ALK-associated Spitz tumor

Activating kinase fusions have recently been described as early oncogenic events that are mutually exclusive with HRAS and BRAF mutations in Spitz tumors.

Molecular biology

 NPM1-ALK
 TPR-ALK
 CLIP1-ALK
 GTF3C2-ALK
 high frequency of chromosome 2 aberrations (where ALK resides, 63%)
 chromosome 1p loss (37%)

In a series (25602801), Spitz tumors with ALK fusions demonstrated unique histopathologic features. Clefts and small vesicle-like spaces were arrayed between plump spindled melanocytes with fibrillar cytoplasm and enlarged nuclei. These melanocytes were typically arrayed in elongated and fusiform nests with radial orientation. The tumors often had extension into the dermis or subcutis with a wedge-shaped or bulbous lower border (45% and 17%, respectively). An infiltrative growth pattern was often present at the periphery of the tumor and was highlighted by ALK immunohistochemistry.

Spitz tumors with ALK rearrangement show distinct histopathologic features that should aid in improving classification of these diagnostically challenging tumors.

References

 Clinical, Histopathologic, and Genomic Features of Spitz Tumors With ALK Fusions. Yeh I, de la Fouchardiere A, Pissaloux D, Mully TW, Garrido MC, Vemula SS, Busam KJ, LeBoit PE, McCalmont TH, Bastian BC. Am J Surg Pathol. 2015 Jan 19. PMID: 25602801