures from human myeloid cell subpopulations. Interestingly, the CD1c+ myeloid DC (mDC) gene signature was most enriched in the LCH CD1a+CD207+ DC transcriptome. Additionally, the BRAFV600E allele was not only localized to CD1a+CD207- DCs and CD1a+CD207+ DCs, but it was also identified in CD1c+ mDCs in LCH lesions. Transcriptomes of CD1a+CD207- DCs were nearly indistinguishable from CD1a+CD207+ DCs (both CD1a+CD207low and CD1a+CD207high subpopulations). Transcription profiles of LCH lesion CD1a+CD207+ DCs and peripheral blood CD1c+ mDCs from healthy donors were compared to identify potential LCH DC-specific biomarkers: HLA-DQB2 expression was significantly increased in LCH lesion CD1a+CD207+ DCs compared with circulating CD1c+ mDCs from healthy donors. HLA-DQB2 antigen was identified on LCH lesion CD1a+CD207- DCs and CD1a+CD207+ DCs as well as on CD1c+(CD1a+CD207-) mDCs, but it was not identified in any other lesion myeloid subpopulations. HLA-DQB2 expression was specific to peripheral blood of patients with BRAFV600E+ peripheral blood mononuclear cells, and HLA-DQB2+CD1c+ blood cells were highly enriched for the BRAFV600E in these patients. These data support a model in which blood CD1c+HLA-DQB2+ mDCs with activated ERK migrate to lesion sites where they differentiate into pathogenic CD1a+CD207+ DCs.
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PMID:Circulating CD1c+ myeloid dendritic cells are potential precursors to LCH lesion CD1a+CD207+ cells. 3189 2


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