Sweat-gland carcinoma with neuroendocrine differentiation (SCAND): an emerging entity characterized by recurrent GATA3 frameshift extension mutations

Summary: A 70-year-old man with history of prostate cancer status-post prostatectomy and radiation developed a suprapubic wound 2 years following treatment. Imaging demonstrated a subcutaneous soft tissue mass in the suprapubic region, associated lymphadenopathy, and numerous lung nodules. An excisional biopsy was performed. Sections showed an infiltrative neoplasm filling the dermis with epidermal pagetoid spread, and extension into the subcutaneous fat with satellite metastasis. Architecturally, the tumor formed expansive lobules of cohesive epithelioid cells with intermixed trabecular areas, and foci with small rosette-like structures infiltrating collagen. Focal luminal differentiation was identified. Cytologically, the cells were characterized by dispersed granular chromatin with singular nucleoli and abundant amphophilic to clear cytoplasm. Mitoses were readily identifiable. Immunohistochemistry demonstrated the cells to be positive for neuroendocrine markers, GATA3, and focal CK7, while androgen receptor, Merkel cell polyomavirus, CK5/6, and p63 were negative. Next generation sequencing identified a GATA3 frameshift extension mutation, consistent with sweat-gland carcinoma with neuroendocrine differentiation (SCAND). The patient was treated with chemotherapy, and subsequent biopsy of enlarging pulmonary nodules confirmed SCAND metastasis. Recognition of the distinct histopathologic and molecular features will aid in the diagnosis of this emerging entity, which appears to carry a poor prognosis.