CASE PRESENTATION
The patient was a 1-year-old male infant born to non-consanguineous
Japanese parents. He presented with multiple subcutaneous tumours of up
to 6.0 cm in diameter when he was 2 weeks old (Fig. 1A). No neurological
abnormality was found except the lack of movement in his right arm. His
laboratory test findings were within normal limits. An enhanced computed
tomography (CT) scan demonstrated subpleural nodular shadows in both
lung fields (Fig. 1B), and multiple low-density areas in the liver (Fig.
1C) and in the right kidney (Figure. 1D). Brain and whole spine magnetic
resonance imaging (MRI) revealed enlargement of the left side of the
medulla, the tumour of cerebellum, and an intra-axial massive tumour
with contrast enhancement in the cervico-thoracic spinal cord. Biopsy of
a cutaneous lesion was performed, and spindle cells with circular
unequal nucleus and light cytoplasm were proliferating between the
dermal collagen fibres (Fig. 2A-C). Immunohistochemical staining showed
that the cells were positive for CD68, CD4, factor XIIIa and CD163 but
negative for CD1a, CD34, CD21, CD35, and s-100 protein. In addition, ALK
D5F3 and ALK1 were positive (Fig. 2D-F). Taken together, the diagnosis
of JXG was made.
The patient did not receive any anti-tumoural treatment at first, and
his developmental retardation became increasingly accentuated in his
first year of life. He could not turn over and he uttered only a few
lallings. He showed abnormal posturing with arched his back induced by
emotional changes or subtle stimulation. Severe foot clonus was also
evoked easily by only touching his lower extremities. In addition, the
spasticity and muscle weakness of the lower extremities progressed. The
patient needed tube feeding owing to dysphagia, and he experienced
severe bronchitis 5 times and a generalised convulsive seizure. At 12
months of age, CT revealed a new lesion in an ischial bone in addition
to the lesions in the liver, kidney and lungs. The lesions in the right
lung became enlarged. MRI revealed that the CNS lesions had also become
progressed (Fig.1 E, F). The NGS-based CGP test,
FoundationOne🄬 CDx was peformed on
the specimens obtained from the
cutaneous lesion. KIF5B-ALK fusion was identified as an activating
mutation. Administration of an ALK-inhibitor for the patient was
discussed in the molecular tumour board called ‘expert panel’, and
approved by the institutional clinical review board for off-label use.
After obtaining informed consent from parents, the patient was given
alectinib at 16 months of age. Two months after the initiation of
alectinib administration, the subcutaneous lesions decreased in size.
MRI revealed that the lesions of the medulla and cerebellum achieved
complete regression (Fig. 1G). The lesion in the cervico-thoracic spinal
cord also regressed (Fig. 1 H). The patient’s condition improved, and he
started ingestion of food orally and could say a few sentences. The
spasticity and clonus of the extremities were relieved. For the 3 months
treatment periods, adverse events were only observed the localized
eczema and fever evaluated as grade 1 according to the Common
Terminology Criteria for Adverse Events version 5.0.