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

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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.