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__TOC__
−==Synonyms / Terminology==
−Obsolete names:
−*Centrocytic malignant lymphoma (obsolete) <ref name=":3">{{Cite journal|last=K|first=Lennert|last2=H|first2=Stein|last3=E|first3=Kaiserling|date=1975|title=Cytological and functional criteria for the classification of malignant lymphomata|url=https://pubmed.ncbi.nlm.nih.gov/52366/|language=en|pmc=PMC2149614|pmid=52366}}</ref>
−*Lymphocytic lymphoma of intermediate differentiation <ref name=":4">{{Cite journal|last=H|first=Kim|last2=Rj|first2=Zelman|last3=Ma|first3=Fox|last4=Jm|first4=Bennett|last5=Cw|first5=Berard|last6=Jj|first6=Butler|last7=Ge|first7=Byrne|last8=Rf|first8=Dorfman|last9=Rj|first9=Hartsock|date=1982|title=Pathology Panel for Lymphoma Clinical Studies: a comprehensive analysis of cases accumulated since its inception|url=https://pubmed.ncbi.nlm.nih.gov/6948126/|language=en|pmid=6948126}}</ref>
−*Mantle zone lymphoma <ref name=":5">{{Cite journal|last=Dd|first=Weisenburger|last2=H|first2=Kim|last3=H|first3=Rappaport|date=1982|title=Mantle-zone lymphoma: a follicular variant of intermediate lymphocytic lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/6895860/|language=en|pmid=6895860}}</ref>
−*Malignant lymphomatous polyposis
−*in situ mantle cell lymphoma (for in situ mantle cell neoplasia)
−==Epidemiology / Prevalence==
−*~ 7% of B cell lymphomas <ref name=":6">{{Cite journal|date=1997|title=A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. The Non-Hodgkin's Lymphoma Classification Project|url=https://pubmed.ncbi.nlm.nih.gov/9166827/|language=en|pmid=9166827}}</ref>
−*2.5%-10% of non-Hodgkin lymphomas <ref name=":7">{{Cite journal|last=Ke|first=Smedby|last2=H|first2=Hjalgrim|date=2011|title=Epidemiology and etiology of mantle cell lymphoma and other non-Hodgkin lymphoma subtypes|url=https://pubmed.ncbi.nlm.nih.gov/21945518/|language=en|pmid=21945518}}</ref>
−*Age adjusted incidence: 0.7/100,000 person years in white population in USA <ref name=":8">{{Cite journal|last=B|first=Aschebrook-Kilfoy|last2=Db|first2=Caces|last3=Nj|first3=Ollberding|last4=Sm|first4=Smith|last5=Bc|first5=Chiu|date=2013|title=An upward trend in the age-specific incidence patterns for mantle cell lymphoma in the USA|url=https://pubmed.ncbi.nlm.nih.gov/23350889/|language=en|pmid=23350889}}</ref>
−*Median age: 60 years<ref name=":9">{{Cite journal|last=Lh|first=Argatoff|last2=Jm|first2=Connors|last3=Rj|first3=Klasa|last4=De|first4=Horsman|last5=Rd|first5=Gascoyne|date=1997|title=Mantle cell lymphoma: a clinicopathologic study of 80 cases|url=https://pubmed.ncbi.nlm.nih.gov/9058729/|language=en|pmid=9058729}}</ref>
−*M:F = 3:1 (range, 1.6-6.8 :1)<ref name=":10">{{Cite journal|last=P|first=Lardelli|last2=Ma|first2=Bookman|last3=J|first3=Sundeen|last4=Dl|first4=Longo|last5=Es|first5=Jaffe|date=1990|title=Lymphocytic lymphoma of intermediate differentiation. Morphologic and immunophenotypic spectrum and clinical correlations|url=https://pubmed.ncbi.nlm.nih.gov/2198813/|language=en|pmid=2198813}}</ref>
−==Clinical Features==
−Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table. Do not delete table.'') </span>
−{| class="wikitable"
−|'''Signs and Symptoms'''
−|<span class="blue-text">EXAMPLE:</span> Asymptomatic (incidental finding on complete blood counts)
−<span class="blue-text">EXAMPLE:</span> B-symptoms (weight loss, fever, night sweats)
−<span class="blue-text">EXAMPLE:</span> Fatigue
−<span class="blue-text">EXAMPLE:</span> Lymphadenopathy (uncommon)
−|-
−|'''Laboratory Findings'''
−|<span class="blue-text">EXAMPLE:</span> Cytopenias
−<span class="blue-text">EXAMPLE:</span> Lymphocytosis (low level)
−|}
−<blockquote class="blockedit">{{Box-round|title=v4:Clinical Features|The content below was from the old template. Please incorporate above.}}</blockquote>
−*Approximately 70% with stage IV disease at presentation
−**Generalized lymphadenopathy, hepatosplenomegaly and bone marrow involvement
−**40-50% with B symptoms
−**Two subtypes based on clinical presentation:
−***More aggressive, with SOX11 overexpression (SOX11+disease), nodal presentation (the most common subtype)
−***More indolent, without SOX11 expression (SOX11-disease), leukemic presentation, and non-nodal disease
−*Peripheral blood:
−**Atypical lymphoid cells: present virtually in all cases by flow cytometry <ref>{{Cite journal|last=A|first=Ferrer|last2=I|first2=Salaverria|last3=F|first3=Bosch|last4=N|first4=Villamor|last5=M|first5=Rozman|last6=S|first6=Beà|last7=E|first7=Giné|last8=A|first8=López-Guillermo|last9=E|first9=Campo|date=2007|title=Leukemic involvement is a common feature in mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/17477385/|language=en|pmid=17477385}}</ref>
−***Atypical lymphoid cells can be detected in the peripheral blood in the absence of lymphocytosis
−***Leukemic involvement: 20 - 70% of patients at diagnosis
−***Leukemic involvement is usually a sign of disease progression
−**Blastoid morphology of the circulating lymphoma cells may mimic acute leukemia
−**A leukemic phase with no or minimal lymph node involvement is possible, [[HAEM5:Leukaemic non-nodal mantle cell lymphoma]]
−***Asymptomatic for long period
−***Splenomegaly
−**Anemia and thrombocytopenia (10%- 40%)
−*Multiple intestinal polyps (lymphomatous polyposis)
−*Progress to blastoid / pleomorphic variant
−**At the time of relapse (~22%)
−<blockquote class="blockedit">{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}</blockquote><ref>Arber, D.A., et al., ''Hematopathology''. 2017, Philadelphia, PA: Elsevier.</ref><blockquote class="blockedit">
−<center><span style="color:Maroon">'''End of V4 Section'''</span>
−----
−<blockquote class="blockedit">
−<center><span style="color:Maroon">'''End of V4 Section'''</span>
−----
−</blockquote>
−</blockquote>
−==Sites of Involvement==
−*Lymph node
−*Bone marrow involvement independent of peripheral blood (50 - 90%), peripheral blood (20 - 70%), spleen (~50%), liver (~20%) <ref name=":11">{{Cite journal|last=J|first=Wasman|last2=Ns|first2=Rosenthal|last3=Dc|first3=Farhi|date=1996|title=Mantle cell lymphoma. Morphologic findings in bone marrow involvement|url=https://pubmed.ncbi.nlm.nih.gov/8712173/|language=en|pmid=8712173}}</ref><ref name=":12">{{Cite journal|last=Ma|first=Vasef|last2=Lj|first2=Medeiros|last3=C|first3=Koo|last4=A|first4=McCourty|last5=Rk|first5=Brynes|date=1997|title=Cyclin D1 immunohistochemical staining is useful in distinguishing mantle cell lymphoma from other low-grade B-cell neoplasms in bone marrow|url=https://pubmed.ncbi.nlm.nih.gov/9291459/|language=en|pmid=9291459}}</ref><ref name=":13">{{Cite journal|last=H|first=Samaha|last2=C|first2=Dumontet|last3=N|first3=Ketterer|last4=I|first4=Moullet|last5=C|first5=Thieblemont|last6=F|first6=Bouafia|last7=E|first7=Callet-Bauchu|last8=P|first8=Felman|last9=F|first9=Berger|date=1998|title=Mantle cell lymphoma: a retrospective study of 121 cases|url=https://pubmed.ncbi.nlm.nih.gov/9697885/|language=en|pmid=9697885}}</ref>
−*Frequent extranodal site involvement : gastrointestinal tract, Waldeyer ring, lungs, pleura, skin, CNS
−**CNS involvement may occur mostly at the time of relapse<ref name=":14">{{Cite journal|last=Cy|first=Cheah|last2=A|first2=George|last3=E|first3=Giné|last4=A|first4=Chiappella|last5=Hc|first5=Kluin-Nelemans|last6=W|first6=Jurczak|last7=K|first7=Krawczyk|last8=H|first8=Mocikova|last9=P|first9=Klener|date=2013|title=Central nervous system involvement in mantle cell lymphoma: clinical features, prognostic factors and outcomes from the European Mantle Cell Lymphoma Network|url=https://pubmed.ncbi.nlm.nih.gov/23616279/|language=en|pmid=23616279}}</ref>
−*Extranodal involvement without lymphadenopathies: 4 - 15%
−==Morphologic Features==
−*Architectural pattern: Diffuse > nodular > mantle zone growth patterns
−**Nodal (> 50% nodular), diffuse growth pattern (< 50% nodular)
−*Cytologic variants: Classic, blastoid, pleomorphic, small cell, marginal zone-like
−*Blastoid and pleomorphic cytologic variants are known as aggressive variants of MCL
−*Classic variant:
−**Small to medium monomorphic lymphoid neoplasm
−**Irregular nuclear border, clumped chromatin and inconspicuous nucleoli
−**No proliferation centers
−**No centroblasts, immunoblasts or paraimmunoblasts
−**Hyalinized vessels
−**Epithelioid histiocytes
−**Follicular dendritic cell (FDC) meshwork
−***Nodular pattern
−****Primary follicle-like pattern
−****Germinal center-like pattern
−***Diffuse pattern
−*Aggressive variants
−**Blastoid: lymphoblast-like in appearance, monomorphic
−***>20 - 30 mitoses per 10 high power fields
−***Resemble lymphoblastic lymphoma
−**Pleomorphic: large cells with irregular nuclear border, cerebriform nuclei, multinucleation, lack of monomorphism
−***Prominent nucleoli and abundant pale cytoplasm
−***Resemble DLBCL
−*Other variants
−**Small cell: small round lymphocytes with more clumped chromatin
−***Resemble CLL
−**Marginal zone-like: abundant pale cytoplasm
−***Resembling marginal zone or monocytoid B cells
−**Lymphoplasmacytic differentiation, some cases <ref name=":15">{{Cite journal|last=Kh|first=Young|last2=Wc|first2=Chan|last3=K|first3=Fu|last4=J|first4=Iqbal|last5=Wg|first5=Sanger|last6=A|first6=Ratashak|last7=Tc|first7=Greiner|last8=Dd|first8=Weisenburger|date=2006|title=Mantle cell lymphoma with plasma cell differentiation|url=https://pubmed.ncbi.nlm.nih.gov/16861965/|language=en|pmid=16861965}}</ref>
−*Bone marrow
−**Nodular, interstitial or paratrabecular or combination
−*Peripheral blood (see below)
−**Similar spectrum seen in tissue sample
−**Nucleoli are sometimes more prominent
−*Spleen
−**White pulp nodules involved (enlarged)
−**Variable involvement of the red pulp
−**Residual naked germinal centers
−**Tumor cells: similar monotonous morphology
−**Some cases may show a marginal zone-like area <ref name=":16">{{Cite journal|last=Ma|first=Piris|last2=M|first2=Mollejo|last3=E|first3=Campo|last4=J|first4=Menárguez|last5=T|first5=Flores|last6=Pg|first6=Isaacson|date=1998|title=A marginal zone pattern may be found in different varieties of non-Hodgkin's lymphoma: the morphology and immunohistology of splenic involvement by B-cell lymphomas simulating splenic marginal zone lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/9777389/|language=en|pmid=9777389}}</ref>
−*Gastrointestinal
−**May mimic lymphoepithelial lesions in marginal zone lymphoma <ref name=":17">{{Cite journal|last=M|first=Fraga|last2=E|first2=Lloret|last3=L|first3=Sanchez-Verde|last4=Jl|first4=Orradre|last5=E|first5=Campo|last6=F|first6=Bosch|last7=Ma|first7=Piris|date=1995|title=Mucosal mantle cell (centrocytic) lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/7657310/|language=en|pmid=7657310}}</ref>
−*Relapse
−**Loss of a mantle zone growth pattern
−**Increase in nuclear size
−**Pleomorphism and chromatin dispersal
−**Increase in mitotic activity and Ki67
−**Cases that are blastoid at diagnosis may relapse with classic morphology <ref name=":18">{{Cite journal|last=N|first=Vogt|last2=W|first2=Klapper|date=2013|title=Variability in morphology and cell proliferation in sequential biopsies of mantle cell lymphoma at diagnosis and relapse: clinical correlation and insights into disease progression|url=https://pubmed.ncbi.nlm.nih.gov/23240716/|language=en|pmid=23240716}}</ref>
−==Immunophenotype==
−<br />
−{| class="wikitable sortable"
−|-
−!Finding!!Marker
−|-
−|Positive (>95%)||cyclin D1
−|-
−|Positive (>90%)||Sox-11
−|-
−|Positive (100%)||B-cell associated markers (CD19, CD20, CD22, CD79a/b)
−|-
−|Positive (>95%)||CD5
−|-
−|Positive
−|CD43
−|-
−|Positive
−|IgM+/- IgD
−|-
−|Positive
−|BCL-2
−|-
−|Positive (flow cytometry)
−|FMC-7
−|-
−|Positive (50% in small subset of cells)
−|MUM1 / IRF4
−|-
−|Positive (subset)
−|MYC
−|-
−|Positive (subset)
−|p53
−|-
−|Positive/ Negative
−|CD10
−|-
−|Positive/ Negative
−|BCL-6
−|-
−|Negative
−|T-cell associated markers (except CD5)
−|-
−|Negative
−|CD200
−|-
−|Negative
−|LEF-1
−|}
−*Ki67 count <ref name=":19">{{Cite journal|last=W|first=Klapper|last2=E|first2=Hoster|last3=O|first3=Determann|last4=I|first4=Oschlies|last5=J|first5=van der Laak|last6=F|first6=Berger|last7=Hw|first7=Bernd|last8=J|first8=Cabeçadas|last9=E|first9=Campo|date=2009|title=Ki-67 as a prognostic marker in mantle cell lymphoma-consensus guidelines of the pathology panel of the European MCL Network|url=https://pubmed.ncbi.nlm.nih.gov/19669190/|language=en|doi=10.1007/s12308-009-0036-x|pmc=PMC2725281|pmid=19669190}}</ref>
−**Five independent high power fields count
−**Avoidance of residual germinal centers, hot spots and proliferating T cells
−**Note: Ki67 index is not sufficient to classify as blastoid or pleomorphic subtype
−**Classical mantle cell lymphoma might also show high cell proliferation<ref name=":20">{{Cite journal|last=O|first=Determann|last2=E|first2=Hoster|last3=G|first3=Ott|last4=H|first4=Wolfram Bernd|last5=C|first5=Loddenkemper|last6=M|first6=Leo Hansmann|last7=Te|first7=Barth|last8=M|first8=Unterhalt|last9=W|first9=Hiddemann|date=2008|title=Ki-67 predicts outcome in advanced-stage mantle cell lymphoma patients treated with anti-CD20 immunochemotherapy: results from randomized trials of the European MCL Network and the German Low Grade Lymphoma Study Group|url=https://pubmed.ncbi.nlm.nih.gov/18077791/|language=en|pmid=18077791}}</ref>
−*p53 in subset; intense expression correlates with ''TP53'' gene mutation
−**Note: no protein expression; on the other hand, cannot predict the homozygous deletions of the locus <ref name=":21">{{Cite journal|last=L|first=Hernandez|last2=T|first2=Fest|last3=M|first3=Cazorla|last4=J|first4=Teruya-Feldstein|last5=F|first5=Bosch|last6=Ma|first6=Peinado|last7=Ma|first7=Piris|last8=E|first8=Montserrat|last9=A|first9=Cardesa|date=1996|title=p53 gene mutations and protein overexpression are associated with aggressive variants of mantle cell lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/8605352/|language=en|pmid=8605352}}</ref>
−*MYC in subset
−**High expression correlates with ''MYC'' translocation <ref name=":22">{{Cite journal|last=Jy|first=Choe|last2=Jy|first2=Yun|last3=Hy|first3=Na|last4=J|first4=Huh|last5=Sj|first5=Shin|last6=Hj|first6=Kim|last7=Jh|first7=Paik|last8=Ya|first8=Kim|last9=Sj|first9=Nam|date=2016|title=MYC overexpression correlates with MYC amplification or translocation, and is associated with poor prognosis in mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/26100211/|language=en|pmid=26100211}}</ref>
−*CD10+ MCL more associated with diffuse growth pattern, blastoid/pleomorphic morphology, and BCL6 expression<ref name=":23">{{Cite journal|last=J|first=Xu|last2=Lj|first2=Medeiros|last3=A|first3=Saksena|last4=M|first4=Wang|last5=J|first5=Zhou|last6=J|first6=Li|last7=Cc|first7=Yin|last8=G|first8=Tang|last9=L|first9=Wang|date=2017|title=CD10-positive mantle cell lymphoma: clinicopathologic and prognostic study of 30 cases|url=https://pubmed.ncbi.nlm.nih.gov/29545910/|language=en|doi=10.18632/oncotarget.23571|pmc=PMC5837746|pmid=29545910}}</ref>
−*CD23: small subset of cases <ref name=":24">{{Cite journal|last=S|first=Kumar|last2=Ga|first2=Green|last3=J|first3=Teruya-Feldstein|last4=M|first4=Raffeld|last5=Es|first5=Jaffe|date=1996|title=Use of CD23 (BU38) on paraffin sections in the diagnosis of small lymphocytic lymphoma and mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/8878025/|language=en|pmid=8878025}}</ref>
−*CD200: May be positive in a subset of SOX11 negative mantle cell lymphomas<ref name=":25">{{Cite journal|last=B|first=Espinet|last2=A|first2=Ferrer|last3=B|first3=Bellosillo|last4=L|first4=Nonell|last5=A|first5=Salar|last6=C|first6=Fernández-Rodríguez|last7=E|first7=Puigdecanet|last8=J|first8=Gimeno|last9=M|first9=Garcia-Garcia|date=2014|title=Distinction between asymptomatic monoclonal B-cell lymphocytosis with cyclin D1 overexpression and mantle cell lymphoma: from molecular profiling to flow cytometry|url=https://pubmed.ncbi.nlm.nih.gov/24352646/|language=en|doi=10.1158/1078-0432.CCR-13-1077|pmc=PMC4488901|pmid=24352646}}</ref> [[HAEM5:Leukaemic non-nodal mantle cell lymphoma]]
−*LEF-1: positive in 4 - 9% of mantle cell lymphomas <ref name=":26">{{Cite journal|last=Dp|first=O'Malley|last2=Jp|first2=Lee|last3=Am|first3=Bellizzi|date=2017|title=Expression of LEF1 in mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/28038713/|language=en|pmid=28038713}}</ref><ref name=":27">{{Cite journal|last=B|first=Sander|last2=L|first2=Quintanilla-Martinez|last3=G|first3=Ott|last4=L|first4=Xerri|last5=I|first5=Kuzu|last6=Jk|first6=Chan|last7=Sh|first7=Swerdlow|last8=E|first8=Campo|date=2016|title=Mantle cell lymphoma--a spectrum from indolent to aggressive disease|url=https://pubmed.ncbi.nlm.nih.gov/26298543/|language=en|pmid=26298543}}</ref>
−*Cyclin D1-negative MCL
−**Morphology, phenotype, gene expression, clinical presentation and evolution similar to cyclin D1-positive MCL <ref name=":28">{{Cite journal|last=K|first=Fu|last2=Dd|first2=Weisenburger|last3=Tc|first3=Greiner|last4=S|first4=Dave|last5=G|first5=Wright|last6=A|first6=Rosenwald|last7=M|first7=Chiorazzi|last8=J|first8=Iqbal|last9=S|first9=Gesk|date=2005|title=Cyclin D1-negative mantle cell lymphoma: a clinicopathologic study based on gene expression profiling|url=https://pubmed.ncbi.nlm.nih.gov/16123218/|language=en|doi=10.1182/blood-2005-04-1753|pmc=PMC1895253|pmid=16123218}}</ref>
−**Positive for Sox-11
−**Frequently express cyclin D2 or cyclin D3 (''IG''-mediated translocations) <ref name=":29">{{Cite journal|last=I|first=Wlodarska|last2=D|first2=Dierickx|last3=V|first3=Vanhentenrijk|last4=K|first4=Van Roosbroeck|last5=H|first5=Pospísilová|last6=F|first6=Minnei|last7=G|first7=Verhoef|last8=J|first8=Thomas|last9=P|first9=Vandenberghe|date=2008|title=Translocations targeting CCND2, CCND3, and MYCN do occur in t(11;14)-negative mantle cell lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/18391076/|language=en|pmid=18391076}}</ref>
−**cyclin E in cases with negative expression of cyclin D and aggressive behavior <ref name=":30">{{Cite journal|last=D|first=Martín-Garcia|last2=A|first2=Navarro|last3=R|first3=Valdés-Mas|last4=G|first4=Clot|last5=J|first5=Gutiérrez-Abril|last6=M|first6=Prieto|last7=I|first7=Ribera-Cortada|last8=R|first8=Woroniecka|last9=G|first9=Rymkiewicz|date=2019|title=CCND2 and CCND3 hijack immunoglobulin light-chain enhancers in cyclin D1 - mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/30538135/|language=en|doi=10.1182/blood-2018-07-862151|pmc=PMC6396173|pmid=30538135}}</ref>
{{DISPLAYTITLE:Mantle cell lymphoma}}
{{DISPLAYTITLE:Mantle cell lymphoma}}
−[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]
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The University Of Texas MD Anderson Cancer Center, Department of Hematopathology, Houston, Texas
The University Of Texas MD Anderson Cancer Center, Department of Hematopathology, Houston, Texas
−==WHO Classification of Disease==
==WHO Classification of Disease==
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|Mantle cell lymphoma
|Mantle cell lymphoma
|}
|}
−==WHO Essential and Desirable Genetic Diagnostic Criteria==
==WHO Essential and Desirable Genetic Diagnostic Criteria==
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*Small to medium sized lymphoid cells (monomorphic, except in pleomorphic variant)
*Small to medium sized lymphoid cells (monomorphic, except in pleomorphic variant)
*Associated with t(11;14)(q13;q32) and cyclin D1 overexpression in over 95% of cases
*Associated with t(11;14)(q13;q32) and cyclin D1 overexpression in over 95% of cases
−*Synonyms/Terminology - Centrocytic malignant lymphoma (obsolete) <ref name=":3" />; Lymphocytic lymphoma of intermediate differentiation <ref name=":4" />; Mantle zone lymphoma <ref name=":5" />; Malignant lymphomatous polyposis; in situ mantle cell lymphoma (for in situ mantle cell neoplasia)
+*Synonyms/Terminology - Centrocytic malignant lymphoma (obsolete) <ref name=":3">{{Cite journal|last=K|first=Lennert|last2=H|first2=Stein|last3=E|first3=Kaiserling|date=1975|title=Cytological and functional criteria for the classification of malignant lymphomata|url=https://pubmed.ncbi.nlm.nih.gov/52366/|language=en|pmc=PMC2149614|pmid=52366}}</ref>; Lymphocytic lymphoma of intermediate differentiation <ref name=":4">{{Cite journal|last=H|first=Kim|last2=Rj|first2=Zelman|last3=Ma|first3=Fox|last4=Jm|first4=Bennett|last5=Cw|first5=Berard|last6=Jj|first6=Butler|last7=Ge|first7=Byrne|last8=Rf|first8=Dorfman|last9=Rj|first9=Hartsock|date=1982|title=Pathology Panel for Lymphoma Clinical Studies: a comprehensive analysis of cases accumulated since its inception|url=https://pubmed.ncbi.nlm.nih.gov/6948126/|language=en|pmid=6948126}}</ref>; Mantle zone lymphoma <ref name=":5">{{Cite journal|last=Dd|first=Weisenburger|last2=H|first2=Kim|last3=H|first3=Rappaport|date=1982|title=Mantle-zone lymphoma: a follicular variant of intermediate lymphocytic lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/6895860/|language=en|pmid=6895860}}</ref>; Malignant lymphomatous polyposis; in situ mantle cell lymphoma (for in situ mantle cell neoplasia)
The <u>epidemiology/prevalence</u> of this disease is detailed below:
The <u>epidemiology/prevalence</u> of this disease is detailed below:
−*~ 7% of B cell lymphomas <ref name=":6" />
+*~ 7% of B cell lymphomas <ref name=":6">{{Cite journal|date=1997|title=A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. The Non-Hodgkin's Lymphoma Classification Project|url=https://pubmed.ncbi.nlm.nih.gov/9166827/|language=en|pmid=9166827}}</ref>
−*2.5%-10% of non-Hodgkin lymphomas <ref name=":7" />
+*2.5%-10% of non-Hodgkin lymphomas <ref name=":7">{{Cite journal|last=Ke|first=Smedby|last2=H|first2=Hjalgrim|date=2011|title=Epidemiology and etiology of mantle cell lymphoma and other non-Hodgkin lymphoma subtypes|url=https://pubmed.ncbi.nlm.nih.gov/21945518/|language=en|pmid=21945518}}</ref>
−*Age adjusted incidence: 0.7/100,000 person years in white population in USA <ref name=":8" />
+*Age adjusted incidence: 0.7/100,000 person years in white population in USA <ref name=":8">{{Cite journal|last=B|first=Aschebrook-Kilfoy|last2=Db|first2=Caces|last3=Nj|first3=Ollberding|last4=Sm|first4=Smith|last5=Bc|first5=Chiu|date=2013|title=An upward trend in the age-specific incidence patterns for mantle cell lymphoma in the USA|url=https://pubmed.ncbi.nlm.nih.gov/23350889/|language=en|pmid=23350889}}</ref>
−*Median age: 60 years<ref name=":9" />
+*Median age: 60 years<ref name=":9">{{Cite journal|last=Lh|first=Argatoff|last2=Jm|first2=Connors|last3=Rj|first3=Klasa|last4=De|first4=Horsman|last5=Rd|first5=Gascoyne|date=1997|title=Mantle cell lymphoma: a clinicopathologic study of 80 cases|url=https://pubmed.ncbi.nlm.nih.gov/9058729/|language=en|pmid=9058729}}</ref>
−*M:F = 3:1 (range, 1.6-6.8 :1)<ref name=":10" />
+*M:F = 3:1 (range, 1.6-6.8 :1)<ref name=":10">{{Cite journal|last=P|first=Lardelli|last2=Ma|first2=Bookman|last3=J|first3=Sundeen|last4=Dl|first4=Longo|last5=Es|first5=Jaffe|date=1990|title=Lymphocytic lymphoma of intermediate differentiation. Morphologic and immunophenotypic spectrum and clinical correlations|url=https://pubmed.ncbi.nlm.nih.gov/2198813/|language=en|pmid=2198813}}</ref>
−The <u>clinical features</u> of this disease are detailed below:
+The <u>clinical features</u> of this disease<ref>Arber, D.A., et al., ''Hematopathology''. 2017, Philadelphia, PA: Elsevier.</ref> are detailed below:
*Approximately 70% with stage IV disease at presentation
*Approximately 70% with stage IV disease at presentation
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*Lymph node
*Lymph node
−*Bone marrow involvement independent of peripheral blood (50 - 90%), peripheral blood (20 - 70%), spleen (~50%), liver (~20%) <ref name=":11" /><ref name=":12" /><ref name=":13" />
+*Bone marrow involvement independent of peripheral blood (50 - 90%), peripheral blood (20 - 70%), spleen (~50%), liver (~20%) <ref name=":11">{{Cite journal|last=J|first=Wasman|last2=Ns|first2=Rosenthal|last3=Dc|first3=Farhi|date=1996|title=Mantle cell lymphoma. Morphologic findings in bone marrow involvement|url=https://pubmed.ncbi.nlm.nih.gov/8712173/|language=en|pmid=8712173}}</ref><ref name=":12">{{Cite journal|last=Ma|first=Vasef|last2=Lj|first2=Medeiros|last3=C|first3=Koo|last4=A|first4=McCourty|last5=Rk|first5=Brynes|date=1997|title=Cyclin D1 immunohistochemical staining is useful in distinguishing mantle cell lymphoma from other low-grade B-cell neoplasms in bone marrow|url=https://pubmed.ncbi.nlm.nih.gov/9291459/|language=en|pmid=9291459}}</ref><ref name=":13">{{Cite journal|last=H|first=Samaha|last2=C|first2=Dumontet|last3=N|first3=Ketterer|last4=I|first4=Moullet|last5=C|first5=Thieblemont|last6=F|first6=Bouafia|last7=E|first7=Callet-Bauchu|last8=P|first8=Felman|last9=F|first9=Berger|date=1998|title=Mantle cell lymphoma: a retrospective study of 121 cases|url=https://pubmed.ncbi.nlm.nih.gov/9697885/|language=en|pmid=9697885}}</ref>
*Frequent extranodal site involvement : gastrointestinal tract, Waldeyer ring, lungs, pleura, skin, CNS
*Frequent extranodal site involvement : gastrointestinal tract, Waldeyer ring, lungs, pleura, skin, CNS
−**CNS involvement may occur mostly at the time of relapse<ref name=":14" />
+**CNS involvement may occur mostly at the time of relapse<ref name=":14">{{Cite journal|last=Cy|first=Cheah|last2=A|first2=George|last3=E|first3=Giné|last4=A|first4=Chiappella|last5=Hc|first5=Kluin-Nelemans|last6=W|first6=Jurczak|last7=K|first7=Krawczyk|last8=H|first8=Mocikova|last9=P|first9=Klener|date=2013|title=Central nervous system involvement in mantle cell lymphoma: clinical features, prognostic factors and outcomes from the European Mantle Cell Lymphoma Network|url=https://pubmed.ncbi.nlm.nih.gov/23616279/|language=en|pmid=23616279}}</ref>
*Extranodal involvement without lymphadenopathies: 4 - 15%
*Extranodal involvement without lymphadenopathies: 4 - 15%
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**Marginal zone-like: abundant pale cytoplasm
**Marginal zone-like: abundant pale cytoplasm
***Resembling marginal zone or monocytoid B cells
***Resembling marginal zone or monocytoid B cells
−**Lymphoplasmacytic differentiation, some cases <ref name=":15" />
+**Lymphoplasmacytic differentiation, some cases <ref name=":15">{{Cite journal|last=Kh|first=Young|last2=Wc|first2=Chan|last3=K|first3=Fu|last4=J|first4=Iqbal|last5=Wg|first5=Sanger|last6=A|first6=Ratashak|last7=Tc|first7=Greiner|last8=Dd|first8=Weisenburger|date=2006|title=Mantle cell lymphoma with plasma cell differentiation|url=https://pubmed.ncbi.nlm.nih.gov/16861965/|language=en|pmid=16861965}}</ref>
*Bone marrow
*Bone marrow
**Nodular, interstitial or paratrabecular or combination
**Nodular, interstitial or paratrabecular or combination
Line 1,029:
Line 825:
**Residual naked germinal centers
**Residual naked germinal centers
**Tumor cells: similar monotonous morphology
**Tumor cells: similar monotonous morphology
−**Some cases may show a marginal zone-like area <ref name=":16" />
+**Some cases may show a marginal zone-like area <ref name=":16">{{Cite journal|last=Ma|first=Piris|last2=M|first2=Mollejo|last3=E|first3=Campo|last4=J|first4=Menárguez|last5=T|first5=Flores|last6=Pg|first6=Isaacson|date=1998|title=A marginal zone pattern may be found in different varieties of non-Hodgkin's lymphoma: the morphology and immunohistology of splenic involvement by B-cell lymphomas simulating splenic marginal zone lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/9777389/|language=en|pmid=9777389}}</ref>
*Gastrointestinal
*Gastrointestinal
−**May mimic lymphoepithelial lesions in marginal zone lymphoma <ref name=":17" />
+**May mimic lymphoepithelial lesions in marginal zone lymphoma <ref name=":17">{{Cite journal|last=M|first=Fraga|last2=E|first2=Lloret|last3=L|first3=Sanchez-Verde|last4=Jl|first4=Orradre|last5=E|first5=Campo|last6=F|first6=Bosch|last7=Ma|first7=Piris|date=1995|title=Mucosal mantle cell (centrocytic) lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/7657310/|language=en|pmid=7657310}}</ref>
*Relapse
*Relapse
**Loss of a mantle zone growth pattern
**Loss of a mantle zone growth pattern
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Line 833:
**Pleomorphism and chromatin dispersal
**Pleomorphism and chromatin dispersal
**Increase in mitotic activity and Ki67
**Increase in mitotic activity and Ki67
−**Cases that are blastoid at diagnosis may relapse with classic morphology <ref name=":18" />
+**Cases that are blastoid at diagnosis may relapse with classic morphology <ref name=":18">{{Cite journal|last=N|first=Vogt|last2=W|first2=Klapper|date=2013|title=Variability in morphology and cell proliferation in sequential biopsies of mantle cell lymphoma at diagnosis and relapse: clinical correlation and insights into disease progression|url=https://pubmed.ncbi.nlm.nih.gov/23240716/|language=en|pmid=23240716}}</ref>
The <u>immunophenotype</u> of this disease is detailed below:
The <u>immunophenotype</u> of this disease is detailed below:
−* Positive (universal) - Cyclin D1 (>95%), Sox-11 (>90%), B-cell associated markers (CD19, CD20, CD22, CD79a/b) (100%, CD5 (>95%), CD43, IgM+/- IgD, BCL-2, FMC-7 (flow cytometry)
+*Positive (universal) - Cyclin D1 (>95%), Sox-11 (>90%), B-cell associated markers (CD19, CD20, CD22, CD79a/b) (100%, CD5 (>95%), CD43, IgM+/- IgD, BCL-2, FMC-7 (flow cytometry)
−* Positive (subset) - MUM1 / IRF4 (50% in small subset of cells), MYC, p53
+*Positive (subset) - MUM1 / IRF4 (50% in small subset of cells), MYC, p53
−* Positive/Negative - CD10, BCL-6
+*Positive/Negative - CD10, BCL-6
−* Negative (universal) - T-cell associated markers (except CD5), CD200, LEF-1
+*Negative (universal) - T-cell associated markers (except CD5), CD200, LEF-1
−*Ki67 count <ref name=":19" />
+*Ki67 count <ref name=":19">{{Cite journal|last=W|first=Klapper|last2=E|first2=Hoster|last3=O|first3=Determann|last4=I|first4=Oschlies|last5=J|first5=van der Laak|last6=F|first6=Berger|last7=Hw|first7=Bernd|last8=J|first8=Cabeçadas|last9=E|first9=Campo|date=2009|title=Ki-67 as a prognostic marker in mantle cell lymphoma-consensus guidelines of the pathology panel of the European MCL Network|url=https://pubmed.ncbi.nlm.nih.gov/19669190/|language=en|doi=10.1007/s12308-009-0036-x|pmc=PMC2725281|pmid=19669190}}</ref>
**Five independent high-power fields count
**Five independent high-power fields count
**Avoidance of residual germinal centers, hot spots and proliferating T cells
**Avoidance of residual germinal centers, hot spots and proliferating T cells
**Note: Ki67 index is not sufficient to classify as blastoid or pleomorphic subtype
**Note: Ki67 index is not sufficient to classify as blastoid or pleomorphic subtype
−**Classical mantle cell lymphoma might also show high cell proliferation<ref name=":20" />
+**Classical mantle cell lymphoma might also show high cell proliferation<ref name=":20">{{Cite journal|last=O|first=Determann|last2=E|first2=Hoster|last3=G|first3=Ott|last4=H|first4=Wolfram Bernd|last5=C|first5=Loddenkemper|last6=M|first6=Leo Hansmann|last7=Te|first7=Barth|last8=M|first8=Unterhalt|last9=W|first9=Hiddemann|date=2008|title=Ki-67 predicts outcome in advanced-stage mantle cell lymphoma patients treated with anti-CD20 immunochemotherapy: results from randomized trials of the European MCL Network and the German Low Grade Lymphoma Study Group|url=https://pubmed.ncbi.nlm.nih.gov/18077791/|language=en|pmid=18077791}}</ref>
*p53 in subset; intense expression correlates with ''TP53'' gene mutation
*p53 in subset; intense expression correlates with ''TP53'' gene mutation
−**Note: no protein expression; on the other hand, cannot predict the homozygous deletions of the locus <ref name=":21" />
+**Note: no protein expression; on the other hand, cannot predict the homozygous deletions of the locus <ref name=":21">{{Cite journal|last=L|first=Hernandez|last2=T|first2=Fest|last3=M|first3=Cazorla|last4=J|first4=Teruya-Feldstein|last5=F|first5=Bosch|last6=Ma|first6=Peinado|last7=Ma|first7=Piris|last8=E|first8=Montserrat|last9=A|first9=Cardesa|date=1996|title=p53 gene mutations and protein overexpression are associated with aggressive variants of mantle cell lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/8605352/|language=en|pmid=8605352}}</ref>
*MYC in subset
*MYC in subset
−**High expression correlates with ''MYC'' translocation <ref name=":22" />
+**High expression correlates with ''MYC'' translocation <ref name=":22">{{Cite journal|last=Jy|first=Choe|last2=Jy|first2=Yun|last3=Hy|first3=Na|last4=J|first4=Huh|last5=Sj|first5=Shin|last6=Hj|first6=Kim|last7=Jh|first7=Paik|last8=Ya|first8=Kim|last9=Sj|first9=Nam|date=2016|title=MYC overexpression correlates with MYC amplification or translocation, and is associated with poor prognosis in mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/26100211/|language=en|pmid=26100211}}</ref>
−*CD10+ MCL more associated with diffuse growth pattern, blastoid/pleomorphic morphology, and BCL6 expression<ref name=":23" />
+*CD10+ MCL more associated with diffuse growth pattern, blastoid/pleomorphic morphology, and BCL6 expression<ref name=":23">{{Cite journal|last=J|first=Xu|last2=Lj|first2=Medeiros|last3=A|first3=Saksena|last4=M|first4=Wang|last5=J|first5=Zhou|last6=J|first6=Li|last7=Cc|first7=Yin|last8=G|first8=Tang|last9=L|first9=Wang|date=2017|title=CD10-positive mantle cell lymphoma: clinicopathologic and prognostic study of 30 cases|url=https://pubmed.ncbi.nlm.nih.gov/29545910/|language=en|doi=10.18632/oncotarget.23571|pmc=PMC5837746|pmid=29545910}}</ref>
−*CD23: small subset of cases <ref name=":24" />
+*CD23: small subset of cases <ref name=":24">{{Cite journal|last=S|first=Kumar|last2=Ga|first2=Green|last3=J|first3=Teruya-Feldstein|last4=M|first4=Raffeld|last5=Es|first5=Jaffe|date=1996|title=Use of CD23 (BU38) on paraffin sections in the diagnosis of small lymphocytic lymphoma and mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/8878025/|language=en|pmid=8878025}}</ref>
−*CD200: May be positive in a subset of SOX11 negative mantle cell lymphomas<ref name=":25" /> [[HAEM5:Leukaemic non-nodal mantle cell lymphoma]]
+*CD200: May be positive in a subset of SOX11 negative mantle cell lymphomas<ref name=":25">{{Cite journal|last=B|first=Espinet|last2=A|first2=Ferrer|last3=B|first3=Bellosillo|last4=L|first4=Nonell|last5=A|first5=Salar|last6=C|first6=Fernández-Rodríguez|last7=E|first7=Puigdecanet|last8=J|first8=Gimeno|last9=M|first9=Garcia-Garcia|date=2014|title=Distinction between asymptomatic monoclonal B-cell lymphocytosis with cyclin D1 overexpression and mantle cell lymphoma: from molecular profiling to flow cytometry|url=https://pubmed.ncbi.nlm.nih.gov/24352646/|language=en|doi=10.1158/1078-0432.CCR-13-1077|pmc=PMC4488901|pmid=24352646}}</ref> [[HAEM5:Leukaemic non-nodal mantle cell lymphoma]]
−*LEF-1: positive in 4 - 9% of mantle cell lymphomas <ref name=":26" /><ref name=":27" />
+*LEF-1: positive in 4 - 9% of mantle cell lymphomas <ref name=":26">{{Cite journal|last=Dp|first=O'Malley|last2=Jp|first2=Lee|last3=Am|first3=Bellizzi|date=2017|title=Expression of LEF1 in mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/28038713/|language=en|pmid=28038713}}</ref><ref name=":27">{{Cite journal|last=B|first=Sander|last2=L|first2=Quintanilla-Martinez|last3=G|first3=Ott|last4=L|first4=Xerri|last5=I|first5=Kuzu|last6=Jk|first6=Chan|last7=Sh|first7=Swerdlow|last8=E|first8=Campo|date=2016|title=Mantle cell lymphoma--a spectrum from indolent to aggressive disease|url=https://pubmed.ncbi.nlm.nih.gov/26298543/|language=en|pmid=26298543}}</ref>
*Cyclin D1-negative MCL
*Cyclin D1-negative MCL
−**Morphology, phenotype, gene expression, clinical presentation and evolution similar to cyclin D1-positive MCL <ref name=":28" />
+**Morphology, phenotype, gene expression, clinical presentation and evolution similar to cyclin D1-positive MCL <ref name=":28">{{Cite journal|last=K|first=Fu|last2=Dd|first2=Weisenburger|last3=Tc|first3=Greiner|last4=S|first4=Dave|last5=G|first5=Wright|last6=A|first6=Rosenwald|last7=M|first7=Chiorazzi|last8=J|first8=Iqbal|last9=S|first9=Gesk|date=2005|title=Cyclin D1-negative mantle cell lymphoma: a clinicopathologic study based on gene expression profiling|url=https://pubmed.ncbi.nlm.nih.gov/16123218/|language=en|doi=10.1182/blood-2005-04-1753|pmc=PMC1895253|pmid=16123218}}</ref>
**Positive for Sox-11
**Positive for Sox-11
−**Frequently express cyclin D2 or cyclin D3 (''IG''-mediated translocations) <ref name=":29" />
+**Frequently express cyclin D2 or cyclin D3 (''IG''-mediated translocations) <ref name=":29">{{Cite journal|last=I|first=Wlodarska|last2=D|first2=Dierickx|last3=V|first3=Vanhentenrijk|last4=K|first4=Van Roosbroeck|last5=H|first5=Pospísilová|last6=F|first6=Minnei|last7=G|first7=Verhoef|last8=J|first8=Thomas|last9=P|first9=Vandenberghe|date=2008|title=Translocations targeting CCND2, CCND3, and MYCN do occur in t(11;14)-negative mantle cell lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/18391076/|language=en|pmid=18391076}}</ref>
−**cyclin E in cases with negative expression of cyclin D and aggressive behavior <ref name=":30" />
+**cyclin E in cases with negative expression of cyclin D and aggressive behavior <ref name=":30">{{Cite journal|last=D|first=Martín-Garcia|last2=A|first2=Navarro|last3=R|first3=Valdés-Mas|last4=G|first4=Clot|last5=J|first5=Gutiérrez-Abril|last6=M|first6=Prieto|last7=I|first7=Ribera-Cortada|last8=R|first8=Woroniecka|last9=G|first9=Rymkiewicz|date=2019|title=CCND2 and CCND3 hijack immunoglobulin light-chain enhancers in cyclin D1 - mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/30538135/|language=en|doi=10.1182/blood-2018-07-862151|pmc=PMC6396173|pmid=30538135}}</ref>
==Links==
==Links==