Orbital spindle cell neoplasm with neural differentiation: diagnostic challenges in the absence of molecular confirmation.

Orbital spindle cell tumors with neural differentiation represent an uncommon and diagnostically challenging entity in clinical practice. We report the case of an 82-year-old man with a history of treated rectal adenocarcinoma, who presented with progressive orbital pain and right-sided proptosis. Computed tomography revealed a soft tissue mass located at the orbital apex, without evidence of bone erosion. Orbital exenteration was performed, and histopathological examination demonstrated an infiltrative high-grade spindle cell neoplasm with a fascicular growth pattern, moderate pleomorphism, and increased mitotic activity. Immunohistochemical analysis showed diffuse positivity for S100 and SOX10, with negative staining for melanocytic, muscular, epithelial, and vascular markers. The Ki-67 proliferative index was elevated (approximately 50%). H3K27me3 immunostaining was not available. Overall, the morphological and immunophenotypic findings were consistent with a spindle cell neoplasm with neural differentiation, suggestive of a malignant peripheral nerve sheath tumor (MPNST, malignant peripheral nerve sheath tumor). This case highlights the diagnostic limitations of these neoplasms in the absence of molecular confirmation and underscores the importance of clinicoradiologic-pathologic correlation in anatomically complex locations such as the orbit. This case emphasizes that, in the absence of molecular confirmation, the diagnosis of MPNST should be considered as an integrative hypothesis based on multidisciplinary correlation. From a surgical standpoint, this case underscores the role of radical procedures such as orbital exenteration in infiltrative orbital apex tumors with suspected high-grade malignancy and extensive involvement of deep orbital structures and neurovascular compromise.