Track: Case Reports

Topic: Melanocytic Neoplasms

Abstract:

Classification of Spitz tumors can present a histopathologic challenge and the determination is often made through characteristic molecular signatures such as tyrosine kinase fusions or HRAS mutations. In cases of atypical Spitz tumors, there may be additional alterations such as CDKN2A mutations and copy-number alterations. Several immunohistochemical (IHC) stains have been developed to screen for these alterations but are less specific than molecular techniques such as fluorescence in situ hybridization (FISH) or next-generation sequencing (NGS). We provide an intriguing case series of three pediatric Spitz tumors with discordant immunohistochemical molecular correlation. All three patients (n=3) were children (ages 4, 4, and 8; female-to-male ratio 2:1) with lesions involving the right scalp, right cheek, and right lateral calf, respectively. Case 1 is diagnosed as an irritated Spitz nevus with diffuse staining for ALK by IHC; however, FISH was negative for ALK gene rearrangements. Case 2 is an atypical Spitz tumor with ALK expression by immunohistochemistry but FISH was negative for ALK gene rearrangements. Oddly, this lesion was driven by a PWWP2A::ROS1 fusion by NGS. These two cases demonstrate that an increased ALK protein expression by IHC does not always compatible with an ALK fusion event. Case 3 consists of a compound Spitz nevus with diffuse staining for pan-TRK by IHC; however, it also was negative for NTRK1/2/3 rearrangements by FISH. While IHCs may be a useful screening tool, all of these cases highlight the value of confirmatory molecular testing in Spitz tumors for definitive characterization.

Catherine Gestrich

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(251) Discordant Immunohistochemical Molecular Correlation in Three Cases of Pediatric Spitz Tumors