HAEM5:Mycosis fungoides: Difference between revisions

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{{DISPLAYTITLE:Mycosis fungoides}}
{{DISPLAYTITLE:Mycosis fungoides}}
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]


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<blockquote class="blockedit">{{Box-round|title=Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Mycosis Fungoides]].
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==Definition / Description of Disease== 
MF is a primary cutaneous T-cell lymphoma (CTCL) of epidermotropic small to medium-sized T lymphocytes presenting with skin patches that progress slowly to plaques and tumors.  The disease is postulated to be caused by skin-homing mature T cells, the majority of which are CD4-positive.  Sézary syndrome (SS) is often used to refer to the leukemic phase of mycosis fungoides.  However, recently studies have suggested that there are major genomic and phenotypical differences between these two entities. <ref>{{Cite journal|last=Campbell|first=James J.|last2=Clark|first2=Rachael A.|last3=Watanabe|first3=Rei|last4=Kupper|first4=Thomas S.|date=2010-08-05|title=Sézary syndrome and mycosis fungoides arise from distinct T-cell subsets: a biologic rationale for their distinct clinical behaviors|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2918332/|journal=Blood|volume=116|issue=5|pages=767–771|doi=10.1182/blood-2009-11-251926|issn=0006-4971|pmc=2918332|pmid=20484084}}</ref> 
==Synonyms / Terminology==
*Cutaneous T-cell lymphoma
*Alibert-Bazin syndrome
==Epidemiology / Prevalence==
*Most common CTCL subtype (54% of CTCL)<ref>{{Cite journal|last=Bradford|first=Porcia T.|last2=Devesa|first2=Susan S.|last3=Anderson|first3=William F.|last4=Toro|first4=Jorge R.|date=2009-05-21|title=Cutaneous lymphoma incidence patterns in the United States: a population-based study of 3884 cases|url=https://pubmed.ncbi.nlm.nih.gov/19279331|journal=Blood|volume=113|issue=21|pages=5064–5073|doi=10.1182/blood-2008-10-184168|issn=1528-0020|pmc=2686177|pmid=19279331}}</ref>
*Incidence 4.1/1,000,000 person/years (increasing)
**Highest in males, blacks, and those over 50 years old<ref>{{Cite journal|last=Criscione|first=Vincent D.|last2=Weinstock|first2=Martin A.|date=2007-07-01|title=Incidence of Cutaneous T-Cell Lymphoma in the United States, 1973-2002|url=http://archderm.jamanetwork.com/article.aspx?doi=10.1001/archderm.143.7.854|journal=Archives of Dermatology|language=en|volume=143|issue=7|doi=10.1001/archderm.143.7.854|issn=0003-987X}}</ref><ref name=":0">{{Cite journal|last=Agar|first=Nita Sally|last2=Wedgeworth|first2=Emma|last3=Crichton|first3=Siobhan|last4=Mitchell|first4=Tracey J.|last5=Cox|first5=Michael|last6=Ferreira|first6=Silvia|last7=Robson|first7=Alistair|last8=Calonje|first8=Eduardo|last9=Stefanato|first9=Catherine M.|date=2010-11-01|title=Survival outcomes and prognostic factors in mycosis fungoides/Sézary syndrome: validation of the revised International Society for Cutaneous Lymphomas/European Organisation for Research and Treatment of Cancer staging proposal|url=https://pubmed.ncbi.nlm.nih.gov/20855822|journal=Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology|volume=28|issue=31|pages=4730–4739|doi=10.1200/JCO.2009.27.7665|issn=1527-7755|pmid=20855822}}</ref><ref>{{Cite journal|last=Hinds|first=Ginette A.|last2=Heald|first2=Peter|date=2009-03|title=Cutaneous T-cell lymphoma in skin of color|url=https://pubmed.ncbi.nlm.nih.gov/19231637|journal=Journal of the American Academy of Dermatology|volume=60|issue=3|pages=359–375; quiz 376–378|doi=10.1016/j.jaad.2008.10.031|issn=1097-6787|pmid=19231637}}</ref>
**Can occur in children and adolescents<ref>{{Cite journal|last=Boccara|first=Olivia|last2=Blanche|first2=Stéphane|last3=de Prost|first3=Yves|last4=Brousse|first4=Nicole|last5=Bodemer|first5=Christine|last6=Fraitag|first6=Sylvie|date=2012-02|title=Cutaneous hematologic disorders in children|url=https://pubmed.ncbi.nlm.nih.gov/21445946|journal=Pediatric Blood & Cancer|volume=58|issue=2|pages=226–232|doi=10.1002/pbc.23103|issn=1545-5017|pmid=21445946}}</ref><ref>{{Cite journal|last=Fink-Puches|first=Regina|last2=Chott|first2=Andreas|last3=Ardigó|first3=Marco|last4=Simonitsch|first4=Ingrid|last5=Ferrara|first5=Gerardo|last6=Kerl|first6=Helmut|last7=Cerroni|first7=Lorenzo|date=2004-09|title=The spectrum of cutaneous lymphomas in patients less than 20 years of age|url=https://pubmed.ncbi.nlm.nih.gov/15461755|journal=Pediatric Dermatology|volume=21|issue=5|pages=525–533|doi=10.1111/j.0736-8046.2004.21500.x|issn=0736-8046|pmid=15461755}}</ref>
*Prevalence 6.4 million people
==Clinical Features==
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table. Do not delete table.'') </span>
{| class="wikitable"
|'''Signs and Symptoms'''
|<span class="blue-text">EXAMPLE:</span> Asymptomatic (incidental finding on complete blood counts)
<span class="blue-text">EXAMPLE:</span> B-symptoms (weight loss, fever, night sweats)
<span class="blue-text">EXAMPLE:</span> Fatigue
<span class="blue-text">EXAMPLE:</span> Lymphadenopathy (uncommon)
|-
|'''Laboratory Findings'''
|<span class="blue-text">EXAMPLE:</span> Cytopenias
<span class="blue-text">EXAMPLE:</span> Lymphocytosis (low level)
|}
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*Pruritic, erythematous or poikilodermatous and atrophic skin lesions with a fine scale
*Progresses over years to decades from patches to plaques and less commonly to nodules/tumors
*Rarely, MF can present with erythroderma without a diagnosis of Sézary syndrome<ref name=":2">Elder DE, Massi D, Scolyer RA, Willemze R. ''WHO Classification of Skin Tumours. 4th edn.'' Lyon, France: International Agency for Research on Cancer; 2018</ref>
*May have symptoms and/or diagnosis of other inflammatory skin diseases (e.g., eczema or psoriasis) for 3 - 4 years prior to the diagnosis of MF<ref>{{Cite journal|last=Kim|first=Youn H.|last2=Liu|first2=Howard L.|last3=Mraz-Gernhard|first3=Serena|last4=Varghese|first4=Anna|last5=Hoppe|first5=Richard T.|date=2003-07-01|title=Long-term Outcome of 525 Patients With Mycosis Fungoides and Sézary Syndrome: Clinical Prognostic Factors and Risk for Disease Progression|url=http://archderm.jamanetwork.com/article.aspx?doi=10.1001/archderm.139.7.857|journal=Archives of Dermatology|language=en|volume=139|issue=7|doi=10.1001/archderm.139.7.857|issn=0003-987X}}</ref>
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==Sites of Involvement==
*Skin     
**'''Typically sun protected areas:'''  trunk, buttock, upper thighs
**'''Some MF variants:''' head and neck, axillae and groin, or acral sites
*Advanced disease - lymph nodes, liver, spleen, lungs and blood
==Morphologic Features==
Pathologic features are variable and may be non-specific with overlap with benign reactive processes.   
*'''Early patch stage:''' superficial band-like or lichenoid infiltrate of lymphocytes and histiocytes; atypical small to medium-sized lymphocytes with cerebriform nuclei confined to basilar epidermis, may have halo and "tag" the basilar layer keratinocytes
*'''Plaque stage:''' Epidermotropism (atypical lymphocytes in epidermis without associated spongiosis); intraepidermal collections of atypical cells (Pautrier microabscesses); papillary dermal fibrosis
*'''Tumor stage:''' Dermal infiltrate more diffuse; may lose epidermotropism
Histologic large cell transformation, defined by >25% of large lymphoid cells in the dermal infiltrate, may occur at any stage, but most commonly in tumor stage mycosis fungoides.  They may be positive or negative for CD30<ref name=":2" />
==Immunophenotype==
The immunologic milieu of mycosis fungoides is predominantly that of  mature memory Th2 gene expression and associated cytokine production.  <ref>{{Cite journal|last=Wilcox|first=Ryan A.|date=2016-01|title=Cutaneous T-cell lymphoma: 2016 update on diagnosis, risk-stratification, and management|url=https://pubmed.ncbi.nlm.nih.gov/26607183|journal=American Journal of Hematology|volume=91|issue=1|pages=151–165|doi=10.1002/ajh.24233|issn=1096-8652|pmc=4715621|pmid=26607183}}</ref> 
The aberrant loss of normal T-cell antigen expression by immunohistochemistry staining is a useful ancillary test in the diagnosis of mycosis fungoides. <ref>{{Cite journal|last=Hristov|first=Alexandra C.|last2=Tejasvi|first2=Trilokraj|last3=Wilcox|first3=Ryan A.|date=2019-07-31|title=Mycosis fungoides and Sézary syndrome: 2019 update on diagnosis, risk‐stratification, and management|url=https://doi.org/10.1002/ajh.25577|journal=American Journal of Hematology|volume=94|issue=9|pages=1027–1041|doi=10.1002/ajh.25577|issn=0361-8609}}</ref>
{| class="wikitable sortable"
|-
!Finding!!Marker
|-
|Positive (T-cell lineage markers)||CD3, CD4, CD45RO
|-
|Variable expression||CD2, CD5, CD7 (often lost, significant only if 90% loss)
|-
|Markers with aberrant expression
|CD8 (CD4:CD8 ratio of 10:1 suggestive of mycosis fungoides), CD30 (may indicate transformation)
|}The majority of lymphocytes in mycosis fungoides express the αβ TCR, but rare cases have been reported that express γδ TCR.
Mycosis fungoides T-cells are T resident memory cells, exhibiting CCR4+/CLA+/L-selectin-/CCR7- expression.  <ref>{{Cite journal|last=Campbell|first=James J.|last2=Clark|first2=Rachael A.|last3=Watanabe|first3=Rei|last4=Kupper|first4=Thomas S.|date=2010-08-05|title=Sézary syndrome and mycosis fungoides arise from distinct T-cell subsets: a biologic rationale for their distinct clinical behaviors|url=https://ashpublications.org/blood/article/116/5/767/107723/S%C3%A9zary-syndrome-and-mycosis-fungoides-arise-from|journal=Blood|language=en|volume=116|issue=5|pages=767–771|doi=10.1182/blood-2009-11-251926|issn=0006-4971|pmc=PMC2918332|pmid=20484084}}</ref>
==WHO Essential and Desirable Genetic Diagnostic Criteria==
==WHO Essential and Desirable Genetic Diagnostic Criteria==
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*No consistent gene fusions
*No consistent gene fusions
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<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:
<blockquote class="blockedit">{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:
* Chromosomal Rearrangements (Gene Fusions)
* Chromosomal Rearrangements (Gene Fusions)
* Individual Region Genomic Gain/Loss/LOH
* Individual Region Genomic Gain/Loss/LOH
* Characteristic Chromosomal Patterns
* Characteristic Chromosomal Patterns
* Gene Mutations (SNV/INDEL)}}</blockquote>
* Gene Mutations (SNV/INDEL)}}</blockquote>
The staging system for mycosis fungoides, which also includes Sézary syndrome, was updated in 2007 by the International Society for Cutaneous Lymphomas (ISCL) and the European Organization of Research and Treatment of Cancer (EORTC) <ref>{{Cite journal|last=Olsen|first=Elise|last2=Vonderheid|first2=Eric|last3=Pimpinelli|first3=Nicola|last4=Willemze|first4=Rein|last5=Kim|first5=Youn|last6=Knobler|first6=Robert|last7=Zackheim|first7=Herschel|last8=Duvic|first8=Madeleine|last9=Estrach|first9=Teresa|date=2007-09-15|title=Revisions to the staging and classification of mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC)|url=https://pubmed.ncbi.nlm.nih.gov/17540844|journal=Blood|volume=110|issue=6|pages=1713–1722|doi=10.1182/blood-2007-03-055749|issn=0006-4971|pmid=17540844}}</ref>.  The revised TNMB staging of MF/SS determines management and treatment, and has been demonstrated to have prognostic significance. <ref name=":0" />  The TNMB staging forms the basis for a risk-adapted approach to treatment of mycosis fungoides.
The staging system for mycosis fungoides, which also includes Sézary syndrome, was updated in 2007 by the International Society for Cutaneous Lymphomas (ISCL) and the European Organization of Research and Treatment of Cancer (EORTC) <ref>{{Cite journal|last=Olsen|first=Elise|last2=Vonderheid|first2=Eric|last3=Pimpinelli|first3=Nicola|last4=Willemze|first4=Rein|last5=Kim|first5=Youn|last6=Knobler|first6=Robert|last7=Zackheim|first7=Herschel|last8=Duvic|first8=Madeleine|last9=Estrach|first9=Teresa|date=2007-09-15|title=Revisions to the staging and classification of mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC)|url=https://pubmed.ncbi.nlm.nih.gov/17540844|journal=Blood|volume=110|issue=6|pages=1713–1722|doi=10.1182/blood-2007-03-055749|issn=0006-4971|pmid=17540844}}</ref>.  The revised TNMB staging of MF/SS determines management and treatment, and has been demonstrated to have prognostic significance. <ref name=":0">{{Cite journal|last=Agar|first=Nita Sally|last2=Wedgeworth|first2=Emma|last3=Crichton|first3=Siobhan|last4=Mitchell|first4=Tracey J.|last5=Cox|first5=Michael|last6=Ferreira|first6=Silvia|last7=Robson|first7=Alistair|last8=Calonje|first8=Eduardo|last9=Stefanato|first9=Catherine M.|date=2010-11-01|title=Survival outcomes and prognostic factors in mycosis fungoides/Sézary syndrome: validation of the revised International Society for Cutaneous Lymphomas/European Organisation for Research and Treatment of Cancer staging proposal|url=https://pubmed.ncbi.nlm.nih.gov/20855822|journal=Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology|volume=28|issue=31|pages=4730–4739|doi=10.1200/JCO.2009.27.7665|issn=1527-7755|pmid=20855822}}</ref>  The TNMB staging forms the basis for a risk-adapted approach to treatment of mycosis fungoides.
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Mycosis fungoides does not have a defining disease specific molecular abnormality.  However, the molecular profile of mycosis fungoides and other CTCLs continues to be investigated.   
Mycosis fungoides does not have a defining disease specific molecular abnormality.  However, the molecular profile of mycosis fungoides and other CTCLs continues to be investigated.   
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<blockquote class='blockedit'>{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}</blockquote><ref>{{Cite journal|last=Mao|first=X.|last2=Lillington|first2=D.|last3=Scarisbrick|first3=J. J.|last4=Mitchell|first4=T.|last5=Czepulkowski|first5=B.|last6=Russell-Jones|first6=R.|last7=Young|first7=B.|last8=Whittaker|first8=S. J.|date=2002-09|title=Molecular cytogenetic analysis of cutaneous T-cell lymphomas: identification of common genetic alterations in Sézary syndrome and mycosis fungoides|url=https://pubmed.ncbi.nlm.nih.gov/12207585|journal=The British Journal of Dermatology|volume=147|issue=3|pages=464–475|doi=10.1046/j.1365-2133.2002.04966.x|issn=0007-0963|pmid=12207585}}</ref><blockquote class="blockedit">
<blockquote class="blockedit">{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}</blockquote><ref>{{Cite journal|last=Mao|first=X.|last2=Lillington|first2=D.|last3=Scarisbrick|first3=J. J.|last4=Mitchell|first4=T.|last5=Czepulkowski|first5=B.|last6=Russell-Jones|first6=R.|last7=Young|first7=B.|last8=Whittaker|first8=S. J.|date=2002-09|title=Molecular cytogenetic analysis of cutaneous T-cell lymphomas: identification of common genetic alterations in Sézary syndrome and mycosis fungoides|url=https://pubmed.ncbi.nlm.nih.gov/12207585|journal=The British Journal of Dermatology|volume=147|issue=3|pages=464–475|doi=10.1046/j.1365-2133.2002.04966.x|issn=0007-0963|pmid=12207585}}</ref><blockquote class="blockedit">
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Complex chromosomal abnormalities have been identified in mycosis fungoides, usually in tumor stage.  Specific translocations have not been identified.   
Complex chromosomal abnormalities have been identified in mycosis fungoides, usually in tumor stage.  Specific translocations have not been identified.   
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|}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.
|}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.


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Although no disease specific molecular abnormalities exist in mycosis fungoides, but some changes are seen more frequently than others.<ref name=":5">{{Cite journal|last=Walia|first=Ritika|last2=Yeung|first2=Cecilia C. S.|date=2020-01-22|title=An Update on Molecular Biology of Cutaneous T Cell Lymphoma|url=https://www.frontiersin.org/article/10.3389/fonc.2019.01558/full|journal=Frontiers in Oncology|volume=9|pages=1558|doi=10.3389/fonc.2019.01558|issn=2234-943X|pmc=PMC6987372|pmid=32039026}}</ref>  Single copy number variations (SCNV) are important mutational drivers for CTCLs and mycosis fungoides and are seen with greater frequency than somatic single nucleotide variations (SSNV) when compared to other cancers with significantly higher SCNV/SSNV ratios.<ref name=":6" /> <ref name=":3" />  Alterations in tumor suppressor genes are frequently implication the pathogenesis of mycosis fungoides, and more than 90% of variants arise from copy number alterations.  <ref name=":6" />   
Although no disease specific molecular abnormalities exist in mycosis fungoides, but some changes are seen more frequently than others.<ref name=":5">{{Cite journal|last=Walia|first=Ritika|last2=Yeung|first2=Cecilia C. S.|date=2020-01-22|title=An Update on Molecular Biology of Cutaneous T Cell Lymphoma|url=https://www.frontiersin.org/article/10.3389/fonc.2019.01558/full|journal=Frontiers in Oncology|volume=9|pages=1558|doi=10.3389/fonc.2019.01558|issn=2234-943X|pmc=PMC6987372|pmid=32039026}}</ref>  Single copy number variations (SCNV) are important mutational drivers for CTCLs and mycosis fungoides and are seen with greater frequency than somatic single nucleotide variations (SSNV) when compared to other cancers with significantly higher SCNV/SSNV ratios.<ref name=":6" /> <ref name=":3" />  Alterations in tumor suppressor genes are frequently implication the pathogenesis of mycosis fungoides, and more than 90% of variants arise from copy number alterations.  <ref name=":6" />   
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(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 />


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==Notes==
==Notes==
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<nowiki>*</nowiki>''Citation of this Page'': “Mycosis fungoides”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Mycosis_fungoides</nowiki>.
<nowiki>*</nowiki>''Citation of this Page'': “Mycosis fungoides”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Mycosis_fungoides</nowiki>.
[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases M]]
[[Category:HAEM5]]
[[Category:DISEASE]]
[[Category:Diseases M]]