Nested Melanoma and Superficial Spreading Melanoma with Prominent Nests—A Retrospective Study on Clinical Characteristics and PRAME Expression

<b>Background:</b> Nested melanoma is a rare subtype of superficial spreading melanoma. Due to its typical histology, characterized by the predominance of large melanocytic nests in an extensive horizontal spread, it is challenging to distinguish it from other benign nested melanocytic lesions. There is a need to identify additional histopathological parameters that can support the diagnosis of nested melanoma. <b>Methods:</b> In this retrospective case-control study, we analyzed immunohistochemical staining for PRAME in 10 cases of superficial spreading melanoma with prominent nests and 26 nested melanomas. Dysplastic melanocytic nevi were used as the control group. <b>Results:</b> We found a diffuse PRAME positivity (>75% of melanocytes) in 60% of superficial spreading melanoma with prominent nests and 19% of nested melanoma cases, whereas the control group showed no diffuse PRAME positivity. Furthermore, using Melan A immunohistochemistry, we found an absence of pagetoid spread in 31% of nested melanoma and single cells in suprabasal epidermal layers in 69% of cases. All cases with no pagetoid spread were PRAME negative, whereas 28% of cases with a mild pagetoid spread demonstrated diffuse PRAME positivity. <b>Conclusions:</b> We found lower PRAME positivity in nested melanoma compared to superficial spreading melanoma with prominent nests. Particularly in cases without pagetoid intraepidermal spread of melanocytes, negative PRAME staining does not rule out the possibility of nested melanoma. The diagnosis should be made based on typical histomorphological and clinical criteria.