RESUMEN
IMPORTANCE: Spitz nevi are benign melanocytic neoplasms that classically present in childhood. Isolated Spitz nevi have been associated with oncogenic gene fusions in approximately 50% of cases. The rare agminated variant of Spitz nevi, thought to arise from cutaneous genetic mosaicism, is characterized by development of clusters of multiple lesions in a segmental distribution, which can complicate surgical removal. Somatic single-nucleotide variants in the HRAS oncogene have been described in agminated Spitz nevi, most of which were associated with an underlying nevus spilus. The use of targeted medical therapy for agminated Spitz nevi is not well understood. OBSERVATIONS: A girl aged 30 months presented with facial agminated Spitz nevi that recurred rapidly and extensively after surgery. Owing to the morbidity of further surgery, referral was made to a molecular tumor board. The patient's archival nevus tissue was submitted for extended immunohistochemical analysis and genetic sequencing. Strong ROS1 protein expression was identified by immunohistochemistry. Consistent with this, analysis of whole-genome sequencing data revealed GOPC-ROS1 fusions. These results indicated likely benefit from the oral tyrosine kinase inhibitor crizotinib, which was administered at a dosage of 280 mg/m2 twice daily. An excellent response was observed in all lesions within 5 weeks, with complete flattening after 20 weeks. CONCLUSIONS AND RELEVANCE: Given the response following crizotinib treatment observed in this case, the kinase fusion was believed to be functionally consequential in the patient's agminated Spitz nevi and likely the driver mutational event for growth of her nevi. The repurposing of crizotinib for GOPC-ROS1 Spitz nevi defines a new treatment option for these lesions, particularly in cases for which surgery is relatively contraindicated.
Asunto(s)
Crizotinib , Nevo de Células Epitelioides y Fusiformes , Neoplasias Cutáneas , Proteínas Adaptadoras Transductoras de Señales , Preescolar , Crizotinib/uso terapéutico , Femenino , Proteínas de la Matriz de Golgi , Humanos , Recurrencia Local de Neoplasia , Nevo de Células Epitelioides y Fusiformes/diagnóstico , Nevo de Células Epitelioides y Fusiformes/tratamiento farmacológico , Nevo de Células Epitelioides y Fusiformes/genética , Proteínas Tirosina Quinasas , Proteínas Proto-Oncogénicas/genética , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/genéticaRESUMEN
Presentamos el caso de un niño de 2 años con múltiples nevos de Spitz agrupados sobre una mácula hiperpigmentada, que seguía un patrón en cuadrante. Los nevos de Spitz múltiples son raros y pueden presentarse de forma diseminada o agrupada. Un tercio de las lesiones agrupadas puede aparecer sobre una mácula hiperpigmentada
We present the case of a 2-year-old boy with multiple Spitz nevi clustered on a hyperpigmented macule that obeyed a quadrant distribution. Multiple Spitz nevi are rare and can be disseminated or clustered. A third of the cases of agminated lesions appear on hyperpigmented macules