Waldenström's macroglobulinemia differential diagnosis: Difference between revisions

Jump to navigation Jump to search
No edit summary
 
(27 intermediate revisions by 6 users not shown)
Line 1: Line 1:
__NOTOC__
__NOTOC__
{{CMG}}{{AE}}{{MGS}}
 
{{Waldenström's macroglobulinemia}}
{{CMG}}; {{AE}} {{S.M.}}{{GRR}} {{Nat}}
[[Image:Home_logo1.png|right|250px|link=http://www.wikidoc.org/index.php/Waldenstr%C3%B6m%27s_macroglobulinemia]]


==Overview==
==Overview==
Waldenström's macroglobulinemia must be differentiated from [[Multiple myeloma]], [[Chronic lymphocytic leukemia]]/[[small lymphocytic lymphoma]], [[B-cell prolymphocytic leukemia]], [[Follicular lymphoma]], [[Mantle cell lymphoma]], and Marginal zone lymphoma. <ref name="UTD"></ref>
[[Waldenström's macroglobulinemia|Waldenstrom's macroglobulinemia]] must be [[Differentiate|differentiated]] from [[multiple myeloma]], [[chronic lymphocytic leukemia]]/[[small lymphocytic lymphoma]], [[b-cell prolymphocytic leukemia]], [[follicular lymphoma]], [[mantle cell lymphoma]], and [[marginal zone lymphoma]].
 
==Differentiating Lymphoplasmacytic lymphoma from other Diseases==
[[Waldenstrom's macroglobulinemia]] must be [[Differentiate|differentiated]] from following other [[B cell]] [[lymphoid]] [[neoplasms]]:
 
{|
! colspan="2" rowspan="4" align="center" style="background:#4479BA; color: #FFFFFF;" + |Disease
! rowspan="4" align="center" style="background:#4479BA; color: #FFFFFF;" + |Etiology (Genetic or other)
! colspan="6" rowspan="2" style="background:#4479BA; color: #FFFFFF;" + |Clinical manifestations
! colspan="2" style="background:#4479BA; color: #FFFFFF;" |Paraclinical findings
! rowspan="4" align="center" style="background:#4479BA; color: #FFFFFF;" + |Associated findings
|-
! colspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" + |Lab findings
|-
! colspan="4" align="center" style="background:#4479BA; color: #FFFFFF;" + |Symptoms
! colspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" + |Signs
! rowspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" + |Immunochemistry
! rowspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" + |Histopathology
|-
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Constitutional symptoms
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Rash
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Abdominal pain
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Diarrhea
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Mass
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Other
|-
! colspan="2" align="center" style="background:#DCDCDC;" + |[[Waldenström's macroglobulinemia]]<br><ref>{{Cite journal
| author = [[Steven P. Treon]], [[Lian Xu]], [[Guang Yang]], [[Yangsheng Zhou]], [[Xia Liu]], [[Yang Cao]], [[Patricia Sheehy]], [[Robert J. Manning]], [[Christopher J. Patterson]], [[Christina Tripsas]], [[Luca Arcaini]], [[Geraldine S. Pinkus]], [[Scott J. Rodig]], [[Aliyah R. Sohani]], [[Nancy Lee Harris]], [[Jason M. Laramie]], [[Donald A. Skifter]], [[Stephen E. Lincoln]] & [[Zachary R. Hunter]]
| title = MYD88 L265P somatic mutation in Waldenstrom's macroglobulinemia
| journal = [[The New England journal of medicine]]
| volume = 367
| issue = 9
| pages = 826–833
| year = 2012
| month = August
| doi = 10.1056/NEJMoa1200710
| pmid = 22931316
}}</ref><ref name="AC">{{cite journal |vauthors=Chi PJ, Pei SN, Huang TL, Huang SC, Ng HY, Lee CT |title=Renal MALT lymphoma associated with Waldenström macroglobulinemia |journal=J. Formos. Med. Assoc. |volume=113 |issue=4 |pages=255–7 |year=2014 |pmid=24685302 |doi=10.1016/j.jfma.2011.02.007 |url=}}</ref><ref name="AC2">{{cite journal |vauthors=Chi PJ, Pei SN, Huang TL, Huang SC, Ng HY, Lee CT |title=Renal MALT lymphoma associated with Waldenström macroglobulinemia |journal=J. Formos. Med. Assoc. |volume=113 |issue=4 |pages=255–7 |year=2014 |pmid=24685302 |doi=10.1016/j.jfma.2011.02.007 |url=}}</ref><ref name="pmid11736938">{{cite journal| author=García-Sanz R, Montoto S, Torrequebrada A, de Coca AG, Petit J, Sureda A et al.| title=Waldenström macroglobulinaemia: presenting features and outcome in a series with 217 cases. | journal=Br J Haematol | year= 2001 | volume= 115 | issue= 3 | pages= 575-82 | pmid=11736938 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11736938  }}</ref><ref name="pmid12720138">{{cite journal| author=Merlini G, Baldini L, Broglia C, Comelli M, Goldaniga M, Palladini G et al.| title=Prognostic factors in symptomatic Waldenstrom's macroglobulinemia. | journal=Semin Oncol | year= 2003 | volume= 30 | issue= 2 | pages= 211-5 | pmid=12720138 | doi=10.1053/sonc.2003.50064 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12720138  }}</ref>
| align="left" style="background:#F5F5F5;" + |
*[[Maturation|Mature]] [[B-cell]] [[Lymphoma]]
*[[Mutation]] of the [[MYD88|MYD88 gene]] (L265P)
*[[Nonsense mutation|Nonsense]] or [[Frameshift mutation|frameshift mutations]] in the CXR4 [[gene]]
| align="left" style="background:#F5F5F5;" + |
*[[Weakness]]
*[[Anorexia]]
*[[Weight loss]]
*[[Fever]]
*
| align="center" style="background:#F5F5F5;" + | –
| align="center" style="background:#F5F5F5;" + |–
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |
*[[Generalization|Generalized]] and [[local]] [[lymphadenopathy]]
| align="left" style="background:#F5F5F5;" + |
*[[Retinal]] [[hemorrhage]] with [[Blurred vision|blurring of vision]]
*[[Vertigo]]
*[[Dizziness]]
*[[Headache]]
*[[Nystagmus]]
*[[Tinnitus]]
*[[Ataxia]]
*[[Bleeding]]
| align="left" style="background:#F5F5F5;" + |[[Expression|Expresses]] pan [[B-cell]] [[antigens]]:
 
*[[CD19]]
*[[CD20]]
*[[CD22]]
*[[CD79A|CD79a]]
*[[CD5]]


==Differentiating Waldenström's macroglobulinemia from other B cell lymphoid neoplasms==
[[Variable]] [[expression]] of:
*[[CD11c]]
*[[CD43]]
*[[CD25]]
Majority [[Expression (genetics)|express]]:
*[[IgM]] [[surface immunoglobulin]]


Waldenström's macroglobulinemia must be differentiated from other B cell lymphoid neoplasms including:
[[Fewmets|Fewer]] [[Expression (genetics)|express]]:
*[[IgG]] or [[Immunoglobulin A|IgA]]
*Lack [[Immunoglobulin D|IgD]]


*[[Chronic lymphocytic leukemia]]/[[small lymphocytic lymphoma]]:
[[Lack (manque)|Lack]] [[expression]] of:
:*Always express CD5, usually CD23 positive<ref name="UTD">Clinical manifestations, pathologic features, and diagnosis of lymphoplasmacytic lymphoma. UpToDate (2015)http://www.uptodate.com/contents/clinical-manifestations-pathologic-features-and-diagnosis-of-lymphoplasmacytic-lymphoma?source=see_link&sectionName=PATHOGENESIS&anchor=H198194648#H198194648 Accessed on November 9, 2015</ref>
*[[CD10]]
*[[Cyclin D1]]
| align="left" style="background: #F5F5F5; padding: 5px;" |
*≥10 percent [[Infiltration (medical)|infiltration]] by small [[lymphocytes]], plasmacytoid [[lymphocytes]], and [[plasma cells]]
*[[Variable]] [[Number|numbers]] of admixed [[Immunoblast|immunoblasts]]
*[[Hyperplasia]] of [[mast cells]] in [[Bone marrow|marrow]] ([[Characteristic impedance|characteristic]] but not [[pathognomonic]])
*[[Diffuse|Diffusely]] [[Effacement|effaced]] [[lymph nodes]]
*Absence of [[proliferation]] centers and [[marginal zone]] type [[differentiation]]
*[[Russell bodies]] (intracytoplasmic [[inclusions]])
*Dutcher [[Body|bodies]] (intranuclear [[inclusions]])
*Prominent [[Epithelioid histiocyte|epithelioid histiocytes]]
| align="left" style="background: #F5F5F5; padding: 5px;" |
*[[Diffuse large B-cell lymphoma]]
*[[Myelodysplastic syndrome]]/[[Acute myeloid leukemia]]
*[[Brain tumor]]
*[[MALT lymphoma|Renal MALT lymphoma]]
|-
! colspan="2" align="center" style="background:#DCDCDC;" + |[[B cell Chronic Lymphocytic Leukemia|B cell chronic lymphocytic leukemia]]/[[small lymphocytic lymphoma]]<br><ref name="KleinTu2001">{{cite journal|last1=Klein|first1=Ulf|last2=Tu|first2=Yuhai|last3=Stolovitzky|first3=Gustavo A.|last4=Mattioli|first4=Michela|last5=Cattoretti|first5=Giorgio|last6=Husson|first6=Hervé|last7=Freedman|first7=Arnold|last8=Inghirami|first8=Giorgio|last9=Cro|first9=Lilla|last10=Baldini|first10=Luca|last11=Neri|first11=Antonino|last12=Califano|first12=Andrea|last13=Dalla-Favera|first13=Riccardo|title=Gene Expression Profiling of B Cell Chronic Lymphocytic Leukemia Reveals a Homogeneous Phenotype Related to Memory B Cells|journal=The Journal of Experimental Medicine|volume=194|issue=11|year=2001|pages=1625–1638|issn=0022-1007|doi=10.1084/jem.194.11.1625}}</ref>


*[[B-cell prolymphocytic leukemia]]:  
| align="left" style="background:#F5F5F5;" + |
:*Express bright surface IgM, CD20 and other B-cell antigens (CD19, CD22, CD79a, FMC7)<ref name="UTD"></ref>
*[[Maturation|Mature]] [[B-cell]] [[Lymphoma]]
*[[Chromosome 13]] [[Abnormality (behavior)|abnormalities]]
*[[Deletion (genetics)|Del]]13q
*[[Deletion (genetics)|Del]]11q
*[[Deletion (genetics)|Del]]17p
*[[Trisomy]] 12
*
| align="left" style="background:#F5F5F5;" + |
33% of [[patients]] [[Presenting symptom|present]] with:
*[[Fever]]
*[[Weight loss]]
*[[Night sweats]]
| align="center" style="background:#F5F5F5;" + |–
| align="center" style="background:#F5F5F5;" + |–
| align="center" style="background:#F5F5F5;" + |–
| align="left" style="background:#F5F5F5;" + |
* Painless [[lymphadenopathy]]
| align="left" style="background:#F5F5F5;" + |
*May be [[asymptomatic]]
*[[Fatigue]]
*[[Recurrence plot|Recurrent]] [[infections]]
*[[Hepatosplenomegaly]]
| align="left" style="background:#F5F5F5;" + |Always [[Expression|expresses:]]
*[[CD5]]
*[[CD38]]
Usually [[Expression|expresses:]]
*[[CD23]]
Dim [[expression]] of:
*[[CD20]]
*[[Surface chemistry|Surface]] [[Immunoglobulin|Ig]]
| align="left" style="background:#F5F5F5;" + |
*Monoclonal [[B cells|small well differentiated]] [[lymphocytes]] with a [[dense]] [[nucleus]], partially aggregated [[chromatin]], no discernible [[nucleoli]], and a narrow border of clear to slightly [[basophilic]] [[cytoplasm]]
*[[Significant figure|Significant]]  [[number]] of [[smudge cells]] or [[basket cells]]
| align="left" style="background:#F5F5F5;" + |
*[[Autoimmune hemolytic anemia]]
*[[Red cell]] [[aplasia]]
*[[Autoimmune]] [[thrombocytopenia]]
|-
! colspan="2" align="center" style="background:#DCDCDC;" + |[[Follicular lymphoma]]<br><ref name="pmid25176983">{{cite journal| author=Ganapathi KA, Pittaluga S, Odejide OO, Freedman AS, Jaffe ES| title=Early lymphoid lesions: conceptual, diagnostic and clinical challenges. | journal=Haematologica | year= 2014 | volume= 99 | issue= 9 | pages= 1421-32 | pmid=25176983 | doi=10.3324/haematol.2014.107938 | pmc=4562530 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25176983  }}</ref><ref name="pmid11877266">{{cite journal| author=Lorsbach RB, Shay-Seymore D, Moore J, Banks PM, Hasserjian RP, Sandlund JT et al.| title=Clinicopathologic analysis of follicular lymphoma occurring in children. | journal=Blood | year= 2002 | volume= 99 | issue= 6 | pages= 1959-64 | pmid=11877266 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11877266  }}</ref><ref>[http://pleiad.umdnj.edu/hemepath/follicular/follicular.html Overview] at [[University of Medicine and Dentistry of New Jersey|UMDNJ]]</ref><ref name="pmid16075463">{{cite journal |author=Bosga-Bouwer AG, Haralambieva E, Booman M, ''et al.'' |title=BCL6 alternative translocation breakpoint cluster region associated with follicular lymphoma grade 3B |journal=Genes Chromosomes Cancer |volume=44 |issue=3 |pages=301–4 |date=November 2005 |pmid=16075463 |doi=10.1002/gcc.20246}}</ref><ref name="pmid7028244">{{cite journal| author=Winberg CD, Nathwani BN, Bearman RM, Rappaport H| title=Follicular (nodular) lymphoma during the first two decades of life: a clinicopathologic study of 12 patients. | journal=Cancer | year= 1981 | volume= 48 | issue= 10 | pages= 2223-35 | pmid=7028244 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7028244  }}</ref>
| align="left" style="background:#F5F5F5;" + |
*[[Maturation|Mature]] [[B-cell]] [[Lymphoma]]
*Reciprocal [[Translocations|translocation]] t(14;18)
*[[Overexpression]] of ''[[BCL2-like 1 (gene)|BCL2]]''
| align="left" style="background:#F5F5F5;" + |20% of [[patients]] [[Presenting symptom|present]] with:


*[[Follicular lymphoma]]:
*[[Fever]]
:*Express CD10, HLA-DR, pan B-cell antigens (CD19, CD20, CD79a), CD21, and surface IgM, IgG, or IgA<ref name="UTD"></ref>
*[[Weight loss]]
:*Bone marrow infiltration of small, cleaved cells that are usually paratrabecular<ref name="pubM">{{cite journal |vauthors=Sahin I, Leblebjian H, Treon SP, Ghobrial IM |title=Waldenström macroglobulinemia: from biology to treatment |journal=Expert Rev Hematol |volume=7 |issue=1 |pages=157–68 |year=2014 |pmid=24405328 |doi=10.1586/17474086.2014.871494 |url=}}</ref>
*[[Night sweats]]
:*Rearrangement of Bcl-2
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |±
| align="left" style="background:#F5F5F5;" + |
* Painless peripheral [[adenopathy]] in the [[cervical]], [[axillary]], [[inguinal]], and/or [[femoral]] regions
*[[Asymptomatic]] large [[abdominal mass]]
| align="left" style="background:#F5F5F5;" + |
*[[Seizures]]
*[[Chest pain]]
*[[Bone pain]]
*[[Cough]]
*[[Dyspnea]]
| align="left" style="background:#F5F5F5;" + |[[Expression (genetics)|Expresses]]:


*[[Multiple myeloma]]:
*[[CD21]]
:*Express CD138, CD38, CD79a, and VS38c and CD56(70%)<ref name="UTD"></ref>
*[[CD23]]
:*Presence of Plasmacytic cell infiltration of bone marrow, osteolytic lesions and [[renal insufficiency]]<ref name="pubM"></ref>
*[[CD10]]
:*Translocation involving chromosome 11 (t 11;14)
*[[HLA-DR]]
*[[CD19]]
*[[CD20]]
*[[CD79a]]


*[[Mantle cell lymphoma]]:
[[Expression (genetics)|Expresses]] [[CD23|Surface]]:
:* Express CD5+ and CD23-, surface IgM and IgD and cyclin D1 in majority of cases<ref name="UTD"></ref>
*[[IgM]]
:*Infiltration of bone marrow by monomorphous, small lymphoid cells with irregular nuclei<ref name="pubM"></ref>
*[[IgG]]
*[[IgA]]
| align="left" style="background:#F5F5F5;" + |
*[[Nodular]] [[growth]] [[pattern]]
| align="left" style="background:#F5F5F5;" + |
*Most common [[Clinical|clinically]] indolent [[NHL]]
*Peripheral [[nerve]] compression
|-
! colspan="2" align="center" style="background:#DCDCDC;" + |[[Mantle cell lymphoma]]<br><ref>{{Cite journal
| author = [[Itziar Salaverria]], [[Cristina Royo]], [[Alejandra Carvajal-Cuenca]], [[Guillem Clot]], [[Alba Navarro]], [[Alejandra Valera]], [[Joo Y. Song]], [[Renata Woroniecka]], [[Grzegorz Rymkiewicz]], [[Wolfram Klapper]], [[Elena M. Hartmann]], [[Pierre Sujobert]], [[Iwona Wlodarska]], [[Judith A. Ferry]], [[Philippe Gaulard]], [[German Ott]], [[Andreas Rosenwald]], [[Armando Lopez-Guillermo]], [[Leticia Quintanilla-Martinez]], [[Nancy L. Harris]], [[Elaine S. Jaffe]], [[Reiner Siebert]], [[Elias Campo]] & [[Silvia Bea]]
| title = CCND2 rearrangements are the most frequent genetic events in cyclin D1(-) mantle cell lymphoma
| journal = [[Blood]]
| volume = 121
| issue = 8
| pages = 1394–1402
| year = 2013
| month = February
| doi = 10.1182/blood-2012-08-452284
| pmid = 23255553
}}</ref><ref>{{Cite journal
| author = [[Markus Tiemann]], [[Carsten Schrader]], [[Wolfram Klapper]], [[Martin H. Dreyling]], [[Elias Campo]], [[Andrew Norton]], [[Francoise Berger]], [[Philip Kluin]], [[German Ott]], [[Stephano Pileri]], [[Ennio Pedrinis]], [[Alfred C. Feller]], [[Hartmut Merz]], [[Dirk Janssen]], [[Martin L. Hansmann]], [[Han Krieken]], [[Peter Moller]], [[Harald Stein]], [[Michael Unterhalt]], [[Wolfgang Hiddemann]] & [[Reza Parwaresch]]
| title = Histopathology, cell proliferation indices and clinical outcome in 304 patients with mantle cell lymphoma (MCL): a clinicopathological study from the European MCL Network
| journal = [[British journal of haematology]]
| volume = 131
| issue = 1
| pages = 29–38
| year = 2005
| month = October
| doi = 10.1111/j.1365-2141.2005.05716.x
| pmid = 16173960
}}</ref><ref>{{Cite journal
| author = [[L. H. Argatoff]], [[J. M. Connors]], [[R. J. Klasa]], [[D. E. Horsman]] & [[R. D. Gascoyne]]
| title = Mantle cell lymphoma: a clinicopathologic study of 80 cases
| journal = [[Blood]]
| volume = 89
| issue = 6
| pages = 2067–2078
| year = 1997
| month = March
| pmid = 9058729
}}</ref><ref>{{Cite journal
| author = [[Markus Tiemann]], [[Carsten Schrader]], [[Wolfram Klapper]], [[Martin H. Dreyling]], [[Elias Campo]], [[Andrew Norton]], [[Francoise Berger]], [[Philip Kluin]], [[German Ott]], [[Stephano Pileri]], [[Ennio Pedrinis]], [[Alfred C. Feller]], [[Hartmut Merz]], [[Dirk Janssen]], [[Martin L. Hansmann]], [[Han Krieken]], [[Peter Moller]], [[Harald Stein]], [[Michael Unterhalt]], [[Wolfgang Hiddemann]] & [[Reza Parwaresch]]
| title = Histopathology, cell proliferation indices and clinical outcome in 304 patients with mantle cell lymphoma (MCL): a clinicopathological study from the European MCL Network
| journal = [[British journal of haematology]]
| volume = 131
| issue = 1
| pages = 29–38
| year = 2005
| month = October
| doi = 10.1111/j.1365-2141.2005.05716.x
| pmid = 16173960
}}</ref><ref>{{Cite journal
| author = [[Julie M. Vose]]
| title = Mantle cell lymphoma: 2017 update on diagnosis, risk-stratification, and clinical management
| journal = [[American journal of hematology]]
| volume = 92
| issue = 8
| pages = 806–813
| year = 2017
| month = August
| doi = 10.1002/ajh.24797
| pmid = 28699667
}}</ref>
| align="left" style="background:#F5F5F5;" + |
*[[Maturation|Mature]] [[B-cell]] [[Lymphoma]]
*[[CD5 (protein)|CD5]] positive [[antigen]] in pre [[germinal center]] of [[B-cell]]
*Monomorphous small to medium [[Size consistency|sized]] [[B lymphocytes]] with [[Irregular lesion|irregular]] [[nuclei]]
*[[Chromosomal translocation]] at t(11:14)
| align="left" style="background:#F5F5F5;" + |
*[[Fatigue]]
*[[Night sweats]]
*[[Weight loss|Weight Loss]]
| align="center" style="background:#F5F5F5;" + |–
| align="center" style="background:#F5F5F5;" + |[[Abdominal distention]]
| align="center" style="background:#F5F5F5;" + | +
| align="left" style="background:#F5F5F5;" + |
*[[Palpable]] [[Mass|masses]] in [[skin]], [[breast]], and [[salivary glands]]
*[[Generalized lymphadenopathy]]
| align="left" style="background:#F5F5F5;" + |
*Extranodal involvement of [[GI tract]], [[lungs]], and [[CNS]]
*[[Mental retardation|Mental Retardation]]
| align="left" style="background:#F5F5F5;" + |Positive for:


*Marginal zone lymphoma:
*[[CD5]]
:*Expresses B cell markers CD19, CD20, and CD22<ref name="UTD"></ref>
*[[B-cell]] [[antigen]]
:*Infiltrates the bone marrow with a characteristic intertrabecular and intrasinusoidal pattern<ref name="pubM"></ref>
*[[Cyclin D1|Cyclin D]] ([[overexpression]])
:*Most common cytogenetic abnormalities are loss of 7q (19%) along with +3q (19%) and +5q (10% )


=References=
[[Cyclin D1|Co-express]] [[Surface chemistry|surface]]:
{{reflist|2}}
 
*[[IgM]]
*[[IgD]]
 
Negative for:
 
* [[CD23]]-
| align="left" style="background:#F5F5F5;" + |
*[[Germinal centers]] filled by small-to-medium [[atypical lymphocytes]]
*[[Nodular]] [[appearance]]
| align="center" style="background:#F5F5F5;" + |_
|-
! rowspan="3" align="center" style="background:#DCDCDC;" + |[[Marginal zone lymphoma]]
! align="center" style="background:#DCDCDC;" + |[[Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue|Extranodal marginal zone B-cell lymphoma]] of [[MALT lymphoma|mucosa-associated lymphoid tissue]] ([[MALT]]) type<br><ref name="sympmalylymmnoingastry">Non-gastric lymphomas – causes, symptoms and treatments. Lymphoma association 2016. https://www.lymphomas.org.uk/sites/default/files/pdfs/Non-Gastric-malt-lymphoma.pdf. Accessed on January 28, 2016</ref><ref name="riskfactorsmaltlymphoma1">Risks of Extranodal marginal zone of mucosa-associated lymphoid tissue (MALT lymphoma). Canadian Cancer Society 2016. http://www.cancer.ca/en/cancer-information/cancer-type/non-hodgkin-lymphoma/non-hodgkin-lymphoma/types-of-nhl/malt-lymphoma/?region=on. Accessed on January 25, 2016</ref><ref name="KinkadeEsan2015">{{cite journal|last1=Kinkade|first1=Zoe|last2=Esan|first2=Olukemi A.|last3=Rosado|first3=Flavia G.|last4=Craig|first4=Michael|last5=Vos|first5=Jeffrey A.|title=Ileal mucosa-associated lymphoid tissue lymphoma presenting with small bowel obstruction: a case report|journal=Diagnostic Pathology|volume=10|issue=1|year=2015|issn=1746-1596|doi=10.1186/s13000-015-0353-6}}</ref><ref name="sympromaltlymphoma2">Symptoms of MALT lymphoma. Cancer research UK 2016. http://www.cancerresearchuk.org/about-cancer/type/non-hodgkins-lymphoma/about/types/mucosaassociated-lymphoid-tissue-lymphoma. Accessed on January 28, 2016</ref><ref name="sympromaltlymphoma22">Symptoms of MALT lymphoma. Cancer research UK 2016. http://www.cancerresearchuk.org/about-cancer/type/non-hodgkins-lymphoma/about/types/mucosaassociated-lymphoid-tissue-lymphoma. Accessed on January 28, 2016</ref><ref name="sympromaltlymphoma1">Signs and symptoms of gastric lymphoma. Wikipedia 2016. https://en.wikipedia.org/wiki/Gastric_lymphoma. Accessed on January 28, 2016</ref><ref name="nongastricorbitlymphomasym1">Clinical presentation of orbital lymphoma. Dr Craig Hacking and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/articles/orbital-lymphoma. Accessed on January 28, 2016</ref><ref name="sympmalylymmnoingastry2">Non-gastric lymphomas – causes, symptoms and treatments. Lymphoma association 2016. https://www.lymphomas.org.uk/sites/default/files/pdfs/Non-Gastric-malt-lymphoma.pdf. Accessed on January 28, 2016</ref><ref>{{cite journal|last1=Taal|first1=B G|last2=Boot|first2=H|last3=van Heerde|first3=P|last4=de Jong|first4=D|last5=Hart|first5=A A|last6=Burgers|first6=J M|title=Primary non-Hodgkin lymphoma of the stomach: endoscopic pattern and prognosis in low versus high grade malignancy in relation to the MALT concept.|journal=Gut|date=1 October 1996|volume=39|issue=4|pages=556–561|doi=10.1136/gut.39.4.556}}</ref><ref name="pmid16950858">{{cite journal| author=Bacon CM, Du MQ, Dogan A| title=Mucosa-associated lymphoid tissue (MALT) lymphoma: a practical guide for pathologists. | journal=J Clin Pathol | year= 2007 | volume= 60 | issue= 4 | pages= 361-72 | pmid=16950858 | doi=10.1136/jcp.2005.031146 | pmc=PMC2001121 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16950858  }}</ref>
| align="left" style="background:#F5F5F5;" + |
*[[Maturation|Mature]] [[B-cell]] [[Lymphoma]]
*[[Recurrence plot|Recurrent]] [[translocations]] such as:
**t(1;14)(p22;q32)
**t(11;18)(q21;q21)
**t(14;18)(q32;q21)
**t(3;14)(p14.1;q32)
| align="left" style="background:#F5F5F5;" + |
*[[B symptoms]] may or may not be [[Presenting symptom|present]]
| align="center" style="background:#F5F5F5;" + |±
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="left" style="background:#F5F5F5;" + |
*Painless or [[painful]][[lymphadenopathy]] which can be [[gastric]] or non-[[gastric]]
*[[Orbital mass causes|Lump in the superior lateral quadrant of the orbit]], [[breast]], [[neck]], or [[salivary gland]]
| align="left" style="background:#F5F5F5;" + |[[Symptoms]] [[Dependent variable|depend]] on the [[Location parameter|location]] of the [[tumor]] and may include:
 
*[[Fatigue]]
*[[Heartburn]]
*[[Fever]]
*[[Cough]] with [[Hemoptysis|blood in sputum]]
*[[Dyspnea|Shortness of breath]]
| align="left" style="background:#F5F5F5;" + |[[B-cell]] [[Association (statistics)|associated]] [[antigens]] that co-[[Expression (genetics)|express]]:
 
* [[BCL-2]]
*[[CD19]]
*[[CD20]]
*[[CD22]]
*[[CD79a]]
Negative for:
*[[CD5]]
*[[CD10]]
*[[CD43]]
*[[Cyclin D1]]
| align="left" style="background:#F5F5F5;" + |
*[[Presenting symptom|Presence]] of [[dense]] [[diffuse]] [[lymphoid]] [[Infiltration (medical)|infiltrate]] of [[Marginal zone|marginal‐zone]] [[Cells (biology)|cells]] in [[lamina propria]]
*Prominent lymphoepithelial [[lesions]] and consisting of small atypical [[Cells (biology)|cells]] with [[monocytoid]] [[Features (pattern recognition)|features]]
| align="left" style="background:#F5F5F5;" + |
*''[[Helicobacter|H. pylori]]'' [[infection]]
*[[Hashimoto's thyroiditis]]
*[[Sjogren’s syndrome]]
*[[Celiac disease]]
|-
! align="center" style="background:#DCDCDC;" + |[[Splenic marginal zone lymphoma]]<br><ref name="pmid11337382">{{cite journal |vauthors=Hernández JM, García JL, Gutiérrez NC, Mollejo M, Martínez-Climent JA, Flores T, González MB, Piris MA, San Miguel JF |title=Novel genomic imbalances in B-cell splenic marginal zone lymphomas revealed by comparative genomic hybridization and cytogenetics |journal=Am. J. Pathol. |volume=158 |issue=5 |pages=1843–50 |date=May 2001 |pmid=11337382 |pmc=1891967 |doi=10.1016/S0002-9440(10)64140-5 |url=}}</ref><ref name="pmid15642391">{{cite journal |vauthors=Andersen CL, Gruszka-Westwood A, Atkinson S, Matutes E, Catovsky D, Pedersen RK, Pedersen BB, Pulczynski S, Hokland P, Jacobsen E, Koch J |title=Recurrent genomic imbalances in B-cell splenic marginal-zone lymphoma revealed by comparative genomic hybridization |journal=Cancer Genet. Cytogenet. |volume=156 |issue=2 |pages=122–8 |date=January 2005 |pmid=15642391 |doi=10.1016/j.cancergencyto.2004.04.026 |url=}}</ref><ref name="pmid20479288">{{cite journal |vauthors=Salido M, Baró C, Oscier D, Stamatopoulos K, Dierlamm J, Matutes E, Traverse-Glehen A, Berger F, Felman P, Thieblemont C, Gesk S, Athanasiadou A, Davis Z, Gardiner A, Milla F, Ferrer A, Mollejo M, Calasanz MJ, Florensa L, Espinet B, Luño E, Wlodarska I, Verhoef G, García-Granero M, Salar A, Papadaki T, Serrano S, Piris MA, Solé F |title=Cytogenetic aberrations and their prognostic value in a series of 330 splenic marginal zone B-cell lymphomas: a multicenter study of the Splenic B-Cell Lymphoma Group |journal=Blood |volume=116 |issue=9 |pages=1479–88 |date=September 2010 |pmid=20479288 |doi=10.1182/blood-2010-02-267476 |url=}}</ref><ref>Splenic marginal zone lymphoma. Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf57e3e27c3994bd5327/. Accessed on December 22, 2015</ref><ref name="pmid12916862">{{cite journal |vauthors=Weng WK, Levy S |title=Hepatitis C virus (HCV) and lymphomagenesis |journal=Leuk. Lymphoma |volume=44 |issue=7 |pages=1113–20 |date=July 2003 |pmid=12916862 |doi=10.1080/1042819031000076972 |url=}}</ref><ref name="pmid11739181">{{cite journal |vauthors=Quinn ER, Chan CH, Hadlock KG, Foung SK, Flint M, Levy S |title=The B-cell receptor of a hepatitis C virus (HCV)-associated non-Hodgkin lymphoma binds the viral E2 envelope protein, implicating HCV in lymphomagenesis |journal=Blood |volume=98 |issue=13 |pages=3745–9 |date=December 2001 |pmid=11739181 |doi= |url=}}</ref><ref name="pmid20530156">{{cite journal |vauthors=Chuang SS, Liao YL, Chang ST, Hsieh YC, Kuo SY, Lu CL, Hwang WS, Lin IH, Tsao CJ, Huang WT |title=Hepatitis C virus infection is significantly associated with malignant lymphoma in Taiwan, particularly with nodal and splenic marginal zone lymphomas |journal=J. Clin. Pathol. |volume=63 |issue=7 |pages=595–8 |date=July 2010 |pmid=20530156 |doi=10.1136/jcp.2010.076810 |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
*[[Maturation|Mature]] [[B-cell]] [[Lymphoma]]
*[[Clonal selection|Clonal]] [[Rearrangement|rearrangements]] of the [[immunoglobulin]] [[genes]] ([[Heavy chains|heavy]] and [[Light chain|light chains]])
**[[Deletion (genetics)|Deletion]] 7q21-32
**[[Translocations]] of the CDK6 [[gene]] [[Location parameter|located]] on 7q21
| align="left" style="background:#F5F5F5;" + |
*[[Fever]]
*[[Weight loss]]
*[[Night sweats]]
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |–
| align="left" style="background:#F5F5F5;" + |
*Painless [[swelling]] in the [[neck]], [[axilla]], [[groin]], [[thorax]], and [[abdomen]].
| align="left" style="background:#F5F5F5;" + |
*[[Chest pain]]
*[[Bone pain]]
| align="left" style="background:#F5F5F5;" + |
*[[CD20]]
*[[CD79a]]
| align="left" style="background:#F5F5F5;" + |
*Small [[lymphocytes]]
*[[Transformation|Transformed]] [[Blast|blasts]]
*[[Epithelial]] [[histocytes]]
*Plasmacytic [[differentiation]] of [[neoplastic]] [[Cells (biology)|cells]]
| align="left" style="background:#F5F5F5;" + |
*[[Hepatitis C]] [[infection]]
|-
! align="center" style="background:#DCDCDC;" + |[[Nodal marginal zone B-cell lymphoma]]<br><ref name="SpinaKhiabanian2016">{{cite journal|last1=Spina|first1=V.|last2=Khiabanian|first2=H.|last3=Messina|first3=M.|last4=Monti|first4=S.|last5=Cascione|first5=L.|last6=Bruscaggin|first6=A.|last7=Spaccarotella|first7=E.|last8=Holmes|first8=A. B.|last9=Arcaini|first9=L.|last10=Lucioni|first10=M.|last11=Tabbo|first11=F.|last12=Zairis|first12=S.|last13=Diop|first13=F.|last14=Cerri|first14=M.|last15=Chiaretti|first15=S.|last16=Marasca|first16=R.|last17=Ponzoni|first17=M.|last18=Deaglio|first18=S.|last19=Ramponi|first19=A.|last20=Tiacci|first20=E.|last21=Pasqualucci|first21=L.|last22=Paulli|first22=M.|last23=Falini|first23=B.|last24=Inghirami|first24=G.|last25=Bertoni|first25=F.|last26=Foa|first26=R.|last27=Rabadan|first27=R.|last28=Gaidano|first28=G.|last29=Rossi|first29=D.|title=The genetics of nodal marginal zone lymphoma|journal=Blood|volume=128|issue=10|year=2016|pages=1362–1373|issn=0006-4971|doi=10.1182/blood-2016-02-696757}}</ref><ref name="canadiancancer">Nodal marginal zone lymphoma . Canadian Cancer Society. http://www.cancer.ca/en/cancer-information/cancer-type/non-hodgkin-lymphoma/non-hodgkin-lymphoma/types-of-nhl/nodal-marginal-zone-lymphoma/?region=nb Accessed on March 4, 2016</ref>
| align="left" style="background:#F5F5F5;" + |
*[[Maturation|Mature]] [[B-cell]] [[Lymphoma]]
*[[Stimulated emission|Stimulation]] of [[antigen]] [[Receptor (biochemistry)|receptor]] by [[autoantigen]] and [[Co-stimulation|co-stimulatory]] [[molecule]] [[CD40 (protein)|CD40]]
*[[Mutation|Mutations]] in [[KMT2D]], PTTPRD, [[NOTCH2]], [[KLF2]]
| align="left" style="background:#F5F5F5;" + |
*[[Fever]]
*[[Weight loss]]
*[[Night sweats]]
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |–
| align="center" style="background:#F5F5F5;" + |–
| align="left" style="background:#F5F5F5;" + |
*Painless [[swelling]] in the [[neck]], [[axilla]], [[groin]], [[thorax]], and [[abdomen]]
*[[Generalization|Generalized]] and [[local]] [[lymphadenopathy]]
| align="left" style="background:#F5F5F5;" + |
*[[Hemorrhage]]
*[[Dyspepsia]]
| align="center" style="background:#F5F5F5;" + |_
| align="left" style="background:#F5F5F5;" + |
*[[Follicular cells]] in [[Reaction|reactive]] zone
*Centrocyte like [[Cells (biology)|cells]] in [[marginal zone lymphoma]]
*Centroblasts
*[[Plasma cell|Plasma cells]]
*[[Immunoblast|Immunoblasts]]
| align="left" style="background:#F5F5F5;" + |
*[[Hepatitis C]] [[infection]]
*[[Chronic (medicine)|Chronic]] [[infectious]] [[conditions]] or [[autoimmune]] [[Process (anatomy)|processes]], such as:
**''[[Helicobacter pylori|H pylori]]'' [[gastritis]]
**[[Hashimoto's thyroiditis|Hashimoto thyroiditis]]
**[[Sjögren's syndrome|Sjögren syndrome]]
|-
! colspan="2" align="center" style="background:#DCDCDC;" + |[[Multiple myeloma|Multiple Myeloma]]<ref name="wiki">Multiple myeloma. Wikipedia (2015) https://en.wikipedia.org/wiki/Multiple_myeloma#Signs_and_symptoms Accessed on September, 20th 2015</ref><ref name="canada">Multiple myeloma. Canadian Cancer Society (2015) http://www.cancer.ca/en/cancer-information/cancer-type/multiple-myeloma/signs-and-symptoms/?region=mb Accessed on September 20th 2015</ref><ref name="gov">Multiple myeloma. Cancer. gov(2015) http://www.cancer.gov/types/myeloma Accessed on September, 20th 2015</ref><ref name="pmid24614435">{{cite journal |vauthors=Reisenbuckler C |title=Multiple myeloma and diagnostic imaging |journal=Radiol Technol |volume=85 |issue=4 |pages=391–410; quiz 411–3 |date=2014 |pmid=24614435 |doi= |url=}}</ref><ref name="pmid26294217">{{cite journal |vauthors=Sergentanis TN, Zagouri F, Tsilimidos G, Tsagianni A, Tseliou M, Dimopoulos MA, Psaltopoulou T |title=Risk Factors for Multiple Myeloma: A Systematic Review of Meta-Analyses |journal=Clin Lymphoma Myeloma Leuk |volume=15 |issue=10 |pages=563–77.e1–3 |date=October 2015 |pmid=26294217 |doi=10.1016/j.clml.2015.06.003 |url=}}</ref><ref name="pmid24130968">{{cite journal |vauthors=Eslick R, Talaulikar D |title=Multiple myeloma: from diagnosis to treatment |journal=Aust Fam Physician |volume=42 |issue=10 |pages=684–8 |date=October 2013 |pmid=24130968 |doi= |url=}}</ref>
 
| align="left" style="background:#F5F5F5;" + |
*[[Chromosomal aberration|Chromosomal aberrations]] or other [[Genetics|genetic]] insults
*[[Malignant]] [[transformation]] of [[plasma cells]]
*[[Clonal selection|Clonal]] [[plasma cell]] [[proliferation]]
*
| align="left" style="background:#F5F5F5;" + |
*Constitutional [[symptoms]] may or may not be present
*[[Diffuse]] [[bone pain]] and [[tenderness]] with [[osteolytic]] [[lesions]]
*Worsens with [[Activity (chemistry)|activity]]
*Usually involves [[spine]] and [[ribs]] ([[axial skeleton]])
*[[Hypercalcemia]] [[symptoms]]:
**[[Polyuria]]
**[[Polydipsia]]
**[[Constipation]]
*[[Loss of appetite]]
*[[Nausea and vomiting]]
*Lethary due to [[anemia]]
*[[Neurological]] [[symptoms]]:
**[[Numbness]] due to [[plasma cell]] [[Infiltration (medical)|infiltration]] of [[nerves]] or anti-[[neuronal]] [[glycoprotein]] [[antibodies]]
**[[Muscle weakness]]
**[[Confusion]]
**[[Dizziness]]
**[[Headache]]
**[[Paralysis]]
**[[Visual]] changes
| align="center" style="background:#F5F5F5;" + |–
| align="center" style="background:#F5F5F5;" + |
*[[Abdominal pain]] due to [[mesenteric]] [[venous thrombosis]]
| align="center" style="background:#F5F5F5;" + |
* No [[diarrhea]]
* [[Constipation]] due to [[hypercalcemia]]
| align="left" style="background:#F5F5F5;" + |
*[[Lymphadenopathy]]
*[[Hepatomegaly]]
*[[Splenomegaly]]
*[[Abdominal tenderness]] (if [[hypercalcemia]] is present)
| align="left" style="background:#F5F5F5;" + |
*[[Bone marrow]] [[failure]]-[[Related changes|related]] [[symptoms]], due to [[Crowdsourcing|crowding]] out of normal [[bone marrow]] [[precursors]] by [[malignant]] [[plasma cells]]:
**[[Easy bruising]], [[nosebleeds]], [[bleeding gums]] due to [[thrombocytopenia]]
**[[Fatigue]], [[weakness]], [[shortness of breath]], [[dizziness]] and [[paleness]] due to [[anemia]]
**[[Recurrence plot|Recurrent]] [[infections]] due to [[leukopenia]]
*[[Thrombosis|Thrombotic]] [[symptoms]], due to [[cancer]]-[[Association (statistics)|associated]] [[thrombosis]] and due to [[lenalidomide]], which increases [[Thrombosis|thrombotic]] [[RiskMetrics|risk]]:
**[[Shortness of breath]] due to [[pulmonary embolism]]
**[[Lower extremity]] [[edema]] due to [[deep vein thrombosis]] and [[renal]] involvement
**[[Abdominal pain]] due to [[mesenteric]] [[venous thrombosis]]
**[[Transient ischemic attack]]
**[[Retinal]] [[hemorrhage]]
*[[Pallor]]
*[[Ecchymoses]]
*[[Purpura]]
*[[Conjuctiva|Conjuctival]] [[pallor]]
*[[Visual]] [[Defect|defects]]
*[[Exudative]] [[retinal detachment]]
*Increased [[adipose]] [[Deposition (physics)|deposition]] around the [[neck]] (if [[dexamethasone]] is [[Usage analysis|used]] for [[therapy]])
*[[Cotton-wool spot|Cotton-wool spots]] may be present
*[[Bone|Bony]] [[tenderness]] along [[cervical]], [[thoracic]], [[lumbar]] [[spine]] and in long [[bones]]
*[[Tinel's sign]] may be present
*[[Phalen's maneuver|Phalen sign]] may be present
*[[Dermatome|Dermatomal]] [[sensory loss]]
*[[Altered sensorium|Altered sensation]]
*[[Neuropathy]]
*[[Neuropathy|Mood alterations (if]] [[hypercalcemia]] is present)
| align="left" style="background:#F5F5F5;" + |[[Expression|Expresses]]:
 
*[[CD138]]
*[[CD38]]
*[[CD79a]]
*VS38c
*Infrequently [[Expression|expresses]] [[CD19]]
*[[CD56]] ([[Expression|expressed]] by 70% of [[myeloma]] [[Cells (biology)|cells]])
*Absent [[Surface immunoglobulin|surface Ig]]
| align="left" style="background:#F5F5F5;" + |
*[[Infiltration (medical)|Infiltration]] of [[plasma cells]] in the [[bone marrow]]
| align="center" style="background:#F5F5F5;" + |[[Relevance|Relevant]] [[History and Physical examination|history]] includes:
 
* [[Review]] of past [[medical history]] for other [[plasma cell]] [[diseases]], [[hematologic]] [[malignancies]], underlying [[Kidney|renal]] [[disease]], and underlying [[bone]] [[disease]]
 
*[[Review]] of [[family history]] for members with positive [[History and Physical examination|history]] of [[hematologic]] [[malignancies]]
*[[Review]] of [[Occupational Medicine|occupational]] [[History and Physical examination|history]] [[Related changes|related]] to farming, [[oil]] industry, or [[Agent Orange]] [[Exposure assessment|exposure]]
|-
! colspan="2" align="center" style="background:#DCDCDC;" + |'''[[B-cell prolymphocytic leukemia]]<ref name="pmid10720137">{{cite journal |author=Lens D, Matutes E, Catovsky D, Coignet LJ |title=Frequent deletions at 11q23 and 13q14 in B cell prolymphocytic leukemia (B-PLL) |journal=Leukemia |volume=14 |issue=3 |pages=427-30 |year=2000 |pmid=10720137 |doi=}}</ref><ref name="pmid96570132">{{cite journal |author=Yamamoto K, Hamaguchi H, Nagata K, Shibuya H, Takeuchi H |title=Splenic irradiation for prolymphocytic leukemia: is it preferable as an initial treatment or not? |journal=Jpn. J. Clin. Oncol. |volume=28 |issue=4 |pages=267–9 |date=April 1998 |pmid=9657013 |doi= 10.1093/jjco/28.4.267|url=http://jjco.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=9657013}}</ref><ref name="urlPathology">{{cite web |url=http://www.med-ed.virginia.edu/courses/path/innes/wcd/lympleuk.cfm |title=Pathology |format= |work= |accessdate=2009-01-31| archiveurl= http://web.archive.org/web/20090207235133/http://www.med-ed.virginia.edu/courses/path/innes/wcd/lympleuk.cfm| archivedate= 7 February 2009 <!--DASHBot-->| deadurl= no}}</ref><ref name="pmid16997373">{{cite journal |author=Crisostomo RH, Fernandez JA, Caceres W |title=Complex karyotype including chromosomal translocation (8;14) (q24;q32) in one case with B-cell prolymphocytic leukemia |journal=Leuk. Res. |volume=31 |issue=5 |pages=699–701 |date=May 2007 |pmid=16997373 |doi=10.1016/j.leukres.2006.06.010 |url=http://linkinghub.elsevier.com/retrieve/pii/S0145-2126(06)00218-9}}</ref><ref name="B-PLL">{{cite web | title = National cancer institute| url = http://seer.cancer.gov/seertools/hemelymph/51f6cf58e3e27c3994bd53f9/ }}</ref><ref name="B-PLL2">{{cite web | title = National cancer institute| url = http://seer.cancer.gov/seertools/hemelymph/51f6cf58e3e27c3994bd53f9/ }}</ref>'''
 
| align="left" style="background:#F5F5F5;" + |
*[[Deletion (genetics)|Deletion]] of [[chromosome 11]]
*[[Chromosome 13]]
| align="left" style="background:#F5F5F5;" + |
*[[Anemia]]
*[[Weight loss]]
*[[Loss of appetite]]
*[[Fever]]
| align="center" style="background:#F5F5F5;" + |–
| align="center" style="background:#F5F5F5;" + |–
| align="center" style="background:#F5F5F5;" + |–
| align="left" style="background:#F5F5F5;" + |
*[[Mass|Massive]] [[splenomegaly]]
*Peripheral [[lymphadenopathy]]
*[[Hepatomegaly]]
| align="left" style="background:#F5F5F5;" + |
*Rapidly rising [[lymphocyte]] count
*[[Thrombocytopenia]]
*[[Pallor]]
*[[Petechiae]]
*[[Bruising]]
*[[Tachycardia]]
*[[Tachypnea]]
| align="left" style="background:#F5F5F5;" + |[[Expression|Expresses]]:
 
*Bright [[Surface chemistry|surface]] [[IgM]]
*[[IgD]] +/-
*[[CD20]]
*[[CD19]]
*[[CD22]]
*[[CD79a]]
*[[FMC7]]
*[[CD5 (protein)|CD5]]
*[[CD45]]
*[[HLA-DR]]
*[[CD23]]+/-
*[[CD38]]
*[[FMC7]]<ref name="pmid16997373" />
 
Doesn't [[Expression|express]]:
 
*[[CD10]]
| align="left" style="background:#F5F5F5;" + |
*[[Prolymphocytes]] comprise >55% of the [[neoplastic]] [[Cells (biology)|cells]]
*[[Bone marrow]] has [[interstitial]] [[pattern]] of [[Infiltration (medical)|infiltration]]
*[[Lymph nodes]] may show [[Vagueness|vague]] [[Nodular|nodularity]], but [[proliferation]] centers are absent
| align="left" style="background:#F5F5F5;" + |
*t(11;14) must be [[Exclusion criteria|excluded]]
*No [[Association (statistics)|associated]] [[paraproteinemia]]
*More common in white [[race]] and Ashkenazi jewish [[male]]
|}
 
{|
|
[[File:BM DD.png|thumb|750px|none| GC-associated lymphoid clones infiltrating the BM osteoblastic niche exhibit mesenchymal features in common with SLO germinal centers.(A–D) Histological examination of B-cell non-Hodgkin lymphoma (B-NHL) patient specimens. (A) The frequency of para-trabecular/osteoblastic localization of lymphoid malignant clones in 197 cases of B-NHL with bone marrow (BM) infiltration. Lymphoid clones of germinal center (GC)-derivation exhibiting preferential tropism for the BM osteoblastic niche include: follicular lymphoma (FL), T-cell rich histiocyte rich diffuse large B-cell lymphoma (TCRBCL), and diffuse large B-cell lymphoma of GC type (DLBCL-GC). Non-GC-related lymphoid clones include: DLBCL- activated B-cell type (ABC); mantle-cell lymmphoma, (MCL); marginal-zone lymphoma, (MZL); lymphoplasmacytic lymphoma, (LPL). (B) Para-trabecular (left panel) and inter-trabecular (right panel) localization of two representative cases of FL with BM infiltration. The distribution of the lymphomatous infiltrates around bone trabeculae or in the inter-trabecular lacunae is highlighted by CD20 immunostaining (inserts). (C–D) FL lymphoid infiltrates localizing within the osteoblastic niche area (left panels) and inter-trabecular BM (right panels) display a stromal architecture reminiscent of that of secondary lymphoid organ (SLO) GCs and are characterized by the expression of BM-MSC markers SPARC (C) and CD146 (right D).[https://openi.nlm.nih.gov/detailedresult.php?img=PMC4108469_onci-3-e28989-g3&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=46 Source: Sangaletti S. et al, Molecular Immunology Unit; Department of Experimental Oncology and Molecular Medicine; Fondazione IRCCS Istituto Nazionale Tumori; Milan, Italy.]]]
|
[[File:Cd19,20.png|thumb|750px|none| Expression of CD19 and CD20 in B-cell lineage.Notes: Illustrative representation of B-cell differentiation, maturation, antigen expression and B-cell neoplasm associated with different stages of B-cell development. Cell lines used in the research study.47–51Abbreviations: GC, germinal center; ALL, acute lymphoblastic leukemia; MCL, Mantle cell lymphoma; FL, follicular lymphoma; BL, Burkitt lymphoma; DLBCL, Diffuse Large B-Cell Lymphoma; MZL, Marginal Zone Lymphoma; CLL/SLL, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma; MALT, Mucosa-Associated lymphoid tissue; WM, Waldenstrom macroglobulinemia; MM, plasma cell myeloma; WSU-BL, Wayne State University-Burkitt lymphoma cell line; WSU-FSCCL, Wayne State University-follicular small cleaved cell lymphoma Cell line; WSU-NHL, Wayne State University-FL grade 3 Cell line; WSU-DLCL and WSU-DLCL2, Wayne State University-Diffuse large B-Cell lymphoma cell line; WSU-WM, Wayne State University-Waldenstrom macroglobulinemia Cell line.[https://openi.nlm.nih.gov/detailedresult.php?img=PMC3767487_cmar-5-225Fig1&query=waldenstrom+macroglobulinaemia&it=xg&req=4&npos=15 Source: Raufi A. et al, Lymphoma Research Laboratory, Wayne State University School of Medicine (WSU-SOM), Gordon Scott Hall for Basic Medical Sciences, Detroit, MI, USA.]]]
|}
 
==References==
{{Reflist|2}}


{{WH}}
{{WH}}
{{WS}}
{{WS}}
[[Category:Disease]]
[[Category:Disease]]
[[Category:Blood]]
[[Category:Blood]]
[[Category:Hematology]]
[[Category:Hematology]]

Latest revision as of 18:30, 15 August 2019


Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Mohsin, M.D.[2]Grammar Reviewer: Natalie Harpenau, B.S.[3]

Overview

Waldenstrom's macroglobulinemia must be differentiated from multiple myeloma, chronic lymphocytic leukemia/small lymphocytic lymphoma, b-cell prolymphocytic leukemia, follicular lymphoma, mantle cell lymphoma, and marginal zone lymphoma.

Differentiating Lymphoplasmacytic lymphoma from other Diseases

Waldenstrom's macroglobulinemia must be differentiated from following other B cell lymphoid neoplasms:

Disease Etiology (Genetic or other) Clinical manifestations Paraclinical findings Associated findings
Lab findings
Symptoms Signs Immunochemistry Histopathology
Constitutional symptoms Rash Abdominal pain Diarrhea Mass Other
Waldenström's macroglobulinemia
[1][2][3][4][5]
+ Expresses pan B-cell antigens:

Variable expression of:

Majority express:

Fewer express:

Lack expression of:

B cell chronic lymphocytic leukemia/small lymphocytic lymphoma
[6]

33% of patients present with:

Always expresses:

Usually expresses:

Dim expression of:

Follicular lymphoma
[7][8][9][10][11]
20% of patients present with: + + ± Expresses:

Expresses Surface:

Mantle cell lymphoma
[12][13][14][15][16]
Abdominal distention + Positive for:

Co-express surface:

Negative for:

_
Marginal zone lymphoma Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type
[17][18][19][20][21][22][23][24][25][26]
± + + Symptoms depend on the location of the tumor and may include: B-cell associated antigens that co-express:

Negative for:

Splenic marginal zone lymphoma
[27][28][29][30][31][32][33]
+ +
Nodal marginal zone B-cell lymphoma
[34][35]
+ _
Multiple Myeloma[36][37][38][39][40][41] Expresses: Relevant history includes:
B-cell prolymphocytic leukemia[42][43][44][45][46][47] Expresses:

Doesn't express:

GC-associated lymphoid clones infiltrating the BM osteoblastic niche exhibit mesenchymal features in common with SLO germinal centers.(A–D) Histological examination of B-cell non-Hodgkin lymphoma (B-NHL) patient specimens. (A) The frequency of para-trabecular/osteoblastic localization of lymphoid malignant clones in 197 cases of B-NHL with bone marrow (BM) infiltration. Lymphoid clones of germinal center (GC)-derivation exhibiting preferential tropism for the BM osteoblastic niche include: follicular lymphoma (FL), T-cell rich histiocyte rich diffuse large B-cell lymphoma (TCRBCL), and diffuse large B-cell lymphoma of GC type (DLBCL-GC). Non-GC-related lymphoid clones include: DLBCL- activated B-cell type (ABC); mantle-cell lymmphoma, (MCL); marginal-zone lymphoma, (MZL); lymphoplasmacytic lymphoma, (LPL). (B) Para-trabecular (left panel) and inter-trabecular (right panel) localization of two representative cases of FL with BM infiltration. The distribution of the lymphomatous infiltrates around bone trabeculae or in the inter-trabecular lacunae is highlighted by CD20 immunostaining (inserts). (C–D) FL lymphoid infiltrates localizing within the osteoblastic niche area (left panels) and inter-trabecular BM (right panels) display a stromal architecture reminiscent of that of secondary lymphoid organ (SLO) GCs and are characterized by the expression of BM-MSC markers SPARC (C) and CD146 (right D).Source: Sangaletti S. et al, Molecular Immunology Unit; Department of Experimental Oncology and Molecular Medicine; Fondazione IRCCS Istituto Nazionale Tumori; Milan, Italy.
Expression of CD19 and CD20 in B-cell lineage.Notes: Illustrative representation of B-cell differentiation, maturation, antigen expression and B-cell neoplasm associated with different stages of B-cell development. Cell lines used in the research study.47–51Abbreviations: GC, germinal center; ALL, acute lymphoblastic leukemia; MCL, Mantle cell lymphoma; FL, follicular lymphoma; BL, Burkitt lymphoma; DLBCL, Diffuse Large B-Cell Lymphoma; MZL, Marginal Zone Lymphoma; CLL/SLL, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma; MALT, Mucosa-Associated lymphoid tissue; WM, Waldenstrom macroglobulinemia; MM, plasma cell myeloma; WSU-BL, Wayne State University-Burkitt lymphoma cell line; WSU-FSCCL, Wayne State University-follicular small cleaved cell lymphoma Cell line; WSU-NHL, Wayne State University-FL grade 3 Cell line; WSU-DLCL and WSU-DLCL2, Wayne State University-Diffuse large B-Cell lymphoma cell line; WSU-WM, Wayne State University-Waldenstrom macroglobulinemia Cell line.Source: Raufi A. et al, Lymphoma Research Laboratory, Wayne State University School of Medicine (WSU-SOM), Gordon Scott Hall for Basic Medical Sciences, Detroit, MI, USA.

References

  1. Steven P. Treon, Lian Xu, Guang Yang, Yangsheng Zhou, Xia Liu, Yang Cao, Patricia Sheehy, Robert J. Manning, Christopher J. Patterson, Christina Tripsas, Luca Arcaini, Geraldine S. Pinkus, Scott J. Rodig, Aliyah R. Sohani, Nancy Lee Harris, Jason M. Laramie, Donald A. Skifter, Stephen E. Lincoln & Zachary R. Hunter (2012). "MYD88 L265P somatic mutation in Waldenstrom's macroglobulinemia". The New England journal of medicine. 367 (9): 826–833. doi:10.1056/NEJMoa1200710. PMID 22931316. Unknown parameter |month= ignored (help)
  2. Chi PJ, Pei SN, Huang TL, Huang SC, Ng HY, Lee CT (2014). "Renal MALT lymphoma associated with Waldenström macroglobulinemia". J. Formos. Med. Assoc. 113 (4): 255–7. doi:10.1016/j.jfma.2011.02.007. PMID 24685302.
  3. Chi PJ, Pei SN, Huang TL, Huang SC, Ng HY, Lee CT (2014). "Renal MALT lymphoma associated with Waldenström macroglobulinemia". J. Formos. Med. Assoc. 113 (4): 255–7. doi:10.1016/j.jfma.2011.02.007. PMID 24685302.
  4. García-Sanz R, Montoto S, Torrequebrada A, de Coca AG, Petit J, Sureda A; et al. (2001). "Waldenström macroglobulinaemia: presenting features and outcome in a series with 217 cases". Br J Haematol. 115 (3): 575–82. PMID 11736938.
  5. Merlini G, Baldini L, Broglia C, Comelli M, Goldaniga M, Palladini G; et al. (2003). "Prognostic factors in symptomatic Waldenstrom's macroglobulinemia". Semin Oncol. 30 (2): 211–5. doi:10.1053/sonc.2003.50064. PMID 12720138.
  6. Klein, Ulf; Tu, Yuhai; Stolovitzky, Gustavo A.; Mattioli, Michela; Cattoretti, Giorgio; Husson, Hervé; Freedman, Arnold; Inghirami, Giorgio; Cro, Lilla; Baldini, Luca; Neri, Antonino; Califano, Andrea; Dalla-Favera, Riccardo (2001). "Gene Expression Profiling of B Cell Chronic Lymphocytic Leukemia Reveals a Homogeneous Phenotype Related to Memory B Cells". The Journal of Experimental Medicine. 194 (11): 1625–1638. doi:10.1084/jem.194.11.1625. ISSN 0022-1007.
  7. Ganapathi KA, Pittaluga S, Odejide OO, Freedman AS, Jaffe ES (2014). "Early lymphoid lesions: conceptual, diagnostic and clinical challenges". Haematologica. 99 (9): 1421–32. doi:10.3324/haematol.2014.107938. PMC 4562530. PMID 25176983.
  8. Lorsbach RB, Shay-Seymore D, Moore J, Banks PM, Hasserjian RP, Sandlund JT; et al. (2002). "Clinicopathologic analysis of follicular lymphoma occurring in children". Blood. 99 (6): 1959–64. PMID 11877266.
  9. Overview at UMDNJ
  10. Bosga-Bouwer AG, Haralambieva E, Booman M; et al. (November 2005). "BCL6 alternative translocation breakpoint cluster region associated with follicular lymphoma grade 3B". Genes Chromosomes Cancer. 44 (3): 301–4. doi:10.1002/gcc.20246. PMID 16075463.
  11. Winberg CD, Nathwani BN, Bearman RM, Rappaport H (1981). "Follicular (nodular) lymphoma during the first two decades of life: a clinicopathologic study of 12 patients". Cancer. 48 (10): 2223–35. PMID 7028244.
  12. Itziar Salaverria, Cristina Royo, Alejandra Carvajal-Cuenca, Guillem Clot, Alba Navarro, Alejandra Valera, Joo Y. Song, Renata Woroniecka, Grzegorz Rymkiewicz, Wolfram Klapper, Elena M. Hartmann, Pierre Sujobert, Iwona Wlodarska, Judith A. Ferry, Philippe Gaulard, German Ott, Andreas Rosenwald, Armando Lopez-Guillermo, Leticia Quintanilla-Martinez, Nancy L. Harris, Elaine S. Jaffe, Reiner Siebert, Elias Campo & Silvia Bea (2013). "CCND2 rearrangements are the most frequent genetic events in cyclin D1(-) mantle cell lymphoma". Blood. 121 (8): 1394–1402. doi:10.1182/blood-2012-08-452284. PMID 23255553. Unknown parameter |month= ignored (help)
  13. Markus Tiemann, Carsten Schrader, Wolfram Klapper, Martin H. Dreyling, Elias Campo, Andrew Norton, Francoise Berger, Philip Kluin, German Ott, Stephano Pileri, Ennio Pedrinis, Alfred C. Feller, Hartmut Merz, Dirk Janssen, Martin L. Hansmann, Han Krieken, Peter Moller, Harald Stein, Michael Unterhalt, Wolfgang Hiddemann & Reza Parwaresch (2005). "Histopathology, cell proliferation indices and clinical outcome in 304 patients with mantle cell lymphoma (MCL): a clinicopathological study from the European MCL Network". British journal of haematology. 131 (1): 29–38. doi:10.1111/j.1365-2141.2005.05716.x. PMID 16173960. Unknown parameter |month= ignored (help)
  14. L. H. Argatoff, J. M. Connors, R. J. Klasa, D. E. Horsman & R. D. Gascoyne (1997). "Mantle cell lymphoma: a clinicopathologic study of 80 cases". Blood. 89 (6): 2067–2078. PMID 9058729. Unknown parameter |month= ignored (help)
  15. Markus Tiemann, Carsten Schrader, Wolfram Klapper, Martin H. Dreyling, Elias Campo, Andrew Norton, Francoise Berger, Philip Kluin, German Ott, Stephano Pileri, Ennio Pedrinis, Alfred C. Feller, Hartmut Merz, Dirk Janssen, Martin L. Hansmann, Han Krieken, Peter Moller, Harald Stein, Michael Unterhalt, Wolfgang Hiddemann & Reza Parwaresch (2005). "Histopathology, cell proliferation indices and clinical outcome in 304 patients with mantle cell lymphoma (MCL): a clinicopathological study from the European MCL Network". British journal of haematology. 131 (1): 29–38. doi:10.1111/j.1365-2141.2005.05716.x. PMID 16173960. Unknown parameter |month= ignored (help)
  16. Julie M. Vose (2017). "Mantle cell lymphoma: 2017 update on diagnosis, risk-stratification, and clinical management". American journal of hematology. 92 (8): 806–813. doi:10.1002/ajh.24797. PMID 28699667. Unknown parameter |month= ignored (help)
  17. Non-gastric lymphomas – causes, symptoms and treatments. Lymphoma association 2016. https://www.lymphomas.org.uk/sites/default/files/pdfs/Non-Gastric-malt-lymphoma.pdf. Accessed on January 28, 2016
  18. Risks of Extranodal marginal zone of mucosa-associated lymphoid tissue (MALT lymphoma). Canadian Cancer Society 2016. http://www.cancer.ca/en/cancer-information/cancer-type/non-hodgkin-lymphoma/non-hodgkin-lymphoma/types-of-nhl/malt-lymphoma/?region=on. Accessed on January 25, 2016
  19. Kinkade, Zoe; Esan, Olukemi A.; Rosado, Flavia G.; Craig, Michael; Vos, Jeffrey A. (2015). "Ileal mucosa-associated lymphoid tissue lymphoma presenting with small bowel obstruction: a case report". Diagnostic Pathology. 10 (1). doi:10.1186/s13000-015-0353-6. ISSN 1746-1596.
  20. Symptoms of MALT lymphoma. Cancer research UK 2016. http://www.cancerresearchuk.org/about-cancer/type/non-hodgkins-lymphoma/about/types/mucosaassociated-lymphoid-tissue-lymphoma. Accessed on January 28, 2016
  21. Symptoms of MALT lymphoma. Cancer research UK 2016. http://www.cancerresearchuk.org/about-cancer/type/non-hodgkins-lymphoma/about/types/mucosaassociated-lymphoid-tissue-lymphoma. Accessed on January 28, 2016
  22. Signs and symptoms of gastric lymphoma. Wikipedia 2016. https://en.wikipedia.org/wiki/Gastric_lymphoma. Accessed on January 28, 2016
  23. Clinical presentation of orbital lymphoma. Dr Craig Hacking and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/articles/orbital-lymphoma. Accessed on January 28, 2016
  24. Non-gastric lymphomas – causes, symptoms and treatments. Lymphoma association 2016. https://www.lymphomas.org.uk/sites/default/files/pdfs/Non-Gastric-malt-lymphoma.pdf. Accessed on January 28, 2016
  25. Taal, B G; Boot, H; van Heerde, P; de Jong, D; Hart, A A; Burgers, J M (1 October 1996). "Primary non-Hodgkin lymphoma of the stomach: endoscopic pattern and prognosis in low versus high grade malignancy in relation to the MALT concept". Gut. 39 (4): 556–561. doi:10.1136/gut.39.4.556.
  26. Bacon CM, Du MQ, Dogan A (2007). "Mucosa-associated lymphoid tissue (MALT) lymphoma: a practical guide for pathologists". J Clin Pathol. 60 (4): 361–72. doi:10.1136/jcp.2005.031146. PMC 2001121. PMID 16950858.
  27. Hernández JM, García JL, Gutiérrez NC, Mollejo M, Martínez-Climent JA, Flores T, González MB, Piris MA, San Miguel JF (May 2001). "Novel genomic imbalances in B-cell splenic marginal zone lymphomas revealed by comparative genomic hybridization and cytogenetics". Am. J. Pathol. 158 (5): 1843–50. doi:10.1016/S0002-9440(10)64140-5. PMC 1891967. PMID 11337382.
  28. Andersen CL, Gruszka-Westwood A, Atkinson S, Matutes E, Catovsky D, Pedersen RK, Pedersen BB, Pulczynski S, Hokland P, Jacobsen E, Koch J (January 2005). "Recurrent genomic imbalances in B-cell splenic marginal-zone lymphoma revealed by comparative genomic hybridization". Cancer Genet. Cytogenet. 156 (2): 122–8. doi:10.1016/j.cancergencyto.2004.04.026. PMID 15642391.
  29. Salido M, Baró C, Oscier D, Stamatopoulos K, Dierlamm J, Matutes E, Traverse-Glehen A, Berger F, Felman P, Thieblemont C, Gesk S, Athanasiadou A, Davis Z, Gardiner A, Milla F, Ferrer A, Mollejo M, Calasanz MJ, Florensa L, Espinet B, Luño E, Wlodarska I, Verhoef G, García-Granero M, Salar A, Papadaki T, Serrano S, Piris MA, Solé F (September 2010). "Cytogenetic aberrations and their prognostic value in a series of 330 splenic marginal zone B-cell lymphomas: a multicenter study of the Splenic B-Cell Lymphoma Group". Blood. 116 (9): 1479–88. doi:10.1182/blood-2010-02-267476. PMID 20479288.
  30. Splenic marginal zone lymphoma. Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf57e3e27c3994bd5327/. Accessed on December 22, 2015
  31. Weng WK, Levy S (July 2003). "Hepatitis C virus (HCV) and lymphomagenesis". Leuk. Lymphoma. 44 (7): 1113–20. doi:10.1080/1042819031000076972. PMID 12916862.
  32. Quinn ER, Chan CH, Hadlock KG, Foung SK, Flint M, Levy S (December 2001). "The B-cell receptor of a hepatitis C virus (HCV)-associated non-Hodgkin lymphoma binds the viral E2 envelope protein, implicating HCV in lymphomagenesis". Blood. 98 (13): 3745–9. PMID 11739181.
  33. Chuang SS, Liao YL, Chang ST, Hsieh YC, Kuo SY, Lu CL, Hwang WS, Lin IH, Tsao CJ, Huang WT (July 2010). "Hepatitis C virus infection is significantly associated with malignant lymphoma in Taiwan, particularly with nodal and splenic marginal zone lymphomas". J. Clin. Pathol. 63 (7): 595–8. doi:10.1136/jcp.2010.076810. PMID 20530156.
  34. Spina, V.; Khiabanian, H.; Messina, M.; Monti, S.; Cascione, L.; Bruscaggin, A.; Spaccarotella, E.; Holmes, A. B.; Arcaini, L.; Lucioni, M.; Tabbo, F.; Zairis, S.; Diop, F.; Cerri, M.; Chiaretti, S.; Marasca, R.; Ponzoni, M.; Deaglio, S.; Ramponi, A.; Tiacci, E.; Pasqualucci, L.; Paulli, M.; Falini, B.; Inghirami, G.; Bertoni, F.; Foa, R.; Rabadan, R.; Gaidano, G.; Rossi, D. (2016). "The genetics of nodal marginal zone lymphoma". Blood. 128 (10): 1362–1373. doi:10.1182/blood-2016-02-696757. ISSN 0006-4971.
  35. Nodal marginal zone lymphoma . Canadian Cancer Society. http://www.cancer.ca/en/cancer-information/cancer-type/non-hodgkin-lymphoma/non-hodgkin-lymphoma/types-of-nhl/nodal-marginal-zone-lymphoma/?region=nb Accessed on March 4, 2016
  36. Multiple myeloma. Wikipedia (2015) https://en.wikipedia.org/wiki/Multiple_myeloma#Signs_and_symptoms Accessed on September, 20th 2015
  37. Multiple myeloma. Canadian Cancer Society (2015) http://www.cancer.ca/en/cancer-information/cancer-type/multiple-myeloma/signs-and-symptoms/?region=mb Accessed on September 20th 2015
  38. Multiple myeloma. Cancer. gov(2015) http://www.cancer.gov/types/myeloma Accessed on September, 20th 2015
  39. Reisenbuckler C (2014). "Multiple myeloma and diagnostic imaging". Radiol Technol. 85 (4): 391–410, quiz 411–3. PMID 24614435.
  40. Sergentanis TN, Zagouri F, Tsilimidos G, Tsagianni A, Tseliou M, Dimopoulos MA, Psaltopoulou T (October 2015). "Risk Factors for Multiple Myeloma: A Systematic Review of Meta-Analyses". Clin Lymphoma Myeloma Leuk. 15 (10): 563–77.e1–3. doi:10.1016/j.clml.2015.06.003. PMID 26294217.
  41. Eslick R, Talaulikar D (October 2013). "Multiple myeloma: from diagnosis to treatment". Aust Fam Physician. 42 (10): 684–8. PMID 24130968.
  42. Lens D, Matutes E, Catovsky D, Coignet LJ (2000). "Frequent deletions at 11q23 and 13q14 in B cell prolymphocytic leukemia (B-PLL)". Leukemia. 14 (3): 427–30. PMID 10720137.
  43. Yamamoto K, Hamaguchi H, Nagata K, Shibuya H, Takeuchi H (April 1998). "Splenic irradiation for prolymphocytic leukemia: is it preferable as an initial treatment or not?". Jpn. J. Clin. Oncol. 28 (4): 267–9. doi:10.1093/jjco/28.4.267. PMID 9657013.
  44. "Pathology". Archived from the original on 7 February 2009. Retrieved 2009-01-31.
  45. 45.0 45.1 Crisostomo RH, Fernandez JA, Caceres W (May 2007). "Complex karyotype including chromosomal translocation (8;14) (q24;q32) in one case with B-cell prolymphocytic leukemia". Leuk. Res. 31 (5): 699–701. doi:10.1016/j.leukres.2006.06.010. PMID 16997373.
  46. "National cancer institute".
  47. "National cancer institute".

Template:WH Template:WS