Non-Hodgkin lymphoma pathophysiology: Difference between revisions

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{{Non-Hodgkin lymphoma}}
{{Non-Hodgkin lymphoma}}


{{CMG}}; {{AE}}  
{{CMG}}; {{AE}} {{Preeti}}
==Overview==
==Overview==
Non Hodgkin's Lymphoma represents a heterogeneous group of [[diseases]] with varied clinical presentation and histological appearance.It arises from cell of the [[lymphoid system]], [[tumors]] are mainly derived from [[B lymphocytes]], but are also from [[T lymphocytes]], or [[natural killer cells]]. [[Lymphomas]] rise from different stages of B and [[T cell]] differentiation. Aberrations in the tightly controlled steps of B cell development can lead to oncogenesis. These aberrations are mainly seen in form of chromosomal translocation.
Non Hodgkin's Lymphoma (NHL) represents a heterogeneous group of [[diseases]] with varied clinical presentation and histological appearance.It arises from cell of the [[lymphoid system]], [[tumors]] are mainly derived from [[B lymphocytes]], but are also from [[T lymphocytes]], or [[natural killer cells]]. [[Lymphomas]] rise from different stages of B and [[T cell]] differentiation. Aberrations in the tightly controlled steps of B cell development can lead to oncogenesis. These aberrations are mainly seen in form of chromosomal translocation. About 85% of NHL's are of B-cell origin and only 15% are derived from T/NK cells. Two specific lymphomas, follicular lymphoma and diffuse large B cell lymphoma, account for about 65% of all non-Hodgkin lymphomas.
 


==Pathophysiology==
==Pathophysiology==
 
*[[Lymphoma|Lymphomas]] can arise from different stages of [[B cell|B cell development]]:
==Pathogenesis==
 
*Lymphomas can arise from different stages of B cell development:
*[[B cell|B cell development]] starts in the primary lymphoid tissue, the [[bone marrow]] and subsequent maturation takes place in secondary [[Lymphatic system|lymphoid tissue]] ([[spleen]] and [[Lymph node|lymph nodes]]).
*[[B cell|B cell development]] starts in the primary lymphoid tissue, the [[bone marrow]] and subsequent maturation takes place in secondary [[Lymphatic system|lymphoid tissue]] ([[spleen]] and [[Lymph node|lymph nodes]]).
*At the [[germinal centers]] of secondary lymphoid tissue [[B cell|B cells]] encounter antigens via [[T cell|T cells]] and then undergo [[affinity maturation]] to produce [[Antibody|immunoglobulins]] of high affinity.
*At the [[germinal centers]] of secondary lymphoid tissue [[B cell|B cells]] encounter antigens via [[T cell|T cells]] and then undergo [[affinity maturation]] to produce [[Antibody|immunoglobulins]] of high affinity.
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*Somatically acquired genetic alterations ( mainly [[Chromosomal translocation|translocations]]) of these processes is probably the underlying cause of lymphomagenesis.
*Somatically acquired genetic alterations ( mainly [[Chromosomal translocation|translocations]]) of these processes is probably the underlying cause of lymphomagenesis.


* The major subtypes of non-hodgkin lymphoma include the following:
* The major subtypes of non-hodgkin lymphoma (NHL) include the following:
** Mature B-cell neoplasms:
** Mature B-cell neoplasms:
*** [[Diffuse large B cell lymphoma]]
*** [[Follicular lymphoma]]
*** [[Burkitt's lymphoma|Burkitt lymphoma]]  
*** [[Burkitt's lymphoma|Burkitt lymphoma]]  
*** [[Diffuse large B cell lymphoma]]  
*** [[Mantle cell lymphoma]]
*** Mantle cell lymphoma
*** [[Hairy cell leukemia]]
*** Small lymphocytic lymphoma
*** Follicular lymphoma
*** Extranodal marginal zone lymphoma
*** Extranodal marginal zone lymphoma
*** Splenic marginal zone lymphoma
*** [[Splenic marginal zone lymphoma]]
*** Lymphoplasmacytic lymphoma
*** [[Multiple myeloma|Plasma cell myeloma]]
** Mature T and NK neoplasms:
** Mature T and NK neoplasms:
*** Adult T-cell lymphoma
*** [[Adult T-cell leukemia|Adult T-cell lymphoma]]
*** Mycosis fungoides
*** [[Mycosis fungoides]]
*** Sezary syndrome
*** [[Sezary syndrome]]
*** Peripheral T cell lymphoma
*** [[Peripheral T cell lymphoma]]


==Genetics==
*About 85% of NHLs are of B-cell origin and only 15% are derived from T/NK cells.<ref name="pmid15992695">{{cite journal| author=Morton LM, Zheng T, Holford TR, Holly EA, Chiu BC, Costantini AS et al.| title=Alcohol consumption and risk of non-Hodgkin lymphoma: a pooled analysis. | journal=Lancet Oncol | year= 2005 | volume= 6 | issue= 7 | pages= 469-76 | pmid=15992695 | doi=10.1016/S1470-2045(05)70214-X | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15992695  }} </ref>
 
*The small remainder stems from [[macrophages]].
Different subtypes of non Hodgkin lymphoma and their genetic involvements::
*These [[tumors]] are characterized by the level of [[differentiation]], the size of the [[cell]] of origin, the origin cell's rate of [[proliferation]], and the histological pattern of growth.
 
*[[Lymphomas]] of small [[lymphocytes]] generally have a more indolent course than those of large [[lymphocytes]], which may have intermediate-grade or high-grade aggressiveness.
{| class="wikitable"
*Two specific lymphomas, [[follicular lymphoma]] and [[diffuse large B cell lymphoma]], account for about 65% of all non-Hodgkin lymphomas.
|+
*The gene-expression profiles of almost all non-Hodgkin lymphomas are a reflection of the equivalent healthy cell of origin from which the [[lymphoma]] is derived.<ref name="pmid15992695">{{cite journal| author=Morton LM, Zheng T, Holford TR, Holly EA, Chiu BC, Costantini AS et al.| title=Alcohol consumption and risk of non-Hodgkin lymphoma: a pooled analysis. | journal=Lancet Oncol | year= 2005 | volume= 6 | issue= 7 | pages= 469-76 | pmid=15992695 | doi=10.1016/S1470-2045(05)70214-X | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15992695  }} </ref>
! colspan="2" rowspan="2" |
*[[Follicular lymphoma]] most commonly results from the t(14;18)(q32;q21) [[translocation]]; this [[translocation]] places BCL2 (which encodes B-cell CLL/lymphoma 2) under control of the IGH enhancer element, leading to constitutive BCL2 expression.<ref name="pmid25174027">{{cite journal| author=Wang SS, Flowers CR, Kadin ME, Chang ET, Hughes AM, Ansell SM et al.| title=Medical history, lifestyle, family history, and occupational risk factors for peripheral T-cell lymphomas: the InterLymph Non-Hodgkin Lymphoma Subtypes Project. | journal=J Natl Cancer Inst Monogr | year= 2014 | volume= 2014 | issue= 48 | pages= 66-75 | pmid=25174027 | doi=10.1093/jncimonographs/lgu012 | pmc=4155466 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25174027  }} </ref>
! rowspan="2" |Pathophysiology
*BCL-2 is an anti-apoptotic protein, and the t(14;18)(q32;q21) translocation results in markedly elevated expression of BCL-2, which blocks the healthy germinal center default program of apoptotic cell death and represents a defining pathogenic feature of [[follicular lymphoma]].<ref name="pmid25174027">{{cite journal| author=Wang SS, Flowers CR, Kadin ME, Chang ET, Hughes AM, Ansell SM et al.| title=Medical history, lifestyle, family history, and occupational risk factors for peripheral T-cell lymphomas: the InterLymph Non-Hodgkin Lymphoma Subtypes Project. | journal=J Natl Cancer Inst Monogr | year= 2014 | volume= 2014 | issue= 48 | pages= 66-75 | pmid=25174027 | doi=10.1093/jncimonographs/lgu012 | pmc=4155466 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25174027  }} </ref><ref name="pmid25174034">{{cite journal| author=Morton LM, Slager SL, Cerhan JR, Wang SS, Vajdic CM, Skibola CF et al.| title=Etiologic heterogeneity among non-Hodgkin lymphoma subtypes: the InterLymph Non-Hodgkin Lymphoma Subtypes Project. | journal=J Natl Cancer Inst Monogr | year= 2014 | volume= 2014 | issue= 48 | pages= 130-44 | pmid=25174034 | doi=10.1093/jncimonographs/lgu013 | pmc=4155467 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25174034  }} </ref>
! rowspan="2" |Symptoms
*Similarly, [[mantle cell lymphoma]] is characterised by the t(11;14)(q13;q32) translocation, which leads to the deregulated expression of [[cyclin D1]].<ref name="pmid28978864">{{cite journal| author=Tamaru JI| title=2016 revision of the WHO classification of lymphoid neoplasms. | journal=Rinsho Ketsueki | year= 2017 | volume= 58 | issue= 10 | pages= 2188-2193 | pmid=28978864 | doi=10.11406/rinketsu.58.2188 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28978864  }} </ref>
! rowspan="2" |History
*Moreover, [[burkitt lymphoma]] overexpresses MYC as a result of the t(8;14)(q24;q32) [[translocation]] or variants.
! rowspan="2" |Physical  Examination
*Recurrent [[translocations]] are less common in [[peripheral T-cell lymphomas]] than in other types of lymphoma, and examples include the characteristic t(2;5) (p23;q35) [[translocation]] seen in [[anaplastic lymphoma kinase]] (ALK)-positive [[anaplastic T-cell lymphoma]] and the t(5;9)(q33;q22) translocation associated with [[Follicular lymphoma|follicular T-cell lymphoma]].<ref name="pmid26980727">{{cite journal| author=Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R et al.| title=The 2016 revision of the World Health Organization classification of lymphoid neoplasms. | journal=Blood | year= 2016 | volume= 127 | issue= 20 | pages= 2375-90 | pmid=26980727 | doi=10.1182/blood-2016-01-643569 | pmc=4874220 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26980727  }} </ref>
! colspan="3" |Laboratory Findings
*Recurrent translocations including t(6;7) (p25;q32) and recurrent gene fusions involving the tumour-suppressor gene [[TP63]] are characteristic of ALK-negative [[anaplastic T-cell lymphoma]].<ref name="pmid26980727">{{cite journal| author=Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R et al.| title=The 2016 revision of the World Health Organization classification of lymphoid neoplasms. | journal=Blood | year= 2016 | volume= 127 | issue= 20 | pages= 2375-90 | pmid=26980727 | doi=10.1182/blood-2016-01-643569 | pmc=4874220 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26980727  }} </ref><ref name="pmid29741263">{{cite journal| author=Matutes E| title=The 2017 WHO update on mature T- and natural killer (NK) cell neoplasms. | journal=Int J Lab Hematol | year= 2018 | volume= 40 Suppl 1 | issue= | pages= 97-103 | pmid=29741263 | doi=10.1111/ijlh.12817 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29741263  }} </ref><br />
|-
!Immunochemistry
!Blood work
!Biospy
|-
| rowspan="7" |B cell lymphoma
|[[Mantle cell lymphoma]]
|
* [[CD5 (protein)|CD5]] positive antigen in pregerminal center of B-cell
* [[Chromosomal translocation]] at '''t(11:14)'''
** Over-express [[cyclin D1]]  
|
* Stage IV disease
* B symptoms,  
* Generalized lymphadenopathy
* Abdominal distention
* Fatigue
* Extranodal involvement of gastrointtestinal (GI) tract, lungs, and central nervous system (CNS)
|
* History of Night sweats
* Weight Loss
|
* Generalized lymphadenopathy
* Hepato-splenomegaly
* Mental Retardation
* Less commonly
** Palpable masses in skin, breast, and salivary glands
|
* CD5<sup>+</sup>
* B-cell antigen positive
** CD19
** CD20
** CD22
* Cyclin D1 is overexpressed.  
|CBC
* Anemia and cytopenias are secondary to bone marrow infiltration
* Lymphocytosis > 4000/µL
* Elevated LDH
*
|
* Germinal centers filled by small-to-medium atypical lymphocytes.
* Nodular appearance may be evident from expansion of the mantle zone in 30-50% of patients early in the disease.
|-
|[[Nodal marginal zone B-cell lymphoma]]
|
* Arise from memory B cells. Include
** Splenic marginal zone lymphoma
** Nodal marginal zone lymphoma
** Extranodal marginal zone lymphoma.
* Stimulation of antigen receptor by autoantigen and co-stimulatory molecule CD40.
|
* Depends largely on its location
* Gastric marginal zone lymphoma  
** Dyspepsia
** Abdominal pain
** Hemorrhage
|
* Chronic infectious conditions or autoimmune processes, such as
** ''H pylori'' gastritis
** Hashimoto thyroiditis
** Sjögren syndrome.
|
|
* AE1/AE3
* B-cell markers CD20, CD79a, CD10, CD23, and bcl-2 are expressed
|
|
* Follicular cells in reactive zone
* Centrocyte like cells in marginal zone lymphoma
|-
|[[Splenic marginal zone lymphoma]]
|
* Clonal rearrangements of the [[immunoglobulin]] genes (heavy and light chains) .
** Deletion 7q21-32
** Translocations of the CDK6 gene located at 7q21.  
|
|
|
|
* [[CD20]]
* [[CD79a]]
|
|
* [[B-cells]] replace the normal [[white pulp]] of the [[spleen]].
* The neoplastic cells compromise
** Small [[lymphocytes]]
** Transformed blasts
* S[[Sinus|inus]] invasion
* Epithelial histocytes
* Plasmacytic differentiation of neoplastic cells.
* '''Splenic Hilar Lymph Nodes'''
** Involved hilar [[lymph nodes]] adjacent to the [[spleen]] show an effaced architecture without preservation of the [[marginal zone]] seen in the spleen
* '''Bone Marrow Biopsy'''
** Splenic marginal zone lymphoma in [[bone marrow]] displays a nodular pattern with morphology similar to what is observed in the splenic [[hilar]] [[lymph nodes]].
|-
|[[Hairy cell leukemia]]
|
* Production of [[Cytokine|cytokines]], such as [[TNF alpha]] and IL-2R, provide important stimuli for [[malignant]] [[B cell|B cells]] proliferation in hairy cell leukemia.
** The ''p38-MAPK-JNK'' cascade
** The ''MEK-ERK'' cascade
** The ''Phosphatidylinositol 3 kinase (PI3K)-AKT'' cascade
|
* [[Fever]]
* [[Night sweat|Night sweats]]
* [[Fatigue]]
* Easy [[bruising]] or [[bleeding]]
* Generalized weakness
* [[Weight loss]]
* Recurrent [[Infection|infections]]
* Early satiety
|
* Review occupational history related to sawdust exposure
* Review any exposure to radiations
* Review any exposure to herbicides or diesel
|
* [[Pallor]],
* [[Petechiae]]
* [[Splenomegaly]]
|
* [[Annexin A1]]  
* [[CD20]]  
* [[CD25]]  
* [[CD103]]  
* [[CD19]]  
* [[CD11c]]
* [[FMC7]]
|
* Tartrate-resistant acid phosphatase  positive
* CBC
** Decreased [[hemoglobin]] concentration
** Decreased [[platelets]] count
**
|
:* Small cells with "fried egg"-like appearance
:* Well-demarcated thread-like [[cytoplasmic]] extensions
:* Clear cytoplasm
:* Central round [[nucleus]]
:* Peri-nuclear clearing ("water-clear rim" appearance)
|-
|[[Plasma cell myeloma]]
|
|
|
|
|
|
|
|-
|[[Diffuse large B-cell lymphoma]]
|
*Germinal centre B-cell-like (GCB)
*Activated B-cell-like (ABC).  
**B cell receptor (BCR) signalling
**B cell migration/adhesion
**Cell-cell interactions in immune niches
**Production and class-switching of immunoglobulins
|
*
|
|
*
|
*
|
* Neutropenia
* Anemia
* Hypergammaglobulinemia
|
 
====Centroblastic====
*Medium-to-large-sized [[Lymphocyte|lymphocytes]]
*Monomorphic
====Immunoblastic::====
*> 90% immunoblasts
*Trapezoid shaped large lymphoid cells with significant [[basophilic]] cytoplasm
====Anaplastic:====
*Very large cells with a round, oval, or polygonal shape that may resemble Reed-Sternberg cells of Hodgkin's lymphoma or Anaplastic Large cell Lymphoma.
|-
|[[Burkitt lymphoma]]
|
* Translocation of chromosome 8 ''[[myc]]'' locus with 3 possible partners (accounting for 90% of translocations):
** The Ig heavy chain region on chromosome 14: t(8;14)
** The kappa light chain locus on chromosome 2: t(2;8)
** The lambda light chain locus on chromosome 22: t(8;22)
|
* [[Fever]]
* [[Night sweats]]
* Unexplained [[weight loss]]
* [[Swollen lymph nodes]] in the neck, axilla, or groin
|
|
* [[Proptosis]]
* Jaw mass
 
* [[Abdominal mass|Abdominal masses]]
* [[Ascites]]
 
* [[Lymphadenopathy|Peripheral lymphadenopathy]]
|
* [[CD19]]
* [[CD20]],
* [[CD22]]
* [[CD10]]
* BCL6.
* BCL2 and TdT.
|
|
:* Medium-sized (~1.5-2x the size of a RBC) with uniform size ("monotonous") -- '''key feature''' (i.e. tumor nuclei size similar to that of [[histiocytes]] or [[endothelial cells]])
:* Round nucleus
:* Small nucleoli
:* [[basophilic]] cytoplasm
:* Brisk mitotic rate and [[apoptotic]] activity
:* Cellular outline usually appears squared off
:* "Starry-sky pattern":
:** The ''stars'' in the pattern are tingible-body macrophages (macrophages containing [[apoptotic]] tumor cells)
:** The tumour cells are the ''sky''
|-
| rowspan="6" |T cell lymphoma
|[[T-cell granular lymphocytic leukemia]]
|
* Disregulation of signaling pathways:
** FAS/FAS-L
** Phosphatidylinositol-3 kinase (PI3K),
** Mitogen-activated proteinkinase/extracellular signal-regulated kinase (MAPK/ERK)
|
Symptoms of T-cell large granular lymphocyte leukemia may include the following:
* Generalised weakness and [[Fatigue (physical)|fatigue]]
* [[Anorexia]]
* Joint pain
* Night sweating
* [[Epistaxis]]
* [[Bone pain]]
* [[Dyspnea]]
|
|
* Usually appear pale and malnourished.
* Cardiac flow murmur
* High-grade fever
* [[Hepatomegaly]]
* [[Splenomegaly]]
|
* [[CD3]]+
* [[TCR]]αβ+
* [[CD4]]-
* [[CD8]]+
|
* Neutropenia
* Anemia
* Hypergammaglobulinemia
|
:* Clonal rearrangements of the [[T-cell receptor]] (TCR) gene
:* Chronic (> 6 months) elevation in large granular lymphocytes (LGLs) in the peripheral blood
:* Large granular lymphocyte count greater than 2.0 × 109/L
:* Lymphocytosis (typically 2-20x109/L)
|-
|[[Mycosis fungoides]] / [[Sézary syndrome]]
|
|
* [[Epidermis (skin)|Epidermal]] [[atrophy]] or poikiloderma
 
* Generalized [[itching]]([[pruritus]])
* [[Pain]] in the affected area of the skin.
* [[Insomnia]]
* Red ([[erythematous]]) patches scattered over the [[skin]] of the [[trunk]] and the [[extremities]]
* [[Weight loss]]
* [[Lymphadenopathy]]
* [[Malaise]] and [[fatigue]]
* [[Anemia]]
* May progress to [[Sezary syndrome]] (Skin involvement plus hematogenous dissemination)
|
|
* Cutaneous manifestaions
|
|
|
|-
|[[Subcutaneous panniculitis-like T-cell lymphoma]]
|
|
|
|
|
|
|
|-
|[[Enteropathy-type intestinal T-cell lymphoma]]
|
|
|
|
|
|
|
|-
|[[Anaplastic large cell lymphoma]]
|
|
|
|
|
|
|
|-
|[[Aggressive NK-cell leukemia]]
|
|
|
|
|
|
|
|}
 
<references />
 
==Associated Conditions==
Conditions associated with [disease name] include:
 
*[Condition 1]
*[Condition 2]
*[Condition 3]
 
==Gross Pathology==
On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
 
==Microscopic Pathology==
On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
 
==References==
{{Reflist|2}}
 
{{WH}}
{{WS}}
[[Category: (name of the system)]]


==Genetics==
==Genetics==
The development of Non-Hodgkin lymphoma is the result of multiple genetic mutations such as:<ref name="pmid21804550">{{cite journal| author=Pasqualucci L, Trifonov V, Fabbri G, Ma J, Rossi D, Chiarenza A et al.| title=Analysis of the coding genome of diffuse large B-cell lymphoma. | journal=Nat Genet | year= 2011 | volume= 43 | issue= 9 | pages= 830-7 | pmid=21804550 | doi=10.1038/ng.892 | pmc=3297422 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21804550  }}</ref><ref name="pmid22343534">{{cite journal| author=Lohr JG, Stojanov P, Lawrence MS, Auclair D, Chapuy B, Sougnez C et al.| title=Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing. | journal=Proc Natl Acad Sci U S A | year= 2012 | volume= 109 | issue= 10 | pages= 3879-84 | pmid=22343534 | doi=10.1073/pnas.1121343109 | pmc=3309757 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22343534  }}</ref>
The development of non-Hodgkin lymphoma is the result of multiple genetic mutations such as:<ref name="pmid21804550">{{cite journal| author=Pasqualucci L, Trifonov V, Fabbri G, Ma J, Rossi D, Chiarenza A et al.| title=Analysis of the coding genome of diffuse large B-cell lymphoma. | journal=Nat Genet | year= 2011 | volume= 43 | issue= 9 | pages= 830-7 | pmid=21804550 | doi=10.1038/ng.892 | pmc=3297422 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21804550  }}</ref><ref name="pmid22343534">{{cite journal| author=Lohr JG, Stojanov P, Lawrence MS, Auclair D, Chapuy B, Sougnez C et al.| title=Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing. | journal=Proc Natl Acad Sci U S A | year= 2012 | volume= 109 | issue= 10 | pages= 3879-84 | pmid=22343534 | doi=10.1073/pnas.1121343109 | pmc=3309757 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22343534  }}</ref>
*[[Mutations]] of the [[B-cell]] receptor genes and [[NFKB]] pathway.
*[[RNA splicing]] [[mutations]] in the [[small lymphocytic lymphoma]].
*[[Genetic mutations]] in histone formation:<ref name="pmid23297126">{{cite journal| author=Green MR, Gentles AJ, Nair RV, Irish JM, Kihira S, Liu CL et al.| title=Hierarchy in somatic mutations arising during genomic evolution and progression of follicular lymphoma. | journal=Blood | year= 2013 | volume= 121 | issue= 9 | pages= 1604-11 | pmid=23297126 | doi=10.1182/blood-2012-09-457283 | pmc=3587323 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23297126  }}</ref>
**[[MLL2]]
**[[MEF2B]]
**[[EZH2]]
**CREBBP
**[[EP300]]
**[[MLL2]]
**[[KMT2D]]
*Mutations in [[CDKN2A]] alters cell cycle control and affects JAK–STAT signalling.
*Upregulation of key signalling pathways such as [[CD79B]], [[MYD88]], [[CARD11]].
*Block to terminal differentiation such as [[BCL6]] translocations and loss of [[PRDM1]].


*Mutations of the B-cell receptor genes and NFKB pathway
== Associated Conditions ==
*RNA splicing mutations in the small lymphocytic lymphoma
* Several conditions are associated with non-Hodgkin's lymphoma depending on the type. However, [[Epstein Barr virus]], [[Human Immunodeficiency Virus|human immunodeficiency virus]], and [[hepatitis C]] infection are commonly present.
*Genetic mutations in histone formation:<ref name="pmid23297126">{{cite journal| author=Green MR, Gentles AJ, Nair RV, Irish JM, Kihira S, Liu CL et al.| title=Hierarchy in somatic mutations arising during genomic evolution and progression of follicular lymphoma. | journal=Blood | year= 2013 | volume= 121 | issue= 9 | pages= 1604-11 | pmid=23297126 | doi=10.1182/blood-2012-09-457283 | pmc=3587323 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23297126  }}</ref>
**MLL2
**MEF2B
**EZH2
**CREBBP
**EP300
**MLL2


==Gross Pathology==
== Gross Pathology ==
On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
*For information on gross pathology findings of [[Follicular lymphoma]], [[Follicular lymphoma pathophysiology#Gross Pathology|click here]].
*For information on gross pathology findings of [[Mantle cell lymphoma]], [[Mantel cell lymphoma pathophysiology#Gross Pathology|click here]].
*For information on gross pathology findings of [[Hairy cell leukemia]], [[hairy cell leukemia pathophysiology#Gross Pathology|click here]].
*For information on gross pathology findings of [[Splenic marginal zone lymphoma]], [[Splenic marginal zone lymphoma pathophysiology#Gross Pathology|click here]].
*For information on gross pathology findings of [[Mycosis fungoides]], [[Mycosis fungoides pathophysiology#Gross Pathology|click here]].
*For information on gross pathology findings of [[Peripheral T cell lymphoma]], [[Peripheral T cell lymphoma pathophysiology#Gross Pathology|click here]].


==Microscopic Pathology==
== Microscopy Pathology ==
On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
*For information on microscopic pathology findings of [[Follicular lymphoma]], [[Follicular lymphoma pathophysiology#Microscopic Pathology|click here]].
*For information on microscopic pathology findings of [[Mantle cell lymphoma]], [[Mantel cell lymphoma pathophysiology#Microscopic Pathology|click here]].
*For information on microscopic pathology findings of [[Hairy cell leukemia]], [[hairy cell leukemia pathophysiology#Microscopic Pathology|click here]].
*For information on microscopic pathology findings of [[Splenic marginal zone lymphoma]], [[Splenic marginal zone lymphoma pathophysiology#Microscopic Pathology|click here]].
*For information on microscopic pathology findings of [[Mycosis fungoides]], [[Mycosis fungoides pathophysiology#Microscopic Pathology|click here]].
*For information on microscopic pathology findings of [[Peripheral T cell lymphoma]], [[Peripheral T cell lymphoma pathophysiology#Microscopic Pathology|click here]].


==References==
==References==

Latest revision as of 20:27, 21 January 2019

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Preeti Singh, M.B.B.S.[2]

Overview

Non Hodgkin's Lymphoma (NHL) represents a heterogeneous group of diseases with varied clinical presentation and histological appearance.It arises from cell of the lymphoid system, tumors are mainly derived from B lymphocytes, but are also from T lymphocytes, or natural killer cells. Lymphomas rise from different stages of B and T cell differentiation. Aberrations in the tightly controlled steps of B cell development can lead to oncogenesis. These aberrations are mainly seen in form of chromosomal translocation. About 85% of NHL's are of B-cell origin and only 15% are derived from T/NK cells. Two specific lymphomas, follicular lymphoma and diffuse large B cell lymphoma, account for about 65% of all non-Hodgkin lymphomas.

Pathophysiology

Genetics

The development of non-Hodgkin lymphoma is the result of multiple genetic mutations such as:[7][8]

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References

  1. ↑ 1.0 1.1 Morton LM, Zheng T, Holford TR, Holly EA, Chiu BC, Costantini AS; et al. (2005). "Alcohol consumption and risk of non-Hodgkin lymphoma: a pooled analysis". Lancet Oncol. 6 (7): 469–76. doi:10.1016/S1470-2045(05)70214-X. PMID 15992695.
  2. ↑ 2.0 2.1 Wang SS, Flowers CR, Kadin ME, Chang ET, Hughes AM, Ansell SM; et al. (2014). "Medical history, lifestyle, family history, and occupational risk factors for peripheral T-cell lymphomas: the InterLymph Non-Hodgkin Lymphoma Subtypes Project". J Natl Cancer Inst Monogr. 2014 (48): 66–75. doi:10.1093/jncimonographs/lgu012. PMC 4155466. PMID 25174027.
  3. ↑ Morton LM, Slager SL, Cerhan JR, Wang SS, Vajdic CM, Skibola CF; et al. (2014). "Etiologic heterogeneity among non-Hodgkin lymphoma subtypes: the InterLymph Non-Hodgkin Lymphoma Subtypes Project". J Natl Cancer Inst Monogr. 2014 (48): 130–44. doi:10.1093/jncimonographs/lgu013. PMC 4155467. PMID 25174034.
  4. ↑ Tamaru JI (2017). "2016 revision of the WHO classification of lymphoid neoplasms". Rinsho Ketsueki. 58 (10): 2188–2193. doi:10.11406/rinketsu.58.2188. PMID 28978864.
  5. ↑ 5.0 5.1 Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R; et al. (2016). "The 2016 revision of the World Health Organization classification of lymphoid neoplasms". Blood. 127 (20): 2375–90. doi:10.1182/blood-2016-01-643569. PMC 4874220. PMID 26980727.
  6. ↑ Matutes E (2018). "The 2017 WHO update on mature T- and natural killer (NK) cell neoplasms". Int J Lab Hematol. 40 Suppl 1: 97–103. doi:10.1111/ijlh.12817. PMID 29741263.
  7. ↑ Pasqualucci L, Trifonov V, Fabbri G, Ma J, Rossi D, Chiarenza A; et al. (2011). "Analysis of the coding genome of diffuse large B-cell lymphoma". Nat Genet. 43 (9): 830–7. doi:10.1038/ng.892. PMC 3297422. PMID 21804550.
  8. ↑ Lohr JG, Stojanov P, Lawrence MS, Auclair D, Chapuy B, Sougnez C; et al. (2012). "Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing". Proc Natl Acad Sci U S A. 109 (10): 3879–84. doi:10.1073/pnas.1121343109. PMC 3309757. PMID 22343534.
  9. ↑ Green MR, Gentles AJ, Nair RV, Irish JM, Kihira S, Liu CL; et al. (2013). "Hierarchy in somatic mutations arising during genomic evolution and progression of follicular lymphoma". Blood. 121 (9): 1604–11. doi:10.1182/blood-2012-09-457283. PMC 3587323. PMID 23297126.


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