2 | CASE REPORT
(Case 1) A 7-year-old boy, who developed diffuse papules on his
trunk and extremities 1 year previously, was admitted to our hospital
due to polydipsia and polyuria. Cranial magnetic resonance imaging (MRI)
revealed swelling of the pituitary gland and multiple T2-hyperinFig.
1A). He had no long bone involvement or other classic radiographic
findings associated with ECD. Histopathological examination of a papule
resected from his waist revealed accumulation of skin dendrocyte-derived
histiocytes, which were positive for CD68 and FXIII, and negative for
S100, CD1a, CD207 (langerin), and BRAF V600E. Therefore, the patient was
diagnosed with systemic JXG.
Although a 1-year LCH-oriented chemotherapy resulted in long-term
stabilization of the disease,6 his gait was unstable,
and he developed ataxia and cognitive deterioration 7 years after
treatment. Cranial MRI revealed widespread T2-hyperintense lesions in
the bilateral cerebellar dentate nuclei, a finding similar to typical
MRI findings in cases of LCH-associated ND (Fig. 1B). Despite monthly
intravenous immunoglobulin (IVIG) therapy, his neurological symptoms
worsened gradually. No genomic data were derived from old formalin-fixed
paraffin-embedded (FFPE) samples due to the low amount of DNA that could
be extracted.
(Case 2) A 1-year-old boy presented with fever, papules on his face,
pancytopenia, and hepatosplenomegaly. He had no long bone involvement or
other classic radiographic associated with ECD. Cranial MRI revealed no
abnormal findings. Histopathological examination of a papule and liver
biopsy revealed proliferation of histiocytes, which were positive for
CD68 and FXIII, and negative for S100, CD1a, CD207, and BRAF-V600E. He
was diagnosed with systemic JXG.
The patient underwent a 1-year LCH-oriented chemotherapy, during which
he achieved complete remission. Although he experienced relapse of the
skin and bone marrow 1 year after the initial treatment, salvage
cladribine monotherapy led to second complete remission. year after the
salvage treatment, he complained of frequent falls, and fluid attenuated
inversion recovery cranial MRI revealed bilateral hyperintense lesions
in the cerebellar dentate nuclei (Fig. 2A). Both his neurological
symptoms and radiological findings improved spontaneously (Fig. 2B).
Droplet digital polymerase chain reaction and next generation sequence
analyses of FFPE samples7,8 failed to detect the
somatic mutations frequently found in histiocytic neoplasms, including
BRAF, MAP2K1, KRAS, NRAS, CSF1R, and ALK.