Abstract:

ALK rearrangements have been identified in approximately 10% of Spitz tumors, with several ALK fusion partners described in the literature. The most commonly reported fusion partners include TPM3 and DCTN1, and other less common ones include MLPH, EEF2, MYO5A, KANK1, TPR, CLIP1, and GTF3C2. Rearrangements in ALK lead to ALK protein overexpression, which is detectable by immunohistochemistry with cytoplasmic localization. Herein, we describe a 13-year-old female who presented with a Spitz tumor that demonstrated distinctive cytoplasmic membranous localization of ALK. Next generation RNA sequencing was performed using a 43-gene targeted hybrid capture based fusion panel, which detected a rare EHBP1-ALK fusion. This translocation is predicted to result in an in-frame fusion protein that includes EHBP1 exons 2-23 and ALK exons 19-29, with a preserved ALK kinase catalytic domain. EHBP1 is an adaptor protein that links endosomes to the actin cytoskeleton and has been demonstrated to have plasma membrane targeting potential. The combined immunohistochemical staining pattern and sequencing results suggest that the 5 fusion partner may dictate the subcellular localization of the ALK fusion oncoprotein. Other studies have found that the ALK fusion partner may also drive certain histopathologic attributes in ALK-rearranged melanocytic neoplasms. This case highlights a hitherto uncharacterized ALK fusion protein with a distinct immunohistochemical pattern and expands the spectrum of ALK-rearranged melanocytic tumors. Further studies are needed to functionally characterize this EHBP1-ALK fusion.

Financial Disclosure:
No current or relevant financial relationships exist.

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Eman Bahrani, MD