Abstract

Spitz tumors comprise a diagnostic category of melanocytic neoplasms with distinct morphological, immunohistochemical and genetic features. While this group includes benign, intermediate/borderline and (rarely) malignant tumors, overall their prognosis is excellent. However, as Spitz tumors with low malignant potential often show atypical cytomorphological features, the differential diagnosis frequently includes melanoma and accurately distinguishing these entities has important prognostic and management implications.

Kinase fusions including ALK, ROS1 and TRK are characteristic of Spitz tumors and positive immunohistochemistry provides compelling evidence for Spitz histogenesis. Multiple different clones of the ALK immunostain are commercially available, including ALK-1, ALK-5A4 and ALK-D5F3, however their relative utility has not yet been defined in Spitz tumors.

This study aimed to characterize the sensitivity, specificity and staining characteristics of the ALK-1, ALK-D5F3 and ALK-5A4 clones in detecting ALK fusions in Spitz tumors.

We identified a cohort of 35 Spitz lesions showing positivity for at least one ALK antibody. In 22/35 (62%) of these cases, ALK-1 was either negative (13/35, 37%) or showed only focal weak positive staining (9/35, 25%), whereas moderate to strong staining was present with ALK-D5F3 in 34/35 cases (97%) and with ALK-5A4 in 27/35 cases (77%).

Immunohistochemistry is a useful tool for confirming the Spitz histogenesis of a melanocytic tumour when it demonstrates the presence of expression of a kinase fusion. Our data suggest that the ALK-1 antibody is significantly less sensitive than ALK-D5F3 and ALK-5A4 antibodies for the detection of ALK-rearranged Spitz tumors and we do not recommend its use for this purpose.