HAEM5:Juvenile xanthogranuloma - Revision history

Richard.Glen at 18:38, 3 February 2026

2026-02-03T18:38:08Z

Richard.Glen: Removed redirect to CNS5:Juvenile xanthogranuloma

2026-02-03T18:36:19Z

Removed redirect to CNS5:Juvenile xanthogranuloma

← Older revision		Revision as of 13:36, 3 February 2026
Line 1:		Line 1:
	~~#REDIRECT~~[[~~CNS5~~:~~Juvenile xanthogranuloma~~]]		egory:DISEASE]]\n[[Category:Diseases J]]"}}}

Richard.Glen: Redirected page to CNS5:Juvenile xanthogranuloma

2026-02-03T18:30:25Z

Redirected page to CNS5:Juvenile xanthogranuloma

Show changes

Greg.Corboy1: Removed display title text

2026-01-13T12:47:20Z

Removed display title text

← Older revision		Revision as of 07:47, 13 January 2026
Line 1:		Line 1:
	~~{{DISPLAYTITLE:Juvenile xanthogranuloma}}~~

	==Primary Author(s)*==		==Primary Author(s)*==

Greg.Corboy1: Removed under construction

2026-01-13T12:46:16Z

Removed under construction

← Older revision		Revision as of 07:46, 13 January 2026
Line 1:		Line 1:
	{{DISPLAYTITLE:Juvenile xanthogranuloma}}		{{DISPLAYTITLE:Juvenile xanthogranuloma}}

	~~[[HAEM5:Table_of_Contents\|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]~~

	~~{{Under Construction}}~~

	==Primary Author(s)*==		==Primary Author(s)*==

Greg.Corboy1 at 12:44, 13 January 2026

2026-01-13T12:44:52Z

← Older revision		Revision as of 07:44, 13 January 2026
Line 4:		Line 4:

	{{Under Construction}}		{{Under Construction}}

	<span style="color:#0070C0">(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ HGVS-based nomenclature for variants], 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 to a table, click within the table and select the > symbol that appears to be given options. 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)*==

Greg.Corboy1: Corrected typos and edited for clarity regarding fusions.

2026-01-13T12:08:09Z

Corrected typos and edited for clarity regarding fusions.

← Older revision		Revision as of 07:08, 13 January 2026
Line 156:		Line 156:
	\|''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~~		Breakpoints in exon 5 or intron 5 of SYK (resulting in alternative splicing through exon skipping) lead to the fusion of SYK exon 6 to ''CLTC'' exon 31

	ETV6::SYK fusion		ETV6::SYK fusion
Line 175:		Line 175:
	\|Unknown		\|Unknown
	\|A pediatric patient with systemic JXG, CNS lesions and KIF5B-ALK fusion achieved clinical improvement with ALK-inhibitor Alectinib therapy. [7]		\|A pediatric patient with systemic JXG, CNS lesions and KIF5B-ALK fusion achieved clinical improvement with ALK-inhibitor Alectinib therapy. [7]
	\|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]
	\|-		\|-
	\|''MRC1::PDGFRB'' fusion		\|''MRC1::PDGFRB'' fusion
Line 185:		Line 185:
	\|Unknown		\|Unknown
	\|Targeted therapy of treatment resistant systemic JXG with Dasatinib showed a steady and dramatic clinical response with a reduction in the size of the primary tumor. [9]		\|Targeted therapy of treatment resistant systemic JXG with Dasatinib showed a steady and dramatic clinical response with a reduction in the size of the primary tumor. [9]
	\|A 3 month old female with a large JXG intra-abdominal tumor involving the greater omentum, intestinal walls and hepatic hilum achieved complete remission without relapse during 24 years of follow up. Testing showed a large deletion of exons 21 and 22 of CSF1R in parallel with MRC1::PDGFRB fusion. [12] IHC staining showed diffuse expression of cyclin D1 in tumor cells.[9] A child with chemotherapy-refractory left chest wall JXG, MRC1::PDGFRB fusion was treated with dasatinib. [12]		\|A 3 month old female with a large JXG intra-abdominal tumor involving the greater omentum, intestinal walls and hepatic hilum achieved complete remission without relapse during 24 years of follow up. Testing showed a large deletion of exons 21 and 22 of CSF1R in parallel with MRC1::PDGFRB fusion. [12] IHC staining showed diffuse expression of cyclin D1 in tumor cells.[9] A child with chemotherapy-refractory left chest wall JXG, MRC1::PDGFRB fusion was treated with dasatinib and demonstrated clinical and radiological reduction in size and metabolic activity of the tumor mass. [12]
	\|-		\|-
	\|''TBL1XR1::BOD1L1'' fusion (and reciprocal BOD1L1::ABHD10)		\|''TBL1XR1::BOD1L1'' fusion (and reciprocal BOD1L1::ABHD10)

Greg.Corboy1: Greg Corboy editing initial page

2025-11-13T11:54:46Z

Greg Corboy editing initial page

← Older revision		Revision as of 06:54, 13 November 2025
Line 268:		Line 268:
	\|Unknown		\|Unknown
	\|May respond to targeted treatment with (MEK) inhibitors. [5]		\|May respond to targeted treatment with (MEK) inhibitors. [5]
	\|Systemic juvenile xanthogranuloma [4]		\|Systemic juvenile xanthogranuloma. [4]<br />
	<br />
	\|-		\|-
	\|''CSF1R'' mutations		\|''CSF1R'' mutations
	\|Kinase driver mutations		\|Kinase driver mutations
	~~-Deletion~~ in exon 12		Deletions in exon 12

	~~-multiple~~ missense mutations in exons 9 and 10		Multiple missense mutations in exons 9 and 10

	~~-large deletion of~~ exons 21 and 22		Large deletions involving exons 21 and 22

	-Alternative CSF1R mutations in exons 9 and 10		Alternative CSF1R mutations in exons 9 and 10

	-Missense mutations in exon 10		Missense mutations in exon 10 [12]

	[12]
	\|Unknown		\|Unknown
	\|Unknown		\|Unknown
Line 290:		Line 287:
	\|Unknown		\|Unknown
	\|CSF-1R-specific small-molecule inhibitors Pexidartinib and BLZ945 is being studied. [11]		\|CSF-1R-specific small-molecule inhibitors Pexidartinib and BLZ945 is being studied. [11]
	\| -Exon 10 mutations affect the extracellular region of CSF-1R and might enhance receptor dimerization. [12]		\| Exon 10 mutations affect the extracellular region of CSF-1R and might enhance receptor dimerization. [12]
	-Large deletion of CSF1R exons 21 and 22 affects the intracellular c-CBL binding domain leading to defective receptor ubiquitination, and degradation [12]		Large deletion of CSF1R exons 21 and 22 affects the intracellular c-CBL binding domain leading to defective receptor ubiquitination, and degradation. [12]


	Children less than ~~2years~~ of age with soft tissue involvement		Children less than 2 years of age with soft tissue involvement. [4] [12]
	[4] [12]
	\|-		\|-
	\|''PIK3CA'' mutations		\|''PIK3CA'' mutations
Line 315:		Line 310:
	\|Unknown		\|Unknown
	\|Unknown		\|Unknown
	\|		\|Neurofibromatosis is associated with JXG.
	\|-		\|-
	\|''KRAS''		\|''KRAS''
Line 357:		Line 352:
	\|Unknown.		\|Unknown.
	Targeted therapy with BRAF-inhibitor dabrafenib needs to be studied further .		Targeted therapy with BRAF-inhibitor dabrafenib needs to be studied further .
	\|~~Pediatric cases with~~ systemic JXG with CNS involvement and ''BRAF'' V600E mutations show male preponderance and are associated with aggressive disease at presentation. ~~These cases needs to be followed up, they probably represent~~ Erdheim–Chester disease.[6]		\|Cases of systemic pediatric JXG with CNS involvement and ''BRAF'' V600E mutations show male preponderance and are associated with aggressive disease at presentation. Erdheim–Chester disease is an important differential diagnosis. [6]
	\|}		\|}
	Note: A more extensive list of mutations can be found in Bioportal (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.		Note: A more extensive list of mutations can be found in Bioportal (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.
Line 380:		Line 375:
	==Genetic Diagnostic Testing Methods==		==Genetic Diagnostic Testing Methods==

	~~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 given there are no recognized molecular diagnostic features~~.		Sequencing is not relevant to establishing the diagnosis, given there are no recognized molecular diagnostic features, but whole exome sequencing, whole transcriptome sequencing, and targeted DNA and/or RNA sequencing may identify ''BRAF, ALK, RET'', and ''NTRK1'' gene rearrangements or other variants that disrupt the ''RAS/RAF/MAPK/ERK'' and ''PI3K/AKT'' pathways.

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

Greg.Corboy1: Greg Corboy editing initial page

2025-11-13T11:12:16Z

Greg Corboy editing initial page

Show changes

Greg.Corboy1: Greg Corboy editing initial page

2025-11-13T11:07:39Z

Greg Corboy editing initial page

← Older revision		Revision as of 06:07, 13 November 2025
Line 44:		Line 44:
	==Epidemiology / Prevalence==		==Epidemiology / Prevalence==

	Juvenile Xanthogranuloma is a rare histiocytic neoplasm comprising about 0.5% of all pediatric tumors~~, seldom~~ seen in in adults. 20-35% cases are congenital~~, shows male predilection~~ and ~~mostly~~ (>70% cases) arise during the first year of life.		Juvenile Xanthogranuloma is a rare histiocytic neoplasm comprising about 0.5% of all pediatric tumors. It is rarely seen in adults. 20-35% cases are congenital and JXG more commonly affects males. Predominantly (>70%) cases arise during the first year of life.

	==Clinical Features==		==Clinical Features==

	JXG lesions are generally asymptomatic; their appearance is typically different in adult and pediatric settings. Infants may present with ≥1 cutaneous, pale yellow-tan, dome-shaped papulonodular lesions. Approximately 5% of patients present with multiple lesions. Typically lesions begin as raised, pink to dark-brown lesions that may become less elevated over time. Spontaneous resolution of some lesions, leaving residual scarring or wrinkling, may occur after months or years. A clinical subtype of JXG called 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; in this context Erdheim–Chester disease is an important differential diagnosis. JXG may occur in patients with neurofibromatosis type 1 and is also reported in Wiskott–Aldrich syndrome.		JXG lesions are generally asymptomatic; their appearance is typically different in adult and pediatric settings. Infants may present with ≥1 cutaneous, pale yellow-tan, dome-shaped papulonodular lesions. Approximately 5% of patients present with multiple lesions. Typically lesions begin as raised, pink to dark-brown lesions that may become less elevated over time. Spontaneous resolution of some lesions, leaving residual scarring or wrinkling, may occur after months or years. A clinical subtype of JXG called 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; in this context Erdheim–Chester disease is an important differential diagnosis. JXG may occur in patients with neurofibromatosis type 1 and is also reported in the context of Wiskott–Aldrich syndrome.
	{\| class="wikitable"		{\| class="wikitable"
	\|'''Signs and Symptoms'''		\|'''Signs and Symptoms'''
Line 63:		Line 63:
	==Sites of Involvement==		==Sites of Involvement==

	JXG involves and is generally confined to skin, head and neck, upper trunk and proximal extremities. Solitary ocular lesions occur but are rare. Other rare extracutaneous sites of involvement include viscera, and ~~paraspinal~~ or intracranial regions.		JXG involves and is generally confined to skin, head and neck, upper trunk and proximal extremities. Solitary ocular lesions occur but are rare. Other rare extracutaneous sites of involvement include viscera, and spinal or intracranial regions.

	==Morphologic Features==		==Morphologic Features==
Line 124:		Line 124:
	\|Unknown		\|Unknown
	\|Unknown		\|Unknown
	\|Often associated with localized xanthogranuloma [3]		\|Often associated with localized xanthogranuloma. [3]
	\|-		\|-
	\|''BRAF'' fusions		\|''BRAF'' fusions
Line 147:		Line 147:
	\|Unknown		\|Unknown
	\|Treatment with RET inhibitor Selpercatinib showed dramatic resolution of disfiguring skin lesions. [11]		\|Treatment with RET inhibitor Selpercatinib showed dramatic resolution of disfiguring skin lesions. [11]
	\|Disseminated cutaneous–xanthogranuloma [11]		\|Disseminated cutaneous–xanthogranuloma. [11]
	\|-		\|-
	\|''SYK'' fusions		\|''SYK'' fusions
Line 181:		Line 181:
	\|Unknown		\|Unknown
	\|Targeted therapy of treatment resistant systemic JXG with Dasatinib showed a steady and dramatic clinical response with a reduction in the size of the primary tumor. [9]		\|Targeted therapy of treatment resistant systemic JXG with Dasatinib showed a steady and dramatic clinical response with a reduction in the size of the primary tumor. [9]
	\|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)
Line 190:		Line 190:
	\|Unknown		\|Unknown
	\|Unknown		\|Unknown
	\|Unifocal soft tissue JXG in the nasopharynx [12]		\|Unifocal soft tissue JXG in the nasopharynx. [12]
	\|}		\|}

Line 264:		Line 264:
	\|Unknown		\|Unknown
	\|May respond to targeted treatment with (MEK) inhibitors. [5]		\|May respond to targeted treatment with (MEK) inhibitors. [5]
	\|Systemic juvenile xanthogranuloma [4]		\|Systemic juvenile xanthogranuloma. [4]
	<br />		<br />
	\|-		\|-
	\|''CSF1R'' mutations		\|''CSF1R'' mutations
	\|Kinase driver mutations		\|Kinase driver mutations
	~~-Deletion~~ in exon 12		Deletions in exon 12

	~~-multiple~~ missense mutations in exons 9 and 10		Multiple missense mutations in exons 9 and 10

	~~-large deletion of~~ exons 21 and 22		Large deletions involving exons 21 and 22

	-Alternative CSF1R mutations in exons 9 and 10		Alternative CSF1R mutations in exons 9 and 10

	-Missense mutations in exon 10		Missense mutations in exon 10 [12]

	[12]
	\|Unknown		\|Unknown
	\|Unknown		\|Unknown
Line 286:		Line 284:
	\|Unknown		\|Unknown
	\|CSF-1R-specific small-molecule inhibitors Pexidartinib and BLZ945 is being studied. [11]		\|CSF-1R-specific small-molecule inhibitors Pexidartinib and BLZ945 is being studied. [11]
	\| -Exon 10 mutations affect the extracellular region of CSF-1R and might enhance receptor dimerization. [12]		\| Exon 10 mutations affect the extracellular region of CSF-1R and might enhance receptor dimerization. [12]
	-Large deletion of CSF1R exons 21 and 22 affects the intracellular c-CBL binding domain leading to defective receptor ubiquitination, and degradation [12]

			Large deletion of CSF1R exons 21 and 22 affects the intracellular c-CBL binding domain leading to defective receptor ubiquitination, and degradation. [12]


	Children less than ~~2years~~ of age with soft tissue involvement		Children less than 2 years of age with soft tissue involvement. [4] [12]
	[4] [12]
	\|-		\|-
	\|''PIK3CA'' mutations		\|''PIK3CA'' mutations
Line 349:		Line 348:
	\|Unknown		\|Unknown
	\|Yes,		\|Yes,
	~~Might represent~~ pediatric Erdheim–Chester disease.		May indicate pediatric Erdheim–Chester disease.
	\|Yes		\|Yes
	Aggressive course		Aggressive course
	\|Unknown.		\|Unknown.
	Targeted therapy with BRAF-inhibitor dabrafenib needs to be studied further .		Targeted therapy with BRAF-inhibitor dabrafenib needs to be studied further .
	\|Pediatric cases with systemic JXG with CNS involvement and ''BRAF'' V600E mutations show male preponderance and are associated with aggressive disease at presentation. ~~These~~ cases ~~needs to be followed up, they probably represent~~ Erdheim–Chester disease.[6]		\|Pediatric cases with systemic JXG with CNS involvement and ''BRAF'' V600E mutations show male preponderance and are associated with aggressive disease at presentation. In such cases Erdheim–Chester disease is an important differential diagnosis. [6]
	\|}		\|}
	Note: A more extensive list of mutations can be found in Bioportal (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.		Note: A more extensive list of mutations can be found in Bioportal (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.
Line 377:		Line 376:
	==Genetic Diagnostic Testing Methods==		==Genetic Diagnostic Testing Methods==

	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.		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==