Sandbox: Langerhans: Difference between revisions

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:* CNS  
:* CNS  
:* Oral cavity   
:* Oral cavity   
* The malignant organ involvement is variable among patients with Langerhans cell histiocytosis. The disease process may range from an isolated cutaneous or bone involvement to a life-threatening multi-system condition.  
* The malignant organ involvement is variable among patients with Langerhans cell histiocytosis. The disease process may range from an isolated cutaneous or bone involvement to a life-threatening multi-system condition.
accumulation of monocytes, macro-phages, and dendritic cells in the affected tissues.
* The exact pathogenesis of Langerhans cell histiocytosis is not fully understood. It is thought that Langerhans cell histiocytosis is the result of either a true neoplastic process or a reactive immune condition.
* Facts consistent with the neoplastic process hypothesis include the following:
:* The infiltration of organs by monoclonal population of pathologic cells
:* The presence of specific recurrent cytogenetic and genomic abnormalities
:* The successful treatment of a subset of disseminated Langerhans cell histiocytosis using chemotherapeutic regimens
* Facts consistent with the reactive immune condition hypothesis include the following:
:* The evidence of spontaneous remissions that may occur among certain cases of Langerhans cell histiocytosis
:* The extensive secretion of multiple cytokines by dendritic cells and bystander-cells (a phenomenon known as cytokine storm)
:* The favorable prognosis and relatively good survival rate among patients with no organ dysfunction
* The excessive Langerhans cells clonal proliferation will initiate a non-specific inflammatory response, which will lead to the accumulation of various immune system cells such as:
:* Eosinophils
:* Macrophages
:* Lymphocytes
:* Multinucleated giant cells
* Langerhans cell histiocytosis may result in bone marrow failure due to malignant cell infiltration of the bone marrow. This can manifest as:
* Langerhans cell histiocytosis may result in bone marrow failure due to malignant cell infiltration of the bone marrow. This can manifest as:
:* Anemia  
:* Anemia  
Line 19: Line 32:
:* Recurrent Infections
:* Recurrent Infections
* The infiltration of the hypothalamic pituitary axis by the malignant Langerhans cells will lead to both anterior and posterior pituitary hormones deficiencies.
* The infiltration of the hypothalamic pituitary axis by the malignant Langerhans cells will lead to both anterior and posterior pituitary hormones deficiencies.
* The excessive Langerhans cells clonal proliferation will initiate a non-specific inflammatory response, which will lead to the accumulation of various immune system cells such as:
 
:* Eosinophils
:* Macrophages
:* Lymphocytes
:* Multinucleated giant cells
==Genetics==
==Genetics==
==Associated Conditions==
==Associated Conditions==
==Gross Pathology==  
==Gross Pathology==  
==Microscopic Pathology==
==Microscopic Pathology==
There are ongoing investigations to determine whether Langerhans cell histiocytosis is a reactive (non-cancerous) or neoplastic (cancerous) process.
Arguments supporting the reactive nature of Langerhans cell histiocytosis include the occurrence of spontaneous remissions, the extensive secretion of multiple cytokines by dendritic cells and bystander-cells (a phenomenon known as cytokine storm) in the lesional tissue, favorable prognosis, and relatively good survival rate in patients without organ dysfunction.[14][15]
On the other hand, the infiltration of organs by monoclonal population of pathologic cells, and the successful treatment of subset of disseminated disease using chemotherapeutic regimens are all consistent with a neoplastic process.[16][17][18]
In addition, a demonstration, using X chromosome–linked DNA probes, of LCH as a monoclonal proliferation provided additional support for the neoplastic origin of this disease.[19]
While clonality is an important attribute of cancer, its presence does not prove that a proliferative process is neoplastic.
Recurrent cytogenetic or genomic abnormalities would also be required to demonstrate convincingly that LCH is a malignancy.
Activating mutation of a protooncogen in the Raf family, the BRAF gene, was detected in 35 of 61 (57%) LCH biopsy samples with mutations being more common in patients younger than 10 years (76%) than in patients aged 10 years and older (44%).[20] This study documented the first recurrent mutation in LCH samples. Two independent studies have confirmed this finding.[21][22] Presence of this activating mutation could support the notion to characterize LCH as myeloproliferative disorder.
Langerhans cell histiocytosis (LCH) is a rare disease involving clonal proliferation of Langerhans cells, abnormal cells deriving from bone marrow and capable of migrating from skin to lymph nodes. Clinically, its manifestations range from isolated bone lesions to multisystem disease. LCH is part of a group of clinical syndromes called histiocytoses, which are characterized by an abnormal proliferation of histiocytes (an archaic term for activated dendritic cells and macrophages). These diseases are related to other forms of abnormal proliferation of white blood cells, such as leukemias and lymphomas.
The disease spectrum results from clonal accumulation and proliferation of cells resembling the epidermal dendritic cells called Langerhans cells, sometimes called Dendritic Cell Histiocytosis. These cells in combination with lymphocytes, eosinophils, and normal histiocytes form typical LCH lesions that can be found in almost any organ.[2] A similar set of diseases has been described in canine histiocytic diseases.

Revision as of 16:33, 2 February 2016


Overview

Pathogenesis

  • Langerhans cell histiocytosis arises from epidermal dendritic cells, which are normally involved in the process of antigen presentation to lymphocytic cells.
  • Langerhans cells originally arise from the bone marrow, then the cells migrate to other organs such as:
  • Skin
  • Lymph nodes
  • Lungs
  • Hypothalamic pituitary axis
  • Gastrointestinal tract
  • CNS
  • Oral cavity
  • The malignant organ involvement is variable among patients with Langerhans cell histiocytosis. The disease process may range from an isolated cutaneous or bone involvement to a life-threatening multi-system condition.
  • The exact pathogenesis of Langerhans cell histiocytosis is not fully understood. It is thought that Langerhans cell histiocytosis is the result of either a true neoplastic process or a reactive immune condition.
  • Facts consistent with the neoplastic process hypothesis include the following:
  • The infiltration of organs by monoclonal population of pathologic cells
  • The presence of specific recurrent cytogenetic and genomic abnormalities
  • The successful treatment of a subset of disseminated Langerhans cell histiocytosis using chemotherapeutic regimens
  • Facts consistent with the reactive immune condition hypothesis include the following:
  • The evidence of spontaneous remissions that may occur among certain cases of Langerhans cell histiocytosis
  • The extensive secretion of multiple cytokines by dendritic cells and bystander-cells (a phenomenon known as cytokine storm)
  • The favorable prognosis and relatively good survival rate among patients with no organ dysfunction
  • The excessive Langerhans cells clonal proliferation will initiate a non-specific inflammatory response, which will lead to the accumulation of various immune system cells such as:
  • Eosinophils
  • Macrophages
  • Lymphocytes
  • Multinucleated giant cells
  • Langerhans cell histiocytosis may result in bone marrow failure due to malignant cell infiltration of the bone marrow. This can manifest as:
  • Anemia
  • Recurrent bleeding
  • Recurrent Infections
  • The infiltration of the hypothalamic pituitary axis by the malignant Langerhans cells will lead to both anterior and posterior pituitary hormones deficiencies.

Genetics

Associated Conditions

Gross Pathology

Microscopic Pathology

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