Lymphoplasmacytic lymphoma differential diagnosis: Difference between revisions

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==Differentiating Lymphoplasmacytic lymphoma from other Diseases==
==Differentiating Lymphoplasmacytic lymphoma from other Diseases==
[[Lymphoplasmacytic lymphoma]] must be differentiated from other [[B cell]] [[lymphoid]] [[neoplasms]] including:
[[Lymphoplasmacytic lymphoma]] must be differentiated from other [[B cell]] [[lymphoid]] [[neoplasms]]  
 
*[[Chronic lymphocytic leukemia]]/[[small lymphocytic lymphoma]]:
:*Always express [[CD5]].
:*Usually [[CD23]] positive.<ref name="CLL">{{cite journal |vauthors=Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner H, Hillmen P, Keating MJ, Montserrat E, Rai KR, Kipps TJ |title=Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines |journal=Blood |volume=111 |issue=12 |pages=5446–56 |year=2008 |pmid=18216293 |pmc=2972576 |doi=10.1182/blood-2007-06-093906 |url=}}</ref>
 
*[[B-cell prolymphocytic leukemia]]:
:*Express bright surface [[Immunoglobulin M|IgM]], [[CD20]] and other [[B-cell]] [[antigens]] ([[CD19]], [[CD22]], [[CD79a]], [[FMC7]]).<ref name=",m">{{cite journal |vauthors=Del Giudice I, Davis Z, Matutes E, Osuji N, Parry-Jones N, Morilla A, Brito-Babapulle V, Oscier D, Catovsky D |title=IgVH genes mutation and usage, ZAP-70 and CD38 expression provide new insights on B-cell prolymphocytic leukemia (B-PLL) |journal=Leukemia |volume=20 |issue=7 |pages=1231–7 |year=2006 |pmid=16642047 |doi=10.1038/sj.leu.2404238 |url=}}</ref><ref name="njl">{{cite journal |vauthors=Ravandi F, O'Brien S |title=Chronic lymphoid leukemias other than chronic lymphocytic leukemia: diagnosis and treatment |journal=Mayo Clin. Proc. |volume=80 |issue=12 |pages=1660–74 |year=2005 |pmid=16342661 |doi=10.4065/80.12.1660 |url=}}</ref>
 
*[[Follicular lymphoma]]:
:*Express [[CD10]], [[HLA-DR]], pan [[B-cell]] [[antigens]] ([[CD19]], [[CD20]], [[CD79a]]), [[CD21]], and surface [[IgM]], [[Immunoglobulin G|IgG]], or [[IgA]].
:*Rearrangement of [[Bcl-2|Bcl-2.]]<ref name="FL">{{cite journal |vauthors=Karube K, Guo Y, Suzumiya J, Sugita Y, Nomura Y, Yamamoto K, Shimizu K, Yoshida S, Komatani H, Takeshita M, Kikuchi M, Nakamura N, Takasu O, Arakawa F, Tagawa H, Seto M, Ohshima K |title=CD10-MUM1+ follicular lymphoma lacks BCL2 gene translocation and shows characteristic biologic and clinical features |journal=Blood |volume=109 |issue=7 |pages=3076–9 |year=2007 |pmid=17138820 |doi=10.1182/blood-2006-09-045989 |url=}}</ref><ref name="FL1">{{cite journal |vauthors=Anderson KC, Bates MP, Slaughenhoupt BL, Pinkus GS, Schlossman SF, Nadler LM |title=Expression of human B cell-associated antigens on leukemias and lymphomas: a model of human B cell differentiation |journal=Blood |volume=63 |issue=6 |pages=1424–33 |year=1984 |pmid=6609729 |doi= |url=}}
:*Bone marrow infiltration of small, cleaved cells that are usually paratrabecular
</ref>
 
*[[Multiple myeloma]]:
:*Express [[CD138]], [[CD38]], [[CD79a]], VS38c and [[CD56]] (70%)
:*Presence of plasmacytic cell infiltration of [[bone marrow]], osteolytic lesions, and [[renal insufficiency]]
:*[[Translocation]] involving [[chromosome 11]] (t11;14)<ref name="UTD">{{cite journal |vauthors=Pangalis GA, Kyrtsonis MC, Kontopidou FN, Vassilakopoulos TP, Siakantaris MP, Dimopoulou MN, Kittas C, Angelopoulou MK |title=Differential diagnosis of Waldenstrom's macroglobulinemia from other low-grade B-cell lymphoproliferative disorders |journal=Semin. Oncol. |volume=30 |issue=2 |pages=201–5 |year=2003 |pmid=12720136 |doi=10.1053/sonc.2003.50046 |url=}}</ref>
 
*[[Mantle cell lymphoma]]:
:* Expresses [[CD5]]+ and [[CD23]]+
:* Expresses surface [[IgM]], [[IgD]], and [[cyclin D1]] in majority of cases
:*Infiltration of [[bone marrow]] by monomorphous small [[lymphoid]] cells with irregular [[nuclei]]<ref name="MCL">{{cite journal |vauthors=Dorfman DM, Pinkus GS |title=Distinction between small lymphocytic and mantle cell lymphoma by immunoreactivity for CD23 |journal=Mod. Pathol. |volume=7 |issue=3 |pages=326–31 |year=1994 |pmid=8058704 |doi= |url=}}</ref><ref name="MCL1">{{cite journal |vauthors=DiRaimondo F, Albitar M, Huh Y, O'Brien S, Montillo M, Tedeschi A, Kantarjian H, Lerner S, Giustolisi R, Keating M |title=The clinical and diagnostic relevance of CD23 expression in the chronic lymphoproliferative disease |journal=Cancer |volume=94 |issue=6 |pages=1721–30 |year=2002 |pmid=11920534 |doi= |url=}}</ref>
 
*[[Marginal zone lymphoma]]:
:*Expresses [[B cell]] markers [[CD19]], [[CD20]], and [[CD22]].
:*Infiltrates the [[bone marrow]] with a characteristic intertrabecular and intrasinusoidal pattern
:*Most common [[cytogenetic]] abnormalities are loss of 7q (19%) along with +3q (19%) and +5q (10% )<ref name="add">{{cite journal |vauthors=Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J, Lister TA, Bloomfield CD |title=World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997 |journal=J. Clin. Oncol. |volume=17 |issue=12 |pages=3835–49 |year=1999 |pmid=10577857 |doi= |url=}}</ref><ref name="asdf">{{cite journal |vauthors=Harris NL, Jaffe ES, Stein H, Banks PM, Chan JK, Cleary ML, Delsol G, De Wolf-Peeters C, Falini B, Gatter KC |title=A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group |journal=Blood |volume=84 |issue=5 |pages=1361–92 |year=1994 |pmid=8068936 |doi= |url=}}</ref>
 
{| class="wikitable"
|+ '''[[Histopathology]], [[immunophenotype]], and [[genetic]] features of [[differential diagnosis]] of [[lymphoplasmacytic lymphoma]]'''
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Disease entity
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Histopathology
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Immunophenotype
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Genetic or other features
|-
| style="background:#DCDCDC;" align="center" + |'''[[Lymphoplasmacytic lymphoma]]'''
| style="background:#F5F5F5;" align="center" + |
* ≥10 percent infiltration by small [[lymphocytes]], plasmacytoid [[lymphocytes]], and [[plasma cells]], with variable numbers of admixed immunoblasts.
 
*Characteristic (but not pathognomonic) [[hyperplasia]] of [[mast cells]] in marrow.
*[[Lymph nodes]] are usually diffusely effaced.
*Absence of [[proliferation]] centers and [[marginal zone]] type [[differentiation]].
| style="background:#F5F5F5;" align="center" + |
* Expression of pan [[B-cell]] [[antigens]] ([[CD19]], [[CD20]], [[CD22]], [[CD79a]]).
 
*Failure to express [[CD5]] in mostly cases.
*Variable expression of [[CD11c]], [[CD43]], [[CD25]].
*Mostly cases have [[IgM]] expression with only fewer expressing [[IgG]] or [[IgA]].
*No [[CD10]] and [[cyclin D1]] [[expression]].
| style="background:#F5F5F5;" align="center" + |
* Majority have a monoclonal [[IgM]] [[paraprotein]].
 
*No specific [[chromosomal abnormalities]].
|-
| style="background:#DCDCDC;" align="center" + |'''[[Chronic lymphocytic leukemia]]/[[small lymphocytic lymphoma]]'''
| style="background:#F5F5F5;" align="center" + |
* "Typical" [[CLL]]/[[SLL]] cells are small mature appearing [[lymphocytes]] with a dense [[nucleus]], partially aggregated [[chromatin]], no discernible [[nucleoli]], and a narrow border of clear to slightly [[basophilic]] [[cytoplasm]].
| style="background:#F5F5F5;" align="center" + |
* Always express [[CD5]].
 
*Usually [[CD23]] positive.
*Dim [[expression]] of [[CD20]] and surface Ig.
| style="background:#F5F5F5;" align="center" + |
* Del13q, del 11q, del17p, [[trisomy]] 12
|-
| style="background:#DCDCDC;" align="center" + |'''[[B-cell prolymphocytic leukemia]]'''
| style="background:#F5F5F5;" align="center" + |
* [[Prolymphocytes]] comprise >55 percent of the [[neoplastic]] cells.
 
*[[Bone marrow]] has [[interstitial]] pattern of [[Infiltration (medical)|infiltration]].
*[[Lymph nodes]] may show vague nodularity, but [[proliferation]] centers are absent.
| style="background:#F5F5F5;" align="center" + |
* Express bright surface [[IgM]] +/- [[IgD]] and bright [[CD20]] as well as other [[B-cell]] [[antigens]] ([[CD19]], [[CD22]], [[CD79a]], [[FMC7]]).
| style="background:#F5F5F5;" align="center" + |
* t(11;14) must be excluded.
 
*No associated [[paraproteinemia]].
|-
| style="background:#DCDCDC;" align="center" + |'''[[Follicular lymphoma]]'''
| style="background:#F5F5F5;" align="center" + |
* [[Nodular]] growth pattern of [[follicle]] center cells (centrocytes and centroblasts).
| style="background:#F5F5F5;" align="center" + |
* Typically express [[CD10]], [[HLA-DR]], pan [[B-cell]] [[antigens]] ([[CD19]], [[CD20]], [[CD79a]]), [[CD21]], and surface [[IgM]], [[IgG]], or [[IgA]].
| style="background:#F5F5F5;" align="center" + |
* t(14;18)
|-
| style="background:#DCDCDC;" align="center" + |'''[[Multiple myeloma]]'''
| style="background:#F5F5F5;" align="center" + |
* [[Infiltration (medical)|Infiltration]] of [[plasma cells]] in the [[bone marrow]].
| style="background:#F5F5F5;" align="center" + |
* Absent Surface Ig.
 
*Expresses [[CD138]], [[CD38]], [[CD79a]], and VS38c.
*Infrequently expresses [[CD19]].
*Approximately 70 percent of myeloma cells will express [[CD56]].
| style="background:#F5F5F5;" align="center" + |
* [[Cytogenetics]] usually abnormal, although there is no specific [[cytogenetic]] abnormality.
|-
| style="background:#DCDCDC;" align="center" + |'''[[Mantle cell lymphoma]]'''
| style="background:#F5F5F5;" align="center" + |
* Monomorphous small to medium-sized [[B lymphocytes]] with irregular [[nuclei]].
| style="background:#F5F5F5;" align="center" + |
* [[CD5]]+ and [[CD23]]-.
 
*Typically co-express surface [[IgM]] and [[IgD]].
*The vast majority over-express [[cyclin D1]].
| style="background:#F5F5F5;" align="center" + |
* t(11;14)
|-
| style="background:#DCDCDC;" align="center" + |'''[[Marginal zone lymphoma]]'''
| style="background:#F5F5F5;" align="center" + |
* Polymorphous infiltrate of small cells with paler-appearing marginal zone-type [[differentiation]] in [[lymph nodes]].
| style="background:#F5F5F5;" align="center" + |
* Expresses [[B cell]] markers [[CD19]], [[CD20]], and [[CD22]], and not [[CD5]], [[CD10]], and [[CD23]].
| style="background:#F5F5F5;" align="center" + |
* [[Chromosomal abnormalities]], usually [[trisomy]] 3 or t(11;18), are found in most cases.
 
*May demonstrate mixed [[cryoglobulinemia]] +/- [[hepatitis C]] [[infection]].
|}


{|
{|

Revision as of 23:58, 24 February 2019


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

Overview

Lymphoplasmacytic lymphoma 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

Lymphoplasmacytic lymphoma must be differentiated from 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
Lymphoplasmacytic lymphoma (Waldenstrom’s macroglobulinemia)
[1][2][3][4][5]
+ Express 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 express

Usually express

Dim expression of

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

Express Surface

  • Most common clinically indolent NHL
  • Peripheral nerve compression
Mantle cell lymphoma
[12][13][14][15][16]
Abdominal distention +

Co-express surface

_
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]
  • Mature B-cell Lymphoma
  • Recurrent translocation of s such as:
    • t(1;14)(p22;q32)
    • t(11;18)(q21;q21)
    • t(14;18)(q32;q21)
    • t(3;14)(p14.1;q32)
  • B symptoms may or may not be present
± + + B-cell associated antigens that co-express

Negative for:

  • Presence of dense diffuse lymphoid infiltrate of marginal‐zone cells in lamina propria
  • prominent lymphoepithelial lesions and consisting of small atypical cells with monocytoid features.
Splenic marginal zone lymphoma
[27][28][29][30][31][32][33]
  • Mature B-cell Lymphoma
  • Clonal rearrangements of the immunoglobulin genes (heavy and light chains)
    • Deletion 7q21-32
    • Translocations of the CDK6 gene located on 7q21
+ +
  • Small lymphocytes
  • Transformed blasts
  • Epithelial histocytes
  • Plasmacytic differentiation of neoplastic cells
Nodal marginal zone B-cell lymphoma
[34][35]
  • Mature B-cell Lymphoma
  • Stimulation of antigen receptor by autoantigen and co-stimulatory molecule CD40
  • Mutations in KMT2D, PTTPRD, NOTCH2, KLF2
+
  • Hemorrhage
  • Dyspepsia
_
  • Follicular cells in reactive zone
  • Centrocyte like cells in marginal zone lymphoma
  • Centroblasts
  • Plasma cells
  • Immunoblasts
  • Hepatitis C infection
  • Chronic infectious conditions or autoimmune processes, such as:
  • H pylori gastritis
  • Hashimoto thyroiditis
  • Sjögren syndrome
Multiple Myeloma[36][37][38][39][40][41]
  • Abdominal pain due to mesenteric venous thrombosis
  • No diarrhea
  • Constipation due to hypercalcemia
_
Expresses
  • CD138
  • CD38,
  • CD79a
  • VS38c
  • Infrequently expresses CD19.
  • CD56 (expressed by 70% of myeloma cells)
  • Absent surface Ig
Relevant history includes:
B-cell prolymphocytic leukemia
Express bright surface IgM +/- IgD and bright CD20 as well as other B-cell antigens (CD19, CD22, CD79a, FMC7)
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

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  9. Overview at UMDNJ
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