Sandbox:MGS: Difference between revisions

Revision as of 19:12, 9 November 2015

Pathogenesis

Waldenström Macroglobulinemia arises from B lymphocytes, which are normally involved in humoral immunity.^[1] The malignant cells in Waldenström Macroglobulinemia are the peripheral B lymphocyte stimulated to undergo somatic hypermutation of the immunoglobulin heavy chain gene, 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
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 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.

Associated Conditions

Pathology

Gross pathology

Microscopic pathology

Immunohistochemistry

Malignant cells in Waldenström Macroglobulinemia express IgM surface immunoglobulin and lack IgD. 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:

↑ ^1.0 ^1.1 ^1.2 Waldenström's macroglobulinemia. Wikipedia (2015)https://en.wikipedia.org/wiki/Waldenström%27s_macroglobulinemia#Pathophysiology Accessed on November 6, 2015
↑ Waldenström macroglobulinemia. Genetics Home Reference (2015)http://ghr.nlm.nih.gov/condition/waldenstrom-macroglobulinemia Accessed on November 9, 2015

[HP-1] 1.0 ^1.1 ^1.2 Waldenström's macroglobulinemia. Wikipedia (2015)https://en.wikipedia.org/wiki/Waldenström%27s_macroglobulinemia#Pathophysiology Accessed on November 6, 2015

[Genetics-2] Waldenström macroglobulinemia. Genetics Home Reference (2015)http://ghr.nlm.nih.gov/condition/waldenstrom-macroglobulinemia Accessed on November 9, 2015

[1]

[2]

@@ Line 1: / Line 1: @@
 ===Pathogenesis===
-Waldenström Macroglobulinemia arises from B lymphocytes, which are normally involved in humoral immunity.
+Waldenström Macroglobulinemia arises from 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>
 The malignant cells in Waldenström Macroglobulinemia are the peripheral B lymphocyte stimulated to undergo somatic hypermutation of the immunoglobulin heavy chain gene, without class switching.
-===Genetics====
-*Development of Waldenström Macroglobulinemia is the result of multiple gene mutations.
+===Genetics===
+*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
 :*CXCR4
-:*ARID1A.
+::*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 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>
-::*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. MYD88 also has role in BTK signaling which also helps in B cell growth and survival.
+::* Patients with Waldenström Macroglobulinemia with co-existing mutation of MYD88 & CXCR4 are more likely to have hyperviscosity syndrome and bone marrow involvement.
-:::* Patients with Waldenström Macroglobulinemia with co-existing mutation of MYD88 & CXCR4 are more likely to have hyperviscosity syndrome and bone marrow involvement.
@@ Line 22: / Line 19: @@
 ====Microscopic pathology====
 ====Immunohistochemistry====
-Malignant cells in Waldenström Macroglobulinemia express igM type of surface immunoglobulin.
+Malignant cells in Waldenström Macroglobulinemia express IgM surface immunoglobulin and lack IgD.
+Lymphocytic component: expresses pan B cell antigens
+Plasma cell component: expresses CD138
-LPL cells express high levels of surface immunoglobulin (sIg), usually of IgM type; surface IgD is usually lacking. Cases in which IgG and IgA are expressed have been described.
+Majority of malignant cells express:
+*Adhesion molecules including:
+:*L-selectin
+:*ICAM-1
+:*CD44
+:*CD11c
+*Lymphocyte function associated antigen 1 (LFA-1)
-The lymphocytic component of these tumors expresses pan B cell antigens (CD19, CD20, CD22, CD79a), while the plasma cell component usually downregulates CD20 and upregulates expression of CD138. The majority express lymphocyte function associated antigen 1 (LFA-1). Adhesion molecules expressed on approximately half of these tumors include L-selectin, ICAM-1, CD44 and CD11c. The cells are variable in their expression of CD43; CD25 or CD11c may be faintly positive in some cases [33-36]. A minority of cases expresses CD5 [37]. CD10, CD103, and CD23 are usually not expressed.
+References:
+{{Reflist}}