Bailey.Glen: Created page with "==Primary Author(s)== Kathleen M. Schieffer, PhD * Ruthann Pfau, PhD TOC ==Cancer Category/Type== * Mature B-Cell Neoplasms ==Cancer Sub-Classification / Subty..."

2023-11-03T17:42:58Z

Created page with "==Primary Author(s)*== * Kathleen M. Schieffer, PhD * Ruthann Pfau, PhD __TOC__ ==Cancer Category/Type== * Mature B-Cell Neoplasms ==Cancer Sub-Classification / Subty..."

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==Primary Author(s)*==

* Kathleen M. Schieffer, PhD
* Ruthann Pfau, PhD

__TOC__

==Cancer Category/Type==

* [[Mature B-Cell Neoplasms]]

==Cancer Sub-Classification / Subtype==

* [[Nodal Marginal Zone Lymphoma]] (NMZL)

==Definition / Description of Disease==

* Paediatric nodal marginal zone lymphoma (pNMZL) is a rare and distinct entity of [[Nodal Marginal Zone Lymphoma|NMZL]] seen in the pediatrics and young adult population<ref name=":1">Swerdlow SH, Campo E, Harris NL et al (eds) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC Press, Lyon, pp 264-265</ref>
* pNMZL typically presents with an indolent course and localized disease<ref name=":1" />, contrary from classic NMZL seen in adults<ref name=":2">Swerdlow SH, Campo E, Harris NL et al (eds) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC Press, Lyon, pp 263-264</ref>
* Typically presents as asymptomatic, localized lymphadenopathy (Stage I)<ref name=":3">{{Cite journal|last=Koo|first=Matthew|last2=Ohgami|first2=Robert S.|date=2017-05|title=Pediatric-type Follicular Lymphoma and Pediatric Nodal Marginal Zone Lymphoma: Recent Clinical, Morphologic, Immunophenotypic, and Genetic Insights|url=https://pubmed.ncbi.nlm.nih.gov/28277421|journal=Advances in Anatomic Pathology|volume=24|issue=3|pages=128–135|doi=10.1097/PAP.0000000000000144|issn=1533-4031|pmid=28277421}}</ref><ref name=":4">{{Cite journal|last=Ronceray|first=Leila|last2=Abla|first2=Oussama|last3=Barzilai-Birenboim|first3=Shlomit|last4=Bomken|first4=Simon|last5=Chiang|first5=Alan Ks|last6=Jazbec|first6=Janez|last7=Kabickova|first7=Edita|last8=Lazic|first8=Jelena|last9=Beishuizen|first9=Auke|date=04 2018|title=Children and adolescents with marginal zone lymphoma have an excellent prognosis with limited chemotherapy or a watch-and-wait strategy after complete resection|url=https://pubmed.ncbi.nlm.nih.gov/29286565|journal=Pediatric Blood & Cancer|volume=65|issue=4|doi=10.1002/pbc.26932|issn=1545-5017|pmid=29286565}}</ref><ref name=":5">{{Cite journal|last=Makarova|first=Olga|last2=Oschlies|first2=Ilske|last3=Müller|first3=Stephanie|last4=Ruf|first4=Stephanie|last5=Zimmermann|first5=Martin|last6=Niggli|first6=Felix|last7=Attarbaschi|first7=Andishe|last8=Kabickova|first8=Edita|last9=Klapper|first9=Wolfram|date=09 2018|title=Excellent outcome with limited treatment in paediatric patients with marginal zone lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/28771659|journal=British Journal of Haematology|volume=182|issue=5|pages=735–739|doi=10.1111/bjh.14868|issn=1365-2141|pmid=28771659}}</ref>
* Laboratory testing: normal serum lactate dehydrogenase (LDH) levels<ref name=":3" /><ref name=":4" /><ref name=":5" />
* Prognosis is typically excellent<ref name=":4" /><ref name=":5" /><ref name=":6">{{Cite journal|last=Quintanilla-Martinez|first=Leticia|last2=Sander|first2=Birgitta|last3=Chan|first3=John K. C.|last4=Xerri|first4=Luc|last5=Ott|first5=German|last6=Campo|first6=Elias|last7=Swerdlow|first7=Steven H.|date=2016-02|title=Indolent lymphomas in the pediatric population: follicular lymphoma, IRF4/MUM1+ lymphoma, nodal marginal zone lymphoma and chronic lymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/26416032|journal=Virchows Archiv: An International Journal of Pathology|volume=468|issue=2|pages=141–157|doi=10.1007/s00428-015-1855-z|issn=1432-2307|pmid=26416032}}</ref>
** Five year event free survival: 94±6%<ref name=":4" />
** Five year overall survival: 100%<ref name=":4" />
* Complete remission follows surgical resection in most patients with limited/localized disease<ref name=":4" /><ref name=":8" />
* Chemotherapy and radiation therapy have also been used for management of limited stage disease<ref name=":4" /><ref name=":8">{{Cite journal|displayauthors=1|last=Taddessee-Heath|first=Lekidelu|date=|title=Marginal zone B-cell lymphoma in children and young adults|url=|journal=Am J Surg Pathol|volume=24|pages=522-531|doi=10.1097/00000478-200304000-00014|pmc=PMC6324530|pmid=12657939|via=}}</ref>

==Synonyms / Terminology==

* Monocytoid B-cell lymphoma
* Parafollicular B-cell lymphoma (obsolete)

==Epidemiology / Prevalence==

* Male: Female 4-20:1<ref name=":3" /><ref name=":5" /><ref name=":6" /><ref name=":8" /><ref name=":0">{{Cite journal|last=Ozawa|first=Michael G.|last2=Bhaduri|first2=Aparna|last3=Chisholm|first3=Karen M.|last4=Baker|first4=Steven A.|last5=Ma|first5=Lisa|last6=Zehnder|first6=James L.|last7=Luna-Fineman|first7=Sandra|last8=Link|first8=Michael P.|last9=Merker|first9=Jason D.|date=10 2016|title=A study of the mutational landscape of pediatric-type follicular lymphoma and pediatric nodal marginal zone lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/27338637|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=29|issue=10|pages=1212–1220|doi=10.1038/modpathol.2016.102|issn=1530-0285|pmc=5047957|pmid=27338637}}</ref><ref name=":7">{{Cite journal|displayauthors=1|last=Liu|first=Qingyan|date=|title=Follicular lymphomas in children and young adults: a comparison of the pediatric variant with usual follicular lymphoma|url=|journal=Am J Surg Pathol|volume=37|pages=333-343|doi=10.1097/PAS.0b013e31826b9b57|pmid=23108024|via=}}</ref><ref name=":9">{{Cite journal|displayauthors=1|last=Rizzo|first=Kathryn|date=|title=Marginal zone lymphomas in children and the young adult population; characterization of genetic aberrations by FISH and RT-PCR|url=|journal=Mol Pathol|volume=23|pages=866-873|doi=10.1038/modpathol.2010.63|pmc=PMC6329460|pmid=20305621|via=}}</ref><ref name=":11">{{Cite journal|last=Ganapathi|first=Karthik A.|last2=Pittaluga|first2=Stefania|last3=Odejide|first3=Oreofe O.|last4=Freedman|first4=Arnold S.|last5=Jaffe|first5=Elaine S.|date=2014-09|title=Early lymphoid lesions: conceptual, diagnostic and clinical challenges|url=https://pubmed.ncbi.nlm.nih.gov/25176983|journal=Haematologica|volume=99|issue=9|pages=1421–1432|doi=10.3324/haematol.2014.107938|issn=1592-8721|pmc=4562530|pmid=25176983}}</ref>
* Median age ~16-17 years (range 1.5-44 years)<ref name=":3" /><ref name=":5" /><ref name=":6" /><ref name=":8" /><ref name=":0" /><ref name=":7" /><ref name=":9" /><ref name=":11" /><ref>{{Cite journal|last=Gitelson|first=Elena|last2=Al-Saleem|first2=Tahseen|last3=Robu|first3=Valentin|last4=Millenson|first4=Michael M.|last5=Smith|first5=Mitchell R.|date=2010-01|title=Pediatric nodal marginal zone lymphoma may develop in the adult population|url=https://pubmed.ncbi.nlm.nih.gov/19863176|journal=Leukemia & Lymphoma|volume=51|issue=1|pages=89–94|doi=10.3109/10428190903349670|issn=1029-2403|pmc=3572776|pmid=19863176}}</ref>
* <2% of non-Hodgkin lymphoma<ref name=":5" /><ref name=":12" />

==Clinical Features==

* Asymptomatic in most<ref name=":6" /><ref name=":8" /><ref name=":11" /><ref name=":12" />
* Peripheral lymphadenopathy<ref name=":6" /><ref name=":8" /><ref name=":11" /><ref name=":12">{{Cite journal|last=Attarbaschi|first=Andishe|last2=Abla|first2=Oussama|last3=Arias Padilla|first3=Laura|last4=Beishuizen|first4=Auke|last5=Burke|first5=G. A. Amos|last6=Brugières|first6=Laurence|last7=Bruneau|first7=Julie|last8=Burkhardt|first8=Birgit|last9=d'Amore|first9=Emanuele S. G.|date=08 2020|title=Rare non-Hodgkin lymphoma of childhood and adolescence: A consensus diagnostic and therapeutic approach to pediatric-type follicular lymphoma, marginal zone lymphoma, and nonanaplastic peripheral T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/32452165|journal=Pediatric Blood & Cancer|volume=67|issue=8|pages=e28416|doi=10.1002/pbc.28416|issn=1545-5017|pmid=32452165}}</ref>

==Sites of Involvement==

* Primarily head and neck lymph nodes<ref name=":3" /><ref name=":5" /><ref name=":6" /><ref name=":0" /><ref name=":7" /><ref name=":8" /><ref name=":9" />

==Morphologic Features==

*
* Effacement of lymph node architecture due to expansion of marginal zone and intrafollicular proliferation
** Expanded marginal zone may be delineated by IgD staining<ref name=":6" /><ref name=":8" />
* Follicular hyperplasia with features of progressive transformation of germinal centers (PTGC)<ref name=":3" /><ref name=":6" /><ref name=":8" /><ref name=":7" />
** May distinguish pNMZL from adult-type [[Nodal Marginal Zone Lymphoma|NMZL]] and nodal [[Paediatric-Type Follicular Lymphoma|paediatric-type follicular lymphoma]]<ref name=":3" /><ref name=":7" />
* Polymorphic infiltrate composed of small- to medium-sized cells with round nuclei and moderate cytoplasm<ref name=":3" /><ref name=":8" />
* Starry-sky appearance of residual hyperplastic germinal centers<ref name=":7" />
==Immunophenotype==

* Similar to adult-type NMZL, pNMZL is almost universally positive for the mature B cell marker CD20 (90-100%) with most cases also expressing the pan-T cell marker CD43 (70-100%)<ref name=":3" /><ref name=":6" /><ref name=":8" /><ref name=":7" /><ref name=":10">{{Cite journal|last=Elenitoba-Johnson|first=K. S.|last2=Kumar|first2=S.|last3=Lim|first3=M. S.|last4=Kingma|first4=D. W.|last5=Raffeld|first5=M.|last6=Jaffe|first6=E. S.|date=1997-01|title=Marginal zone B-cell lymphoma with monocytoid B-cell lymphocytes in pediatric patients without immunodeficiency. A report of two cases|url=https://pubmed.ncbi.nlm.nih.gov/8980374|journal=American Journal of Clinical Pathology|volume=107|issue=1|pages=92–98|doi=10.1093/ajcp/107.1.92|issn=0002-9173|pmid=8980374}}</ref>
* A subset of pNMZL express BCL2 (40-50%) and IgD (20-30%)<ref name=":3" /><ref name=":6" /><ref name=":8" />
* pNMZL cells are negative for the germinal center markers CD10, BCL6, CD23, and the T cell markers CD3, CD5<ref name=":3" /><ref name=":6" /><ref name=":8" /><ref name=":9" />
* CD279/PD-1 staining present in reactive germinal centers of pNMZL, compared to positive staining at the periphery of germinal centers in nodal [[Paediatric-Type Follicular Lymphoma|pediatric-type follicular lymphoma]]<ref name=":7" />

{| class="wikitable sortable"
|-
!Finding!!Marker
|-
|Positive (universal)||CD19, CD20, sIg (bright, monoclonal), CD43
|-
|Positive (subset)||BCL2, CD279/PD-1, IgD
|-
|Negative (universal)||CD10, BCL6, CD23, CD5, CD3, LEF1
|}

==Chromosomal Rearrangements (Gene Fusions)==

* No chromosomal rearrangements or gene fusions associated with pNMZL<ref name=":0" />
* Clonal rearrangements of immunoglobulin (Ig) region detected in most cases<ref name=":3" /><ref name=":9" />

==Characteristic Chromosomal Aberrations / Patterns==

* No characteristic chromosomal aberrations or patterns reported

==Genomic Gain/Loss/LOH==

* Trisomy 3 and 18 are infrequently described chromosomal aberrations reported in pNMZL<ref name=":9" />
** These chromosome gains have also been described in adult-type NMZL<ref name=":2" /><ref>{{Cite journal|last=Rinaldi|first=Andrea|last2=Mian|first2=Michael|last3=Chigrinova|first3=Ekaterina|last4=Arcaini|first4=Luca|last5=Bhagat|first5=Govind|last6=Novak|first6=Urban|last7=Rancoita|first7=Paola M. V.|last8=De Campos|first8=Cassio P.|last9=Forconi|first9=Francesco|date=2011-02-03|title=Genome-wide DNA profiling of marginal zone lymphomas identifies subtype-specific lesions with an impact on the clinical outcome|url=https://pubmed.ncbi.nlm.nih.gov/21115979|journal=Blood|volume=117|issue=5|pages=1595–1604|doi=10.1182/blood-2010-01-264275|issn=1528-0020|pmid=21115979}}</ref><ref>{{Cite journal|last=Dierlamm|first=J.|last2=Pittaluga|first2=S.|last3=Wlodarska|first3=I.|last4=Stul|first4=M.|last5=Thomas|first5=J.|last6=Boogaerts|first6=M.|last7=Michaux|first7=L.|last8=Driessen|first8=A.|last9=Mecucci|first9=C.|date=1996-01-01|title=Marginal zone B-cell lymphomas of different sites share similar cytogenetic and morphologic features|url=https://pubmed.ncbi.nlm.nih.gov/8547655|journal=Blood|volume=87|issue=1|pages=299–307|issn=0006-4971|pmid=8547655}}</ref>

{| class="wikitable sortable"
|-
!Chromosome Number!!Gain/Loss/Amp/LOH!!Region
!Prevalence<ref name=":3" />
!Reference
|-
|3||Gain||Whole chromosome
|0-20%
|<ref name=":9" />
|-
|18||Gain||Whole chromosome
|0-5%
|<ref name=":9" />
|-
|13
|Gain
|Whole chromosome
|0-5%
|<ref name=":10" />
|}

==Gene Mutations (SNV/INDEL)==

* Genes reported to be altered in adult-type NMZL, including ''MLL2 (KMT2D), PTPRD, NOTCH2, KLF2,'' and ''BRAF'',<ref>{{Cite journal|last=Spina|first=Valeria|last2=Khiabanian|first2=Hossein|last3=Messina|first3=Monica|last4=Monti|first4=Sara|last5=Cascione|first5=Luciano|last6=Bruscaggin|first6=Alessio|last7=Spaccarotella|first7=Elisa|last8=Holmes|first8=Antony B.|last9=Arcaini|first9=Luca|date=09 08, 2016|title=The genetics of nodal marginal zone lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/27335277|journal=Blood|volume=128|issue=10|pages=1362–1373|doi=10.1182/blood-2016-02-696757|issn=1528-0020|pmc=5016706|pmid=27335277}}</ref><ref>{{Cite journal|last=Pillonel|first=V.|last2=Juskevicius|first2=D.|last3=Ng|first3=C. K. Y.|last4=Bodmer|first4=A.|last5=Zettl|first5=A.|last6=Jucker|first6=D.|last7=Dirnhofer|first7=S.|last8=Tzankov|first8=A.|date=11 2018|title=High-throughput sequencing of nodal marginal zone lymphomas identifies recurrent BRAF mutations|url=https://pubmed.ncbi.nlm.nih.gov/29556019|journal=Leukemia|volume=32|issue=11|pages=2412–2426|doi=10.1038/s41375-018-0082-4|issn=1476-5551|pmc=6224405|pmid=29556019}}</ref> have not been described in pNMZL<ref name=":0" />
* While no recurrent somatic variations have been identified in pNMZL, a somatic variant in ''AMOTL1'' (NM_130847, p.Ala891Thr) was reported in a single individual with pNMZL<ref name=":0" />
** Missense alterations in ''AMOTL1'' have been reported in adult splenic marginal zone lymphoma (p.Ala424Thr and p.Val361Ile)<ref>{{Cite journal|last=Parry|first=Marina|last2=Rose-Zerilli|first2=Matthew J. J.|last3=Gibson|first3=Jane|last4=Ennis|first4=Sarah|last5=Walewska|first5=Renata|last6=Forster|first6=Jade|last7=Parker|first7=Helen|last8=Davis|first8=Zadie|last9=Gardiner|first9=Anne|date=2013|title=Whole exome sequencing identifies novel recurrently mutated genes in patients with splenic marginal zone lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/24349473|journal=PloS One|volume=8|issue=12|pages=e83244|doi=10.1371/journal.pone.0083244|issn=1932-6203|pmc=3862727|pmid=24349473}}</ref><ref>{{Cite journal|last=Rossi|first=Davide|last2=Trifonov|first2=Vladimir|last3=Fangazio|first3=Marco|last4=Bruscaggin|first4=Alessio|last5=Rasi|first5=Silvia|last6=Spina|first6=Valeria|last7=Monti|first7=Sara|last8=Vaisitti|first8=Tiziana|last9=Arruga|first9=Francesca|date=2012-08-27|title=The coding genome of splenic marginal zone lymphoma: activation of NOTCH2 and other pathways regulating marginal zone development|url=https://pubmed.ncbi.nlm.nih.gov/22891273|journal=The Journal of Experimental Medicine|volume=209|issue=9|pages=1537–1551|doi=10.1084/jem.20120904|issn=1540-9538|pmc=3428941|pmid=22891273}}</ref> and other cancers ([https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=122769838 COSMIC], [http://www.cbioportal.org/ cBioPortal], [https://pedcbioportal.kidsfirstdrc.org/ PedcBioPortal])

{| class="wikitable sortable"
|-
!Gene!!Mutation!!Oncogene/Tumor Suppressor/Other!!Presumed Mechanism (LOF/GOF/Other; Driver/Passenger)!!Prevalence
!Reference
|-
|''AMOTL1''||Missense||Oncogene/Tumor Suppressor*||Uncertain||1 patient of 4 total (25%)
|<ref name=":0" />
|}
<nowiki>*</nowiki>The role in cancer is context dependent

===Other Mutations===

* Additional studies are needed to assess the spectrum of somatic variation in pNMZL. A single report evaluated the genetic landscape of pNMZL by whole exome sequencing (n=4) identified missense changes in the following genes: ''AMOTL1, SCAF1, SELPLG, FAM5B, KLHDC4, RAX, PEG3, CHPF, ACTRT3, NRCAM, CHMP1A, CISH, TTC17, NLE1<ref name=":0" />''

==Epigenomics (Methylation)==

* None

==Genes and Main Pathways Involved==

* ''AMOTL1'' encodes angiomotin like-1 which associates with tight junctions and regulates the Hippo signaling pathway<ref>{{Cite journal|last=Yi|first=Chunling|last2=Troutman|first2=Scott|last3=Fera|first3=Daniela|last4=Stemmer-Rachamimov|first4=Anat|last5=Avila|first5=Jacqueline L.|last6=Christian|first6=Neepa|last7=Persson|first7=Nathalie Luna|last8=Shimono|first8=Akihiko|last9=Speicher|first9=David W.|date=2011-04-12|title=A tight junction-associated Merlin-angiomotin complex mediates Merlin's regulation of mitogenic signaling and tumor suppressive functions|url=https://pubmed.ncbi.nlm.nih.gov/21481793|journal=Cancer Cell|volume=19|issue=4|pages=527–540|doi=10.1016/j.ccr.2011.02.017|issn=1878-3686|pmc=3075552|pmid=21481793}}</ref><ref>{{Cite journal|last=Lv|first=Meng|last2=Shen|first2=Yanwei|last3=Yang|first3=Jiao|last4=Li|first4=Shuting|last5=Wang|first5=Biyuan|last6=Chen|first6=Zheling|last7=Li|first7=Pan|last8=Liu|first8=Peijun|last9=Yang|first9=Jin|date=2017|title=Angiomotin Family Members: Oncogenes or Tumor Suppressors?|url=https://pubmed.ncbi.nlm.nih.gov/28656002|journal=International Journal of Biological Sciences|volume=13|issue=6|pages=772–781|doi=10.7150/ijbs.19603|issn=1449-2288|pmc=5485632|pmid=28656002}}</ref>

==Diagnostic Testing Methods==

* Histopathology and immunophenotyping
* Molecular testing (i.e. clonality assessment)

==Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)==

* No genomic findings currently assist in diagnosis, prognostication, or therapeutic decisions

==Familial Forms==

* Not described

==Other Information==

* None

==Links==

* [[Nodal Marginal Zone Lymphoma]]
* [[Paediatric-Type Follicular Lymphoma]]

==References==
<references />
#

==Notes==
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome.

HAEM4Backup:Paediatric Nodal Marginal Zone Lymphoma - Revision history

Bailey.Glen: Created page with "==Primary Author(s)*== * Kathleen M. Schieffer, PhD * Ruthann Pfau, PhD __TOC__ ==Cancer Category/Type== * Mature B-Cell Neoplasms ==Cancer Sub-Classification / Subty..."

Bailey.Glen: Created page with "==Primary Author(s)== Kathleen M. Schieffer, PhD * Ruthann Pfau, PhD TOC ==Cancer Category/Type== * Mature B-Cell Neoplasms ==Cancer Sub-Classification / Subty..."