HAEM5:In situ mantle cell neoplasm: Difference between revisions
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{{DISPLAYTITLE:In situ mantle cell neoplasm}} | {{DISPLAYTITLE:In situ mantle cell neoplasm}} | ||
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]] | [[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]] | ||
{{Under Construction}} | {{Under Construction}} | ||
<blockquote class= | <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:In Situ Mantle Cell Neoplasia]]. | ||
}}</blockquote> | }}</blockquote> | ||
<span style="color:#0070C0">(General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ <u>HGVS-based nomenclature for variants</u>], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see </span><u>[[Author_Instructions]]</u><span style="color:#0070C0"> and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>].)</span> | |||
==Primary Author(s)*== | ==Primary Author(s)*== | ||
Rina Kansal, MD; Versiti Blood Center of Wisconsin | Rina Kansal, MD; Versiti Blood Center of Wisconsin | ||
==WHO Classification of Disease== | |||
{| class="wikitable" | |||
!Structure | |||
!Disease | |||
|- | |||
|Book | |||
|Haematolymphoid Tumours (5th ed.) | |||
|- | |||
|Category | |||
|B-cell lymphoid proliferations and lymphomas | |||
|- | |||
|Family | |||
|Mature B-cell neoplasms | |||
|- | |||
|Type | |||
|Mantle cell lymphoma | |||
|- | |||
|Subtype(s) | |||
|In situ mantle cell neoplasm | |||
|} | |||
==Related Terminology== | |||
= | {| class="wikitable" | ||
|+ | |||
|Acceptable | |||
|In situ mantle cell neoplasia | |||
|- | |||
|Not Recommended | |||
|In situ mantle cell lymphoma; mantle cell lymphoma–like B cells of uncertain/undetermined significance | |||
|} | |||
==Gene Rearrangements== | |||
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span> | |||
{| class="wikitable sortable" | |||
|- | |||
!Driver Gene!!Fusion(s) and Common Partner Genes!!Molecular Pathogenesis!!Typical Chromosomal Alteration(s) | |||
!Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease) | |||
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | |||
!Established Clinical Significance Per Guidelines - Yes or No (Source) | |||
!Clinical Relevance Details/Other Notes | |||
|- | |||
|<span class="blue-text">EXAMPLE:</span> ''ABL1''||<span class="blue-text">EXAMPLE:</span> ''BCR::ABL1''||<span class="blue-text">EXAMPLE:</span> The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1.||<span class="blue-text">EXAMPLE:</span> t(9;22)(q34;q11.2) | |||
|<span class="blue-text">EXAMPLE:</span> Common (CML) | |||
|<span class="blue-text">EXAMPLE:</span> D, P, T | |||
|<span class="blue-text">EXAMPLE:</span> Yes (WHO, NCCN) | |||
|<span class="blue-text">EXAMPLE:</span> | |||
The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference). BCR::ABL1 is generally favorable in CML (add reference). | |||
|- | |||
|<span class="blue-text">EXAMPLE:</span> ''CIC'' | |||
|<span class="blue-text">EXAMPLE:</span> ''CIC::DUX4'' | |||
|<span class="blue-text">EXAMPLE:</span> Typically, the last exon of ''CIC'' is fused to ''DUX4''. The fusion breakpoint in ''CIC'' is usually intra-exonic and removes an inhibitory sequence, upregulating ''PEA3'' genes downstream of ''CIC'' including ''ETV1'', ''ETV4'', and ''ETV5''. | |||
|<span class="blue-text">EXAMPLE:</span> t(4;19)(q25;q13) | |||
|<span class="blue-text">EXAMPLE:</span> Common (CIC-rearranged sarcoma) | |||
|<span class="blue-text">EXAMPLE:</span> D | |||
| | |||
|<span class="blue-text">EXAMPLE:</span> | |||
== | ''DUX4'' has many homologous genes; an alternate translocation in a minority of cases is t(10;19), but this is usually indistinguishable from t(4;19) by short-read sequencing (add references). | ||
|- | |||
|<span class="blue-text">EXAMPLE:</span> ''ALK'' | |||
|<span class="blue-text">EXAMPLE:</span> ''ELM4::ALK'' | |||
Other fusion partners include ''KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1'' | |||
|<span class="blue-text">EXAMPLE:</span> Fusions result in constitutive activation of the ''ALK'' tyrosine kinase. The most common ''ALK'' fusion is ''EML4::ALK'', with breakpoints in intron 19 of ''ALK''. At the transcript level, a variable (5’) partner gene is fused to 3’ ''ALK'' at exon 20. Rarely, ''ALK'' fusions contain exon 19 due to breakpoints in intron 18. | |||
|<span class="blue-text">EXAMPLE:</span> N/A | |||
|<span class="blue-text">EXAMPLE:</span> Rare (Lung adenocarcinoma) | |||
|<span class="blue-text">EXAMPLE:</span> T | |||
| | |||
|<span class="blue-text">EXAMPLE:</span> | |||
Both balanced and unbalanced forms are observed by FISH (add references). | |||
|- | |||
|<span class="blue-text">EXAMPLE:</span> ''ABL1'' | |||
|<span class="blue-text">EXAMPLE:</span> N/A | |||
|<span class="blue-text">EXAMPLE:</span> Intragenic deletion of exons 2–7 in ''EGFR'' removes the ligand-binding domain, resulting in a constitutively active tyrosine kinase with downstream activation of multiple oncogenic pathways. | |||
|<span class="blue-text">EXAMPLE:</span> N/A | |||
|<span class="blue-text">EXAMPLE:</span> Recurrent (IDH-wildtype Glioblastoma) | |||
|<span class="blue-text">EXAMPLE:</span> D, P, T | |||
| | |||
| | |||
|- | |||
| | |||
| | |||
| | |||
| | |||
| | |||
| | |||
| | |||
| | |||
|} | |||
The balanced translocation t(11;14)(q13;q32) is characteristic of mantle cell lymphoma and was identified in all cases of histologically identified in situ mantle cell neoplasm (whenever it was examined for in addition to the overexpression of cyclin D1 protein). | |||
{| class="wikitable sortable" | |||
|- | |||
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence | |||
!Diagnostic Significance (Yes, No or Unknown) | |||
!Prognostic Significance (Yes, No or Unknown) | |||
!Therapeutic Significance (Yes, No or Unknown) | |||
!Notes | |||
|- | |||
|t(11;14)(q13;q32)||''CCND1''::''IGH''|| || | |||
|Yes | |||
|Not yet known, if any, prognostic significance of t(11;14) in in situ mantle cell neoplasm; | |||
a subset of mantle cell lymphoma with the t(11;14) may have good prognosis<ref>{{Cite journal|last=Orchard|first=Jenny|last2=Garand|first2=Richard|last3=Davis|first3=Zadie|last4=Babbage|first4=Gavin|last5=Sahota|first5=Surinder|last6=Matutes|first6=Estella|last7=Catovsky|first7=Daniel|last8=Thomas|first8=Peter W.|last9=Avet-Loiseau|first9=Hervé|date=2003-06-15|title=A subset of t(11;14) lymphoma with mantle cell features displays mutated IgVH genes and includes patients with good prognosis, nonnodal disease|url=https://pubmed.ncbi.nlm.nih.gov/12609845|journal=Blood|volume=101|issue=12|pages=4975–4981|doi=10.1182/blood-2002-06-1864|issn=0006-4971|pmid=12609845}}</ref> | |||
|Not yet known, if any | |||
|The t(11;14) is characteristic of in situ mantle cell neoplasm and overt mantle cell lymphoma in the appropriate morphology and clinical context. However, this translocation may also be present in other lymphoid neoplasms and has also been identified in healthy individuals at a lower incidence than the t(14;18) translocation in healthy individuals.<ref>{{Cite journal|last=Hirt|first=Carsten|last2=Schüler|first2=Frank|last3=Dölken|first3=Lars|last4=Schmidt|first4=Christian A.|last5=Dölken|first5=Gottfried|date=2004-08-01|title=Low prevalence of circulating t(11;14)(q13;q32)-positive cells in the peripheral blood of healthy individuals as detected by real-time quantitative PCR|url=https://pubmed.ncbi.nlm.nih.gov/15265798|journal=Blood|volume=104|issue=3|pages=904–905|doi=10.1182/blood-2004-02-0738|issn=0006-4971|pmid=15265798}}</ref><ref>{{Cite journal|last=Nambiar|first=Mridula|last2=Raghavan|first2=Sathees C.|date=2010-01|title=Prevalence and analysis of t(14;18) and t(11;14) chromosomal translocations in healthy Indian population|url=https://pubmed.ncbi.nlm.nih.gov/19488754|journal=Annals of Hematology|volume=89|issue=1|pages=35–43|doi=10.1007/s00277-009-0755-1|issn=1432-0584|pmid=19488754}}</ref><ref>{{Cite journal|last=Lecluse|first=Y.|last2=Lebailly|first2=P.|last3=Roulland|first3=S.|last4=Gac|first4=A.-C.|last5=Nadel|first5=B.|last6=Gauduchon|first6=P.|date=2009-06|title=t(11;14)-positive clones can persist over a long period of time in the peripheral blood of healthy individuals|url=https://pubmed.ncbi.nlm.nih.gov/19242498|journal=Leukemia|volume=23|issue=6|pages=1190–1193|doi=10.1038/leu.2009.31|issn=1476-5551|pmid=19242498}}</ref> | |||
|} | |||
==Individual Region Genomic Gain/Loss/LOH== | |||
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene rearrangements. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Can refer to CGC workgroup tables as linked on the homepage if applicable. Please include references throughout the table. Do not delete the table.'') </span> | |||
{| class="wikitable sortable" | |||
|- | |||
!Chr #!!Gain, Loss, Amp, LOH!!Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]!!Relevant Gene(s) | |||
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | |||
!Established Clinical Significance Per Guidelines - Yes or No (Source) | |||
!Clinical Relevance Details/Other Notes | |||
|- | |||
|<span class="blue-text">EXAMPLE:</span> | |||
7 | |||
|<span class="blue-text">EXAMPLE:</span> Loss | |||
|<span class="blue-text">EXAMPLE:</span> | |||
chr7 | |||
|<span class="blue-text">EXAMPLE:</span> | |||
Unknown | |||
|<span class="blue-text">EXAMPLE:</span> D, P | |||
|<span class="blue-text">EXAMPLE:</span> No | |||
|<span class="blue-text">EXAMPLE:</span> | |||
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference). Monosomy 7/7q deletion is associated with a poor prognosis in AML (add references). | |||
|- | |||
|<span class="blue-text">EXAMPLE:</span> | |||
8 | |||
|<span class="blue-text">EXAMPLE:</span> Gain | |||
|<span class="blue-text">EXAMPLE:</span> | |||
chr8 | |||
|<span class="blue-text">EXAMPLE:</span> | |||
Unknown | |||
|<span class="blue-text">EXAMPLE:</span> D, P | |||
| | |||
|<span class="blue-text">EXAMPLE:</span> | |||
Common recurrent secondary finding for t(8;21) (add references). | |||
|- | |||
|<span class="blue-text">EXAMPLE:</span> | |||
17 | |||
|<span class="blue-text">EXAMPLE:</span> Amp | |||
|<span class="blue-text">EXAMPLE:</span> | |||
17q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb] | |||
|<span class="blue-text">EXAMPLE:</span> | |||
''ERBB2'' | |||
|<span class="blue-text">EXAMPLE:</span> D, P, T | |||
| | |||
|<span class="blue-text">EXAMPLE:</span> | |||
Amplification of ''ERBB2'' is associated with HER2 overexpression in HER2 positive breast cancer (add references). Add criteria for how amplification is defined. | |||
|- | |||
| | |||
| | |||
| | |||
| | |||
| | |||
| | |||
| | |||
|} | |||
These have not been studied specifically for in situ mantle cell neoplasm. | |||
== | {| class="wikitable sortable" | ||
|- | |||
!Chr #!!Gain / Loss / Amp / LOH!!Minimal Region Genomic Coordinates [Genome Build]!!Minimal Region Cytoband | |||
!Diagnostic Significance (Yes, No or Unknown) | |||
!Prognostic Significance (Yes, No or Unknown) | |||
!Therapeutic Significance (Yes, No or Unknown) | |||
!Notes | |||
|- | |||
|<span class="blue-text">EXAMPLE:</span> | |||
7 | |||
|<span class="blue-text">EXAMPLE:</span> Loss | |||
|<span class="blue-text">EXAMPLE:</span> | |||
chr7:1- 159,335,973 [hg38] | |||
|<span class="blue-text">EXAMPLE:</span> | |||
chr7 | |||
|Yes | |||
|Yes | |||
|No | |||
|<span class="blue-text">EXAMPLE:</span> | |||
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference). | |||
|- | |||
|<span class="blue-text">EXAMPLE:</span> | |||
8 | |||
|<span class="blue-text">EXAMPLE:</span> Gain | |||
|<span class="blue-text">EXAMPLE:</span> | |||
chr8:1-145,138,636 [hg38] | |||
|<span class="blue-text">EXAMPLE:</span> | |||
chr8 | |||
|No | |||
|No | |||
|No | |||
|<span class="blue-text">EXAMPLE:</span> | |||
Common recurrent secondary finding for t(8;21) (add reference). | |||
|} | |||
==Characteristic Chromosomal or Other Global Mutational Patterns== | |||
Put your text here and fill in the table <span style="color:#0070C0">(I''nstructions: Included in this category are alterations such as hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis; microsatellite instability; homologous recombination deficiency; mutational signature pattern; etc. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span> | |||
{| class="wikitable sortable" | |||
|- | |||
!Chromosomal Pattern | |||
!Molecular Pathogenesis | |||
!Prevalence - | |||
Common >20%, Recurrent 5-20% or Rare <5% (Disease) | |||
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | |||
!Established Clinical Significance Per Guidelines - Yes or No (Source) | |||
!Clinical Relevance Details/Other Notes | |||
|- | |||
|<span class="blue-text">EXAMPLE:</span> | |||
Co-deletion of 1p and 18q | |||
|<span class="blue-text">EXAMPLE:</span> See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference). | |||
|<span class="blue-text">EXAMPLE:</span> Common (Oligodendroglioma) | |||
|<span class="blue-text">EXAMPLE:</span> D, P | |||
| | |||
| | |||
|- | |||
|<span class="blue-text">EXAMPLE:</span> | |||
Microsatellite instability - hypermutated | |||
| | |||
|<span class="blue-text">EXAMPLE:</span> Common (Endometrial carcinoma) | |||
|<span class="blue-text">EXAMPLE:</span> P, T | |||
| | |||
| | |||
|- | |||
| | |||
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| | |||
| | |||
| | |||
| | |||
|} | |||
==Gene Mutations (SNV/INDEL)== | |||
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent or common as well either disease defining and/or clinically significant. If a gene has multiple mechanisms depending on the type or site of the alteration, add multiple entries in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Details on clinical significance such as prognosis and other important information such as concomitant and mutually exclusive mutations can be provided in the notes section. Please include references throughout the table. Do not delete the table.'') </span> | |||
{| class="wikitable sortable" | |||
|- | |||
!Gene!!Genetic Alteration!!Tumor Suppressor Gene, Oncogene, Other!!Prevalence - | |||
Common >20%, Recurrent 5-20% or Rare <5% (Disease) | |||
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | |||
!Established Clinical Significance Per Guidelines - Yes or No (Source) | |||
!Clinical Relevance Details/Other Notes | |||
|- | |||
|<span class="blue-text">EXAMPLE:</span>''EGFR'' | |||
<br /> | |||
|<span class="blue-text">EXAMPLE:</span> Exon 18-21 activating mutations | |||
|<span class="blue-text">EXAMPLE:</span> Oncogene | |||
|<span class="blue-text">EXAMPLE:</span> Common (lung cancer) | |||
|<span class="blue-text">EXAMPLE:</span> T | |||
|<span class="blue-text">EXAMPLE:</span> Yes (NCCN) | |||
|<span class="blue-text">EXAMPLE:</span> Exons 18, 19, and 21 mutations are targetable for therapy. Exon 20 T790M variants cause resistance to first generation TKI therapy and are targetable by second and third generation TKIs (add references). | |||
|- | |||
|<span class="blue-text">EXAMPLE:</span> ''TP53''; Variable LOF mutations | |||
<br /> | |||
|<span class="blue-text">EXAMPLE:</span> Variable LOF mutations | |||
|<span class="blue-text">EXAMPLE:</span> Tumor Supressor Gene | |||
|<span class="blue-text">EXAMPLE:</span> Common (breast cancer) | |||
|<span class="blue-text">EXAMPLE:</span> P | |||
| | |||
|<span class="blue-text">EXAMPLE:</span> >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer. | |||
|- | |||
|<span class="blue-text">EXAMPLE:</span> ''BRAF''; Activating mutations | |||
|<span class="blue-text">EXAMPLE:</span> Activating mutations | |||
|<span class="blue-text">EXAMPLE:</span> Oncogene | |||
|<span class="blue-text">EXAMPLE:</span> Common (melanoma) | |||
|<span class="blue-text">EXAMPLE:</span> T | |||
| | |||
| | |||
|- | |||
| | |||
| | |||
| | |||
| | |||
| | |||
| | |||
| | |||
|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content. | |||
There are numerous publications for gene mutations in overt mantle cell lymphoma. A recent systematic meta-analysis of 32 studies published during 2006 to 2019, excluding review articles, detailed the findings for gene mutations in mantle cell lymphoma by analyzing 2127 individual overt mantle cell lymphoma patients and 2173 samples that were included in the analyzed studies.<ref name=":10">{{Cite journal|last=Hill|first=Holly A.|last2=Qi|first2=Xinyue|last3=Jain|first3=Preetesh|last4=Nomie|first4=Krystle|last5=Wang|first5=Yucai|last6=Zhou|first6=Shouhao|last7=Wang|first7=Michael L.|date=2020-07-14|title=Genetic mutations and features of mantle cell lymphoma: a systematic review and meta-analysis|url=https://pubmed.ncbi.nlm.nih.gov/32598477|journal=Blood Advances|volume=4|issue=13|pages=2927–2938|doi=10.1182/bloodadvances.2019001350|issn=2473-9537|pmc=7362354|pmid=32598477}}</ref> These studies included the nodal and the leukemic forms of overt mantle cell lymphoma. As per this meta-analysis, in overt mantle cell lymphoma tumor or bone marrow samples at diagnosis or baseline, the most frequent genetic abnormalities occurred in the ''ATM'' (43.5%), ''TP53'' (26.8%), ''CDKN2A'' (23.9%), ''CCND1'' (20.2%), ''NSD2'' (15.0%), ''KMT2A'' (8.9%), ''S1PR1'' (8.6%), and ''CARD11'' (8.5%) genes.<ref name=":10" /> Aberrations in ''IGH'' (38.4%) and ''MYC'' (20.8%) were detected primarily through cytogenetic methods, also in those same tumor specimens.<ref name=":10" /> | |||
However, there have not yet been any studies that have examined in situ mantle cell neoplasm (without an overt lymphoma) for gene mutations. | |||
{| class="wikitable sortable" | |||
|- | |||
!Gene; Genetic Alteration!!Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)!!Prevalence (COSMIC / TCGA / Other)!!Concomitant Mutations!!Mutually Exclusive Mutations | |||
!Diagnostic Significance (Yes, No or Unknown) | |||
!Prognostic Significance (Yes, No or Unknown) | |||
!Therapeutic Significance (Yes, No or Unknown) | |||
!Notes | |||
|- | |||
|<span class="blue-text">EXAMPLE:</span> TP53; Variable LOF mutations | |||
<span class="blue-text">EXAMPLE:</span> | |||
EGFR; Exon 20 mutations | |||
<span class="blue-text">EXAMPLE:</span> BRAF; Activating mutations | |||
|<span class="blue-text">EXAMPLE:</span> TSG | |||
|<span class="blue-text">EXAMPLE:</span> 20% (COSMIC) | |||
<span class="blue-text">EXAMPLE:</span> 30% (add Reference) | |||
|<span class="blue-text">EXAMPLE:</span> IDH1 R123H | |||
|<span class="blue-text">EXAMPLE:</span> EGFR amplification | |||
| | |||
| | |||
| | |||
|<span class="blue-text">EXAMPLE:</span> Excludes hairy cell leukemia (HCL) (add reference). | |||
<br /> | |||
|} | |||
Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content. | |||
==Epigenomic Alterations== | |||
Epigenomic alterations have been studied in overt mantle cell lymphoma.<ref name=":11">{{Cite journal|last=Nadeu|first=Ferran|last2=Martin-Garcia|first2=David|last3=Clot|first3=Guillem|last4=Díaz-Navarro|first4=Ander|last5=Duran-Ferrer|first5=Martí|last6=Navarro|first6=Alba|last7=Vilarrasa-Blasi|first7=Roser|last8=Kulis|first8=Marta|last9=Royo|first9=Romina|date=2020-09-17|title=Genomic and epigenomic insights into the origin, pathogenesis, and clinical behavior of mantle cell lymphoma subtypes|url=https://pubmed.ncbi.nlm.nih.gov/32584970|journal=Blood|volume=136|issue=12|pages=1419–1432|doi=10.1182/blood.2020005289|issn=1528-0020|pmc=7498364|pmid=32584970}}</ref> In situ mantle cell neoplasia has not yet been studied. | |||
==Genes and Main Pathways Involved== | |||
In those individuals without an overt lymphoma, in situ mantle cell neoplasm is often considered to be, or might be similar to being a tissue counterpart of rare circulating t(11:14) positive lymphocytes in peripheral blood. While overt mantle cell lymphoma involves dysregulated cell cycle and DNA damage response pathways, the steps of the development of an overt mantle cell lymphoma from an in situ mantle cell neoplasm are not yet understood. | |||
<br /> | |||
{| class="wikitable sortable" | |||
|- | |||
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome | |||
|- | |||
|<span class="blue-text">EXAMPLE:</span> BRAF and MAP2K1; Activating mutations | |||
|<span class="blue-text">EXAMPLE:</span> MAPK signaling | |||
|<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation | |||
|- | |||
|<span class="blue-text">EXAMPLE:</span> CDKN2A; Inactivating mutations | |||
|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation | |||
|<span class="blue-text">EXAMPLE:</span> Unregulated cell division | |||
|- | |||
|<span class="blue-text">EXAMPLE:</span> KMT2C and ARID1A; Inactivating mutations | |||
|<span class="blue-text">EXAMPLE:</span> Histone modification, chromatin remodeling | |||
|<span class="blue-text">EXAMPLE:</span> Abnormal gene expression program | |||
|} | |||
==Genetic Diagnostic Testing Methods== | |||
Fluorescence ''in situ'' hybridization (FISH) for the t(11;14) translocation is the most commonly used method, in conjunction with immunohistochemistry for the overexpression of cyclin D1 in the neoplastic mantle cells. Both FISH and immunohistochemistry may be performed on paraffin-embedded tissue sections to allow identification of the abnormalities within specific cells (neoplastic) in the histologic sections. | |||
Conventional cytogenetics performed on involved lymphoid tissues is also used by some laboratories.<ref name=":4">{{Cite journal|last=Espinet|first=Blanca|last2=Solé|first2=Francesc|last3=Pedro|first3=Carme|last4=Garcia|first4=Mar|last5=Bellosillo|first5=Beatriz|last6=Salido|first6=Marta|last7=Florensa|first7=Lourdes|last8=Camacho|first8=Francisca I.|last9=Baró|first9=Teresa|date=2005-11|title=Clonal proliferation of cyclin D1-positive mantle lymphocytes in an asymptomatic patient: an early-stage event in the development or an indolent form of a mantle cell lymphoma?|url=https://pubmed.ncbi.nlm.nih.gov/16260278|journal=Human Pathology|volume=36|issue=11|pages=1232–1237|doi=10.1016/j.humpath.2005.08.021|issn=0046-8177|pmid=16260278}}</ref> | |||
==Familial Forms== | |||
Overt mantle cell lymphoma has been reported to occur in families with other family members having lymphoproliferative disorders, including chronic lymphocytic leukemia. These reports are limited to small studies and case reports of overt mantle cell lymphoma, with yet unexplained or rarely explained genetic basis for the familial occurrence of overt mantle cell lymphoma in these families. Conversely, rare cases of overt mantle cell lymphoma with germline mutations have been reported but the clinical and family history are usually not available in these reported cases wherein tumor specimens were examined, with or without germline specimen analysis. | |||
Nevertheless, an in situ mantle cell neoplasm has not been reported to occur in a familial manner or in any of the reported overt mantle cell lymphoma cases with an identifed germline alteration. | |||
The incidence and prevalence of familial overt mantle cell lymphoma are currently unknown. Also to note is that earlier instances of familial chronic lymphoproliferative disorders that included chronic lymphocytic leukemia might have included cases of mantle cell lymphoma. Specifically, the analysis for familial risk among 153,115 Swedish patients with hematologic malignancies included 18,521 patients with chronic lymphocytic leukemia (CLL), including 8,043 (43.4%; 8043/18521) CLL patients diagnosed during the same time period when mantle cell lymphoma was not yet diagnosed.<ref>{{Cite journal|last=Sud|first=Amit|last2=Chattopadhyay|first2=Subhayan|last3=Thomsen|first3=Hauke|last4=Sundquist|first4=Kristina|last5=Sundquist|first5=Jan|last6=Houlston|first6=Richard S.|last7=Hemminki|first7=Kari|date=2019-09-19|title=Analysis of 153 115 patients with hematological malignancies refines the spectrum of familial risk|url=https://pubmed.ncbi.nlm.nih.gov/31395603|journal=Blood|volume=134|issue=12|pages=960–969|doi=10.1182/blood.2019001362|issn=1528-0020|pmc=6789511|pmid=31395603}}</ref> | |||
In one Spanish study of 85 patients with overt mantle cell lymphoma, 2 (2.4%) patients with overt mantle cell lymphoma were identified that had first degree relatives with another lymphoproliferative disorder.<ref name=":12">{{Cite journal|last=Tort|first=Frederic|last2=Camacho|first2=Emma|last3=Bosch|first3=Francesc|last4=Harris|first4=Nancy Lee|last5=Montserrat|first5=Emili|last6=Campo|first6=Elias|date=2004-03|title=Familial lymphoid neoplasms in patients with mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/15020270|journal=Haematologica|volume=89|issue=3|pages=314–319|issn=1592-8721|pmid=15020270}}</ref> A third overt mantle cell lymphoma patient was reported in the same publication with familial lymphoproliferative neoplasms.<ref name=":12" /> One of those 3 patients was diagnosed as mantle cell lymphoma after re-review of previous pathology, with a previous diagnosis of chronic lymphocytic leukemia.<ref name=":12" /> | |||
In another study of 109 patients with hematologic malignancies, one case of overt mantle cell lymphoma among 7 examined cases of non-Hodgkin lymphomas was identified to harbor a 15 bp deletion in the ''CHEK2'' gene both in the overt tumor sample and in the germline.<ref name=":13">{{Cite journal|last=Hangaishi|first=Akira|last2=Ogawa|first2=Seishi|last3=Qiao|first3=Ying|last4=Wang|first4=Lili|last5=Hosoya|first5=Noriko|last6=Yuji|first6=Koichiro|last7=Imai|first7=Yoichi|last8=Takeuchi|first8=Kengo|last9=Miyawaki|first9=Shuichi|date=2002-04-15|title=Mutations of Chk2 in primary hematopoietic neoplasms|url=https://pubmed.ncbi.nlm.nih.gov/11949635|journal=Blood|volume=99|issue=8|pages=3075–3077|doi=10.1182/blood.v99.8.3075|issn=0006-4971|pmid=11949635}}</ref> Similarly, a heterozygous germline abnormality in the ''ATM'' gene was found in 1 of 4 normal tissue samples associated with 4 overt MCL tumor specimens in one study;<ref name=":14">{{Cite journal|last=Camacho|first=Emma|last2=Hernández|first2=Luis|last3=Hernández|first3=Silvia|last4=Tort|first4=Frederic|last5=Bellosillo|first5=Beatriz|last6=Beà|first6=Silvia|last7=Bosch|first7=Francesc|last8=Montserrat|first8=Emili|last9=Cardesa|first9=Antonio|date=2002-01-01|title=ATM gene inactivation in mantle cell lymphoma mainly occurs by truncating mutations and missense mutations involving the phosphatidylinositol-3 kinase domain and is associated with increasing numbers of chromosomal imbalances|url=https://pubmed.ncbi.nlm.nih.gov/11756177|journal=Blood|volume=99|issue=1|pages=238–244|doi=10.1182/blood.v99.1.238|issn=0006-4971|pmid=11756177}}</ref> in a recent whole genome sequencing study of overt mantle cell lymphoma tumor and normal specimens, germline mutations in ''ATM'' and ''CHEK2'' genes were reported in 7 and 2 cases, respectively.<ref name=":11" /> A personal history of cancer other than mantle cell lymphoma or a family history of cancer was unavailable for these cases.<ref name=":11" /><ref name=":13" /><ref name=":14" /> | |||
Notably, the germline basis of familial mantle cell lymphoma was recently described in one Chinese patient with maternally inherited Lynch syndrome (with co-segregation of a ''MLH1'' variant), paternal history of a diffuse large B-cell lymphoma in the father, and follicular lymphoma in one sibling.<ref name=":15">{{Cite journal|last=Wang|first=Xiaogan|last2=Song|first2=Yuqin|last3=Chen|first3=Wei|last4=Ding|first4=Ning|last5=Liu|first5=Weiping|last6=Xie|first6=Yan|last7=Wang|first7=Yinan|last8=Zhu|first8=Jun|last9=Zeng|first9=Changqing|date=2021-01|title=Germline variants of DNA repair genes in early onset mantle cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/33191405|journal=Oncogene|volume=40|issue=3|pages=551–563|doi=10.1038/s41388-020-01542-2|issn=1476-5594|pmid=33191405}}</ref> The index patient with overt mantle cell lymphoma also developed a colonic adenocarcinoma due to mismatch repair defects.<ref name=":15" /> | |||
==Additional Information== | |||
This disease is <u>defined/characterized</u> as detailed below: | |||
*The Latin phrase “in situ” means “in the natural or original position or place”, as per the Merriam-Webster dictionary. In normal benign lymphoid tissues, the mantle zones of lymphoid follicles are formed by naïve mature B-cells after maturation from precursor B-cells in the bone marrow. In situ mantle cell neoplasm is a pre-malignant neoplasm composed of mantle cells “in their natural position” that harbor, in addition, the t(11;14) balanced translocation characteristic of mantle cell lymphoma with the overexpression of cyclin D1 protein. | |||
*An in situ mantle cell neoplasm may precede, co-exist with, or may occur after the development of an overt mantle cell lymphoma. This pre-malignant neoplasm is more often identified in patients newly diagnosed with an overt mantle cell lymphoma in whom a retrospective examination of a prior reactive-appearing lymph node or lymphoid tissue biopsy shows the presence of in situ mantle cell neoplasm. In situ mantle cell neoplasm is only rarely diagnosed in lymph nodes diagnosed as benign or reactive lymphoid hyperplasia after biopsy for enlargement or other symptomatic causes. The diagnostic criteria for in situ mantle cell neoplasm are currently based primarily on histopathologic examination (description in the morphologic features section). The pathologic diagnosis of in situ mantle cell neoplasm requires distinguishing from two major disease entities: (1) reactive lymphoid hyperplasia, and (2) mantle cell lymphoma with a mantle zone pattern. Of note, in situ mantle cell neoplasm may co-exist with any overt mature B-cell lymphoma, including as a component of a composite lymphoma. | |||
*Synonyms/terminology - In situ mantle cell neoplasia, term used in the revised 4<sup>th</sup> edition World Health Organization classification<ref>Swerdlow SH, et al., (2017). Mantle cell lymphoma, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p290.</ref> and in the International Consensus Classification of mature lymphoid neoplasms<ref>{{Cite journal|last=Campo|first=Elias|last2=Jaffe|first2=Elaine S.|last3=Cook|first3=James R.|last4=Quintanilla-Martinez|first4=Leticia|last5=Swerdlow|first5=Steven H.|last6=Anderson|first6=Kenneth C.|last7=Brousset|first7=Pierre|last8=Cerroni|first8=Lorenzo|last9=de Leval|first9=Laurence|date=2022-06-02|title=The International Consensus Classification of Mature Lymphoid Neoplasms: A Report from the Clinical Advisory Committee|url=https://pubmed.ncbi.nlm.nih.gov/35653592|journal=Blood|pages=blood.2022015851|doi=10.1182/blood.2022015851|issn=1528-0020|pmid=35653592}}</ref>; in situ mantle cell lymphoma (historical); mantle cell lymphoma in situ (historical); mantle cell lymphoma (MCL)-like B-cells of undetermined significance<ref>{{Cite journal|last=Fend|first=Falko|last2=Cabecadas|first2=José|last3=Gaulard|first3=Philippe|last4=Jaffe|first4=Elaine S.|last5=Kluin|first5=Philip|last6=Kuzu|first6=Isinsu|last7=Peterson|first7=Loann|last8=Wotherspoon|first8=Andrew|last9=Sundström|first9=Christer|date=2012-09|title=Early lesions in lymphoid neoplasia: Conclusions based on the Workshop of the XV. Meeting of the European Association of Hematopathology and the Society of Hematopathology, in Uppsala, Sweden|url=https://pubmed.ncbi.nlm.nih.gov/24307917|journal=Journal of Hematopathology|volume=5|issue=3|doi=10.1007/s12308-012-0148-6|issn=1868-9256|pmc=3845020|pmid=24307917}}</ref> (historical) | |||
[[File:Schematic_showing_two_main_routes_for_the_development_of_overt_mantle_cell_lymphoma_from_an_in_situ_mantle_cell_neoplasm.jpg|alt=|none|thumb]]The <u>epidemiology/prevalence</u> of this disease is detailed below: | |||
*The real prevalence of in situ mantle cell neoplasm is currently unknown. The published literature for in situ mantle cell neoplasm is limited primarily to case reports, including collectively studied cases,<ref name=":0">{{Cite journal|last=Carvajal-Cuenca|first=Alejandra|last2=Sua|first2=Luz F.|last3=Silva|first3=Nhora M.|last4=Pittaluga|first4=Stefania|last5=Royo|first5=Cristina|last6=Song|first6=Joo Y.|last7=Sargent|first7=Rachel L.|last8=Espinet|first8=Blanca|last9=Climent|first9=Fina|date=2012-02|title=In situ mantle cell lymphoma: clinical implications of an incidental finding with indolent clinical behavior|url=https://pubmed.ncbi.nlm.nih.gov/22058203|journal=Haematologica|volume=97|issue=2|pages=270–278|doi=10.3324/haematol.2011.052621|issn=1592-8721|pmc=3269489|pmid=22058203}}</ref> and retrospective studies of cases of reactive lymphoid hyperplasia,<ref name=":0" /><ref name=":1">{{Cite journal|last=Adam|first=Patrick|last2=Schiefer|first2=Ana-Iris|last3=Prill|first3=Sophie|last4=Henopp|first4=Tobias|last5=Quintanilla-Martínez|first5=Leticia|last6=Bösmüller|first6=Hans-Christian|last7=Chott|first7=Andreas|last8=Fend|first8=Falko|date=2012-12|title=Incidence of preclinical manifestations of mantle cell lymphoma and mantle cell lymphoma in situ in reactive lymphoid tissues|url=https://pubmed.ncbi.nlm.nih.gov/22790016|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=25|issue=12|pages=1629–1636|doi=10.1038/modpathol.2012.117|issn=1530-0285|pmid=22790016}}</ref> lymph nodes in specimens resected for cancer,<ref name=":2">{{Cite journal|last=Bermudez|first=Glenda|last2=González de Villambrosía|first2=Sonia|last3=Martínez-López|first3=Azahara|last4=Batlle|first4=Ana|last5=Revert-Arce|first5=José B.|last6=Cereceda Company|first6=Laura|last7=Ortega Bezanilla|first7=César|last8=Piris|first8=Miguel A.|last9=Montes-Moreno|first9=Santiago|date=2016-07|title=Incidental and Isolated Follicular Lymphoma In Situ and Mantle Cell Lymphoma In Situ Lack Clinical Significance|url=https://pubmed.ncbi.nlm.nih.gov/26945339|journal=The American Journal of Surgical Pathology|volume=40|issue=7|pages=943–949|doi=10.1097/PAS.0000000000000628|issn=1532-0979|pmid=26945339}}</ref> and lymph nodes and other organized lymphoid tissues resected for any non-hematologic cause prior to the diagnosis of overt mantle cell lymphoma<ref name=":3">{{Cite journal|last=Teixeira Mendes|first=Larissa Sena|last2=Wotherspoon|first2=Andrew|date=2016-02|title=The relationship between overt and in-situ lymphoma: a retrospective study of follicular and mantle cell lymphoma cases|url=https://pubmed.ncbi.nlm.nih.gov/26052648|journal=Histopathology|volume=68|issue=3|pages=461–463|doi=10.1111/his.12753|issn=1365-2559|pmid=26052648}}</ref>. | |||
{| class="wikitable" | {| class="wikitable" | ||
|+Table 1. Cohorts of tissues studied to detect in situ mantle cell neoplasm | |+Table 1. Cohorts of tissues studied to detect in situ mantle cell neoplasm | ||
| Line 38: | Line 399: | ||
!N patients studied | !N patients studied | ||
!In situ mantle cell neoplasm, N cases detected in the study | !In situ mantle cell neoplasm, N cases detected in the study | ||
|- | |- | ||
|Retrospective study of cyclin D1 immunohistochemical stains in 100 consecutive cases of lymphoid hyperplasia to detect in situ mantle cell neoplasm<ref name=":0" /> | |Retrospective study of cyclin D1 immunohistochemical stains in 100 consecutive cases of lymphoid hyperplasia to detect in situ mantle cell neoplasm<ref name=":0" /> | ||
|100 | |100 | ||
|0 (zero) by cyclin D1 stain<ref name=":0" /> | |0 (zero) by cyclin D1 stain<ref name=":0" /> | ||
|- | |- | ||
|100 cases of reactive hyperplasia in lymph nodes studied by conventional cytogenetics<ref name=":4" | |100 cases of reactive hyperplasia in lymph nodes studied by conventional cytogenetics<ref name=":4" /> | ||
|100 | |100 | ||
|0 (zero) clonal chromosomal abnormalities by conventional cytogenetics<ref name=":4" /> | |0 (zero) clonal chromosomal abnormalities by conventional cytogenetics<ref name=":4" /> | ||
|- | |- | ||
|Retrospective study of cyclin D1 immunohistochemical stains in reactive lymph nodes in surgical resection specimens of 131 consecutive patients with no history of lymphoma during a 3-month period<ref name=":1" /> | |Retrospective study of cyclin D1 immunohistochemical stains in reactive lymph nodes in surgical resection specimens of 131 consecutive patients with no history of lymphoma during a 3-month period<ref name=":1" /> | ||
|131 | |131 | ||
|0 (zero) by cyclin D1 stain<ref name=":1" /> | |0 (zero) by cyclin D1 stain<ref name=":1" /> | ||
|- | |- | ||
|Retrospective study of lymph nodes (<u>></u> 0.5 cm size) resected with cancer in 341 consecutive patients diagnosed with colorectal (n= 201) and breast carcinoma (n= 140) during 1998-2000<ref name=":2" /> | |Retrospective study of lymph nodes (<u>></u> 0.5 cm size) resected with cancer in 341 consecutive patients diagnosed with colorectal (n= 201) and breast carcinoma (n= 140) during 1998-2000<ref name=":2" /> | ||
|341 | |341 | ||
|2 (0.58%) by cyclin D1 stain<ref name=":2" /> | |2 (0.58%) by cyclin D1 stain<ref name=":2" /> | ||
|- | |- | ||
|Retrospective study of previous resections of lymph nodes and organized lymphoid tissues due to non-hematologic indications for surgery in 126 patients with overt mantle cell lymphoma<ref name=":3" /> | |Retrospective study of previous resections of lymph nodes and organized lymphoid tissues due to non-hematologic indications for surgery in 126 patients with overt mantle cell lymphoma<ref name=":3" /> | ||
|126 | |126 | ||
|2 (1.58%) by cyclin D1 stain<ref name=":3" /> | |2 (1.58%) by cyclin D1 stain<ref name=":3" /> | ||
|- | |- | ||
|Retrospective study of all morphologically reactive lymph nodes and benign-appearing extranodal lymphoid infiltrates predating lymphoma diagnosis in patients diagnosed with overt mantle cell lymphoma<ref name=":1" /> | |Retrospective study of all morphologically reactive lymph nodes and benign-appearing extranodal lymphoid infiltrates predating lymphoma diagnosis in patients diagnosed with overt mantle cell lymphoma<ref name=":1" /> | ||
| Line 75: | Line 424: | ||
|0 (zero) cases reported with typical in situ mantle cell neoplasm by cyclin D1 stain;<ref name=":1" /> | |0 (zero) cases reported with typical in situ mantle cell neoplasm by cyclin D1 stain;<ref name=":1" /> | ||
in 6 cases, minimal infiltration by cyclin D1 positive neoplastic mantle cells was identified at extranodal sites<ref name=":1" /> | in 6 cases, minimal infiltration by cyclin D1 positive neoplastic mantle cells was identified at extranodal sites<ref name=":1" /> | ||
|}The <u>clinical features</u> of this disease are detailed below: | |||
|} | |||
* Signs and symptoms - In situ mantle cell neoplasm alone is asymptomatic and is therefore, found incidentally in lymph nodes and lymphoid tissues examined for other causes. However, since it may co-exist with an overt mantle cell lymphoma (nodal or leukemic), the signs and symptoms may vary according to the situation. The presence of B-symptoms (weight loss, fever, night sweats), fatigue, or generalized lymphadenopathy should lead to the suspicion of an overt lymphoma. | |||
* Laboratory findings - Similarly, there should be no cytopenias or lymphocytosis due to the presence of only an in situ mantle cell neoplasm. Nevertheless, small or even minute populations of light chain restricted B-cells may be detected in peripheral blood by flow cytometric immunophenotyping in the absence of increased peripheral blood lymphocyte counts. In cases of composite lymphomas, flow cytometric immunophenotypic analysis of the lymph node or lymphoid tissues may show the presence of two neoplastic B-cell populations that may prompt further or retrospective histopathologic evaluation, including for cyclin D1 immunohistochemistry on tissue sections. | |||
*In a biopsy of an enlarged lymph node or extra-nodal lymphoid tissue: in biopsies performed with suspicion of a lymphoproliferative disease, in situ mantle cell neoplasm may co-exist with another mature B-cell lymphoma or with Castleman disease. Peripheral blood and/or bone marrow may be involved in addition to the histologic presence of in situ mantle cell neoplasm in lymphoid tissues. | * The clinical features at presentation or diagnosis may depend on the situations in which the in situ mantle cell neoplasm is diagnosed, including as follows: | ||
*In previous biopsies retrospectively examined after the diagnosis of an overt mantle cell lymphoma. | **In a biopsy of an enlarged lymph node or extra-nodal lymphoid tissue: in biopsies performed with suspicion of a lymphoproliferative disease, in situ mantle cell neoplasm may co-exist with another mature B-cell lymphoma or with Castleman disease. Peripheral blood and/or bone marrow may be involved in addition to the histologic presence of in situ mantle cell neoplasm in lymphoid tissues. | ||
*As an incidental finding in lymph nodes and lymphoid tissues examined for other causes, including lymph nodes in resected cancer specimens and lymphoid tissues in inflammatory conditions. | **In previous biopsies retrospectively examined after the diagnosis of an overt mantle cell lymphoma. | ||
**As an incidental finding in lymph nodes and lymphoid tissues examined for other causes, including lymph nodes in resected cancer specimens and lymphoid tissues in inflammatory conditions. | |||
* The individual patient-level table below (with the preceding summary) shows the variability in clinical features and outcome among 31 previously reported patients diagnosed histologically with an in situ mantle cell neoplasm, along with the background in which in situ mantle cell neoplasia arose in these patients. | |||
**Notably, 29% (9/31) of these in situ mantle cell neoplasm cases occurred in a background of a composite lymphoma comprised of another mature B-cell lymphoma, with follicular lymphoma (FL) being the most frequent, followed by chronic lymphocytic leukemia (CLL), and marginal zone lymphoma (nodal and extranodal types). | |||
**Among the remaining 22 patients, 31.8% (7/22), 6 males and one female, developed an overt mantle cell lymphoma after 1-20 years. This development to an overt lymphoma occurred at 2y, 4y, 4y, 4y, 10y, and 20 y after a histologically diagnosable in situ mantle cell neoplasm for the initial overt mantle cell lymphoma and after 1 year for relapsed mantle cell lymphoma. | |||
***An additional 22.7% (5/22) received chemotherapy or radiotherapy for lymphoma. | |||
***An additional 9% (2/22) patients, both women, had leukemic involvement by mantle cell lymphoma and were alive with disease at long-term follow-up of 12 y and 19.5 y. | |||
***One additional patient (1/22, 4.5%) died at 1.3 y. | |||
***27% (6/22) patients did not develop overt lymphoma at 0.08y, 0.66 y, 1 y, 3y, 5y, and 16 y follow-up. | |||
***Follow-up not available for one (1/22) patient. | |||
*Notably, 29% (9/31) of these in situ mantle cell neoplasm cases occurred in a background of a composite lymphoma comprised of another mature B-cell lymphoma, with follicular lymphoma (FL) being the most frequent, followed by chronic lymphocytic leukemia (CLL), and marginal zone lymphoma (nodal and extranodal types). | |||
*Among the remaining 22 patients, 31.8% (7/22), 6 males and one female, developed an overt mantle cell lymphoma after 1-20 years. This development to an overt lymphoma occurred at 2y, 4y, 4y, 4y, 10y, and 20 y after a histologically diagnosable in situ mantle cell neoplasm for the initial overt mantle cell lymphoma and after 1 year for relapsed mantle cell lymphoma. | |||
**An additional 22.7% (5/22) received chemotherapy or radiotherapy for lymphoma. | |||
**An additional 9% (2/22) patients, both women, had leukemic involvement by mantle cell lymphoma and were alive with disease at long-term follow-up of 12 y and 19.5 y. | |||
**One additional patient (1/22, 4.5%) died at 1.3 y. | |||
**27% (6/22) patients did not develop overt lymphoma at 0.08y, 0.66 y, 1 y, 3y, 5y, and 16 y follow-up. | |||
**Follow-up not available for one (1/22) patient. | |||
{| class="wikitable" | {| class="wikitable" | ||
| Line 337: | Line 672: | ||
|} | |} | ||
The <u>sites of involvement</u> of this disease are detailed below: | |||
* Nodal and extranodal: virtually any lymphoid tissue sites in the body may be involved. | |||
* Bone marrow (BM) and peripheral blood (PB) may be involved by leukemic mantle cell lymphoma in patients with a histologic diagnosis of in situ mantle cell neoplasm in a lymph node or lymphoid tissue. In those cases, BM or PB involvement by neoplastic mantle cell lymphoma cells would be considered leukemic involvement (and not “in situ mantle cell neoplasm” in PB or BM). | |||
The <u>morphologic features</u> of this disease are detailed below: | |||
* In situ mantle cell neoplasm is characterized by the presence of cyclin D1 positive, SOX11 positive or negative, CD5 positive or negative, CD20 positive neoplastic B-cells in unexpanded mantle zones surrounding follicle centers in lymph nodes or extranodal lymphoid tissues. Rarely, the neoplastic mantle cells may also be present in the follicle center and identified only by immunohistochemical stains. The nodal architecture is preserved and is typically reactive-appearing except for the presence of the neoplastic in situ mantle cells that are identified by immunohistochemical staining for cyclin D1. The diagnosis can be difficult or may not even be possible to render solely by hematoxylin and eosin (H&E) stain morphology. | |||
* In situ mantle cell neoplasm must be differentiated from overt mantle cell lymphoma with a mantle zone pattern. In contrast with an in situ mantle cell neoplasm, overt mantle cell lymphoma may show any of the following features: greater follicle density than in a reactive lymph node, focal obliteration of nodal architecture, focally fused mantle zones, interfollicular neoplastic mantle cell nodules, and expanded mantle zones with monotonous or densely packed neoplastic mantle cells with slight to moderately irregular nuclear contours, slightly more open nuclear chromatin, inconspicuous nucleoli and scant cytoplasm. | |||
* Notably, in mantle cell lymphoma with a mantle zone pattern, the lymph node architecture may also be preserved, as reported.<ref name=":7">{{Cite journal|last=Richard|first=P.|last2=Vassallo|first2=J.|last3=Valmary|first3=S.|last4=Missoury|first4=R.|last5=Delsol|first5=G.|last6=Brousset|first6=P.|date=2006-09|title="In situ-like" mantle cell lymphoma: a report of two cases|url=https://pubmed.ncbi.nlm.nih.gov/16935977|journal=Journal of Clinical Pathology|volume=59|issue=9|pages=995–996|doi=10.1136/jcp.2005.030783|issn=0021-9746|pmc=1860464|pmid=16935977}}</ref> In those two cases, a high index of suspicion due to monotonous mantle cells with slight nuclear irregularity and the clinical history of lymphadenopathy at other sites led to a cyclin D1 stain and the accurate diagnosis of an overt mantle cell lymphoma.<ref name=":7" /> | |||
The <u>immunophenotype</u> of this disease is detailed below: | |||
* Immunohistochemistry for cyclin D1 is required for the diagnosis of in situ mantle cell neoplasm in virtually all cases. The neoplastic cells are CD20 positive B-cells that co-express cyclin D1. | |||
* Theoretically, cyclin D1 negative mantle cell lymphoma may also have an in situ neoplastic component but that has not yet been reported. | |||
Neoplastic cells Positive (universal) - CD20, cyclin D1 | |||
Neoplastic cells Positive (subset of cases) - CD5, SOX11 | |||
Neoplastic cells Negative (universal) - CD3 | |||
Neoplastic cells Negative (subset of cases) - CD5, SOX11 | |||
==Links== | ==Links== | ||
[[Mantle | [[HAEM5:Mantle cell lymphoma]] | ||
[[ | [[HAEM5:Leukaemic non-nodal mantle cell lymphoma]] | ||
[[Chronic | [[HAEM5:Chronic lymphocytic leukaemia/small lymphocytic lymphoma]] | ||
National Comprehensive Cancer Network (NCCN) Guidelines. B-cell Lymphomas. Version 5.2022 — July 12, 2022. Accessed July 25, 2022[https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf] | National Comprehensive Cancer Network (NCCN) Guidelines. B-cell Lymphomas. Version 5.2022 — July 12, 2022. Accessed July 25, 2022[https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf] | ||
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<nowiki>*</nowiki>''Citation of this Page'': “In situ mantle cell neoplasm”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:In_situ_mantle_cell_neoplasm</nowiki>.[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases I]] | <nowiki>*</nowiki>''Citation of this Page'': “In situ mantle cell neoplasm”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:In_situ_mantle_cell_neoplasm</nowiki>. | ||
[[Category:HAEM5]] | |||
[[Category:DISEASE]] | |||
[[Category:Diseases I]] | |||