NR1D1exon6::MAML2exon2 Fusion-Positive Sarcomas: Two Additional Cases of an Emerging Soft Tissue Tumor Entity

NR1D1::MAML1/L2 fusion-positive sarcomas constitute an emerging subtype of undifferentiated sarcomas, histopathologically composed of epithelioid and spindle cells. We describe two NR1D1exon6::MAML2exon2 fusion-positive sarcomas occurring in the occipital region of a 53-year-old female patient and the left shoulder of a 25-year-old male patient. Histopathologically, the former tumor comprised spindle and polygonal-shaped/epithelioid cells, while the latter comprised epithelioid cells. Immunohistochemically, the cells of the first tumor were positive for keratin cocktail (AE1/AE3), EMA, and p40. The other tumor lacked any epithelial marker immunoexpression and showed SATB2 positivity. Both the tumors were SMARCB1 proficient. While the former tumor was initially diagnosed as a sarcomatoid carcinoma, the latter was diagnosed as an undifferentiated sarcoma. Both patients underwent surgical resection as the primary treatment. One patient received adjuvant radiotherapy, whereas the other received ifosfamide and doxorubicin-based therapy. However, both the patients developed progressive disease, with one developing lung metastasis during relapse. There was a suboptimal response to chemotherapy in both patients. This study highlights the clinicopathological features of two rare and emerging sarcomas. It further emphasizes the value of high-throughput molecular testing, such as next-generation sequencing in the undifferentiated epithelioid, and spindle-cell sarcomas to identify the prognostic subtypes and differentiate these neoplasms from their histopathological mimics.