MEIS1::NCOA1 Primitive Spindle Cell Sarcoma of the Kidney : Report of 7 Cases of a Distinctive Clinicopathologic Entity.

Primitive sarcomas harboring the MEIS1::NCOA2 gene fusion were originally described in the kidney in 2018, and subsequently reported in other organs. These variably cellular neoplasms feature monomorphic primitive plump spindle cells forming nodules and whorls in addition to nondescript fascicular, solid, and storiform patterns. They lack skeletal muscle differentiation in contrast to the primarily intraosseous rhabdomyosarcomas that harbor the same gene fusion. We describe 7 new primary primitive renal sarcomas with MEIS1::NCOA1 gene fusions. Although their morphology overlaps with that described in MEIS1::NCOA2 renal sarcoma, 3 of the 7 cases contained adipose tissue. The majority had intimately admixed entrapped cystic epithelial elements and demonstrated patchy immunoreactivity for estrogen receptor and nuclear labeling for WT1 protein, leading to the differential diagnosis of malignant mixed epithelial stromal tumor (MEST) in 4 cases and metanephric stromal tumor in one. The neoplasms demonstrate a broad spectrum of clinicopathologic features ranging from a bland low-grade neoplasm that metastasized 9 years after diagnosis to a high-grade sarcoma with multiple recurrences, ultimately leading to patient death in under 1 year. In summary, MEIS1::NCOA1 primitive sarcomas overlap with the previously described MEIS1::NCOA2 primitive renal sarcomas and represent a distinctive renal neoplasm that can be mistaken for malignant MEST. Grade ranges from low to high but even low-grade neoplasms require long-term clinical follow-up.