ALK rearrangements occur in up to 10% of spitzoid melanocytic neoplasms. No reported cases have shown homozygous deletion of 9p21 (CDKN2A) or gains of 6p25 (RREB1) or 11q13 (CCND1), which have been associated with aggressive clinical behavior. Here we report 2 unique cases. Case 1 occurred in a 9-year-old male with a 14-mm nodule on the anterior left thigh. Biopsy revealed an ALK-positive Spitz tumor containing an irregular nodule of densely packed melanocytes with increased mitoses and loss of p16 immunoreactivity. FISH analysis showed homozygous deletion of 9p21 and gain of 6p25. Sentinel lymph node biopsy revealed small subcapsular foci of tumor. Case 2 occurred in a 7-year-old female with a 12-mm nodule on the anterior right ankle. Biopsy revealed an ALK-positive Spitz tumor containing an expansile nodule of pleomorphic epithelioid melanocytes with numerous mitoses and loss of p16 immunoreactivity. By FISH, the nodule showed homozygous deletion of 9p21 and gains of 6p25 and 11q13. Our cases show the transformation of tumors produced by an activating kinase fusion gene (ALK) through secondary genetic changes including loss of tumor suppressor activity (CDKN2A). Long-term follow up will be important to further define the behavior of these unique Spitz tumors.
Keywords: 9p21 homozygous deletion; ALK; Spitz tumor; spitzoid melanoma.
© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.