Multiple myeloma pathophysiology: Difference between revisions
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==Pathophysiology== | ==Pathophysiology== | ||
* Multiple myeloma develops in post-germinal center [[B lymphocytes]] | * Multiple myeloma develops in post-germinal center [[B lymphocytes]]. | ||
* Proliferation of a [[plasma cell]] clone and genomic instability leads to further [[mutations]] and [[translocations]] | * Proliferation of a [[plasma cell]] clone and genomic instability leads to further [[mutations]] and [[translocations]]. | ||
* Production of [[cytokine]]s (especially [[Interleukin 6|IL-6]]) by the plasma cells causes much of their localised damage, such as [[osteoporosis]], and creates a microenvironment in which the [[malignant]] cells thrive. [[Angiogenesis]] (the attraction of new blood vessels) is increased | * Production of [[cytokine]]s (especially [[Interleukin 6|IL-6]]) by the plasma cells causes much of their localised damage, such as [[osteoporosis]], and creates a microenvironment in which the [[malignant]] cells thrive. [[Angiogenesis]] (the attraction of new blood vessels) is increased. | ||
* The produced antibodies are deposited in various organs, leading to renal failure, [[polyneuropathy]] and various other multiple myeloma associated symptoms | * The produced antibodies are deposited in various organs, leading to renal failure, [[polyneuropathy]] and various other multiple myeloma associated symptoms. | ||
==Genetics== | ==Genetics== | ||
*A genetic mutation results in dysregulation of the [[oncogene]] which is thought to be an important initiating event in the pathogenesis of multiple myeloma | *A genetic mutation results in dysregulation of the [[oncogene]] which is thought to be an important initiating event in the pathogenesis of multiple myeloma. | ||
*A [[chromosomal translocation]] between the immunoglobulin heavy chain gene (on the fourteenth [[chromosome]], locus 14q32) and an [[oncogene]] (often 11q13, 4p16.3, 6p21, 16q23 and 20q11<ref name="Kyle">Kyle RA, Rajkumar SV. ''Multiple myeloma.'' [[N Engl J Med]] 2004;351:1860-73. PMID 15509819.</ref>) is frequently observed in patients with multiple myeloma | *A [[chromosomal translocation]] between the immunoglobulin heavy chain gene (on the fourteenth [[chromosome]], locus 14q32) and an [[oncogene]] (often 11q13, 4p16.3, 6p21, 16q23 and 20q11<ref name="Kyle">Kyle RA, Rajkumar SV. ''Multiple myeloma.'' [[N Engl J Med]] 2004;351:1860-73. PMID 15509819.</ref>) is frequently observed in patients with multiple myeloma. | ||
*The chromosome 14 abnormality is observed in about 50% of all cases of myeloma. Deletion of (parts of) the thirteenth chromosome is also observed in about 50% of cases | *The chromosome 14 abnormality is observed in about 50% of all cases of myeloma. Deletion of (parts of) the thirteenth chromosome is also observed in about 50% of cases. | ||
==Gross Pathology== | ==Gross Pathology== | ||
Revision as of 14:09, 17 September 2015
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Multiple myeloma is a disorder affecting post germinal center B lymphocytes. A chromosomal translocation between the immunoglobulin heavy chain gene and one of many oncogenes leads to dysregulated multiplication of plasma cells. This leads to a localized damage, resulting in punched out bony lesions as well as various organ damage among other symptoms.
Pathophysiology
- Multiple myeloma develops in post-germinal center B lymphocytes.
- Proliferation of a plasma cell clone and genomic instability leads to further mutations and translocations.
- Production of cytokines (especially IL-6) by the plasma cells causes much of their localised damage, such as osteoporosis, and creates a microenvironment in which the malignant cells thrive. Angiogenesis (the attraction of new blood vessels) is increased.
- The produced antibodies are deposited in various organs, leading to renal failure, polyneuropathy and various other multiple myeloma associated symptoms.
Genetics
- A genetic mutation results in dysregulation of the oncogene which is thought to be an important initiating event in the pathogenesis of multiple myeloma.
- A chromosomal translocation between the immunoglobulin heavy chain gene (on the fourteenth chromosome, locus 14q32) and an oncogene (often 11q13, 4p16.3, 6p21, 16q23 and 20q11[1]) is frequently observed in patients with multiple myeloma.
- The chromosome 14 abnormality is observed in about 50% of all cases of myeloma. Deletion of (parts of) the thirteenth chromosome is also observed in about 50% of cases.
Gross Pathology
-
Vertebras in multiple myeloma
(Image courtesy of Melih Aktan M.D.) -
Calvarium in multiple myeloma.
(Image courtesy of Melih Aktan M.D.)
Microscopic Pathology
-
![Multiple Myeloma slide showing plasma cells with large nucleus and scant cytoplasm [2]](/images/a/a5/Multiple_Myeloma.jpg)
Multiple Myeloma slide showing plasma cells with large nucleus and scant cytoplasm [2] -
Bone marrow aspiration in multiple myeloma.
(Image courtesy of Melih Aktan M.D.) -
Bone marrow biopsy in multiple myeloma.
(Image courtesy of Melih Aktan M.D.) -
Bone marrow in multiple myeloma.
(Image courtesy of Melih Aktan M.D.) -
Bone marrow in multiple myeloma.
(Image courtesy of Melih Aktan M.D.)
![Multiple Myeloma slide showing plasma cells with large nucleus and scant cytoplasm [2]](/index.php/File:Multiple_Myeloma.jpg)
References
- ↑ Kyle RA, Rajkumar SV. Multiple myeloma. N Engl J Med 2004;351:1860-73. PMID 15509819.
- ↑ http://picasaweb.google.com/mcmumbi/USMLEIIImages