Compendium of Cancer Genome Aberrations

HAEM5:Primary cutaneous marginal zone lymphoma: Difference between revisions

[unchecked revision][unchecked revision]
← Older edit
VisualWikitext
No edit summary
 
(8 intermediate revisions by 2 users not shown)
Line 1: Line 1:
{{DISPLAYTITLE:Primary cutaneous marginal zone lymphoma}}
{{DISPLAYTITLE:Primary cutaneous marginal zone lymphoma}}
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]


Line 10: Line 9:


Molly Walkenhorst, DO and Shivani Golem, PhD, FACMG
Molly Walkenhorst, DO and Shivani Golem, PhD, FACMG
__TOC__
==WHO Classification of Disease==
==WHO Classification of Disease==


Line 35: Line 31:
|}
|}


==Definition / Description of Disease==
==Related Terminology==
 
Primary cutaneous marginal zone lymphoma (PCMZL) is an indolent non-Hodgkin lymphoma arising in skin without evidence of extracutaneous disease at the time of diagnosis. The tumor is comprised of monotypic, CD5-negative, CD10-positive neoplastic small B-cells with monotypic plasma cells, and a variable number of reactive T-cells infiltrating the dermis, often forming follicles with reactive germinal centers. Clonal immunoglobulin rearrangement may be present, thus determining the subtype as class-switched versus non-class-switched heavy-chain immunophenotype. There must be no evidence of extracutaneous disease at the time of diagnosis and other cutaneous lymphomas must be excluded. 
 
Put your text here <span style="color:#0070C0">(''Instructions: Brief description of approximately one paragraph - include disease context relative to other WHO classification categories, diagnostic criteria if applicable, and differential diagnosis if applicable. Other classifications can be referenced for comparison.'') </span>
 
==Synonyms / Terminology==
 
*Primary cutaneous marginal zone lymphoproliferative disorder (acceptable)
*Primary cutaneous immunocytoma (historical; no longer in use)
*Primary cutaneous plasmacytoma (historical; no longer in use)
 
==Epidemiology / Prevalence==
 
*30-40% of all primary cutaneous B-cell lymphomas
*Predominantly affects adults in the fifth and sixth decades of life
*Male preponderance
*Unknown etiology in most cases
*Possible causes include chronic antigenic stimulation by intradermally applied antigens (e.g. tattoo pigments, vaccines, tick-borne bacteria, etc.)
*Association with ''Borrelia burgdorferi'' infection in endemic Europe but not associated in USA or Asia
*Patients tend to have increased gastrointestinal disorders and various autoimmune diseases as well


==Clinical Features==
*
*Present with multifocal or, less frequently, solitary red or violaceous plaques or nodules
==Sites of Involvement==
*Skin
**Most commonly on the trunk and arms
==Morphologic Features==
*Dense dermal infiltrate composed of:
**Small lymphocytes
**Plasma cells
***Located at periphery of lymphoid infiltrates or in subepidermal compartment
***Heavy chain immunophenotype show different morphologies:
****Non-class-switched forms
*****Sheets of B-lymphocytes and few T-lymphocytes
*****Scattered plasma cells
****Class-switched forms
*****Large number of reactive T-lymphocytes but can occasionally be obscured by the neoplastic B cells
*****Peripherally clustered monotypic plasma cells
**Follicles with reactive germinal centers (most cases)
**clusters of plasmacytoid dendritic cells at periphery of infiltrates
==Immunophenotype==
*Neoplastic B cells have the following immunophenotype:
{| class="wikitable sortable"
|-
!Finding!!Marker
|-
|Positive
|CD20
|-
|Positive
|CD22
|-
|Positive
|CD79a
|-
|Positive||BCL2
|-
|Negative||CD5
|-
|Negative||CD10
|-
|Negative||BCL6
|-
|Negative
|Cyclin D1
|}
* Associated reactive germinal centers B cells
** BCL6 positive
** BCL2 negative
*Plasmacytoid dendritic cells
**CD123 positive
*Plasma cells
**CD138 and CD79a positive
**Plasma cells often have monotypic expression of immunoglobulin light chains
**The immunoglobulin heavy chain can be either non-class-switched or class-switched
***Non-class-switched heavy chain
****Produce IgM
****Positive for CXCR3 expression
****Approximately 10% of cases have IgM positivity
***Class-switched heavy chain
****Produce IgG, IgA, or IgE
****No expression of CXCR3
****Approximately 90% of cases have IgG, IgA, or IgE positivity
**IgG4 expressed by plasma cells in 13-35% of cases, though not related to IgG4-related disease.
==WHO Essential and Desirable Genetic Diagnostic Criteria==
<span style="color:#0070C0">(''Instructions: The table will have the diagnostic criteria from the WHO book <u>autocompleted</u>; remove any <u>non</u>-genetics related criteria. If applicable, add text about other classification'' ''systems that define this entity and specify how the genetics-related criteria differ.'')</span>
{| class="wikitable"
|+
|WHO Essential Criteria (Genetics)*
|
|-
|WHO Desirable Criteria (Genetics)*
|
|-
|Other Classification
|
|}
<nowiki>*</nowiki>Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the [https://tumourclassification.iarc.who.int/home <u>WHO Classification of Tumours</u>].
==Related Terminology==
<span style="color:#0070C0">(''Instructions: The table will have the related terminology from the WHO <u>autocompleted</u>.)''</span>
{| class="wikitable"
{| class="wikitable"
|+
|+
|Acceptable
|Acceptable
|
|Primary cutaneous marginal zone lymphoproliferative disorder
|-
|-
|Not Recommended
|Not Recommended
|
|Primary cutaneous immunocytoma; primary cutaneous plasmacytoma
|}
|}


Line 246: Line 132:


==Individual Region Genomic Gain/Loss/LOH==
==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>
None
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Chr #!!'''Gain, Loss, Amp, LOH'''!!'''Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]'''!!'''Relevant Gene(s)'''
!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'''
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!'''Clinical Relevance Details/Other Notes'''
!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.
|-
|-
|
|
Line 299: Line 149:
|}
|}


None
==Characteristic Chromosomal or Other Global Mutational Patterns==
 
None
 
 
 
 
 
 
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable. Do not delete table.'') </span>
 
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Chr #!!Gain / Loss / Amp / LOH!!Minimal Region Genomic Coordinates [Genome Build]!!Minimal Region Cytoband
!Chromosomal Pattern
!Diagnostic Significance (Yes, No or Unknown)
!Molecular Pathogenesis
!Prognostic Significance (Yes, No or Unknown)
!Prevalence -
!Therapeutic Significance (Yes, No or Unknown)
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Notes
!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>
|
 
|
chr7:1- 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).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (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==
<br />
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>
==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"
{| class="wikitable sortable"
|-
|-
!Chromosomal Pattern
!Gene!!Genetic Alteration!!Tumor Suppressor Gene, Oncogene, Other!!Prevalence -
!Molecular Pathogenesis
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!'''Prevalence -'''
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T  
'''Common >20%, Recurrent 5-20% or Rare <5% (Disease)'''
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T'''
!Clinical Relevance Details/Other Notes
!'''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>
|<span class="blue-text">EXAMPLE:</span> ''TP53''; Variable LOF mutations
Co-deletion of 1p and 18q
<br />
|<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> Variable LOF mutations
|<span class="blue-text">EXAMPLE:</span> Common (Oligodendroglioma)
|<span class="blue-text">EXAMPLE:</span> Tumor Supressor Gene
|<span class="blue-text">EXAMPLE:</span> D, P
|<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>
|<span class="blue-text">EXAMPLE:</span> ''BRAF''; Activating mutations
Microsatellite instability - hypermutated
|<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
|
|
|<span class="blue-text">EXAMPLE:</span> Common (Endometrial carcinoma)
|<span class="blue-text">EXAMPLE:</span> P, T
|
|
|-
|
|
|-
|
|
|
|
Line 386: Line 214:
|
|
|
|
|}
|}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.
 
None
 
 
 
 


 
<br />
 
Put your text here <span style="color:#0070C0">(''EXAMPLE PATTERNS: 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. Do not delete table.'')</span>


{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Chromosomal Pattern
!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)
!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>
Co-deletion of 1p and 18q
|Yes
|No
|No
|<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).
|}
==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 and common as well as either disease defining and/or clinically significant. Can include references 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. Do not delete table.'') </span>
{| 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)
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
Line 509: Line 306:
==Additional Information==
==Additional Information==


*Favorable prognosis
This disease is <u>defined/characterized</u> as detailed below:
**5-year disease-specific survival rate >98%
 
*Recurrence is common
*Primary cutaneous marginal zone lymphoma (PCMZL) is an indolent non-Hodgkin lymphoma arising in skin without evidence of extracutaneous disease at the time of diagnosis. The tumor is comprised of monotypic, CD5-negative, CD10-positive neoplastic small B-cells with monotypic plasma cells, and a variable number of reactive T-cells infiltrating the dermis, often forming follicles with reactive germinal centers. Clonal immunoglobulin rearrangement may be present, thus determining the subtype as class-switched versus non-class-switched heavy-chain immunophenotype. There must be no evidence of extracutaneous disease at the time of diagnosis and other cutaneous lymphomas must be excluded. It has a favorable prognosis (5-year disease-specific survival rate >98%), recurrence is common, and 4% of patients will have extracutaneous spread, particularly in patients with longstanding multifocal disease.
*4% of patients will have extracutaneous spread, particularly in patients with longstanding multifocal disease
 
The <u>epidemiology/prevalence</u> of this disease is detailed below:
 
*30-40% of all primary cutaneous B-cell lymphomas
*Predominantly affects adults in the fifth and sixth decades of life
*Male preponderance
*Unknown etiology in most cases
*Possible causes include chronic antigenic stimulation by intradermally applied antigens (e.g. tattoo pigments, vaccines, tick-borne bacteria, etc.)
*Association with ''Borrelia burgdorferi'' infection in endemic Europe but not associated in USA or Asia
*Patients tend to have increased gastrointestinal disorders and various autoimmune diseases as well
 
The <u>clinical features</u> of this disease are detailed below:
 
Signs and symptoms - Present with multifocal or, less frequently, solitary red or violaceous plaques or nodules
 
Laboratory findings - N/A
 
The <u>sites of involvement</u> of this disease are detailed below:
 
*Skin (most commonly on the trunk and arms)
 
The <u>morphologic features</u> of this disease are detailed below:
 
Dense dermal infiltrate composed of:
 
*Small lymphocytes
*Plasma cells
**Located at periphery of lymphoid infiltrates or in subepidermal compartment
**Heavy chain immunophenotype show different morphologies:
***Non-class-switched forms
****Sheets of B-lymphocytes and few T-lymphocytes
****Scattered plasma cells
***Class-switched forms
****Large number of reactive T-lymphocytes but can occasionally be obscured by the neoplastic B cells
****Peripherally clustered monotypic plasma cells
*Follicles with reactive germinal centers (most cases)
*Clusters of plasmacytoid dendritic cells at periphery of infiltrates
 
The <u>immunophenotype</u> of this disease is detailed below:
 
*Positive (neoplastic B cells) - CD20, CD22, CD79a, BCL2
*Negative (neoplastic B cells) - CD5, CD10, BCL6, Cyclin D1
 
*Positive (associated reactive germinal centers B cells) - BCL6
*Negative (associated reactive germinal centers B cells) - BCL2
*Positive (plasmacytoid dendritic cells) - CD123
*Positive (plasma cells) - CD138, CD79a
**Plasma cells often have monotypic expression of immunoglobulin light chains
**The immunoglobulin heavy chain can be either non-class-switched or class-switched
***Non-class-switched heavy chain
****Produce IgM
****Positive for CXCR3 expression
****Approximately 10% of cases have IgM positivity
***Class-switched heavy chain
****Produce IgG, IgA, or IgE
****No expression of CXCR3
****Approximately 90% of cases have IgG, IgA, or IgE positivity
**IgG4 expressed by plasma cells in 13-35% of cases, though not related to IgG4-related disease.


==Links==
==Links==
Line 521: Line 375:




(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''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''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">)</span>
(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''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''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">)</span><references />
 
==Notes==
==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 [[Leadership|''<u>Associate Editor</u>'']] or other CCGA representative.  When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.
<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 [[Leadership|''<u>Associate Editor</u>'']] or other CCGA representative.  When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.
Retrieved from "https://test.ccga.io/index.php/HAEM5:Primary_cutaneous_marginal_zone_lymphoma"