Sweat Gland Carcinoma With Neuroendocrine Differentiation (SCAND) Harboring a Novel GATA3 Frameshift Extension...

Sweat-gland carcinoma with neuroendocrine differentiation (SCAND) is a rare cutaneous adnexal carcinoma. Here we report a case of aggressive SCAND originating in the suprapubic area of an elderly male with lung and spinal cord metastasis. Sections from an excisional biopsy showed an infiltrative neoplasm filling the dermis with extension into the subcutaneous fat. Immunohistochemical studies showed expression of neuroendocrine markers, resulting in an initial diagnosis of metastatic neuroendocrine carcinoma. Next-generation sequencing identified a novel GATA3 frameshift extension mutation (p.F410Hfs), consistent with SCAND. Structural modeling showed the mutation in the final exon to result in an extended C-terminal domain and altered protein structure similar to other cases. We hypothesize the C-terminal protein extension may affect interactions with the adjacent zinc finger domain, potentially influencing transcriptional activity. This case expands the molecular spectrum of SCAND and supports its recognition as a distinct clinicopathologic entity. Recognition of the distinct histopathologic and molecular features aids in the diagnosis of this emerging entity, which appears to carry a poor prognosis. Further studies are needed to better understand the oncogenic role of the GATA3 extension mutations and to establish optimal management strategies.