NR1D1::MAML3 Fusion in an Aggressive Mesenchymal Neoplasm

Abstract

NR1D1-rearranged tumors are distinct mesenchymal neoplasms with epithelioid morphology and aggressive potential. This report presents an 85-year-old male with a slow-growing sternal mass identified as a pseudo-cyst, characterized by a dense proliferation of epithelioid tumor cells. These cells exhibited pale cytoplasm and uniform oval nuclei, with some areas of spindle cells and extensive necrosis. The mitotic count was 12 per 1.7 mm². Immunohistochemical analysis showed positivity for EMA, ERG, AE1AE3, and CK7, but negativity for SMA, desmin, CD117, CD31, SOX10, MelanA, synaptophysin, INSM1, CK20, CD34, TTF1, WT1, caldesmon, myogenin, and collagen IV. INI1 expression was preserved. The Ki67 index was high. Whole-transcriptome sequencing revealed an in-frame NR1D1::MAML3 fusion, retaining two key protein domains of NR1D1. Nine months post-diagnosis, the patient developed pleural, bilateral lung, and bone metastases. This case underscores the necessity of molecular analysis for precise tumor classification, given the tumor's varied morphological features and poor prognosis.