Waldenström's macroglobulinemia pathophysiology: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
No edit summary
No edit summary
Line 1: Line 1:
The clinical manifestations of Waldenström Macroglobulinemia depend on two different factors.
===Pathogenesis===
*Hyperviscosity syndrome & vascular complications due to secretion of Monoclonal igM.  
Waldenström Macroglobulinemia is uncontrolled clonal proliferation of terminally differentiated B lymphocytes, which are normally involved in humoral immunity.<ref name="HP">Waldenström's macroglobulinemia. Wikipedia (2015)https://en.wikipedia.org/wiki/Waldenström%27s_macroglobulinemia#Pathophysiology Accessed on November 6, 2015</ref>
:*IgM paraprotein occasionally has:
In Waldenström Macroglobulinemia, peripheral B lymphocyte are stimulated to undergo somatic hypermutation of the immunoglobulin heavy chain gene in the germinal center, without class switching.  
:*Rheumatoid factor activity,  
:*antimyelin activity that can contribute to peripheral neuropathy, and
:*Immunologically related lupus anticoagulant activity.


*Infiltration of bone marrow, spleen and lymph nodes by neoplastic lymphoplasmacytic cells.  
===Genetics===
:*Less commonly, infiltration of liver, lungs, GI tract, kidneys, skin, eyes, and central nervous system (CNS) can also occur.
*Development of Waldenström Macroglobulinemia is the result of multiple gene mutations.<ref name="HP">Epidemiology, pathogenesis, clinical manifestations and diagnosis of Waldenström macroglobulinemia. UpToDate (2015)http://www.uptodate.com/contents/epidemiology-pathogenesis-clinical-manifestations-and-diagnosis-of-waldenstrom-macroglobulinemia?source=see_link Accessed on November 9, 2015</ref>
*Genes involved in pathogenesis of Waldenström Macroglobulinemia are:
:*MYD88 L265P in chromosome 3p22.2
:*CXCR4
::*MYD88: has a role in toll-like receptor and interleukin-1 receptor signaling causing activation of transcription factors of the NF-kB family. Thus, activating point mutation of MYD88 augments growth and survival of both normal and neoplastic B cells by preventing apoptosis. MYD88 also has role in BTK signaling which also helps in B cell growth and survival. Point mutation of MYD88 leads to leucine (L) to proline (P) substitution in codon 265 (L265P) of MYD88 and produces constantly overactive protein causing proliferation of malignant cells that should normally undergo apoptosis.<ref name="HP">Epidemiology, pathogenesis, clinical manifestations and diagnosis of Waldenström macroglobulinemia. UpToDate (2015)http://www.uptodate.com/contents/epidemiology-pathogenesis-clinical-manifestations-and-diagnosis-of-waldenstrom-macroglobulinemia?source=see_link Accessed on November 9, 2015</ref><ref name="Genetics">Waldenström macroglobulinemia. Genetics Home Reference (2015)http://ghr.nlm.nih.gov/condition/waldenstrom-macroglobulinemia Accessed on November 9, 2015</ref>
::* Patients with Waldenström Macroglobulinemia with co-existing mutation of MYD88 & CXCR4 are more likely to have hyperviscosity syndrome and bone marrow involvement.


==References==
:*40-60 percent of patients with Waldenström Macroglobulinemia are associated with deletions of 6q21.<ref name="HP">Epidemiology, pathogenesis, clinical manifestations and diagnosis of Waldenström macroglobulinemia. UpToDate (2015)http://www.uptodate.com/contents/epidemiology-pathogenesis-clinical-manifestations-and-diagnosis-of-waldenstrom-macroglobulinemia?source=see_link Accessed on November 9, 2015</ref>


===Associated Conditions===
===Pathology===
====Gross pathology====
====Microscopic pathology====
====Immunohistochemistry====
Malignant cells in Waldenström Macroglobulinemia express IgM surface immunoglobulin and lack IgD.<ref name="HP">Epidemiology, pathogenesis, clinical manifestations and diagnosis of Waldenström macroglobulinemia. UpToDate (2015)http://www.uptodate.com/contents/epidemiology-pathogenesis-clinical-manifestations-and-diagnosis-of-waldenstrom-macroglobulinemia?source=see_link Accessed on November 9, 2015</ref>
Lymphocytic component: expresses pan B cell antigens
Plasma cell component: expresses CD138
Majority of malignant cells express:
*Adhesion molecules including:
:*L-selectin
:*ICAM-1
:*CD44
:*CD11c
*Lymphocyte function associated antigen 1 (LFA-1)
References:
{{Reflist}}
{{Reflist}}

Revision as of 19:51, 9 November 2015

Pathogenesis

Waldenström Macroglobulinemia is uncontrolled clonal proliferation of terminally differentiated B lymphocytes, which are normally involved in humoral immunity.[1] In Waldenström Macroglobulinemia, peripheral B lymphocyte are stimulated to undergo somatic hypermutation of the immunoglobulin heavy chain gene in the germinal center, without class switching.

Genetics

  • Development of Waldenström Macroglobulinemia is the result of multiple gene mutations.[1]
  • Genes involved in pathogenesis of Waldenström Macroglobulinemia are:
  • MYD88 L265P in chromosome 3p22.2
  • CXCR4
  • MYD88: has a role in toll-like receptor and interleukin-1 receptor signaling causing activation of transcription factors of the NF-kB family. Thus, activating point mutation of MYD88 augments growth and survival of both normal and neoplastic B cells by preventing apoptosis. MYD88 also has role in BTK signaling which also helps in B cell growth and survival. Point mutation of MYD88 leads to leucine (L) to proline (P) substitution in codon 265 (L265P) of MYD88 and produces constantly overactive protein causing proliferation of malignant cells that should normally undergo apoptosis.[1][2]
  • Patients with Waldenström Macroglobulinemia with co-existing mutation of MYD88 & CXCR4 are more likely to have hyperviscosity syndrome and bone marrow involvement.
  • 40-60 percent of patients with Waldenström Macroglobulinemia are associated with deletions of 6q21.[1]


Associated Conditions

Pathology

Gross pathology

Microscopic pathology

Immunohistochemistry

Malignant cells in Waldenström Macroglobulinemia express IgM surface immunoglobulin and lack IgD.[1]

Lymphocytic component: expresses pan B cell antigens

Plasma cell component: expresses CD138

Majority of malignant cells express:

  • Adhesion molecules including:
  • L-selectin
  • ICAM-1
  • CD44
  • CD11c
  • Lymphocyte function associated antigen 1 (LFA-1)

References:

  1. ↑ 1.0 1.1 1.2 1.3 1.4 Waldenström's macroglobulinemia. Wikipedia (2015)https://en.wikipedia.org/wiki/Waldenström%27s_macroglobulinemia#Pathophysiology Accessed on November 6, 2015
  2. ↑ Waldenström macroglobulinemia. Genetics Home Reference (2015)http://ghr.nlm.nih.gov/condition/waldenstrom-macroglobulinemia Accessed on November 9, 2015
Retrieved from "https://www.wikidoc.org/index.php?title=Waldenström%27s_macroglobulinemia_pathophysiology&oldid=1184958"