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[[Image:Lymphoma macro.jpg | thumb | 200px | right | Lymphoma at [[cut-up]]. (WC/Emmanuelm)]]
'''Lymphoma''' is almost a specialty for itself.  It can be subclassified a number of ways.   
'''Lymphoma''' is almost a specialty for itself.  It can be subclassified a number of ways.   


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A general introduction to haematopathology is in the ''[[haematopathology]]'' article.
A general introduction to haematopathology is in the ''[[haematopathology]]'' article.
==General==
The presentations are variable and similar to that of other malignancies. They may include:
*Mass effect.
*Weight loss.
*Fever.
*Night sweats.
*Infection.
*Incidental:
**Routine blood work for something unrelated.
**Life insurance work-up.
===B symptoms===
*May be seen in [[Hodgkin lymphoma]] and non-Hodgkin lymphoma.
*Presence correlates with higher stage.
*Predictor of poor prognosis independent of stage.
All of 'em are required to call "B symptoms"<ref name=pmid5121694>{{Cite journal  | last1 = Carbone | first1 = PP. | last2 = Kaplan | first2 = HS. | last3 = Musshoff | first3 = K. | last4 = Smithers | first4 = DW. | last5 = Tubiana | first5 = M. | title = Report of the Committee on Hodgkin's Disease Staging Classification. | journal = Cancer Res | volume = 31 | issue = 11 | pages = 1860-1 | month = Nov | year = 1971 | doi =  | PMID = 5121694 | URL = http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=5121694 }}</ref> - mnemonic ''These '''B'''othersome features cause '''W'''ednesday '''N'''ight '''F'''ever'':<ref>URL: [http://www.internalizemedicine.com/2011/12/bury-buzzword-b-symptoms.html http://www.internalizemedicine.com/2011/12/bury-buzzword-b-symptoms.html]. Accessed on: 28 March 2012.</ref>
*Weight loss - >10% in 6 months.
*Night sweats.
*Fever - 38 degree C that is unexplained.
Note:
*''A symptoms'' do '''not''' exist. The term comes from the staging system. In the "A" of the staging system the above symptoms are '''a'''bsent.


==Lymphoma classification==
==Lymphoma classification==
Lymphomas can be divided into:
Lymphomas can be divided into:
*Hodgkin's lymphoma.
*[[Hodgkin's lymphoma]].
*Non-Hodgkin's lymphoma (NHL).
*Non-Hodgkin's lymphoma (NHL).


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Two most common NHLs:
Two most common NHLs:
*Follicular lymphoma (FL).
*[[Follicular lymphoma]] (FL).
*Diffuse large B-cell lymphoma (DLBCL).
*[[Diffuse large B-cell lymphoma]] (DLBCL).


===Leukemia as a med student===
===Leukemia as a med student===
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*[[Acute myeloid leukemia]] (AML).
*[[Acute myeloid leukemia]] (AML).
*[[Chronic myeloid leukemia]] (CML).
*[[Chronic myeloid leukemia]] (CML).
*Chronic lymphoid leukemia (CLL) - relatively good prognosis.
*[[Chronic lymphocytic leukemia]] (CLL) - relatively good prognosis.


===Histologic classification===
===Histologic classification===
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|}
|}


===Histologic terms===
====Histologic terms====
*Lymphomas = cells look discohesive, may be difficult to differentiate from poor differentiated carcinoma.
*Lymphomas = cells look discohesive, may be difficult to differentiate from poor differentiated carcinoma.
*Auer rods = Acute myeloid leukemia.
*[[Auer rods]] = [[acute myeloid leukemia]].
**Granular cytoplasmic rod (0.5-1 x4-6 micrometres).
**Granular cytoplasmic rod (0.5-1 x4-6 micrometres).
**Not pathognomonic.
*Reed-Sternberg cells = [[Hodgkin's lymphoma]].
*Reed-Sternberg cells = [[Hodgkin's lymphoma]].
**Large cell - very large nucleus.
**Large cell - very large nucleus.
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Others:
Others:
*AE1/AE3 -- to r/o carcinoma.
*[[AE1/AE3]] -ve -- to r/o carcinoma.


====T cell markers====
====T cell markers====
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====Follicular dendritic cells====
====Follicular dendritic cells====
*CD23 -- follicular dendritic cells.
*CD23 -- follicular dendritic cells.
*CD21 -- follicular dendritic cells.
*CD21 -- follicular dendritic cells, considered more sensitive than CD23.<ref name=pmid16280657>{{Cite journal  | last1 = Troxell | first1 = ML. | last2 = Schwartz | first2 = EJ. | last3 = van de Rijn | first3 = M. | last4 = Ross | first4 = DT. | last5 = Warnke | first5 = RA. | last6 = Higgins | first6 = JP. | last7 = Natkunam | first7 = Y. | title = Follicular dendritic cell immunohistochemical markers in angioimmunoblastic T-cell lymphoma. | journal = Appl Immunohistochem Mol Morphol | volume = 13 | issue = 4 | pages = 297-303 | month = Dec | year = 2005 | doi =  | PMID = 16280657 }}</ref>


====Hodgkin's lymphoma====
====Hodgkin's lymphoma====
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*TdT.
*TdT.
*CD34.
*CD34.
===Molecular pathology===
{{Main|Molecular pathology}}
{{Main|Molecular pathology tests}}
*T cell clonality study.
*B cell clonality study.
====Chromosomal translocations====
{{Main|Chromosomal_translocations#Lymphoma}}


==Hodgkin's lymphoma==
==Hodgkin's lymphoma==
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==Intravascular lymphoma==
==Intravascular lymphoma==
*[[AKA]] ''angiotropic lymphoma'', ''intravascular malignant lymphomatosis'', ''malignant angioendotheliomatosis''
*Rare.
*Rare.
*Usually B-cell lineage (see below ''intravascular large B-cell lymphoma'').
*Usually B-cell lineage (see ''[[intravascular large B-cell lymphoma]]'').
**May be T-cell lineage.<ref name=pmid20337769>{{cite journal |author=Wang L, Li C, Gao T |title=Cutaneous intravascular anaplastic large cell lymphoma |journal=J Cutan Pathol |volume= |issue= |pages= |year=2010 |month=March |pmid=20337769 |doi=10.1111/j.1600-0560.2010.01538.x |url=}}</ref>
**May be T-cell lineage.<ref name=pmid20337769>{{cite journal |author=Wang L, Li C, Gao T |title=Cutaneous intravascular anaplastic large cell lymphoma |journal=J Cutan Pathol |volume= |issue= |pages= |year=2010 |month=March |pmid=20337769 |doi=10.1111/j.1600-0560.2010.01538.x |url=}}</ref>
===Intravascular large B-cell lymphoma===
====General====
*[[AKA]] ''angiotropic lymphoma'', ''intravascular malignant lymphomatosis'', ''malignant angioendotheliomatosis''.
=====Clinical=====
*Often a non-specific presentation.<ref name=pmid11579120>{{cite journal |author=Lapkuviene O, Forchetti D, Roepke JE |title=Unusual sites of involvement by hematologic malignancies. Case 1. Intravascular large B-cell lymphoma presenting with CNS symptoms |journal=J. Clin. Oncol. |volume=19 |issue=19 |pages=3988–91 |year=2001 |month=October |pmid=11579120 |doi= |url=http://jco.ascopubs.org/content/19/19/3988.full}}</ref>
**+/-Fever.
**+/-Multiple infarcts.
**+/-Non-specific skin lesions.
====Microscopic====
Features:
*Abundant atypical intravascular lymphoid cells that are:
**Large (~2-3X size of a mature lymphocyte or RBC).
**Nucleolus prominent.
Notes:
*It may be hard to find RBCs in the vessels.
*Looks sorta like a [[DLBCL]] -- but is intravascular.
Images:
*[[WC]]:
**[http://commons.wikimedia.org/wiki/File:Intravascular_lymphoma_-_high_mag.jpg Intravascular lymphoma - high mag. (WC)].
*www:
**[http://jco.ascopubs.org/content/19/19/3988/F1.expansion.html ILBCL (ascopubs.org)].<ref name=pmid11579120/>
**[http://theoncologist.alphamedpress.org/cgi/content/full/11/8/923/F1 ILBCL in bone marrow (alphamedpress.org)].
**[http://annonc.oxfordjournals.org/content/13/9/1503/F1.expansion.html ILBCL - various images (oxfordjournals.org)].
**[http://path.upmc.edu/cases/case473/images/fig01a.jpg ILBCL (upmc.edu)].<ref>URL: [http://path.upmc.edu/cases/case473.html http://path.upmc.edu/cases/case473.html]. Accessed on: 21 January 2012.</ref>
**[http://path.upmc.edu/cases/case697.html ILBCL - several images (upmc.edu)].
====IHC====
Features:<ref name=pmid11579120/>
*CD20 +ve - '''key feature'''.
*CD3 -ve.
*CD34 -ve.


==Burkitt's lymphoma==
==Burkitt's lymphoma==
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**Images: [http://en.wikipedia.org/wiki/File:Auer_rods.PNG Auer rods (WP)], [http://www.healthsystem.virginia.edu/internet/hematology/HessImages/Acute-myelogenous-leukemia-M4-100x-Auer-rods-website-arrow.jpg Auer rods (virginia.edu)].
**Images: [http://en.wikipedia.org/wiki/File:Auer_rods.PNG Auer rods (WP)], [http://www.healthsystem.virginia.edu/internet/hematology/HessImages/Acute-myelogenous-leukemia-M4-100x-Auer-rods-website-arrow.jpg Auer rods (virginia.edu)].


==Enteropathy-associated T cell lymphoma==
==Enteropathy-associated T-cell lymphoma==
===General===
*Abbreviated ''EATL''.
*Abbreviated ''EATL''.
*[[AKA]] ''enteropathy-type T cell lymphoma'' (ETTL).
*[[AKA]] ''enteropathy-type T-cell lymphoma'' (ETTL).
*T cell lymphoma due to [[celiac sprue]].
{{Main|Enteropathy-associated T-cell lymphoma}}
 
===Microscopic===
Features:
*Epithelium preserved.
*Small lymphoid cells in the mucosa and submucosa.
 
Image: [http://commons.wikimedia.org/wiki/File:Enteropathy-associated_T_cell_lymphoma_-_low_mag.jpg EATL (WC)].


==Angioimmunoblastic T-cell lymphoma==
==Angioimmunoblastic T-cell lymphoma==
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Features:
Features:
*Intermediate size cells with:
*Intermediate size cells with:
**+/-Vesicular nuclei.
**+/-[[Vesicular nuclei]].
**Clear, moderate cytoplasm.
**Clear, moderate cytoplasm.
*"Empty" sinus; subcapsular sinuses "open".
*"Empty" sinus; subcapsular sinuses "open".
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*Abbreviated ''PMBL''.
*Abbreviated ''PMBL''.
*[[AKA]] ''primary mediastinal large B-cell lymphoma''.
*[[AKA]] ''primary mediastinal large B-cell lymphoma''.
 
{{Main|Primary mediastinal B-cell lymphoma}}
===General===
Features:<ref name=pmid19074109 >{{Cite journal  | last1 = Johnson | first1 = PW. | last2 = Davies | first2 = AJ. | title = Primary mediastinal B-cell lymphoma. | journal = Hematology Am Soc Hematol Educ Program | volume =  | issue =  | pages = 349-58 | month =  | year = 2008 | doi = 10.1182/asheducation-2008.1.349 | PMID = 19074109 }}</ref><ref name=pmid20207294>{{Cite journal  | last1 = Coso | first1 = D. | last2 = Rey | first2 = J. | last3 = Bouabdallah | first3 = R. | title = [Primary mediastinal B-cell lymphoma] | journal = Rev Pneumol Clin | volume = 66 | issue = 1 | pages = 32-5 | month = Feb | year = 2010 | doi = 10.1016/j.pneumo.2009.12.007 | PMID = 20207294 }}</ref>
*Rare.
*Young adults.
*[[Mediastinum]].
 
===Microscopic===
Features:
*Similar to [[DLBCL]].
 
Images:
*[[WC]]:
**[http://commons.wikimedia.org/wiki/File:Primary_mediastinal_large_B-cell_lymphoma_-_very_high_mag.jpg PMBL - very high mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Primary_mediastinal_large_B-cell_lymphoma_-_intermed_mag.jpg PMBL - intermed. mag. (WC)].
*www:
**[http://path.upmc.edu/cases/case371.html PMBL - several images (upmc.edu)].


==Anaplastic large cell lymphoma==
==Anaplastic large cell lymphoma==
*Abbreviated ''ALCL''.
*Abbreviated ''ALCL''.
 
{{Main|Anaplastic large cell lymphoma}}
===General===
*May look a lot like a carcinoma.
**Often subcapsular in LNs.
*Usually T-cell derived.
*May be isolated to the [[skin]] - good prognosis.
 
Alk IHC (systemic form):
* +ve = good prognosis.
* -ve = bad prognosis.
 
===Microscopic===
Features:
*Large cells with eosinophilic cytoplasm.
*Usually appear cohesive.
*May be subcapsular in a [[lymph node]] and mimic a carcinoma.
*''Hallmark cells'' = "horseshoe-shaped or donut-shaped nucleus + eosinophilic paranuclear region"<ref name=pmid17941004>{{Cite journal  | last1 = Rapkiewicz | first1 = A. | last2 = Wen | first2 = H. | last3 = Sen | first3 = F. | last4 = Das | first4 = K. | title = Cytomorphologic examination of anaplastic large cell lymphoma by fine-needle aspiration cytology. | journal = Cancer | volume = 111 | issue = 6 | pages = 499-507 | month = Dec | year = 2007 | doi = 10.1002/cncr.23120 | PMID = 17941004 | url=http://onlinelibrary.wiley.com/doi/10.1002/cncr.23120/full}}</ref><ref name=pmid12419758>{{Cite journal  | last1 = Ponzoni | first1 = M. | last2 = Terreni | first2 = MR. | last3 = Ciceri | first3 = F. | last4 = Ferreri | first4 = AJ. | last5 = Gerevini | first5 = S. | last6 = Anzalone | first6 = N. | last7 = Valle | first7 = M. | last8 = Pizzolito | first8 = S. | last9 = Arrigoni | first9 = G. | title = Primary brain CD30+ ALK1+ anaplastic large cell lymphoma ('ALKoma'): the first case with a combination of 'not common' variants. | journal = Ann Oncol | volume = 13 | issue = 11 | pages = 1827-32 | month = Nov | year = 2002 | doi =  | PMID = 12419758 }}</ref> - '''key feature'''.
**The donut-shaped version is also known as a "wreath cell"<ref>{{Cite journal  | last1 = Amin | first1 = HM. | last2 = Lai | first2 = R. | title = Pathobiology of ALK+ anaplastic large-cell lymphoma. | journal = Blood | volume = 110 | issue = 7 | pages = 2259-67 | month = Oct | year = 2007 | doi = 10.1182/blood-2007-04-060715 | PMID = 17519389 | url=http://bloodjournal.hematologylibrary.org/content/110/7/2259.full.html}}</ref> - large (multi-nucleated) cells with (morphologically) one toroidal-shaped nucleus.
 
DDx:
*[[Hodgkin's lymphoma]].
*Carcinoma.
 
Images:
*[[WC]]:
**[http://commons.wikimedia.org/wiki/File:Anaplastic_large_cell_lymphoma_-_very_high_mag.jpg ALCL - very high mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Anaplastic_large_cell_lymphoma_-_cropped_-_very_high_mag.jpg ALCL - cropped - very high mag. (WC)].
*www:
**[http://path.upmc.edu/cases/case363.html ALCL - several images (upmc.edu)].
**[http://path.upmc.edu/cases/case557.html Small cell variant of ALCL - several images (upmc.edu)].
 
===IHC===
Features:
*CD30 +ve.
*ALK-1 -ve/+ve; strongly supports ALCL Dx if +ve.
*CD45 +ve.
*CD4 +ve.
*CD3 -ve/+ve.
*CD7 -ve/+ve.
*EMA +ve.
 
===Molecular===
*t(2,5)(p23;q35)<ref name=pmid8547653>{{cite journal |author=Lamant L, Meggetto F, al Saati T, ''et al.'' |title=High incidence of the t(2;5)(p23;q35) translocation in anaplastic large cell lymphoma and its lack of detection in Hodgkin's disease. Comparison of cytogenetic analysis, reverse transcriptase-polymerase chain reaction, and P-80 immunostaining |journal=Blood |volume=87 |issue=1 |pages=284–91 |year=1996 |month=January |pmid=8547653 |doi= |url=}}</ref> - can be detected with [[FISH]] break apart probe.


==Cutaneous T cell lymphoma==
==Cutaneous T cell lymphoma==
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===IHC===
===IHC===
*CF57 +ve.
*CD57 +ve -- '''important'''.
*CD3 +ve.
*CD5 +ve.
*CD45 +ve.


==Lymphoplasmacytic lymphoma==
==Lymphoplasmacytic lymphoma==
*May be referred to as ''Waldenström macroglobulinemia'', a hyperviscosity syndrome, that arises from it.
:''Waldenström macroglobulinemia'' redirects here.
===General===
===General===
Features:<ref name=Ref_PCPBoD8_325>{{Ref PCPBoD8|325}}</ref>
Features:<ref name=Ref_PCPBoD8_325>{{Ref PCPBoD8|325}}</ref>
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*Secretes monoclonal IgM.
*Secretes monoclonal IgM.


Clinical:<ref name=Ref_PCPBoD8_325>{{Ref PCPBoD8|325}}</ref>
Note:
*Symptoms of blood hyperviscosity (visual impairment, neurologic impairment, bleeding, cryoglobulinemia).
*''Waldenström macroglobulinemia'' is a type of lymphoplasmacytic lymphoma<ref name=pmid22507796>{{Cite journal  | last1 = Gertz | first1 = MA. | title = Waldenström macroglobulinemia. | journal = Hematology | volume = 17 Suppl 1 | issue =  | pages = 112-6 | month = Apr | year = 2012 | doi = 10.1179/102453312X13336169156212 | PMID = 22507796 }}</ref> - it is characterized by:
**''Hyperviscosity syndrome''.
**Bony destruction (seen in [[multiple myeloma]]) is absent.<ref name=Ref_PCPBoD8_325>{{Ref PCPBoD8|325}}</ref>
**Over 90% of patients have the MYD88 L265P somatic mutation.<ref name=pmid=22931316>{{cite journal |vauthors=Treon SP, Xu L, Yang G, Zhou Y, Liu X, Cao Y, Sheehy P, Manning RJ, Patterson CJ, Tripsas C, Arcaini L, Pinkus GS, Rodig SJ, Sohani AR, Harris NL, Laramie JM, Skifter DA, Lincoln SE, Hunter ZR |title=MYD88 L265P somatic mutation in Waldenström's macroglobulinemia |journal=N Engl J Med |volume=367 |issue=9 |pages=826–33 |date=August 2012 |pmid=22931316 |doi=10.1056/NEJMoa1200710 |url=}}</ref>
 
====Clinical====
Features:<ref name=Ref_PCPBoD8_325>{{Ref PCPBoD8|325}}</ref>
*Symptoms of blood hyperviscosity - these include:
**Visual impairment.
**Neurologic impairment.
**Bleeding.
**[[Cryoglobulinemia]] - may have ''Raynaud phenomenon''.
*Hemolysis.
*Hemolysis.
*Bence-Jones proteinuria - seen in over half of patients.<ref name=pmid11797112>{{Cite journal  | last1 = Kyrtsonis | first1 = MC. | last2 = Vassilakopoulos | first2 = TP. | last3 = Angelopoulou | first3 = MK. | last4 = Siakantaris | first4 = P. | last5 = Kontopidou | first5 = FN. | last6 = Dimopoulou | first6 = MN. | last7 = Boussiotis | first7 = V. | last8 = Gribabis | first8 = A. | last9 = Konstantopoulos | first9 = K. | title = Waldenström's macroglobulinemia: clinical course and prognostic factors in 60 patients. Experience from a single hematology unit. | journal = Ann Hematol | volume = 80 | issue = 12 | pages = 722-7 | month = Dec | year = 2001 | doi = 10.1007/s00277-001-0385-8 | PMID = 11797112 }}</ref>
Treatment:
*Watchful waiting or chemotherapy.
*Hyperviscosity syndrome: plasmapheresis.


===Microscopic===
===Microscopic===
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*Plasmacytoid lymphocytes.  
*Plasmacytoid lymphocytes.  
*Mixed inflammatory infiltrate with [[mast cell]]s, [[plasma cell]]s, lymphocytes.
*Mixed inflammatory infiltrate with [[mast cell]]s, [[plasma cell]]s, lymphocytes.
DDx:
*[[Plasma cell neoplasm]].


===IHC===
===IHC===
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*CD25 +ve.
*CD25 +ve.
*CD45 +ve.
*CD45 +ve.
*HTLV-1 +ve.


Others:<ref name=pmid19165640/>
Others:<ref name=pmid19165640/>
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*[[AKA]] ''extranodal natural kill lymphoma''
*[[AKA]] ''extranodal natural kill lymphoma''
*[[AKA]] ''angiocentric lymphoma''.
*[[AKA]] ''angiocentric lymphoma''.
 
{{Main|Extranodal NK/T-cell lymphoma, nasal type}}
===General===
*Common in east Asia.<ref name=pmid18283711>{{Cite journal  | last1 = Suzuki | first1 = R. | last2 = Takeuchi | first2 = K. | last3 = Ohshima | first3 = K. | last4 = Nakamura | first4 = S. | title = Extranodal NK/T-cell lymphoma: diagnosis and treatment cues. | journal = Hematol Oncol | volume = 26 | issue = 2 | pages = 66-72 | month = Jun | year = 2008 | doi = 10.1002/hon.847 | PMID = 18283711 }}</ref>
*Strong association with [[EBV]].
 
===Microscopic===
Features:
*Atypical lymphoid cells:
**[[Nucleoli]].
**[[Nuclear pleomorphism]].
**Cells centered around vessels (angiocentric).
***May destroy small and medium sized arterioles.
 
Images:
*[http://path.upmc.edu/cases/case231/micro.html Extranodal NK/T-cell lymphoma, nasal type - case 1 - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case310.html Extranodal NK/T-cell lymphoma, nasal type - case 2 - several images (upmc.edu)].
 
===IHC===
Features:<ref name=pmid17064952>{{Cite journal  | last1 = Al-Hakeem | first1 = DA. | last2 = Fedele | first2 = S. | last3 = Carlos | first3 = R. | last4 = Porter | first4 = S. | title = Extranodal NK/T-cell lymphoma, nasal type. | journal = Oral Oncol | volume = 43 | issue = 1 | pages = 4-14 | month = Jan | year = 2007 | doi = 10.1016/j.oraloncology.2006.03.011 | PMID = 17064952 }}</ref>
*CD2 +ve.
*CD3 +ve (cytoplasmic).
*CD56 +ve.
 
Others:<ref>URL: [http://path.upmc.edu/cases/case310.html http://path.upmc.edu/cases/case310.html]. Accessed on: 14 January 2012.</ref>
*TIA-1 +ve.
*CD7 +ve.
*EBER +ve.


==Table of lymphoma==
==Table of lymphoma==
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| lymph node usually, germinal center
| lymph node usually, germinal center
| sheets of large discohesive cells; if only nodular = follicular lymphoma
| sheets of large discohesive cells; if only nodular = follicular lymphoma
| MIB-1 >40%
| MIB1 >40%
| none / like follicular lymphoma t(14,18) / c-MYC (like Burkitt lymphoma)
| none / like follicular lymphoma t(14,18) / c-MYC (like Burkitt lymphoma)
| poor prognosis
| poor prognosis
Maxwell
4

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