CIC‐NUTM1 fusion: A case which expands the spectrum of NUT‐rearranged epithelioid malignancies. Issue 9 (14th August 2018) - Schaefer, Inga‐Marie
Abstract: NUT carcinoma (NC) shows very aggressive clinical behavior, occurs predominantly in the thorax and head and neck region of children and adults, and is defined by the presence of NUT (aka NUTM1 ) rearrangement, mostly BRD4‐NUTM1 fusion resulting from t(15;19)(q13; p13.1). So‐called "NUT variants" harbor alternate fusions between NUTM1 and BRD3, NSD3, ZNF532, or unknown partners. Rare cases of pediatric tumors with CIC‐NUTM1 fusion were recently reported in somatic soft tissue, brain, and kidney. However, such cases have not been identified in adult patients and the presence of a fusion between CIC, characteristic of CIC ‐rearranged sarcoma, and NUTM1 —a defining feature of NC—poses a diagnostic challenge. We herein report a case of malignant epithelioid neoplasm with myoepithelial features harboring CIC‐NUTM1 fusion arising in soft tissue of the head in a 60‐year‐old man. Immunohistochemistry revealed strong expression of NUT, but only weak ETV4 staining and negativity for keratins, EMA, p40, CD99, and WT1. SMARCB1 expression was retained. Fluorescence in situ hybridization and targeted next‐generation sequencing identified a CIC‐NUTM1 fusion resulting from t(15;19)(q14;q13.2). In light of morphologic features that overlap with those of NC from typical anatomical sites we have seen previously, the tumor was best classified as falling within the NC spectrum rather than CIC ‐associated sarcoma. This case highlights the emerging diagnostic challenges generated by newly detected gene fusions of unknown clinical and biologic significance. Careful integration of cytogenetic, molecular, and immunohistochemical findings with morphologic appearances in the diagnostic workup of undifferentiated neoplasms is essential.