HAEM5:Juvenile xanthogranuloma: Difference between revisions

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.

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.   

|Asymptomatic in the beginning

|Abnormal blood count, liver enzymes, metabolic tests

Cytopenia if bone marrow involved

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.   

*Unencapsulated, circumscribed lesions composed of classic histiocytes, large xanthomatous histiocytes, foamy histiocytes and Touton giant cells..

*Touton giant cells or foreign body giant cells may be present

|Disseminated JXG with ''GAB2::BRAF'' fusion showed favorable response to treatment with Trametinib (MEK1/2 inhibitor). [5].

|BRAF gene fusions are more often seen in adult and Juvenile JXG as compared with other histiocytic disorders. [10]

|Disseminated cutaneous–xanthogranuloma. [11]

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

Children between 2months and 2 years of age with soft tissue involvement and no or limited cutaneous involvement. [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)

|Unifocal soft tissue JXG in the nasopharynx. [12]

|Systemic juvenile xanthogranuloma. [4]

Deletions in exon 12

Multiple missense mutations in exons 9 and 10

Large deletions involving exons 21 and 22  

Alternative CSF1R mutations in exons 9 and 10

Missense mutations in exon 10 [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]

Children less than 2 years of age with soft tissue involvement. [4] [12]

|Yes,

May indicate pediatric Erdheim–Chester disease.

|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]

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.