Cytoplasmic ERβ Localization and NTS/NTSR1 Expression in Uterine Leiomyosarcoma: An Immunohistochemical Insight

Uterine leiomyosarcoma (LMS) is a rare and aggressive malignancy with diagnostic challenges, particularly in cases with overlapping histological features with atypical leiomyoma or smooth muscle tumors of uncertain malignant potential. We report a comparative immunohistochemical analysis of LMS, leiomyoma, and adjacent myometrium obtained from a 40-year-old woman with discordant pathological diagnoses. LMS tissue showed increased Ki67 and NTS/NTSR1 immunoreactivity together with a distinctive cytoplasmic localization of estrogen receptor beta (ERβ), in contrast to the predominantly nuclear localization observed in leiomyoma and normal myometrium. Importantly, focal areas within adjacent morphologically non-neoplastic myometrium exhibited an immunophenotype resembling LMS, including cytoplasmic ERβ localization and increased Ki67 and NTS/NTSR1 expression. These observations suggest a potential association between ERβ subcellular localization, NTS/NTSR1 signaling, and molecular alterations occurring during uterine smooth muscle tumorigenesis. However, given the single-case nature of this report, these findings should be considered exploratory and require validation in larger studies. The diagnostic message conveyed by these images may assist in the interpretation of diagnostically challenging cases and provide a basis for future investigation.