Abstract:

Pediatric spitzoid tumors present a diagnostic challenge given the lack of reliable diagnostic criteria that can predict the biologic behavior of these lesions. At this time, molecular aberrations of the tumor suppressor p16 have been of particular interest as homozygous loss of 9p, which contains the gene CDKN2A, has been noted to portend significantly more aggressive disease course in AST and spitzoid melanoma. Several diagnostic algorithms suggest using p16 IHC as an initial screening tool followed by FISH only when p16 loss is detected. However, both literature and routine clinical practice abound with reports of discordant results between p16 IHC and FISH. Herein, we will compare two clinically and histologically similar cases that displayed discordant p16 IHC and CDKN2A FISH results. Two 8-year-old patients, one male and one female, presented with nodules arising on the ear. Histologically, both lesions are circumscribed with diffuse, expansile nests of epithelioid to spindled cells with voluminous cytoplasm and prominent nuclei with atypia and mitotic figures descending deeply into the dermis without evidence of maturation. P16 staining was predominantly lost with blush cytoplasmic staining in rare cells in the male patient and strong nuclear and cytoplasmic staining retained in the female patient. Follow up FISH results demonstrated no CDKN2A abnormalities for the male patient and 80% CDKN2A abnormality in the female patient. Furthermore, we retrospectively reviewed 42 atypical pediatric spitzoid tumors in pre-pubescent children (<10 years-old) and adolescents (11-19 years-old) demonstrating that p16 expression by IHC appropriately correlated with the status of CDKN2A gene by FISH in only 62% cases. In 38% of cases p16 expression did not accurately reflect CDKN2A gene status. Therefore, p16 IHC should be used with caution as a screening diagnostic tool in the decision to perform FISH analysis on ambiguous spitzoid tumors of childhood.

Financial Disclosure:
No current or relevant financial relationships exist.

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Amber Souers, MD