Difference between revisions of "Lymphoma"

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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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*Lambda.
*Lambda.
*CD56<ref>URL: [http://www.ncbi.nlm.nih.gov/omim/116930 http://www.ncbi.nlm.nih.gov/omim/116930]. Accessed on: 31 August 2010.</ref> -- also +ve in NK/T cell lymphomas.
*CD56<ref>URL: [http://www.ncbi.nlm.nih.gov/omim/116930 http://www.ncbi.nlm.nih.gov/omim/116930]. Accessed on: 31 August 2010.</ref> -- also +ve in NK/T cell lymphomas.
*CD57 -- +ve in T-cell large granular lymphocytic leukemia.<ref>URL: [http://www.nature.com/bmt/journal/v33/n1/full/1704298a.html http://www.nature.com/bmt/journal/v33/n1/full/1704298a.html]. Accessed on: 31 August 2010.</ref>.
*CD57 -- +ve in [[T-cell large granular lymphocytic leukemia]].<ref>URL: [http://www.nature.com/bmt/journal/v33/n1/full/1704298a.html http://www.nature.com/bmt/journal/v33/n1/full/1704298a.html]. Accessed on: 31 August 2010.</ref>.
*CD138.
*CD138.


====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:
*[http://commons.wikimedia.org/wiki/File:Intravascular_lymphoma_-_high_mag.jpg Intravascular lymphoma - high mag. (WC)].
*[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)].
====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==
*Abbreviated ''AITL''.
===General===
*Rare.
**Common among T-cell lymphomas.
*Middle age ''or'' elderly.


===Microscopic===
===Microscopic===
Features:
Features:
*Clear cytoplasm.
*Intermediate size cells with:
**+/-[[Vesicular nuclei]].
**Clear, moderate cytoplasm.
*"Empty" sinus; subcapsular sinuses "open".
*"Empty" sinus; subcapsular sinuses "open".
Images:
*[http://www.ijpmonline.org/viewimage.asp?img=IndianJPatholMicrobiol_2010_53_4_640_72010_f4.jpg AITL (ijpmonline.org)].<ref name=pmid21045384>{{Cite journal  | last1 = Bal | first1 = M. | last2 = Gujral | first2 = S. | last3 = Gandhi | first3 = J. | last4 = Shet | first4 = T. | last5 = Epari | first5 = S. | last6 = Subramanian | first6 = PG. | title = Angioimmunoblastic T-Cell lymphoma: a critical analysis of clinical, morphologic and immunophenotypic features. | journal = Indian J Pathol Microbiol | volume = 53 | issue = 4 | pages = 640-5 | month =  | year =  | doi = 10.4103/0377-4929.72010 | PMID = 21045384 | URL = http://www.ijpmonline.org/text.asp?2010/53/4/640/72010 }}</ref>
*[http://path.upmc.edu/cases/case650.html AITL - several images (upmc.edu)]


===IHC===
===IHC===
Features - positives:<ref name=pmid21045384/>
*CD3 +ve.
*CD5 +ve.
*CD43 +ve.
Others:
*CD4 +ve and CD8 +ve with CD4>CD8.
*CD20 +ve/-ve!
*CD10 +ve/-ve!
*CD21 +ve -- prominent FDC meshworks;<ref>URL: [http://path.upmc.edu/cases/case650/dx.html http://path.upmc.edu/cases/case650/dx.html]. Accessed on: 27 January 2012.</ref> tumour cell not +ve.
Negatives:
*CD30 -ve.<ref name=pmid21045384/>
*CD15 -ve.<ref name=pmid21045384/>
*CD7 -ve.
*CD7 -ve.
*CD20 +ve.
*TIA-1 -ve.
*TIA-1 -ve.


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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:
*[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)].


==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)].
 
===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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*[http://www.flickr.com/photos/32549645@N02/3040759595/ Sézary cell (flickr.com)].
*[http://www.flickr.com/photos/32549645@N02/3040759595/ Sézary cell (flickr.com)].
*[http://www.wadsworth.org/chemheme/heme/glass/cytopix/slide015_sezary2.jpg Sézary cell (wadsworth.org)].
*[http://www.wadsworth.org/chemheme/heme/glass/cytopix/slide015_sezary2.jpg Sézary cell (wadsworth.org)].
==T-cell large granular lymphocytic leukemia==
===General===
*May be seen in the context of [[Felty syndrome]].
===Microscopic===
Features:
*Large cell lymphoma.
Images:
*[http://path.upmc.edu/cases/case695.html T-cell large granular lymphocytic leukemia (upmc.edu)].
===IHC===
*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>
 
====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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===Microscopic===
===Microscopic===
Features:<ref name=Ref_PCPBoD8_328>{{Ref PCPBoD8|328}}</ref>
Features:<ref name=Ref_PCPBoD8_328>{{Ref PCPBoD8|328}}</ref>
*Cloverleaf nuclei; nuclei with multiple lobulations.
*Cloverleaf nuclei.
**Nuclei with multiple lobulations.
 
Image:
*[http://www.pathpedia.com/education/eatlas/histopathology/blood_cells/adult_t-cell_leukemia_htlv1-positive_acute_form/adult-t-cell-leukemia-htlv1-%5B2-bl095-2%5D.jpeg?Width=600&Height=450&Format=4 Cloverleaf nucleus (pathpedia.com)].<ref>URL: [http://www.pathpedia.com/education/eatlas/histopathology/blood_cells/adult_t-cell_leukemia_htlv1-positive_acute_form.aspx http://www.pathpedia.com/education/eatlas/histopathology/blood_cells/adult_t-cell_leukemia_htlv1-positive_acute_form.aspx]. Accessed on: 7 February 2012.</ref>
 
===IHC===
Features:<ref name=pmid19165640>{{Cite journal  | last1 = Bittencourt | first1 = AL. | last2 = Barbosa | first2 = HS. | last3 = Vieira | first3 = MD. | last4 = Farré | first4 = L. | title = Adult T-cell leukemia/lymphoma (ATL) presenting in the skin: clinical, histological and immunohistochemical features of 52 cases. | journal = Acta Oncol | volume = 48 | issue = 4 | pages = 598-604 | month =  | year = 2009 | doi = 10.1080/02841860802657235 | PMID = 19165640 |URL = http://informahealthcare.com/doi/pdf/10.1080/02841860802657235 }}</ref>
*CD3 +ve.
*CD5 +ve.
*CD25 +ve.
*CD45 +ve.
*HTLV-1 +ve.
 
Others:<ref name=pmid19165640/>
*CD7 -ve.
*CD20 -ve.
*CD79a -ve.


==Hepatosplenic T-cell lymphoma==
==Hepatosplenic T-cell lymphoma==
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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

Latest revision as of 19:37, 31 July 2016

Lymphoma at cut-up. (WC/Emmanuelm)

Lymphoma is almost a specialty for itself. It can be subclassified a number of ways.

This article is an introduction to lymphoma. An introduction to lymph nodes and lymph node pathology that is not lymphoma are in the articles lymph node and lymph node pathology.

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"[1] - mnemonic These Bothersome features cause Wednesday Night Fever:[2]

  • 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 absent.

Lymphoma classification

Lymphomas can be divided into:

Other categorizations:

  • T cell lymphomas (rare).
  • B cell lymphomas (more common).

Two most common NHLs:

Leukemia as a med student

Histologic classification

  1. "Size".
  2. Nodularity.

"Size"

  • The single most important factor for classifying lymphomas.
  • Not really based on size.
"Large" "Small" Utility
Nucleoli present absent most discriminative
Size >2x RBC dia. <2x RBC dia. moderate
Chromatin pattern "open" (pale) "closed" moderate/minimal
Cytoplasm mold-minimal
basophilic cytoplasm 		scant cytoplasm minimal

Histologic terms

  • Lymphomas = cells look discohesive, may be difficult to differentiate from poor differentiated carcinoma.
  • Auer rods = acute myeloid leukemia.
    • Granular cytoplasmic rod (0.5-1 x4-6 micrometres).
    • Not pathognomonic.
  • Reed-Sternberg cells = Hodgkin's lymphoma.
    • Large cell - very large nucleus.
      • Classically binucleated.
  • Russell bodies = plasmacytoma (+others).
    • Eosinophilic, large, homogenous immunoglobulin-containing inclusions.[3]
      • Mott cell is a cell that contains Russell bodies.[3]
  • Effacement of nodal architecture.
  • Loss of proliferation centers.

IHC

General

  • CD45.
    • AKA common lymphocyte antigen.
    • Useful to differentiate from carcinomas (e.g. small cell carcinoma).

Others:

T cell markers

  • CD2 -- T cell marker (all T cells).
  • CD3 -- T cell marker (all T cells).
    • CD4 -- subset of T cells.
    • CD8 -- subset of T cells.
  • CD7 -- often lost first in T cell lymphomas.
  • CD5 -- +ve in CLL & mantle cell lymphoma.
  • CD43 -- +ve in mantle cell lymphoma
  • ALK1[4] - prognostic in anaplastic large cell lymphoma (ALCL).[5]
  • TIA1 - cytotoxic T-cell.[6]
  • Granzyme B.

B cell markers

  • CD10 -- follicle center.
  • BCL6 -- follicle center.
  • BCL2 -- normally negative in germinal centers (GCs), marks T cell; +ve in small B cell lymphomas.
  • MUM1 -- -ve in follicular lymphoma, +ve in DLBCL that did not arise from follicular lymphoma.

Plasma cell

Follicular dendritic cells

  • CD23 -- follicular dendritic cells.
  • CD21 -- follicular dendritic cells, considered more sensitive than CD23.[10]

Hodgkin's lymphoma

Classic
  • CD30 +ve -- Hodgkin's lymphoma (most sensitive).
  • CD15 +ve.
  • PAX5 +ve.
  • EMA -ve.
  • EBER +ve/-ve.

Others:

  • CD20, CD45: weak +ve or -ve.
NLPHL
  • CD20 +ve.
  • CD30 -ve, CD15 -ve.
  • EMA +ve/-ve.
  • EBER -ve.

Others

  • Myeloperoxidase - in PMNs.
  • Glycophorin C.
  • CD61 -- megakaryocytes.
  • TdT.
  • CD34.

Molecular pathology

Main article: Molecular pathology
Main article: Molecular pathology tests
  • T cell clonality study.
  • B cell clonality study.

Chromosomal translocations

Main article: Chromosomal_translocations#Lymphoma

Hodgkin's lymphoma

Main article: Hodgkin's lymphoma

General

  • Abbreviated HL.

Microscopic

By definition, HL has Reed-Sternberg cells (RSCs).

Classical HL

Features (classic HL):

  • Reed-Sternberg cell.
    • Large binucleated cell.
      • May be multinucleated.
      • May have a horseshoe-like shape.
    • Macronucleolus - approximately the size of a RBC (~8 micrometers).
    • Well-defined cell border.

Notes:

  • Large mononuclear cells are common (so called "mononuclear RSCs") but not diagnostic.

Images (classic HL):

Subtypes

There are four CHL subtypes:[11]

  1. Nodular sclerosis CHL - ~70% of CHL.
    • Mixed cellular background - T cell, plasma cells, eosinophils, neutrophils and histiocytes.
    • Nodular sclerosing fibrosis - thick strands fibrosis.
  2. Mixed cellularity CHL - ~20-25% of CHL.
    • Like nodular sclerosis - but no fibrosis.
    • May be associated with HIV infection.[12]
  3. Lymphocyte-rich CHL - rare.
    • T lymphocytes only (no mix of cells).
  4. Lymphocyte-depleted CHL - rare.
    • May be associated with HIV infection.[12]

Memory device:

  • The subtypes prevalence is in reverse alphabetical order.

Nodular lymphocyte-predominant HL

Features (nodular lymphocyte-predominant Hodgkin's lymphoma):

  • Popcorn cell (previously known as Lymphocytic & histiocytic cell (L&H cell)[13]) - variant of RSC:
    • Cells (relatively) small (compared to classic RSCs).
    • Lobulated nucleus - key feature.
    • Small nucleoli.
  • Subtle nodularity at low power (2.5x or 5x objective).

Images (NLPHL):

Small cell lymphomas

Main article: Small cell lymphomas

This grouping includes:

  • Follicular lymphoma.
  • Marginal zone lymphoma.
    • Nodal marginal zone lymphoma.
    • Extranodal marginal zone lymphoma (MALT lymphoma).
    • Splenic marginal zone lymphoma.
  • Mantle zone lymphoma.
  • Small lymphocytic lymphoma (SLL) / chronic lymphocytic leukemia (CLL).
  • Hairy cell leukemia.

Diffuse large B-cell lymphoma

Main article: Diffuse large B cell lymphoma

General

  • Abbreviated DLBCL.

Microscopic

Features:[14]

  • Large cells -- 4-5 times the diameter of a small lymphocytes.
  • Typically have marked cell-to-cell variation in size and shape.
  • Cytoplasm usu. basophilic and moderate in abundance.
  • +/-Prominent nucleoli, may be peripheral and/or multiple.

Notes:

  • Large bizarre cells can occasionally mimic Reed-Sternberg cells, seen in Hodgkin lymphoma.

Intravascular lymphoma

Burkitt's lymphoma

Main article: Burkitt lymphoma

General

  • Abbreviated BL.
  • Subtyped by etiology.

Microscopic

Features:

  • "Starry-sky pattern":
    • The stars in the pattern are: tingible-body macrophages.
      • Tingible-body macrophages = macrophages containing apoptotic tumour cells.
    • The tumour cells are the sky.
  • Tumour cells:[16]
    • Medium-sized (~1.5-2x the size of a RBC) with uniform size ("monotonous") -- key feature.
    • Round nucleus.
    • Small nucleoli.
    • Relatively abundant cytoplasm.
    • Brisk mitotic rate.

Image: Starry-sky pattern - Ed Uthman (WC).

Plasma cell neoplasms

Main article: Plasma cell neoplasms
  • These arise from plasma cells.
  • AKA plasma cell myeloma, plasmacytoma.
  • Multiple myeloma (a clinical diagnosis) fits into this category.

Acute myeloid leukemia

General

  • May afflicits young adult.
  • Males>females.

Complications

  • Chloroma - soft tissue mass.
  • Leukostasis.
    • Occurs - lungs and brain.[17]
  • Hyperviscosity syndrome.
  • Spontaneous bleeding with low platelet counts.

Classification

There are two classifications:

  1. FAB (French-American-British) - based on histologic appearance/maturation.
  2. WHO classification.

Histology

Enteropathy-associated T-cell lymphoma

  • Abbreviated EATL.
  • AKA enteropathy-type T-cell lymphoma (ETTL).
Main article: Enteropathy-associated T-cell lymphoma

Angioimmunoblastic T-cell lymphoma

  • Abbreviated AITL.

General

  • Rare.
    • Common among T-cell lymphomas.
  • Middle age or elderly.

Microscopic

Features:

  • Intermediate size cells with:
  • "Empty" sinus; subcapsular sinuses "open".

Images:

IHC

Features - positives:[19]

  • CD3 +ve.
  • CD5 +ve.
  • CD43 +ve.

Others:

  • CD4 +ve and CD8 +ve with CD4>CD8.
  • CD20 +ve/-ve!
  • CD10 +ve/-ve!
  • CD21 +ve -- prominent FDC meshworks;[20] tumour cell not +ve.

Negatives:

  • CD30 -ve.[19]
  • CD15 -ve.[19]
  • CD7 -ve.
  • TIA-1 -ve.

Primary mediastinal B-cell lymphoma

  • Abbreviated PMBL.
  • AKA primary mediastinal large B-cell lymphoma.
Main article: Primary mediastinal B-cell lymphoma

Anaplastic large cell lymphoma

  • Abbreviated ALCL.
Main article: Anaplastic large cell lymphoma

Cutaneous T cell lymphoma

See Dermatologic neoplasms.

General

  • Abbreviated as CTCL.
    • Sézary syndrome is a subset of CTCL.

Microscopic

Features:[21]

  • Cerebriform nucleus (Sézary cell):[22]
    • Hyperchromatic.
    • "Convoluted" = twisted, coiled.[23]

Images:

T-cell large granular lymphocytic leukemia

General

Microscopic

Features:

  • Large cell lymphoma.

Images:

IHC

  • CD57 +ve -- important.
  • CD3 +ve.
  • CD5 +ve.
  • CD45 +ve.

Lymphoplasmacytic lymphoma

Waldenström macroglobulinemia redirects here.

General

Features:[24]

  • B cell neoplasm.
  • Secretes monoclonal IgM.

Note:

  • Waldenström macroglobulinemia is a type of lymphoplasmacytic lymphoma[25] - it is characterized by:

Clinical

Features:[24]

  • Symptoms of blood hyperviscosity - these include:
    • Visual impairment.
    • Neurologic impairment.
    • Bleeding.
    • Cryoglobulinemia - may have Raynaud phenomenon.
  • Hemolysis.
  • Bence-Jones proteinuria - seen in over half of patients.[26]

Treatment:

  • Watchful waiting or chemotherapy.
  • Hyperviscosity syndrome: plasmapheresis.

Microscopic

Features:[24]

DDx:

IHC

Features:[27]

  • PAX5 +ve.
  • CD20 +ve.
  • CD38 +ve.
  • CD138 +ve.

Others:[27]

  • CD5 -ve.
  • CD10 -ve.
  • CD23 -ve.
  • CyclinD1 -ve.
  • CD3 -ve.
  • CD7 -ve.

Adult T-cell leukemia/lymphoma

General

  • Etiology: Human T-cell Lymphoma Virus 1 (HTLV-1).[28]
  • Poor prognosis ~ 1 year survival with treatment.

Microscopic

Features:[29]

  • Cloverleaf nuclei.
    • Nuclei with multiple lobulations.

Image:

IHC

Features:[31]

  • CD3 +ve.
  • CD5 +ve.
  • CD25 +ve.
  • CD45 +ve.
  • HTLV-1 +ve.

Others:[31]

  • CD7 -ve.
  • CD20 -ve.
  • CD79a -ve.

Hepatosplenic T-cell lymphoma

Main article: Hepatosplenic T-cell lymphoma

Extranodal NK/T-cell lymphoma, nasal type

  • Abbreviated as ENKL or ENKTCL.
  • AKA extranodal natural kill lymphoma
  • AKA angiocentric lymphoma.
Main article: Extranodal NK/T-cell lymphoma, nasal type

Table of lymphoma

B cell lymphomas

Name Size of cells Site Histomorphology IHC Translocations Clinical Prevalence DDx
Follicular lymphoma small (centrocytes) lymph node, germinal center abundant atypical follicles (lack GC polarity, lack polar mantle zone), effaced sinuses, scattered large cells (centroblasts) CD10+, bcl-6+[32] t(14,18) usually indolent, may transform to DLBCL very common DLBCL, other small cell lymphomas
Mantle cell lymphoma small, monomorphic lymph node, mantle zone monomorphic lymphoid, abundant mitoses. +/-scattered epithelioid histiocytes, sclerosed blood vessels CD5+, CD23-, CD43+, cyclin D1+[32] t(11;14)(q13;q32)[33] indolent ??? uncommon other small cell lymphomas, PTGC, Castleman disease, Burkitt's lymphoma
Extranodal marginal zone lymphoma (MALT lymphoma) small mucosa-associated lymphoid tissue, GI tract + elsewhere +/- lymphepithelial lesion (cluster of 3+ cells in epithelium) CD21+, CD11c+, CD5-, CD23-[32] ??? indolent ??? common other small cell lymphomas, neuroendocrine tumours
Precursor B-cell lymphoblastic lymphoma/ leukemia small lymph node ???, bone marrow nuclei slightly large than resting lymphocytes, scant basophilic cytoplasm, irregular nuclear membrane, no nucleoli, stippled chromatin[34] CD10+, CD5-, TdT+, CD99+[32] +/-t(12;21)[35] aggressive ??? uncommon small cell lymphomas
Hairy cell leukemia small bone marrow, peripheral blood perinuclear clearing, clear cytoplasm, central nucleus CD25+, CD103+, CD5-[36] translocations ? splenomegaly, no lymphadenopathy, pancytopenia, good prognosis with Tx uncommon small cell leukemias/lymphomas (e.g. SMZL)
Burkitt's lymphoma medium, monomorphic lymph node, germinal center (???) tingible-body macrophages ("starry sky" appearance), round nucleus, small nucleoli, mitoses +++ CD10+, BCL6+, BCL2- t(8;14) (q24;q32) rapid growth, may be associated with EBV, HIV/AIDS uncommon DLBCL, mantle cell lymphoma
Diffuse large B cell lymphoma large cells (>2x RBC, often larger), variable size lymph node usually, germinal center sheets of large discohesive cells; if only nodular = follicular lymphoma MIB1 >40% none / like follicular lymphoma t(14,18) / c-MYC (like Burkitt lymphoma) poor prognosis very common Burkitt lymphoma, ALCL, Hodgkin lymphoma
Primary mediastinal B-cell lymphoma large (>2x RBC, often larger), variable size mediastinum histomorphology ? IHC ? translocations ? predominantly young adults, better prognosis than DLBCL uncommon DLBCL
B cell small lymphocytic lymphoma /
chronic lymphocytic leukemia 		small lymph node (???) proliferation centres CD5+, CD23+, CD43+, cyclin D1- trisomy 12; deletions of 11q, 13q, 17p[37] good prognosis / indolent course common other small cell lymphomas

T cell lymphomas

Name Size of cells Site Histomorphology IHC Translocations Clinical Prevalence DDx
Angioimmunoblastic lymphoma size of cells ? site ? histomorphology ? IHC ? translocations ? clinical ? prevalence ? DDx ?
Enteropathy-type T cell lymphoma size of cells ? site ? histomorphology ? IHC ? translocations ? clinical ? prevalence ? DDx ?
Precursor lymphoblastic lymphoma / leukemia size of cells ? site ? histomorphology ? IHC ? translocations ? clinical ? prevalence ? DDx ?
Adult T-cell lymphoma / leukemia size of cells ? site ? cloverleaf nuclei (multilobular nuclei) IHC ? translocations ? poor prognosis ~ 1 year survival w/ Tx; d/t HTLV-1 prevalence ? DDx ?
Peripheral T cell lymphoma (NOS) size of cells ? site ? histomorphology ? TIA-1+ translocations ? clinical ? prevalence ? DDx ?
Anaplastic large cell lymphoma large deep & subcapsular sinuses of LN eosinophilic cytoplasm, nucleoli, often cohesive, wreath cell (C-shaped nucleus) CD30+/-, Alk+/-, CD4+, CD3- t(2,5)(p23;q35)[38] clinical ? uncommon carcinoma
Extranodal NK/T cell lymphoma nasal type large ??? nasal ??? histomorphology ? EBER+, CD16+, CD56+, CD57-, TIA-1+, Granzyme B+ translocations ? common in East Asia uncommon DDx ?
Blastic NK cell lymphoma size of cells ? site ? histomorphology ? IHC ? translocations ? clinical ? prevalence ? DDx ?

See also

References

  1. ↑ Carbone, PP.; Kaplan, HS.; Musshoff, K.; Smithers, DW.; Tubiana, M. (Nov 1971). "Report of the Committee on Hodgkin's Disease Staging Classification.". Cancer Res 31 (11): 1860-1. PMID 5121694.
  2. ↑ URL: http://www.internalizemedicine.com/2011/12/bury-buzzword-b-symptoms.html. Accessed on: 28 March 2012.
  3. ↑ 3.0 3.1 Alanen A, Pira U, Lassila O, Roth J, Franklin RM (March 1985). "Mott cells are plasma cells defective in immunoglobulin secretion". Eur. J. Immunol. 15 (3): 235–42. PMID 3979421.
  4. ↑ URL: http://www.ncbi.nlm.nih.gov/omim/601284. Accessed on: 31 August 2010.
  5. ↑ Pittaluga S, Wlodarska I, Pulford K, et al. (August 1997). "The monoclonal antibody ALK1 identifies a distinct morphological subtype of anaplastic large cell lymphoma associated with 2p23/ALK rearrangements". Am. J. Pathol. 151 (2): 343–51. PMC 1858018. PMID 9250148. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1858018/.
  6. ↑ URL: http://www.ncbi.nlm.nih.gov/omim/603518. Accessed on: 18 August 2010.
  7. ↑ URL: http://www.ncbi.nlm.nih.gov/omim/167414. Accessed on: 18 August 2010.
  8. ↑ URL: http://www.ncbi.nlm.nih.gov/omim/116930. Accessed on: 31 August 2010.
  9. ↑ URL: http://www.nature.com/bmt/journal/v33/n1/full/1704298a.html. Accessed on: 31 August 2010.
  10. ↑ Troxell, ML.; Schwartz, EJ.; van de Rijn, M.; Ross, DT.; Warnke, RA.; Higgins, JP.; Natkunam, Y. (Dec 2005). "Follicular dendritic cell immunohistochemical markers in angioimmunoblastic T-cell lymphoma.". Appl Immunohistochem Mol Morphol 13 (4): 297-303. PMID 16280657.
  11. ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 567. ISBN 978-0781765275.
  12. ↑ 12.0 12.1 Sissolak G, Sissolak D, Jacobs P (April 2010). "Human immunodeficiency and Hodgkin lymphoma". Transfus. Apher. Sci. 42 (2): 131–9. doi:10.1016/j.transci.2010.01.008. PMID 20138008.
  13. ↑ Küppers R, Rajewsky K, Braeuninger A, Hansmann ML (March 1998). "L&H cells in lymphocyte-predominant Hodgkin's disease". N. Engl. J. Med. 338 (11): 763–4; author reply 764–5. doi:10.1056/NEJM199803123381113. PMID 9499174.
  14. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 676 (???). ISBN 0-7216-0187-1.
  15. ↑ Wang L, Li C, Gao T (March 2010). "Cutaneous intravascular anaplastic large cell lymphoma". J Cutan Pathol. doi:10.1111/j.1600-0560.2010.01538.x. PMID 20337769.
  16. ↑ Bellan C, Lazzi S, De Falco G, Nyongo A, Giordano A, Leoncini L (March 2003). "Burkitt's lymphoma: new insights into molecular pathogenesis". J. Clin. Pathol. 56 (3): 188–92. PMC 1769902. PMID 12610094. http://jcp.bmj.com/cgi/pmidlookup?view=long&pmid=12610094.
  17. ↑ AML. Harrison's 16th Ed.
  18. ↑ AG. 8 July, 2009.
  19. ↑ 19.0 19.1 19.2 19.3 Bal, M.; Gujral, S.; Gandhi, J.; Shet, T.; Epari, S.; Subramanian, PG.. "Angioimmunoblastic T-Cell lymphoma: a critical analysis of clinical, morphologic and immunophenotypic features.". Indian J Pathol Microbiol 53 (4): 640-5. doi:10.4103/0377-4929.72010. PMID 21045384.
  20. ↑ URL: http://path.upmc.edu/cases/case650/dx.html. Accessed on: 27 January 2012.
  21. ↑ URL: http://emedicine.medscape.com/article/209091-overview. Accessed on: 19 August 2010.
  22. ↑ URL: http://emedicine.medscape.com/article/204529-diagnosis. Accessed on: 19 August 2010.
  23. ↑ URL: http://dictionary.reference.com/browse/convoluted. Accessed on: 19 August 2010.
  24. ↑ 24.0 24.1 24.2 24.3 Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 325. ISBN 978-1416054542.
  25. ↑ Gertz, MA. (Apr 2012). "Waldenström macroglobulinemia.". Hematology 17 Suppl 1: 112-6. doi:10.1179/102453312X13336169156212. PMID 22507796.
  26. ↑ Kyrtsonis, MC.; Vassilakopoulos, TP.; Angelopoulou, MK.; Siakantaris, P.; Kontopidou, FN.; Dimopoulou, MN.; Boussiotis, V.; Gribabis, A. et al. (Dec 2001). "Waldenström's macroglobulinemia: clinical course and prognostic factors in 60 patients. Experience from a single hematology unit.". Ann Hematol 80 (12): 722-7. doi:10.1007/s00277-001-0385-8. PMID 11797112.
  27. ↑ 27.0 27.1 Liu, EB.; Zhang, PH.; Li, ZQ.; Sun, Q.; Yang, QY.; Fang, LH.; Sun, FJ.; Qiu, LG. (May 2010). "[Clinicopathologic features of lymphoplasmacytic lymphoma].". Zhonghua Bing Li Xue Za Zhi 39 (5): 308-12. PMID 20654153.
  28. ↑ Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 327. ISBN 978-1416054542.
  29. ↑ Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 328. ISBN 978-1416054542.
  30. ↑ URL: http://www.pathpedia.com/education/eatlas/histopathology/blood_cells/adult_t-cell_leukemia_htlv1-positive_acute_form.aspx. Accessed on: 7 February 2012.
  31. ↑ 31.0 31.1 Bittencourt, AL.; Barbosa, HS.; Vieira, MD.; Farré, L. (2009). "Adult T-cell leukemia/lymphoma (ATL) presenting in the skin: clinical, histological and immunohistochemical features of 52 cases.". Acta Oncol 48 (4): 598-604. doi:10.1080/02841860802657235. PMID 19165640.
  32. ↑ 32.0 32.1 32.2 32.3 Lester, Susan Carole (2005). Manual of Surgical Pathology (2nd ed.). Saunders. pp. 95. ISBN 978-0443066450.
  33. ↑ URL: http://atlasgeneticsoncology.org/Anomalies/t1114ID2021.html. Accessed on: 10 August 2010.
  34. ↑ Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 315. ISBN 978-1416054542.
  35. ↑ Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 317. ISBN 978-1416054542.
  36. ↑ URL: http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=cmed&part=A34022&rendertype=table&id=A34029. Accessed on: 20 August 2010.
  37. ↑ Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 318. ISBN 978-1416054542.
  38. ↑ Lamant L, Meggetto F, al Saati T, et al. (January 1996). "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". Blood 87 (1): 284–91. PMID 8547653.
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