Publication date: Mar 08, 2019
Spitzoid neoplasms typically affect young individuals and include Spitz nevus, atypical Spitz tumor and Spitzoid melanoma. Spitz tumors can exhibit gene fusions involving the receptor tyrosine kinases NTRK1, NTRK3, ALK, ROS1, RET, or MET, or, the serine-threonine kinase BRAF. Since most studies have been based on adult cases, we studied ALK fusions in Spitz nevi occurring in pediatric patients. 27 cases were screened for ALK expression by immunohistochemistry and 6 positive cases were identified. These cases were studied further using the TruSight RNA Fusion Panel and in 4 cases, exon 20 of the ALK gene was found to be fused to exon 14 of the MLPH (melanophilin) gene, a gene fusion that has only been reported in a Spitz nevus in an adult. The remaining 2 cases showed no fusion of ALK with any gene. The cases with the MLPH-ALK fusion showed a similar histology to that described for Spitz nevi with ALK fusions, with spindle-shaped and epithelioid melanocytes in fusiform nests with a plexiform growth pattern and infiltrative border. We created a breakapart FISH assay for MLPH and all 4 cases with the MLPH-ALK fusion were positive, while the other 23 cases in the study were negative. Thus, ALK and MLPH were fused only to each other in our series. Melanophilin is part of the melanosome trafficking apparatus together with MYO5a, TPM3 and RAB27a, all constitutively expressed in melanocytes. Kinase fusions involving MYO5a and TPM3 have been reported in Spitz tumors, and our series adds MLPH to this group.
Chung, C.T., Marrano, P., Swanson, D., Dickson, B.C., and Thorner, P.S. Fusion of ALK to the melanophilin gene MLPH in pediatric Spitz nevi. 21947. 2019 Hum Pathol.
- Clinical genome sequencing uncovers potentially targetable truncations and fusions of MAP3K8 in spitzoid and other melanomas.
- Dermoscopy of Spitz/Reed naevi and management.
- Giant Congenital Melanocytic Nevus Treated With Trametinib.
- Genomic testing of a single patient reveals a gene commonly mutated in pediatric melanoma
- New clinical genomic testing helps identify genomic mutations that drive childhood melanoma