NUT carcinoma: case report and tumor microenvironment analysis using VEGFA, STAT3 and CD163 markers
Case report, Immunohistochemistry, Angiogenesis, Immunosuppression, Tumor-associated macrophage.
NUT carcinoma (NC) is a rare neoplasm with rapidly progressing affecting both sexes across all age groups, with primary tumors most commonly located in the mediastinum and genetically characterized by a translocation involving the NUTM1 gene and one of the following genes: BRD4, BRD3, BRD2, NSD3, ZNF532, or ZNF592. Generally, resistance to conventional therapies and high toxicity of available treatments are the main challenges associated with this disease. In this context, the present study aimed to characterize a case of NC diagnosed in 2019 in Natal, Rio Grande do Norte, Brazil, and to analyze the tumor microenvironment using VEGFA, STAT3, and CD163 markers through immunohistochemistry (IHC). For these purposes, the patient’s medical record and imaging exams were used for clinical characterization, hematoxylin and eosin-stained histopathological slides were obtained for capturing histopathological images, and paraffin-embedded tumor tissue samples were acquired for IHC testing. The clinical case involved a 28- year-old man with a primary tumor located in the nasal cavity and metastasis in the T11 thoracic vertebra. He underwent conventional therapies, including surgical resection, chemotherapy, and radiotherapy; however, the tumor showed resistance to these treatments, progressed rapidly, and the patient died 21 months after diagnosis. Histopathological analyses revealed a monomorphic population of round tumor cells, PMN infiltration, hemorrhagic foci, and the presence of macrophages, findings that guided the choice of three additional IHC markers, all of which showed positivity in the tumor sample. In this context, VEGFA overexpression suggests intense angiogenic activity, STAT3 presence indicates signaling that promotes resistance to apoptosis and immunosuppression, and CD163+ macrophages suggest a strong infiltration of immunosuppressive cells in the tumor microenvironment. Thus, these markers may assist in monitoring NC, providing information on metastatic potential, inflammatory activity, and tumor resistance to treatments, as well as promoting the development of immunotherapybased approaches.