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HAEM5:Mantle cell lymphoma (view source)

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[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]

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<blockquote class='blockedit'>{{Box-round|title=Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Mantle Cell Lymphoma]].

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<blockquote class="blockedit">{{Box-round|title=Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Mantle Cell Lymphoma]].

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==Primary Author(s)*==

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* Mahsa Khanlari, MD

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*Mahsa Khanlari, MD

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* Zhenya Tang, MD, PhD

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*Zhenya Tang, MD, PhD

The University Of Texas MD Anderson Cancer Center, Department of Hematopathology, Houston, Texas

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|Mantle cell lymphoma

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~~==Definition / Description of Disease==~~

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* Clinically aggressive, mature B cell lymphoma

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* Small to medium sized lymphoid cells (monomorphic, except in pleomorphic variant)

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* Associated with t(11;14)(q13;q32) and cyclin D1 overexpression in over 95% of cases

==Synonyms / Terminology==

Obsolete names:

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*Centrocytic malignant lymphoma (obsolete) <ref>{{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>

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*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>

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*Lymphocytic lymphoma of intermediate differentiation <ref>{{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>

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*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>

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*Mantle zone lymphoma <ref>{{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>

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*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)

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==Epidemiology / Prevalence==

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*~ 7% of B cell lymphomas <ref>{{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>

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*~ 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>

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*2.5%-10% of non-Hodgkin lymphomas <ref>{{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>

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*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>

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*Age adjusted incidence: 0.7/100,000 person years in white population in USA <ref>{{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>

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*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>

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*Median age: 60 years<ref>{{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>

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*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>

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*M:F = 3:1 (range, 1.6-6.8 :1)<ref>{{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>

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*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==

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<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Features|The content below was from the old template. Please incorporate above.}}</blockquote>

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<blockquote class="blockedit">{{Box-round|title=v4:Clinical Features|The content below was from the old template. Please incorporate above.}}</blockquote>

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**Generalized lymphadenopathy, hepatosplenomegaly and bone marrow involvement

**40-50% with B symptoms

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** Two subtypes based on clinical presentation:

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**Two subtypes based on clinical presentation:

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*** More aggressive, with SOX11 overexpression (SOX11+disease), nodal presentation (the most common subtype)

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***More aggressive, with SOX11 overexpression (SOX11+disease), nodal presentation (the most common subtype)

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*** More indolent, without SOX11 expression (SOX11-disease), leukemic presentation, and non-nodal disease

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***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

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***Leukemic involvement is usually a ~~the~~ sign of disease progression

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***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]]

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<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">

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<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>'''End of V4 Section'''

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*Lymph node

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*Bone marrow involvement independent of peripheral blood (50 - 90%), peripheral blood (20 - 70%), spleen (~50%), liver (~20%) <ref>{{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>{{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>{{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>

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*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

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**CNS involvement may occur mostly at the time of relapse<ref>{{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>

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**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%

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**Marginal zone-like: abundant pale cytoplasm

***Resembling marginal zone or monocytoid B cells

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**Lymphoplasmacytic differentiation, some cases <ref>{{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>

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**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

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**Residual naked germinal centers

**Tumor cells: similar monotonous morphology

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**Some cases may show a marginal zone-like area <ref>{{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>

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**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

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**May mimic lymphoepithelial lesions in marginal zone lymphoma <ref>{{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>

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**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

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**Pleomorphism and chromatin dispersal

**Increase in mitotic activity and Ki67

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**Cases that are blastoid at diagnosis may relapse with classic morphology <ref>{{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>

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**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==

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{| class="wikitable sortable"

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*Ki67 count <ref>{{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>

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*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

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**Classical mantle cell lymphoma might also show high cell proliferation<ref>{{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>

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**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

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**Note: no protein expression; on the other hand, cannot predict the homozygous deletions of the locus <ref>{{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>

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**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

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**High expression correlates with ''MYC'' translocation <ref>{{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>

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**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>

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*CD10+ MCL more associated with diffuse growth pattern, blastoid/pleomorphic morphology, and BCL6 expression<ref>{{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>

+

*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>{{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>

+

*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>{{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]]

+

*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>{{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>{{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>

+

*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>{{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>

+

**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>{{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>

+

**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>{{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>

+

**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>

==WHO Essential and Desirable Genetic Diagnostic Criteria==

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−

<blockquote class='blockedit'>{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}</blockquote>

+

<blockquote class="blockedit">{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}</blockquote>

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−

<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>{{Cite journal|last=Martín-Garcia|first=David|last2=Navarro|first2=Alba|last3=Valdés-Mas|first3=Rafael|last4=Clot|first4=Guillem|last5=Gutiérrez-Abril|first5=Jesús|last6=Prieto|first6=Miriam|last7=Ribera-Cortada|first7=Inmaculada|last8=Woroniecka|first8=Renata|last9=Rymkiewicz|first9=Grzegorz|date=02 28, 2019|title=CCND2 and CCND3 hijack immunoglobulin light-chain enhancers in cyclin D1- mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/30538135|journal=Blood|volume=133|issue=9|pages=940–951|doi=10.1182/blood-2018-07-862151|issn=1528-0020|pmc=6396173|pmid=30538135}}</ref><blockquote class="blockedit">

+

<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>{{Cite journal|last=Martín-Garcia|first=David|last2=Navarro|first2=Alba|last3=Valdés-Mas|first3=Rafael|last4=Clot|first4=Guillem|last5=Gutiérrez-Abril|first5=Jesús|last6=Prieto|first6=Miriam|last7=Ribera-Cortada|first7=Inmaculada|last8=Woroniecka|first8=Renata|last9=Rymkiewicz|first9=Grzegorz|date=02 28, 2019|title=CCND2 and CCND3 hijack immunoglobulin light-chain enhancers in cyclin D1- mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/30538135|journal=Blood|volume=133|issue=9|pages=940–951|doi=10.1182/blood-2018-07-862151|issn=1528-0020|pmc=6396173|pmid=30538135}}</ref><blockquote class="blockedit">

<center>'''End of V4 Section'''

----

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<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:

+

<blockquote class="blockedit">{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:

* Chromosomal Rearrangements (Gene Fusions)

* Individual Region Genomic Gain/Loss/LOH

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* Gene Mutations (SNV/INDEL)}}</blockquote>

−

* Median survival: 5 - 7 years

+

*Median survival: 5 - 7 years

−

** Mantle cell lymphoma international prognostic index (clinical), MIPI <ref>{{Cite journal|last=E|first=Hoster|last2=M|first2=Dreyling|last3=W|first3=Klapper|last4=C|first4=Gisselbrecht|last5=A|first5=van Hoof|last6=Hc|first6=Kluin-Nelemans|last7=M|first7=Pfreundschuh|last8=M|first8=Reiser|last9=B|first9=Metzner|date=2008|title=A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/17962512/|language=en|pmid=17962512}}</ref>

+

**Mantle cell lymphoma international prognostic index (clinical), MIPI <ref>{{Cite journal|last=E|first=Hoster|last2=M|first2=Dreyling|last3=W|first3=Klapper|last4=C|first4=Gisselbrecht|last5=A|first5=van Hoof|last6=Hc|first6=Kluin-Nelemans|last7=M|first7=Pfreundschuh|last8=M|first8=Reiser|last9=B|first9=Metzner|date=2008|title=A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/17962512/|language=en|pmid=17962512}}</ref>

−

** Age, performance status, lactate dehydrogenase, leukocyte count

+

**Age, performance status, lactate dehydrogenase, leukocyte count

−

** 3 morphologic groups with significantly different prognoses

+

**3 morphologic groups with significantly different prognoses

−

* Adverse outcome (histopathology / molecular)

+

*Adverse outcome (histopathology / molecular)

−

** High mitotic rate (> 50/mm2) <ref>{{Cite journal|last=M|first=Tiemann|last2=C|first2=Schrader|last3=W|first3=Klapper|last4=Mh|first4=Dreyling|last5=E|first5=Campo|last6=A|first6=Norton|last7=F|first7=Berger|last8=P|first8=Kluin|last9=G|first9=Ott|date=2005|title=Histopathology, cell proliferation indices and clinical outcome in 304 patients with mantle cell lymphoma (MCL): a clinicopathological study from the European MCL Network|url=https://pubmed.ncbi.nlm.nih.gov/16173960/|language=en|pmid=16173960}}</ref>

+

**High mitotic rate (> 50/mm2) <ref>{{Cite journal|last=M|first=Tiemann|last2=C|first2=Schrader|last3=W|first3=Klapper|last4=Mh|first4=Dreyling|last5=E|first5=Campo|last6=A|first6=Norton|last7=F|first7=Berger|last8=P|first8=Kluin|last9=G|first9=Ott|date=2005|title=Histopathology, cell proliferation indices and clinical outcome in 304 patients with mantle cell lymphoma (MCL): a clinicopathological study from the European MCL Network|url=https://pubmed.ncbi.nlm.nih.gov/16173960/|language=en|pmid=16173960}}</ref>

−

** Ki67 or MIB1 IHC stains (> 30%) <ref>{{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>

+

**Ki67 or MIB1 IHC stains (> 30%) <ref>{{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>

−

** Blastoid and pleomorphic variants <ref>{{Cite journal|last=E|first=Hoster|last2=A|first2=Rosenwald|last3=F|first3=Berger|last4=Hw|first4=Bernd|last5=S|first5=Hartmann|last6=C|first6=Loddenkemper|last7=Tf|first7=Barth|last8=N|first8=Brousse|last9=S|first9=Pileri|date=2016|title=Prognostic Value of Ki-67 Index, Cytology, and Growth Pattern in Mantle-Cell Lymphoma: Results From Randomized Trials of the European Mantle Cell Lymphoma Network|url=https://pubmed.ncbi.nlm.nih.gov/26926679/|language=en|pmid=26926679}}</ref>

+

**Blastoid and pleomorphic variants <ref>{{Cite journal|last=E|first=Hoster|last2=A|first2=Rosenwald|last3=F|first3=Berger|last4=Hw|first4=Bernd|last5=S|first5=Hartmann|last6=C|first6=Loddenkemper|last7=Tf|first7=Barth|last8=N|first8=Brousse|last9=S|first9=Pileri|date=2016|title=Prognostic Value of Ki-67 Index, Cytology, and Growth Pattern in Mantle-Cell Lymphoma: Results From Randomized Trials of the European Mantle Cell Lymphoma Network|url=https://pubmed.ncbi.nlm.nih.gov/26926679/|language=en|pmid=26926679}}</ref>

−

** ''MYC'' rearrangement <ref>{{Cite journal|last=Z|first=Hu|last2=Lj|first2=Medeiros|last3=Z|first3=Chen|last4=W|first4=Chen|last5=S|first5=Li|last6=Sn|first6=Konoplev|last7=X|first7=Lu|last8=Lv|first8=Pham|last9=Kh|first9=Young|date=2017|title=Mantle Cell Lymphoma With MYC Rearrangement: A Report of 17 Patients|url=https://pubmed.ncbi.nlm.nih.gov/27776009/|language=en|pmid=27776009}}</ref><ref name=":0" />

+

**''MYC'' rearrangement <ref>{{Cite journal|last=Z|first=Hu|last2=Lj|first2=Medeiros|last3=Z|first3=Chen|last4=W|first4=Chen|last5=S|first5=Li|last6=Sn|first6=Konoplev|last7=X|first7=Lu|last8=Lv|first8=Pham|last9=Kh|first9=Young|date=2017|title=Mantle Cell Lymphoma With MYC Rearrangement: A Report of 17 Patients|url=https://pubmed.ncbi.nlm.nih.gov/27776009/|language=en|pmid=27776009}}</ref><ref name=":0" />

−

** ''TP53'' mutation / overexpression / loss (17p) <ref name=":1">{{Cite journal|last=Mh|first=Delfau-Larue|last2=W|first2=Klapper|last3=F|first3=Berger|last4=F|first4=Jardin|last5=J|first5=Briere|last6=G|first6=Salles|last7=O|first7=Casasnovas|last8=P|first8=Feugier|last9=C|first9=Haioun|date=2015|title=High-dose cytarabine does not overcome the adverse prognostic value of CDKN2A and TP53 deletions in mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/26022239/|language=en|pmid=26022239}}</ref>

+

**''TP53'' mutation / overexpression / loss (17p) <ref name=":1">{{Cite journal|last=Mh|first=Delfau-Larue|last2=W|first2=Klapper|last3=F|first3=Berger|last4=F|first4=Jardin|last5=J|first5=Briere|last6=G|first6=Salles|last7=O|first7=Casasnovas|last8=P|first8=Feugier|last9=C|first9=Haioun|date=2015|title=High-dose cytarabine does not overcome the adverse prognostic value of CDKN2A and TP53 deletions in mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/26022239/|language=en|pmid=26022239}}</ref>

−

** Either ''TP53'' mutations or deletions or both associates with poor prognosis<ref name=":2">{{Cite journal|last=S|first=Ferrero|last2=D|first2=Rossi|last3=A|first3=Rinaldi|last4=A|first4=Bruscaggin|last5=V|first5=Spina|last6=Cw|first6=Eskelund|last7=A|first7=Evangelista|last8=R|first8=Moia|last9=I|first9=Kwee|date=2020|title=KMT2D mutations and TP53 disruptions are poor prognostic biomarkers in mantle cell lymphoma receiving high-dose therapy: a FIL study|url=https://pubmed.ncbi.nlm.nih.gov/31537689/|language=en|doi=10.3324/haematol.2018.214056|pmc=PMC7271566|pmid=31537689}}</ref>

+

**Either ''TP53'' mutations or deletions or both associates with poor prognosis<ref name=":2">{{Cite journal|last=S|first=Ferrero|last2=D|first2=Rossi|last3=A|first3=Rinaldi|last4=A|first4=Bruscaggin|last5=V|first5=Spina|last6=Cw|first6=Eskelund|last7=A|first7=Evangelista|last8=R|first8=Moia|last9=I|first9=Kwee|date=2020|title=KMT2D mutations and TP53 disruptions are poor prognostic biomarkers in mantle cell lymphoma receiving high-dose therapy: a FIL study|url=https://pubmed.ncbi.nlm.nih.gov/31537689/|language=en|doi=10.3324/haematol.2018.214056|pmc=PMC7271566|pmid=31537689}}</ref>

−

*** Elevated Ki-67

+

***Elevated Ki-67

−

*** Higher MIPI-c classes

+

***Higher MIPI-c classes

−

*** Blastoid morphology

+

***Blastoid morphology

−

*** Impact on survival independent of these risk factors

+

***Impact on survival independent of these risk factors

−

*** Higher levels of MRD positivity after allo-stem cell transplant

+

***Higher levels of MRD positivity after allo-stem cell transplant

−

** ''CDKN2A'' deletion (9p) <ref name=":1" />

+

**''CDKN2A'' deletion (9p) <ref name=":1" />

−

** Gains in 3q, deletions of 9q <ref>{{Cite journal|last=I|first=Salaverria|last2=A|first2=Zettl|last3=S|first3=Beà|last4=V|first4=Moreno|last5=J|first5=Valls|last6=E|first6=Hartmann|last7=G|first7=Ott|last8=G|first8=Wright|last9=A|first9=Lopez-Guillermo|date=2007|title=Specific secondary genetic alterations in mantle cell lymphoma provide prognostic information independent of the gene expression-based proliferation signature|url=https://pubmed.ncbi.nlm.nih.gov/17296973/|language=en|doi=10.1200/JCO.2006.08.4251|pmc=PMC2366164|pmid=17296973}}</ref>

+

**Gains in 3q, deletions of 9q <ref>{{Cite journal|last=I|first=Salaverria|last2=A|first2=Zettl|last3=S|first3=Beà|last4=V|first4=Moreno|last5=J|first5=Valls|last6=E|first6=Hartmann|last7=G|first7=Ott|last8=G|first8=Wright|last9=A|first9=Lopez-Guillermo|date=2007|title=Specific secondary genetic alterations in mantle cell lymphoma provide prognostic information independent of the gene expression-based proliferation signature|url=https://pubmed.ncbi.nlm.nih.gov/17296973/|language=en|doi=10.1200/JCO.2006.08.4251|pmc=PMC2366164|pmid=17296973}}</ref>

−

** Patients with ''KMT2D'' mutation <ref name=":2" />

+

**Patients with ''KMT2D'' mutation <ref name=":2" />

−

*** Chemo-immunotherapy failure

+

***Chemo-immunotherapy failure

−

*** High-risk patients based on MIPI-C

+

***High-risk patients based on MIPI-C

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<blockquote class='blockedit'>{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}</blockquote>

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<blockquote class="blockedit">{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}</blockquote>

Secondary chromosomal aberrations<ref>{{Cite journal|last=C|first=Royo|last2=I|first2=Salaverria|last3=Em|first3=Hartmann|last4=A|first4=Rosenwald|last5=E|first5=Campo|last6=S|first6=Beà|date=2011|title=The complex landscape of genetic alterations in mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/21945515/|language=en|pmid=21945515}}</ref>

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<blockquote class='blockedit'>{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}</blockquote>

+

<blockquote class="blockedit">{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}</blockquote>

*''CCND1'' rearrangement; t(11;14)(q13;q32)

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*Cyclin D2 (''CCND2'') rearrangements by FISH in 55%-70% of cyclin D1-negative cases

*Almost all cyclin D1-negative mantle cell lymphomas carry ''CCND2/CCND3'' rearrangements with immunoglobulin genes (including a novel IGK/L enhancer hijacking mechanism)

−

*A broad spectrum of secondary chromosomal aberrations have been reported, especially in MCL with bone marrow and peripheral blood involvement<ref>{{Cite journal|last=Royo|first=Cristina|last2=Salaverria|first2=Itziar|last3=Hartmann|first3=Elena M.|last4=Rosenwald|first4=Andreas|last5=Campo|first5=Elías|last6=Beà|first6=Sílvia|date=2011-11|title=The complex landscape of genetic alterations in mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/21945515|journal=Seminars in Cancer Biology|volume=21|issue=5|pages=322–334|doi=10.1016/j.semcancer.2011.09.007|issn=1096-3650|pmid=21945515}}</ref>.

+

*A broad spectrum of secondary chromosomal aberrations have been reported, especially in MCL with bone marrow and peripheral blood involvement<ref>{{Cite journal|last=Royo|first=Cristina|last2=Salaverria|first2=Itziar|last3=Hartmann|first3=Elena M.|last4=Rosenwald|first4=Andreas|last5=Campo|first5=Elías|last6=Beà|first6=Sílvia|date=2011-11|title=The complex landscape of genetic alterations in mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/21945515|journal=Seminars in Cancer Biology|volume=21|issue=5|pages=322–334|doi=10.1016/j.semcancer.2011.09.007|issn=1096-3650|pmid=21945515}}</ref>.

*Tetraploidy is more frequent in pleomorphic (80%) and blastoid (36%) variants than in classic MCLs (8%) <ref>{{Cite journal|last=G|first=Ott|last2=J|first2=Kalla|last3=Mm|first3=Ott|last4=B|first4=Schryen|last5=T|first5=Katzenberger|last6=Jg|first6=Müller|last7=Hk|first7=Müller-Hermelink|date=1997|title=Blastoid variants of mantle cell lymphoma: frequent bcl-1 rearrangements at the major translocation cluster region and tetraploid chromosome clones|url=https://pubmed.ncbi.nlm.nih.gov/9028966/|language=en|pmid=9028966}}</ref>

*t(8;14)(q24;q32)/MYC-IGH in small subset of cases <ref name=":0">{{Cite journal|last=L|first=Wang|last2=G|first2=Tang|last3=Lj|first3=Medeiros|last4=J|first4=Xu|last5=W|first5=Huang|last6=Cc|first6=Yin|last7=M|first7=Wang|last8=P|first8=Jain|last9=P|first9=Lin|date=2020|title=MYC rearrangement but not extra MYC copies is an independent prognostic factor in patients with mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/32273477/|language=en|pmid=32273477}}</ref><ref>{{Cite journal|last=Un|first=Vaishampayan|last2=An|first2=Mohamed|last3=Mc|first3=Dugan|last4=Re|first4=Bloom|last5=M|first5=Palutke|date=2001|title=Blastic mantle cell lymphoma associated with Burkitt-type translocation and hypodiploidy|url=https://pubmed.ncbi.nlm.nih.gov/11722412/|language=en|pmid=11722412}}</ref>

+

{| class="wikitable"

−

|Parameter

+

|Parameter

|n

|%

|-

−

!'''''CCND2'' translocation'''

+

!'''''CCND2'' translocation'''

!

Line 698: Line 694:

!'''13'''

|-

−

! '''CCND2-break'''

+

!'''CCND2-break'''

!2/40

!'''5'''

|-

−

| '''CCDND2-?'''

+

|'''CCDND2-?'''

|'''2/40'''

|'''5'''

|-

−

| '''Negative'''

+

|'''Negative'''

|'''18/40'''

|'''45'''

Line 763: Line 759:

|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ cBioportal], [https://cancer.sanger.ac.uk/cosmic COSMIC], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

−

<blockquote class='blockedit'>{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}}</blockquote>

+

<blockquote class="blockedit">{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}}</blockquote>

Line 778: Line 774:

|-

|CARD11

−

|B-cell receptor signaling

+

|B-cell receptor signaling

|8.5-16.3%

|-

Line 786: Line 782:

|-

|BTK

−

|B-cell receptor signaling

+

|B-cell receptor signaling

|5.5-17.1%

|-

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|-

|CCND1

−

|CDK kinase regulator

+

|CDK kinase regulator

|20.2-27.7%

|-

Line 802: Line 798:

|-

|SMARCA4

−

|Chromatin modification

+

|Chromatin modification

|14.9-18.7%

|-

Line 818: Line 814:

|-

|ATM

−

|DNA damage response

+

|DNA damage response

|43.5-57.6%

|-

|KMT2D

−

|Histone modification

+

|Histone modification

|18.4-21.8%

|-

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|-

|IGH

−

|Immune response

+

|Immune response

|21.5-38.4%

|-

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|-

|TET2

−

|Myelopoiesis

+

|Myelopoiesis

|5.6-14.1%

|-

|NOTCH1

−

|NOTCH signaling pathway

+

|NOTCH signaling pathway

|10.8-14.8%

|-

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|-

|UBR5

−

|Protein ligases

+

|Protein ligases

|17.8%

|-

|TP53

−

|Tumor suppressor

+

|Tumor suppressor

|26.8-43.0%

|-

Line 887: Line 883: −

<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>{{Cite journal|last=Rosenquist|first=R.|last2=Beà|first2=S.|last3=Du|first3=M.-Q.|last4=Nadel|first4=B.|last5=Pan-Hammarström|first5=Q.|date=11 2017|title=Genetic landscape and deregulated pathways in B-cell lymphoid malignancies|url=https://pubmed.ncbi.nlm.nih.gov/28631441|journal=Journal of Internal Medicine|volume=282|issue=5|pages=371–394|doi=10.1111/joim.12633|issn=1365-2796|pmid=28631441}}</ref><blockquote class="blockedit">

+

<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>{{Cite journal|last=Rosenquist|first=R.|last2=Beà|first2=S.|last3=Du|first3=M.-Q.|last4=Nadel|first4=B.|last5=Pan-Hammarström|first5=Q.|date=11 2017|title=Genetic landscape and deregulated pathways in B-cell lymphoid malignancies|url=https://pubmed.ncbi.nlm.nih.gov/28631441|journal=Journal of Internal Medicine|volume=282|issue=5|pages=371–394|doi=10.1111/joim.12633|issn=1365-2796|pmid=28631441}}</ref><blockquote class="blockedit">

<center>'''End of V4 Section'''

----

Line 924: Line 920:

|}

−

<blockquote class='blockedit'>{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}</blockquote>

+

<blockquote class="blockedit">{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}</blockquote>

Please refer to Gene Mutations (SNV/INDEL)

Line 933: Line 929:

==Genetic Diagnostic Testing Methods==

−

* Tissue biopsy (lymph node / extranodal sites): monomorphic proliferation of small to intermediate sized B cells with overexpression of cyclin D1 or SOX11

+

*Tissue biopsy (lymph node / extranodal sites): monomorphic proliferation of small to intermediate sized B cells with overexpression of cyclin D1 or SOX11

−

* t(11;14)(q13;q32) ''IGH/CCND1''

+

*t(11;14)(q13;q32) ''IGH/CCND1''

−

* MRD is defined as the minimal traceable persistence of lymphoma cells after a successful treatment.

+

*MRD is defined as the minimal traceable persistence of lymphoma cells after a successful treatment.

−

* Many methods to monitor MRD have been published

+

*Many methods to monitor MRD have been published

−

* The most sensitive and the most commonly used and best standardized approach in MCL: allele-specific oligonucleotide (ASO) quantitative polymerase chain reaction (qPCR) method <ref>{{Cite journal|last=Ferrero|first=Simone|last2=Dreyling|first2=Martin|last3=European Mantle Cell Lymphoma Network|date=07 2017|title=Minimal residual disease in mantle cell lymphoma: are we ready for a personalized treatment approach?|url=https://pubmed.ncbi.nlm.nih.gov/28655809|journal=Haematologica|volume=102|issue=7|pages=1133–1136|doi=10.3324/haematol.2017.167627|issn=1592-8721|pmc=5566011|pmid=28655809}}</ref>

+

*The most sensitive and the most commonly used and best standardized approach in MCL: allele-specific oligonucleotide (ASO) quantitative polymerase chain reaction (qPCR) method <ref>{{Cite journal|last=Ferrero|first=Simone|last2=Dreyling|first2=Martin|last3=European Mantle Cell Lymphoma Network|date=07 2017|title=Minimal residual disease in mantle cell lymphoma: are we ready for a personalized treatment approach?|url=https://pubmed.ncbi.nlm.nih.gov/28655809|journal=Haematologica|volume=102|issue=7|pages=1133–1136|doi=10.3324/haematol.2017.167627|issn=1592-8721|pmc=5566011|pmid=28655809}}</ref>

==Familial Forms==

−

* Family history of leukemia may elevate risks particularly among men with mantle-cell lymphomas (OR = 3.1, 95% CI = 1.6-6.2)<ref>{{Cite journal|last=Ss|first=Wang|last2=Sl|first2=Slager|last3=P|first3=Brennan|last4=Ea|first4=Holly|last5=S|first5=De Sanjose|last6=L|first6=Bernstein|last7=P|first7=Boffetta|last8=Jr|first8=Cerhan|last9=M|first9=Maynadie|date=2007|title=Family history of hematopoietic malignancies and risk of non-Hodgkin lymphoma (NHL): a pooled analysis of 10 211 cases and 11 905 controls from the International Lymphoma Epidemiology Consortium (InterLymph)|url=https://pubmed.ncbi.nlm.nih.gov/17185468/|language=en|doi=10.1182/blood-2006-06-031948|pmc=PMC1852242|pmid=17185468}}</ref>

+

*Family history of leukemia may elevate risks particularly among men with mantle-cell lymphomas (OR = 3.1, 95% CI = 1.6-6.2)<ref>{{Cite journal|last=Ss|first=Wang|last2=Sl|first2=Slager|last3=P|first3=Brennan|last4=Ea|first4=Holly|last5=S|first5=De Sanjose|last6=L|first6=Bernstein|last7=P|first7=Boffetta|last8=Jr|first8=Cerhan|last9=M|first9=Maynadie|date=2007|title=Family history of hematopoietic malignancies and risk of non-Hodgkin lymphoma (NHL): a pooled analysis of 10 211 cases and 11 905 controls from the International Lymphoma Epidemiology Consortium (InterLymph)|url=https://pubmed.ncbi.nlm.nih.gov/17185468/|language=en|doi=10.1182/blood-2006-06-031948|pmc=PMC1852242|pmid=17185468}}</ref>

==Additional Information==

−

~~Put your text here~~

+

This disease is defined/characterized as detailed below:

+

*Clinically aggressive, mature B cell lymphoma

+

*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

+

*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)

+

The epidemiology/prevalence of this disease is detailed below:

+

*~ 7% of B cell lymphomas <ref name=":6" />

+

*2.5%-10% of non-Hodgkin lymphomas <ref name=":7" />

+

*Age adjusted incidence: 0.7/100,000 person years in white population in USA <ref name=":8" />

+

*Median age: 60 years<ref name=":9" />

+

*M:F = 3:1 (range, 1.6-6.8 :1)<ref name=":10" />

+

The clinical features of this disease are detailed below:

+

*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%)

+

The sites of involvement of this disease are detailed below:

+

*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" />

+

*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" />

+

*Extranodal involvement without lymphadenopathies: 4 - 15%

+

The morphologic features of this disease are detailed below:

+

*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" />

+

*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" />

+

*Gastrointestinal

+

**May mimic lymphoepithelial lesions in marginal zone lymphoma <ref name=":17" />

+

*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" />

+

The immunophenotype 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 (subset) - MUM1 / IRF4 (50% in small subset of cells), MYC, p53

+

* Positive/Negative - CD10, BCL-6

+

* Negative (universal) - T-cell associated markers (except CD5), CD200, LEF-1

+

*Ki67 count <ref name=":19" />

+

**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" />

+

*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" />

+

*MYC in subset

+

**High expression correlates with ''MYC'' translocation <ref name=":22" />

+

*CD10+ MCL more associated with diffuse growth pattern, blastoid/pleomorphic morphology, and BCL6 expression<ref name=":23" />

+

*CD23: small subset of cases <ref name=":24" />

+

*CD200: May be positive in a subset of SOX11 negative mantle cell lymphomas<ref name=":25" /> [[HAEM5:Leukaemic non-nodal mantle cell lymphoma]]

+

*LEF-1: positive in 4 - 9% of mantle cell lymphomas <ref name=":26" /><ref name=":27" />

+

*Cyclin D1-negative MCL

+

**Morphology, phenotype, gene expression, clinical presentation and evolution similar to cyclin D1-positive MCL <ref name=":28" />

+

**Positive for Sox-11

+

**Frequently express cyclin D2 or cyclin D3 (''IG''-mediated translocations) <ref name=":29" />

+

**cyclin E in cases with negative expression of cyclin D and aggressive behavior <ref name=":30" />

==Links==

Line 958: Line 1,076:

(use the "Cite" icon at the top of the page) (''Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted''''.'') <references />

−

~~'''~~

+

==Notes==

Line 966: Line 1,084:

<nowiki>*</nowiki>''Citation of this Page'': “Mantle cell lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Mantle_cell_lymphoma</nowiki>.

−

[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases M]]

+

[[Category:HAEM5]]

+

[[Category:DISEASE]]

+

[[Category:Diseases M]]

Jennelleh

Bureaucrats, Editors, Administrators

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