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.