Multiple myeloma pathophysiology: Difference between revisions
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==Overview== | ==Overview== | ||
Multiple myeloma arises from post-germinal center [[B lymphocytes]], that are normally involved in production of human immunoglobulins.<ref>Multiple myeloma. Radiopaedia (2015)http://radiopaedia.org/articles/multiple-myeloma-1 Accessed on September, 20th 2015</ref><ref>Multiple myeloma. Wikipedia (2015)https://en.wikipedia.org/wiki/Multiple_myeloma#Pathophysiology</ref><ref>Multiple myeloma. Medlineplus (2015)https://www.nlm.nih.gov/medlineplus/multiplemyeloma.html | Multiple myeloma arises from post-germinal center [[B lymphocytes]], that are normally involved in production of human immunoglobulins.<ref name="radio">Multiple myeloma. Radiopaedia (2015)http://radiopaedia.org/articles/multiple-myeloma-1 Accessed on September, 20th 2015</ref><ref name="wiki">Multiple myeloma. Wikipedia (2015)https://en.wikipedia.org/wiki/Multiple_myeloma#Pathophysiology Accessed on September, 20th 2015</ref><ref name="Med">Multiple myeloma. Medlineplus (2015)https://www.nlm.nih.gov/medlineplus/multiplemyeloma.html Accessed on September, 20th 2015</ref name="national"><ref>Multiple myeloma. National cancer institute (2015) Accessed on September, 20th 2015</ref> Development of multiple myeloma is the result of multiple genetic [[translocation]]s between the [[Heavy-chain immunoglobulin|immunoglobulin heavy chain]] gene and [[oncogenes]] which lead to dysregulated multiplication of [[plasma cells]].<ref name="wiki">Multiple myeloma. Wikipedia (2015)https://en.wikipedia.org/wiki/Multiple_myeloma#Pathophysiology Accessed on September, 20th 2015</ref><ref name="Med">Multiple myeloma. Medlineplus (2015)https://www.nlm.nih.gov/medlineplus/multiplemyeloma.html Accessed on September, 20th 2015</ref> On microscopic histopathological analysis, abundant [[eosinophilic]] [[cytoplasm]], eccentrically placed nucleus, and russell bodies are characteristic findings of multiple myeloma.<ref name="patho">Multiple myeloma. Librepathology (2015)http://www.wikidoc.org/index.php?title=Multiple_myeloma_pathophysiology&action=edit§ion=1 Accessed on September, 20th 2015</ref> | ||
abundant [[eosinophilic]] [[cytoplasm]], eccentrically placed nucleus, and russell bodies are characteristic findings of multiple myeloma.<ref>Multiple myeloma. Librepathology (2015)http://www.wikidoc.org/index.php?title=Multiple_myeloma_pathophysiology&action=edit§ion=1</ref> | |||
==Pathogenesis== | ==Pathogenesis== | ||
*Multiple myeloma arises from post-germinal center [[B lymphocytes]], that are normally involved in production of human [[immunoglobulins]].<ref>Multiple myeloma. Wikipedia (2015)https://en.wikipedia.org/wiki/Multiple_myeloma#Pathophysiology</ref><ref>Multiple myeloma. Medlineplus (2015)https://www.nlm.nih.gov/medlineplus/multiplemyeloma.html</ref><ref>What is multiple myeloma. Canadian Cancer Society (2015) http://www.cancer.ca/en/cancer-information/cancer-type/multiple-myeloma/multiple-myeloma/?region=mb Accessed on September, 20th 2015</ref> | *Multiple myeloma arises from post-germinal center [[B lymphocytes]], that are normally involved in production of human [[immunoglobulins]].<ref name="wiki">Multiple myeloma. Wikipedia (2015)https://en.wikipedia.org/wiki/Multiple_myeloma#Pathophysiology Accessed on September, 20th 2015</ref><ref name="Med">Multiple myeloma. Medlineplus (2015)https://www.nlm.nih.gov/medlineplus/multiplemyeloma.html Accessed on September, 20th 2015</ref><ref name="Canadian">What is multiple myeloma. Canadian Cancer Society (2015) http://www.cancer.ca/en/cancer-information/cancer-type/multiple-myeloma/multiple-myeloma/?region=mb Accessed on September, 20th 2015</ref> | ||
*Malignant plasma cell infiltrates haemopoietic sites such as the red bone marrow where they interfere with the production of normal blood cells.<ref>Multiple myeloma. Radiopaedia (2015)http://radiopaedia.org/articles/multiple-myeloma-1 Accessed on September, 20th 2015</ref> <ref>Multiple myeloma. Wikipedia (2015)https://en.wikipedia.org/wiki/Multiple_myeloma#Pathophysiology</ref><ref>Multiple myeloma. Medlineplus (2015)https://www.nlm.nih.gov/medlineplus/multiplemyeloma.html</ref><ref>What is multiple myeloma. Canadian Cancer Society (2015) http://www.cancer.ca/en/cancer-information/cancer-type/multiple-myeloma/multiple-myeloma/?region=mb Accessed on September, 20th 2015</ref> | *Malignant plasma cell infiltrates haemopoietic sites such as the red bone marrow where they interfere with the production of normal blood cells.<ref name="radio">Multiple myeloma. Radiopaedia (2015)http://radiopaedia.org/articles/multiple-myeloma-1 Accessed on September, 20th 2015</ref><ref name="wiki">Multiple myeloma. Wikipedia (2015)https://en.wikipedia.org/wiki/Multiple_myeloma#Pathophysiology Accessed on September, 20th 2015</ref><ref name="Med">Multiple myeloma. Medlineplus (2015)https://www.nlm.nih.gov/medlineplus/multiplemyeloma.html Accessed on September, 20th 2015</ref><ref name="Canadian">What is multiple myeloma. Canadian Cancer Society (2015) http://www.cancer.ca/en/cancer-information/cancer-type/multiple-myeloma/multiple-myeloma/?region=mb Accessed on September, 20th 2015</ref> | ||
*Distribution of multiple myeloma mirrors that of red bone marrow in older individuals, and thus multiple myeloma is mostly encountered in the axial skeleton and proximal appendicular skeleton such as:<ref>Multiple myeloma. Radiopaedia (2015)http://radiopaedia.org/articles/multiple-myeloma-1 Accessed on September, 20th 2015</ref> | *Distribution of multiple myeloma mirrors that of red bone marrow in older individuals, and thus multiple myeloma is mostly encountered in the axial skeleton and proximal appendicular skeleton such as:<ref name="radio">Multiple myeloma. Radiopaedia (2015)http://radiopaedia.org/articles/multiple-myeloma-1 Accessed on September, 20th 2015</ref> | ||
:#Vertebrae (most common) | :#Vertebrae (most common) | ||
:#Ribs | :#Ribs | ||
| Line 18: | Line 17: | ||
:#Long bones | :#Long bones | ||
:#Extra skeletal structures (extraosseous myeloma): rare | :#Extra skeletal structures (extraosseous myeloma): rare | ||
*Abnormal antibodies are produced in multiple myeloma and are deposited in various organs around the body leading to multiple complications such as [[nephropathy]], [[polyneuropathy]], and [[cardiomyopathy]].<ref>Multiple myeloma. Wikipedia (2015) https://en.wikipedia.org/wiki/Multiple_myeloma#Pathophysiology</ref><ref> | *Abnormal antibodies are produced in multiple myeloma and are deposited in various organs around the body leading to multiple complications such as [[nephropathy]], [[polyneuropathy]], and [[cardiomyopathy]].<ref name="wiki">Multiple myeloma. Wikipedia (2015)https://en.wikipedia.org/wiki/Multiple_myeloma#Pathophysiology Accessed on September, 20th 2015</ref></ref name="national"><ref>Multiple myeloma. National cancer institute (2015) Accessed on September, 20th 2015</ref> | ||
* Production of [[cytokine]]s (especially [[Interleukin 6|IL-6]]) by malignant plasma cells in multiple myeloma causes much of their localised damage, such as [[osteoporosis]]. The produced cytokines also increase angiogenesis and create a microenvironment in which the [[malignant]] plasma cells can thrive.<ref>Multiple myeloma. Wikipedia (2015) https://en.wikipedia.org/wiki/Multiple_myeloma#Pathophysiology</ref> <ref>What is multiple myeloma. Canadian Cancer Society (2015) http://www.cancer.ca/en/cancer-information/cancer-type/multiple-myeloma/multiple-myeloma/?region=mb Accessed on September, 20th 2015</ref> | * Production of [[cytokine]]s (especially [[Interleukin 6|IL-6]]) by malignant plasma cells in multiple myeloma causes much of their localised damage, such as [[osteoporosis]]. The produced cytokines also increase angiogenesis and create a microenvironment in which the [[malignant]] plasma cells can thrive.<ref name="wiki">Multiple myeloma. Wikipedia (2015)https://en.wikipedia.org/wiki/Multiple_myeloma#Pathophysiology Accessed on September, 20th 2015</ref><ref name="Canadian">What is multiple myeloma. Canadian Cancer Society (2015) http://www.cancer.ca/en/cancer-information/cancer-type/multiple-myeloma/multiple-myeloma/?region=mb Accessed on September, 20th 2015</ref> | ||
*Multiple myeloma may result in renal failure due to either glomerular deposition of [[amyloid]] or tubular damage from excretion of [[light chain]]s called [[Bence Jones protein]]s. This can manifest as [[Fanconi syndrome]] (type II [[renal tubular acidosis]]).<ref>Multiple myeloma. Wikipedia (2015) https://en.wikipedia.org/wiki/Multiple_myeloma#Pathophysiology</ref><ref>Multiple myeloma. Radiopaedia (2015)http://radiopaedia.org/articles/multiple-myeloma-1 Accessed on September, 20th 2015</ref><ref>What is multiple myeloma. Canadian Cancer Society (2015) http://www.cancer.ca/en/cancer-information/cancer-type/multiple-myeloma/multiple-myeloma/?region=mb Accessed on September, 20th 2015</ref> | *Multiple myeloma may result in renal failure due to either glomerular deposition of [[amyloid]] or tubular damage from excretion of [[light chain]]s called [[Bence Jones protein]]s. This can manifest as [[Fanconi syndrome]] (type II [[renal tubular acidosis]]).<ref name="wiki">Multiple myeloma. Wikipedia (2015)https://en.wikipedia.org/wiki/Multiple_myeloma#Pathophysiology Accessed on September, 20th 2015</ref><ref name="radio">Multiple myeloma. Radiopaedia (2015)http://radiopaedia.org/articles/multiple-myeloma-1 Accessed on September, 20th 2015</ref><ref name="Canadian">What is multiple myeloma. Canadian Cancer Society (2015) http://www.cancer.ca/en/cancer-information/cancer-type/multiple-myeloma/multiple-myeloma/?region=mb Accessed on September, 20th 2015</ref> | ||
*Immune deficiency occurs in multiple myeloma as the majority of the overproduced antibodies are ineffective monoclonal antibodies produced by malignant plasma cell.<ref>Multiple myeloma. Wikipedia (2015) https://en.wikipedia.org/wiki/Multiple_myeloma#Pathophysiology</ref> | *Immune deficiency occurs in multiple myeloma as the majority of the overproduced antibodies are ineffective monoclonal antibodies produced by malignant plasma cell.<ref name="wiki">Multiple myeloma. Wikipedia (2015)https://en.wikipedia.org/wiki/Multiple_myeloma#Pathophysiology Accessed on September, 20th 2015</ref> | ||
==Genetics== | ==Genetics== | ||
*Normally the immune system keeps the proliferation of B cells and the secretion of antibodies under tight control. When chromosomes and genes are damaged, often through rearrangement, this control is lost.<ref>Multiple myeloma. Wikipedia (2015)https://en.wikipedia.org/wiki/Multiple_myeloma#Pathophysiology</ref> | *Normally the immune system keeps the proliferation of B cells and the secretion of antibodies under tight control. When chromosomes and genes are damaged, often through rearrangement, this control is lost.<ref name="wiki">Multiple myeloma. Wikipedia (2015)https://en.wikipedia.org/wiki/Multiple_myeloma#Pathophysiology Accessed on September, 20th 2015</ref> | ||
*Often, a promoter gene moves (or translocates) to a chromosome where it stimulates overproduction of an antibody gene.<ref>Multiple myeloma. Wikipedia (2015)https://en.wikipedia.org/wiki/Multiple_myeloma#Pathophysiology</ref> | *Often, a promoter gene moves (or translocates) to a chromosome where it stimulates overproduction of an antibody gene.<ref name="wiki">Multiple myeloma. Wikipedia (2015)https://en.wikipedia.org/wiki/Multiple_myeloma#Pathophysiology Accessed on September, 20th 2015</ref> | ||
*This genetic mutation results in dysregulation of the [[oncogene]] which is thought to be an important initiating event in the pathogenesis of multiple myeloma. | *This genetic mutation results in dysregulation of the [[oncogene]] which is thought to be an important initiating event in the pathogenesis of multiple myeloma. | ||
*The genes involved in the pathogenesis of multiple myeloma include heavy chain gene (on the chromosome 14, locus 14q32), chromosome 13, and [[oncogenes]] (often 11q13, 4p16.3, 6p21, 16q23 and 20q11).<ref name="pmid15509819">{{cite journal| author=Kyle RA, Rajkumar SV| title=Multiple myeloma. | journal=N Engl J Med | year= 2004 | volume= 351 | issue= 18 | pages= 1860-73 | pmid=15509819 | doi=10.1056/NEJMra041875 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15509819 }} </ref> | *The genes involved in the pathogenesis of multiple myeloma include heavy chain gene (on the chromosome 14, locus 14q32), chromosome 13, and [[oncogenes]] (often 11q13, 4p16.3, 6p21, 16q23 and 20q11).<ref name="pmid15509819">{{cite journal| author=Kyle RA, Rajkumar SV| title=Multiple myeloma. | journal=N Engl J Med | year= 2004 | volume= 351 | issue= 18 | pages= 1860-73 | pmid=15509819 | doi=10.1056/NEJMra041875 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15509819 }} </ref> | ||
*A familial predisposition to myeloma exists. Hyperphosphorylation of the paratarg proteins, a tendency which is inherited in an autosomal dominant manner, appears to be a common mechanism in these families. This tendency is more common in African American patients with myeloma and may contribute to the higher rates of myeloma in this group.<ref>Multiple myeloma. Wikipedia (2015)https://en.wikipedia.org/wiki/Multiple_myeloma#Pathophysiology Accessed on September, 20th 2015</ref><ref name="pmid23926460">{{cite journal| author=Koura DT, Langston AA| title=Inherited predisposition to multiple myeloma. | journal=Ther Adv Hematol | year= 2013 | volume= 4 | issue= 4 | pages= 291-7 | pmid=23926460 | doi=10.1177/2040620713485375 | pmc=PMC3734900 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23926460 }} </ref> | *A familial predisposition to myeloma exists. Hyperphosphorylation of the paratarg proteins, a tendency which is inherited in an autosomal dominant manner, appears to be a common mechanism in these families. This tendency is more common in African American patients with myeloma and may contribute to the higher rates of myeloma in this group.<ref name="wiki">Multiple myeloma. Wikipedia (2015)https://en.wikipedia.org/wiki/Multiple_myeloma#Pathophysiology Accessed on September, 20th 2015</ref><ref name="pmid23926460">{{cite journal| author=Koura DT, Langston AA| title=Inherited predisposition to multiple myeloma. | journal=Ther Adv Hematol | year= 2013 | volume= 4 | issue= 4 | pages= 291-7 | pmid=23926460 | doi=10.1177/2040620713485375 | pmc=PMC3734900 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23926460 }} </ref> | ||
==Gross Pathology== | ==Gross Pathology== | ||
| Line 37: | Line 36: | ||
==Microscopic Pathology== | ==Microscopic Pathology== | ||
On microscopic histopathological analysis, multiple myeloma is characterized by the following:<ref>Multiple myeloma. Librepathology(2015)http:// | On microscopic histopathological analysis, multiple myeloma is characterized by the following:<ref name="patho">Multiple myeloma. Librepathology (2015)http://www.wikidoc.org/index.php?title=Multiple_myeloma_pathophysiology&action=edit§ion=1 Accessed on September, 20th 2015</ref> | ||
:*Abundant eosinophilic [[cytoplasm]]. | :*Abundant eosinophilic [[cytoplasm]]. | ||
:*Eccentrically placed [[nucleus]]. | :*Eccentrically placed [[nucleus]]. | ||
| Line 52: | Line 51: | ||
Image:Bone marrow in multiple myeloma 0001.jpg|Bone marrow in multiple myeloma. <br> (Image courtesy of Melih Aktan M.D.) | Image:Bone marrow in multiple myeloma 0001.jpg|Bone marrow in multiple myeloma. <br> (Image courtesy of Melih Aktan M.D.) | ||
Image:Bone marrow in multiple myeloma 0002.jpg|Bone marrow in multiple myeloma. <br> (Image courtesy of Melih Aktan M.D.) | Image:Bone marrow in multiple myeloma 0002.jpg|Bone marrow in multiple myeloma. <br> (Image courtesy of Melih Aktan M.D.) | ||
File:Multiple myeloma intermed mag.jpg|Multiple myeloma slide with intermediate magnification<ref> | File:Multiple myeloma intermed mag.jpg|Multiple myeloma slide with intermediate magnification<ref name="patho">Multiple myeloma. Librepathology (2015)http://www.wikidoc.org/index.php?title=Multiple_myeloma_pathophysiology&action=edit§ion=1 Accessed on September, 20th 2015</ref> | ||
File:Multiple myeloma.jpg|Multiple myeloma slide with high magnification<ref> | File:Multiple myeloma.jpg|Multiple myeloma slide with high magnification<ref name="patho">Multiple myeloma. Librepathology (2015)http://www.wikidoc.org/index.php?title=Multiple_myeloma_pathophysiology&action=edit§ion=1 Accessed on September, 20th 2015</ref> | ||
Russell bodies.jpg|Multiple myeloma slide with russell bodies<ref> | Russell bodies.jpg|Multiple myeloma slide with russell bodies<ref name="patho">Multiple myeloma. Librepathology (2015)http://www.wikidoc.org/index.php?title=Multiple_myeloma_pathophysiology&action=edit§ion=1 Accessed on September, 20th 2015</ref> | ||
</gallery> | </gallery> | ||
Revision as of 14:21, 23 September 2015
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Multiple myeloma Microchapters |
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Multiple myeloma pathophysiology On the Web |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2]
Overview
Multiple myeloma arises from post-germinal center B lymphocytes, that are normally involved in production of human immunoglobulins.[1][2] Development of multiple myeloma is the result of multiple genetic translocations between the immunoglobulin heavy chain gene and oncogenes which lead to dysregulated multiplication of plasma cells.[2][3] On microscopic histopathological analysis, abundant eosinophilic cytoplasm, eccentrically placed nucleus, and russell bodies are characteristic findings of multiple myeloma.[4]
Pathogenesis
- Multiple myeloma arises from post-germinal center B lymphocytes, that are normally involved in production of human immunoglobulins.[2][3][5]
- Malignant plasma cell infiltrates haemopoietic sites such as the red bone marrow where they interfere with the production of normal blood cells.[1][2][3][5]
- Distribution of multiple myeloma mirrors that of red bone marrow in older individuals, and thus multiple myeloma is mostly encountered in the axial skeleton and proximal appendicular skeleton such as:[1]
- Vertebrae (most common)
- Ribs
- Skull
- Shoulder girdle
- Pelvis
- Long bones
- Extra skeletal structures (extraosseous myeloma): rare
- Abnormal antibodies are produced in multiple myeloma and are deposited in various organs around the body leading to multiple complications such as nephropathy, polyneuropathy, and cardiomyopathy.[2]</ref name="national">[6]
- Production of cytokines (especially IL-6) by malignant plasma cells in multiple myeloma causes much of their localised damage, such as osteoporosis. The produced cytokines also increase angiogenesis and create a microenvironment in which the malignant plasma cells can thrive.[2][5]
- Multiple myeloma may result in renal failure due to either glomerular deposition of amyloid or tubular damage from excretion of light chains called Bence Jones proteins. This can manifest as Fanconi syndrome (type II renal tubular acidosis).[2][1][5]
- Immune deficiency occurs in multiple myeloma as the majority of the overproduced antibodies are ineffective monoclonal antibodies produced by malignant plasma cell.[2]
Genetics
- Normally the immune system keeps the proliferation of B cells and the secretion of antibodies under tight control. When chromosomes and genes are damaged, often through rearrangement, this control is lost.[2]
- Often, a promoter gene moves (or translocates) to a chromosome where it stimulates overproduction of an antibody gene.[2]
- This genetic mutation results in dysregulation of the oncogene which is thought to be an important initiating event in the pathogenesis of multiple myeloma.
- The genes involved in the pathogenesis of multiple myeloma include heavy chain gene (on the chromosome 14, locus 14q32), chromosome 13, and oncogenes (often 11q13, 4p16.3, 6p21, 16q23 and 20q11).[7]
- A familial predisposition to myeloma exists. Hyperphosphorylation of the paratarg proteins, a tendency which is inherited in an autosomal dominant manner, appears to be a common mechanism in these families. This tendency is more common in African American patients with myeloma and may contribute to the higher rates of myeloma in this group.[2][8]
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
On microscopic histopathological analysis, multiple myeloma is characterized by the following:[4]
- Abundant eosinophilic cytoplasm.
- Eccentrically placed nucleus.
- Clock face morphology of the nucleus due to chromatin clumps around the edges.
- Russell bodies which are eosinophilic, large (10-15 micrometres), homogenous immunoglobulin-containing inclusions.
- Dutcher bodies which are PAS stain +ve intranuclear crystalline rods.
- Shown below is a series of microscopic images seen in multiple myeloma:
-
![Multiple Myeloma slide showing plasma cells with large nucleus and scant cytoplasm [9]](/images/a/a5/Multiple_Myeloma.jpg)
Multiple Myeloma slide showing plasma cells with large nucleus and scant cytoplasm [9]
-
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 with intermediate magnification[4]](/images/4/40/Multiple_myeloma_intermed_mag.jpg)
Multiple myeloma slide with intermediate magnification[4]
-
![Multiple myeloma slide with high magnification[4]](/images/d/d5/Multiple_myeloma.jpg)
Multiple myeloma slide with high magnification[4]
-
![Multiple myeloma slide with russell bodies[4]](/images/a/ad/Russell_bodies.jpg)
Multiple myeloma slide with russell bodies[4]
![Multiple Myeloma slide showing plasma cells with large nucleus and scant cytoplasm [9]](/index.php/File:Multiple_Myeloma.jpg)
![Multiple myeloma slide with intermediate magnification[4]](/index.php/File:Multiple_myeloma_intermed_mag.jpg)
![Multiple myeloma slide with high magnification[4]](/index.php/File:Multiple_myeloma.jpg)
![Multiple myeloma slide with russell bodies[4]](/index.php/File:Russell_bodies.jpg)
References
- ↑ 1.0 1.1 1.2 1.3 Multiple myeloma. Radiopaedia (2015)http://radiopaedia.org/articles/multiple-myeloma-1 Accessed on September, 20th 2015
- ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 Multiple myeloma. Wikipedia (2015)https://en.wikipedia.org/wiki/Multiple_myeloma#Pathophysiology Accessed on September, 20th 2015
- ↑ 3.0 3.1 3.2 Multiple myeloma. Medlineplus (2015)https://www.nlm.nih.gov/medlineplus/multiplemyeloma.html Accessed on September, 20th 2015
- ↑ 4.0 4.1 4.2 4.3 4.4 Multiple myeloma. Librepathology (2015)http://www.wikidoc.org/index.php?title=Multiple_myeloma_pathophysiology&action=edit§ion=1 Accessed on September, 20th 2015
- ↑ 5.0 5.1 5.2 5.3 What is multiple myeloma. Canadian Cancer Society (2015) http://www.cancer.ca/en/cancer-information/cancer-type/multiple-myeloma/multiple-myeloma/?region=mb Accessed on September, 20th 2015
- ↑ Multiple myeloma. National cancer institute (2015) Accessed on September, 20th 2015
- ↑ Kyle RA, Rajkumar SV (2004). "Multiple myeloma". N Engl J Med. 351 (18): 1860–73. doi:10.1056/NEJMra041875. PMID 15509819.
- ↑ Koura DT, Langston AA (2013). "Inherited predisposition to multiple myeloma". Ther Adv Hematol. 4 (4): 291–7. doi:10.1177/2040620713485375. PMC 3734900. PMID 23926460.
- ↑ http://picasaweb.google.com/mcmumbi/USMLEIIImages