Compendium of Cancer Genome Aberrations

HAEM5:Juvenile xanthogranuloma: Difference between revisions

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


Juvenile Xanthogranuloma (JXG) is a clonal expansion of non–Langerhans cell histiocytes with dermal macrophage phenotype.<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>
Juvenile Xanthogranuloma (JXG) is a clonal expansion of non–Langerhans cell histiocytes with dermal macrophage phenotype.  


==Synonyms / Terminology==
==Synonyms / Terminology==


Juvenile Xanthogranuloma <span style="color:#0070C0">(''Instructions: Include currently used terms and major historical ones, adding “(historical)” after the latter.'') </span>
Juvenile Xanthogranuloma  


==Epidemiology / Prevalence==
==Epidemiology / Prevalence==
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==Clinical Features==
==Clinical Features==


JXG are generally asymptomatic. Infants may present with ≥1 cutaneous, pale yellow-tan, dome-shaped papulonodular lesions, approximately5% patients show multiple lesions. These lesions begin as raised, pink to dark brown lesions that might get flatten later and heal/ scar within few months or years. A clinical subtype of JXG- benign cephalic histiocytosis occurs in head and neck of young children, asymptomatic, self-healing papular lesions. The lesions are often large, solitary and persistent in adults which needs exclusion of Erdheim–Chester disease. JXG may occur in patients with neurofibromatosis type 1, also reported in Wiskott–Aldrich syndrome.   <span style="color:#0070C0">(''Instruction: Can include references in the table. Do not delete table.'') </span>
JXG are generally asymptomatic. Infants may present with ≥1 cutaneous, pale yellow-tan, dome-shaped papulonodular lesions, approximately5% patients show multiple lesions. These lesions begin as raised, pink to dark brown lesions that might get flatten later and heal/ scar within few months or years. A clinical subtype of JXG- benign cephalic histiocytosis occurs in head and neck of young children, asymptomatic, self-healing papular lesions. The lesions are often large, solitary and persistent in adults which needs exclusion of Erdheim–Chester disease. JXG may occur in patients with neurofibromatosis type 1, also reported in Wiskott–Aldrich syndrome.
{| class="wikitable"
{| class="wikitable"
|'''Signs and Symptoms'''
|'''Signs and Symptoms'''
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==Sites of Involvement==
==Sites of Involvement==


JXG involves and is generally confined to skin, head and neck, upper trunk and proximal extremities. Rarely ocular involvement, solitary lesion noted. Other extracutaneous sites of involvement- visceral, spinal, or intracranial area also reported rarely.   <span style="color:#0070C0">(''Instruction: Indicate physical sites; <span class="blue-text">EXAMPLE:</span> nodal, extranodal, bone marrow'') </span>
JXG involves and is generally confined to skin, head and neck, upper trunk and proximal extremities. Rarely ocular involvement, solitary lesion noted. Other extracutaneous sites of involvement- visceral, spinal, or intracranial area also reported rarely.


==Morphologic Features==
==Morphologic Features==
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*Mononuclear or multinucleated histiocytes with kidney shaped/oval nuclei, variable numbers of lymphocytes, neutrophils, and eosinophils.
*Mononuclear or multinucleated histiocytes with kidney shaped/oval nuclei, variable numbers of lymphocytes, neutrophils, and eosinophils.
*Touton giant cells or foreign body giant cells may be present.
*Touton giant cells or foreign body giant cells may be present
 
{| class="wikitable"
|+'''WHO Diagnostic criteria'''
!Essential
!A circumscribed lesion comprising histiocytes (commonly foamy) lacking significant nuclear pleomorphism; dermal macrophage immunophenotype (CD68, CD163, and factor XIIIa); negativity for CD1a, CD207 (langerin), and ALK
|-
|'''Desirable'''
|Touton giant cells; clinical exclusion of Erdheim–Chester disease.
|}


==Immunophenotype==
==Immunophenotype==
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 sortable"
{| class="wikitable sortable"
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==Chromosomal Rearrangements (Gene Fusions)==
==Chromosomal Rearrangements (Gene Fusions)==
Put your text here and fill in the table


{| class="wikitable sortable"
{| class="wikitable sortable"
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!Notes
!Notes
|-
|-
|NTRK1 fusions||TPM3::NTRK1 fusion
|''NTRK1'' fusions||''TPM3::NTRK1 fusion''
PRDX1–NTRK1
''PRDX1–NTRK1''
|Unknown||Unknown
|Unknown||Unknown
|Unknown
|Unknown
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|Often associated with localized xanthogranuloma [3]
|Often associated with localized xanthogranuloma [3]
|-
|-
|BRAF fusions
|''BRAF'' fusions
|FNBP1-BRAF  
|''FNBP1-BRAF''
RNF11-BRAF
''RNF11-BRAF''


''MS4A6A::BRAF'' ''BICD2::BRAF''
''MS4A6A::BRAF'' ''BICD2::BRAF''


GAB2-BRAF
''GAB2-BRAF''
|Unknown
|Unknown
|Unknown
|Unknown
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|BRAF gene fusions are more often seen in adult and Juvenile JXG as compared with other histiocytic disorders. [10]
|BRAF gene fusions are more often seen in adult and Juvenile JXG as compared with other histiocytic disorders. [10]
|-
|-
|RET fusions
|''RET'' fusions
|NCOA4–RET rearrangement
|''NCOA4–RET'' rearrangement
|Unknown
|Unknown
|Unknown
|Unknown
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|Disseminated cutaneous–xanthogranuloma [11]
|Disseminated cutaneous–xanthogranuloma [11]
|-
|-
|SYK fusions
|''SYK'' fusions
|CLTC::SYK fusions
|''CLTC::SYK'' fusions


-exon 5 or intron 5 of SYK that lead to fusion of CLTC exon 31 to SYK exon 6
-exon 5 or intron 5 of SYK that lead to fusion of ''CLTC'' exon 31 to ''SYK'' exon 6


ETV6::SYK fusion
ETV6::SYK fusion
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Children between 2months and 2 years of age with soft tissue involvement and no or limited cutaneous involvement. [12]
Children between 2months and 2 years of age with soft tissue involvement and no or limited cutaneous involvement. [12]
|-
|-
|ALK fusions/rearrangements
|''ALK'' fusions/rearrangements
|KIF5B–ALK
|''KIF5B::ALK''
TPM3–ALK
''TPM3::ALK''
|Unknown
|Unknown
|Unknown
|Unknown
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|A unique group of infants with an aggressive form of JXG with spleen, liver, and bone marrow showed infiltration with histiocytes with activating ALK fusions. [8] KIF5B–ALK seen in systemic JXG with CNS involvement. [7] child with JXG of soft tissue
|A unique group of infants with an aggressive form of JXG with spleen, liver, and bone marrow showed infiltration with histiocytes with activating ALK fusions. [8] KIF5B–ALK seen in systemic JXG with CNS involvement. [7] child with JXG of soft tissue
|-
|-
|''MRC1-PDGFRB'' fusion
|''MRC1::PDGFRB'' fusion
|t(5;10)(q32; p12.33) translocation
|t(5;10)(q32; p12.33) translocation
|in-frame ''MRC1-PDGFRB'' gene fusion
|in-frame ''MRC1-PDGFRB'' gene fusion
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|JXG case showing large deletion of CSF1R exons 21 and 22 and  MRC1::PDGFRB fusion was a 3 month old female with large intra-abdominal tumor involving greater omentum, intestinal walls and liver hilum. Achieved complete remission without relapse during 24 years of follow up. [12] IHC staining showed diffuse expression of cyclin D1 in tumor cells.[9] . Child with  chemotherapy-refractory left chest wall JXG, MRC1::PDGFRB fusion was treated with dasatinib. [12]
|JXG case showing large deletion of CSF1R exons 21 and 22 and  MRC1::PDGFRB fusion was a 3 month old female with large intra-abdominal tumor involving greater omentum, intestinal walls and liver hilum. Achieved complete remission without relapse during 24 years of follow up. [12] IHC staining showed diffuse expression of cyclin D1 in tumor cells.[9] . Child with  chemotherapy-refractory left chest wall JXG, MRC1::PDGFRB fusion was treated with dasatinib. [12]
|-
|-
|TBL1XR1::BOD1L1 fusion  (and reciprocal BOD1L1::ABHD10)
|''TBL1XR1::BOD1L1'' fusion  (and reciprocal BOD1L1::ABHD10)
|Unknown
|Unknown
|Unknown
|Unknown
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==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 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"
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!Therapeutic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
!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).
|-
|-
|17
|17
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|}
|}
==Characteristic Chromosomal Patterns==
==Characteristic Chromosomal Patterns==
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"
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!Therapeutic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
!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).
|-
|-
|Gains on 1q and 11q
|Gains on 1q and 11q
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|}
|}
==Gene Mutations (SNV / INDEL)==
==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"
{| class="wikitable sortable"
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!Notes
!Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span> TP53; Variable LOF mutations
|''MAP2K1''
 
<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 />
|-
|MAP2K1
|p.T28I, p.L37P,p.E129Q, p.Y130C
|p.T28I, p.L37P,p.E129Q, p.Y130C
|Unknown
|Unknown
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<br />
<br />
|-
|-
|CSF1R mutations
|''CSF1R'' mutations
|Kinase driver mutations
|Kinase driver mutations
-Deletion in exon 12
-Deletion in exon 12
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[4] [12]
[4] [12]
|-
|-
|PIK3CA mutations
|''PIK3CA'' mutations
|Unknown
|Unknown
|Unknown
|Unknown
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|[4]
|[4]
|-
|-
|NF1
|''NF1''
|Unknown
|Unknown
|Unknown
|Unknown
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|
|
|-
|-
|KRAS
|''KRAS''
|p.G12D
|p.G12D
|Unknown
|Unknown
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|[4]
|[4]
|-
|-
|NRAS
|''NRAS''
|p.Q61R
|p.Q61R
|Unknown
|Unknown
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|[4]
|[4]
|-
|-
|ARAF
|''ARAF''
|p.N217K or p.F351L
|p.N217K or p.F351L
|Unknown
|Unknown
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==Epigenomic Alterations==
==Epigenomic Alterations==


Put your text here
Not listed


==Genes and Main Pathways Involved==
==Genes and Main Pathways Involved==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table. Do not delete table.'')</span>
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
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|-
|-
|''NRAS'', ''KRAS'', ''ARAF'', ''MAP2K1'', and ''CSF1R, NTRK1 and BRAF gene fusions''
|''NRAS'', ''KRAS'', ''ARAF'', ''MAP2K1'', and ''CSF1R, NTRK1 and BRAF gene fusions''
|MAPK/ERK pathway alterations
|''MAPK/ERK'' pathway alterations
|Increased cell growth, proliferation, differentiation, apoptosis and stress responses
|Increased cell growth, proliferation, differentiation, apoptosis and stress responses
|-
|-
|''PIK3CD'' mutations
|''PIK3CD'' mutations
|PI3K pathway
|''PI3K'' pathway
|Unregulated cell survival, growth, and proliferation
|Unregulated cell survival, growth, and proliferation
|}
|}
==Genetic Diagnostic Testing Methods==
==Genetic Diagnostic Testing Methods==


Put your text here
Other diagnostic tests like Next-generation sequencing (NGS), Whole exome sequencing, whole transcriptome sequencing and targeted DNA and/or RNA sequencing that can be helpful for identification of mutations in the ''RAS/RAF/MAPK/ERK'' and ''PI3K/AKT'' pathway genes or ''BRAF, ALK, RET'', and ''NTRK1'' gene rearrangements. These tests are currently not utilized for diagnosis.


==Familial Forms==
==Familial Forms==


Put your text here <span style="color:#0070C0">(''Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.'') </span>
Not listed


==Additional Information==
==Additional Information==


Put your text here
Not listed


==Links==
==Links==


Put your text placeholder here (or anywhere appropriate on the page) and use the "Link" icon at the top of the page <span style="color:#0070C0">(''Instructions: Highlight text to which you want to add a link in this section or elsewhere, select the "Link" icon at the top of the page, and search the name of the internal page to which you want to link this text, or enter an external internet address by including the "<nowiki>http://www</nowiki>." portion.'')</span>
==References ==
<references />


==References==
<br />
(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted.''</span> <span style="color:#0070C0">''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''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">) </span> <references />
 
'''EXAMPLE Book'''


#John  Chan et al., Juvenile xanthogranuloma, in: WHO Classification of Tumours Editorial Board. Haematolymphoid tumours. Lyon (France): International Agency for Research on Cancer; 2024. . (WHO classification of tumours series, 5th ed.; vol. 11). <nowiki>https://publications.iarc.who.int/637</nowiki>.
#John  Chan et al., Juvenile xanthogranuloma, in: WHO Classification of Tumours Editorial Board. Haematolymphoid tumours. Lyon (France): International Agency for Research on Cancer; 2024. . (WHO classification of tumours series, 5th ed.; vol. 11). <nowiki>https://publications.iarc.who.int/637</nowiki>.
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