View source for Diffuse large B cell lymphoma classification

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{{Diffuse large B cell lymphoma}}
{{CMG}}; {{AE}} {{AS}} {{AHS}}

==Overview==
Diffuse large [[B cell]] [[lymphoma]] may be classified based on location into [[Nodal marginal zone lymphoma|nodal]] and [[Extranodal NK-T-cell lymphoma|extranodal]] disease and based on [[pathological]] and [[clinical]] features.

==Classification==
===Classification Based on Location===
[[Diffuse large B cell lymphoma]] may be classified based on location:

*[[Nodal (protein)|Nodal]] disease
*[[Extranodal NK-T-cell lymphoma|Extranodal]] disease

===Classification Based on Pathological and Clinical Features===

According to the updated [[World Health Organization|WHO]] classification, diffuse large B cell lymphoma may be classified based on pathological and clinical features into the following:
===Diffuse large B cell lymphoma, not otherwise specified===

*[[Diffuse large B cell lymphoma|Diffuse large B-cell lymphoma]], [[NOS]] (represents more than 80% of cases of [[large B-cell lymphomas]])

*Molecular subtypes: GCB subtype, about 60%; ABC subtype, about 25–30%; unclassifiable, about 10–15%; new molecular entities recently characterized

=====Diagnostic features=====
Diffuse [[proliferation]] of medium or large [[Lymphatic system|lymphoid]] [[B cell|B cells]] typically expressing [[CD19]], [[CD20]], [[CD22]], [[CD79a]], [[PAX5]], and surface or cytoplasmic [[immunoglobulin]]; [[Molecule|molecular]] [[techniques]] (e.g., [[GEP]]) or [[IHC]]-based algorithms recommended to classify subtypes

=====Clinical Features and Outcome=====

*The [[median]] age is 65–70 yr

*[[Nodal marginal zone B-cell lymphoma|Nodal]] presentation is the most common and 30–40% of cases are primary [[Extranodal NK-T-cell lymphoma|extranodal]]

*[[prognosis]] is variable

===Other Large B Cell Lymphoma (DLBCL) type===
===='''T-cell/histiocyte-rich large B cell lymphoma (rare)'''====    

*Few large [[B cell|B cells]] embedded in a background of [[T cell|T cells]] and histiocytes; distinguish from [[nodular]] [[lymphocyte]]-predominant [[Hodgkin's lymphoma|Hodgkin lymphoma]]
*Commonly found in middle-aged men, advanced stage with extranodal involvement ([[liver]], [[spleen]], [[bone marrow]]); poor prognosis
*

==== '''Primary diffuse large B cell lymphoma of the central nervous system (rare)''' ====

*Typically ABC subtype; frequent loss of [[Human leukocyte antigen|HLA]] class I/II; frequent mutation of ''MYD88''
*Exclusively in [[CNS]] or [[Intraocular lymphoma|intraocular]] region, rare systemic involvement; poor [[prognosis]]; specialized treatment with [[CNS]]-penetrating agents, with or without [[radiation]] therapy, required; targeted therapies under [[Investigational drug|investigation]]
*

==== '''Primary Cutaneous DLBCL, Leg type (rare)''' ====

*Typically ABC subtype; frequent mutation of [[MYD88]]; distinguish from other [[Skin|cutaneous]] [[B-cell lymphoma]]
*Typically in elderly patients and women; presents with [[skin nodules]] in lower [[Leg|legs]]; 10–15% of cases arise in other sites; poor [[prognosis]]
*

==== '''EBV-positive diffuse large B-cell lymphoma, NOS (rare)''' ====

*Variable [[Histology|histologic]] features, including [[Hodgkin's lymphoma|Hodgkin]]-like lesions, [[Monomorphic adenoma|monomorphic]] to [[Polymorphism (biology)|polymorphic]] patterns; [[Epstein Barr virus|EBV]] detectable in [[tumor]] and frequently in serum
*Typically in patients older than 50 yr; more frequent in Asia and Latin America than elsewhere; [[Extranodal NK-T-cell lymphoma|extranodal]] involvement common; [[prognosis]] varies

==== '''EBV-positive mucocutaneous ulcer (rare)''' ====

*[[Polymorphism (biology)|Polymorphic]] [[infiltrate]] with frequent [[Hodgkin's lymphoma|Hodgkin]]-like cells; [[Epstein Barr virus|EBV]] is detectable in [[tumor]]
*Presents as [[Localized Lymph Node Enlargement|localized]], [[Ulcer|ulcerated]] lesions in [[oral mucosa]], [[Intestines|intestine]], or [[skin]]; dissemination is rare; commonly occurs as iatrogenic or age-related disease in [[Immunodeficiency|immunocompromised]] patients; favorable prognosis; consider reduction of [[Immunosuppression|immunosuppressive therapy]]
*

==== '''Diffuse large B-cell lymphoma associated with chronic inflammation (rare)''' ====

*Morphologically similar to [[Diffuse large B cell lymphoma|DLBCL]], NOS but strongly associated with [[Epstein Barr virus|EBV]]; also called [[Pleural empyema|pyothorax]]-associated [[lymphoma]], when associated with chronic [[pyothorax]]
*Occurs in context of [[chronic inflammation]], involving pleural cavity or other sites such as [[bone]] and [[Joint|joints]]; [[male]] predominance; poor [[prognosis]]
*

==== '''Lymphomatoid granulomatosis (rare)''' ====

*[[Epstein Barr virus|EBV]]-driven angiocentric and angiodestructive [[lymphoproliferation]] with reactive [[T cell|T cells]]; grade based on proportion of [[Epstein Barr virus|EBV]] positive [[B cell|B cells]] and cytologic features
*Commonly involves extranodal sites ([[lung]] >90%); often in context of [[immunodeficiency]]; prognosis varies; no standard therapy
*

==== '''Large B-cell lymphoma with ''IRF4'' rearrangement (rare)''' ====

*Strong [[expression]] of IRF4/MUM1, usually with ''[[IRF4]]'' rearrangement; [[diffuse]]-to-[[Follicular lymphoma|follicular]] [[Morphological computation|morphologic]] features; distinguish from [[Pediatrics|pediatric]]-type [[follicular lymphoma]]
*Commonly in [[Child|children]] and [[Young adult|young adults]]; typically involves Waldeyer’s ring or [[cervical lymph nodes]]; favorable prognosis
*

==== '''Primary mediastinal (thymic) large B-cell lymphoma (around 6% of large B-cell cases)''' ====

*Putative [[Thymus|thymic]] [[B cell|B-cell]] origin; medium-to-large [[B cell|B cells]], frequently with [[sclerosis]]; distinctive [[phenotype]] ([[CD30]], [[CD23]], [[PDL1]], [[PDL2]]) and unique GEP signature; frequent 9p21 [[amplification]], [[genomic]] alterations of ''[[CIITA]]''
*Typically in [[Young adult|young adults]], [[female]] [[Predominance diagram|predominance]]; [[Mediastinum|mediastinal]] prominence with local [[Invasive (medical)|invasion]]; can involve other nodal or extranodal sites ([[kidney]] and [[liver]]); prognosis varies; [[DA-EPOCH-R]] an option
*

==== '''Intravascular large B-cell lymphoma (rare)''' ====

*[[Lymphoma]] cells exclusively within [[Luminal|lumina]] of small or intermediate [[vessels]]; [[bone marrow]] and [[skin]] [[biopsy]] may be useful to establish [[diagnosis]]
*Wide [[intravascular]] [[dissemination]] ([[lung]], [[bone marrow]], [[skin]], [[CNS]], [[kidney]]), often associated with [[fever of unknown origin]] or [[Neurology|neurologic]] or [[Skin|cutaneous]] symptoms; poor [[prognosis]]
*

==== '''ALK-positive large B-cell lymphoma (rare)''' ====

*[[ALKK|ALK]]-[[positive]] large [[B cell|B cells]], immunoblastic features and [[plasma cell]] [[phenotype]], typically [[CD20]]-negative
*Typically in young men with [[generalized lymphadenopathy]]; prognosis varies
*

==== '''Plasmablastic lymphoma (rare)''' ====

*[[Immunoblastic Lymphadenopathy|Immunoblastic]] or [[plasmablastic]] [[B cell|B cells]], plasma-cell phenotype ([[CD138]]-[[positive]], [[CD20]]-[[Negative-sense|negative]]), often [[Epstein Barr virus|EBV]]-[[positive]]; distinguish from [[multiple myeloma]]
*Often associated with [[HIV AIDS|HIV infection]] or [[immunosuppression]]; frequently [[Extranodal NK-T-cell lymphoma|extranodal]]; poor [[prognosis]]; consider more intensive regimens
*

==== '''HHV8-positive diffuse large B-cell lymphoma (rare)''' ====

*[[HHV8]]-[[positive]] [[Immunoglobulin M|IgM]] lambda [[plasmablasts]]; often associated with [[HHV8]]-positive multicentric Castleman disease
*Often associated with [[HIV AIDS|HIV infection]]; [[lymphadenopathy]] and [[splenomegaly]] are common; poor prognosis; no standard therapy
*

==== '''Primary effusion lymphoma (rare)''' ====

*[[Immunoblastic Lymphadenopathy|Immunoblastic]] or [[plasmablastic]] B cells, [[HHV8]]-positive and usually [[Epstein Barr virus|EBV]]-[[positive]]; [[plasma-cell]] [[phenotype]] lacking usual [[B cell|B-cell]] markers; [[CD20]]-negative
*Often associated with [[HIV AIDS|HIV infection]] or [[immunosuppression]]; presents as [[Pleural cavity|pleural]], [[pericardial]], or [[Peritoneum|peritoneal]] [[Serous fluid|serous]] [[effusions]], often without detectable [[Tumor cell|tumor]] mass; poor [[prognosis]]; DA-EPOCH an option
*

==== '''High-grade B-cell lymphoma''' ====

*'''High-grade B-cell lymphoma''' with ''[[MYCBPAP (gene)|MYC]]'' and ''[[BCL2-like 1|BCL2]]'' and/or ''[[BCL6]]'' rearrangements or both (doublehit or triple-hit lymphoma) (4–8% of [[Large B-cell lymphoma|large B-cell]] cases)
*Variable [[Morphology (biology)|morphology]], including DLBCL, [[B-cell lymphoma]] unclassifiable (with features intermediate between [[Diffuse large B cell lymphoma|DLBCL]] and [[Burkitt's lymphoma|Burkitt lymphoma]]), and blastoid features; ''[[MYCBP|MYC]]'' and ''[[BCL2-like 1|BCL2]]'' and/or ''[[BCL6]]'' rearrangements, detected by [[Fluorescence in situ hybridization|FISH]]
*Frequently aggressive clinical presentation; higher risk of [[CNS]] involvement; poor prognosis; consider more intensive immunochemotherapy regimens, such as DA-EPOCH-R

==== '''High-grade B-cell lymphoma, NOS (rare)''' ====

*[[Heterogeneous]] category; often has [[morphologic features]] intermediate between [[Diffuse large B cell lymphoma|DLBCL]] and [[Burkitt's lymphoma|Burkitt lymphoma]]; lacks [[MYCBP|MYC]] and [[BCL2-like 1|BCL2]] and/or [[BCL6]] rearrangements
*Frequently aggressive [[clinical presentation]]; increased risk of [[CNS]] involvement; poor [[prognosis]]; consider more intensive [[immunochemotherapy]] [[regimens]]
*

==== '''B-cell lymphoma, unclassifiable''' ====

*[[B-cell lymphoma]], unclassifiable, with features intermediate between [[Diffuse large B cell lymphoma|diffuse large B-cell lymphoma]] and classic [[Hodgkin's lymphoma|Hodgkin lymphoma]] (grey-zone lymphoma) (rare)
*Overlapping [[Morphological computation|morphologic]] or [[immunophenotypic]] features, or both, between [[Diffuse large B cell lymphoma|DLBCL]] and classic [[Hodgkin's lymphoma|Hodgkin lymphoma]]
*[[Male]] [[Predominance diagram|predominance]], younger age (20–40 yr); [[mediastinal]] presentation most common (80% of cases) but can occur in other sites; [[prognosis]] varies; no standard therapy, consider therapy suitable for [[Diffuse large B cell lymphoma|DLBCL]] or [[Hodgkin's lymphoma|Hodgkin lymphoma]]

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