{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T20:28:43Z","timestamp":1777926523776,"version":"3.51.4"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T00:00:00Z","timestamp":1626998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Vaginal adenocarcinomas (VAC) are most often reported after intrauterine exposition to diethylstilbestrol (DES). Rarely, VACs are reported as a malignant transformation of vaginal adenosis or endometriosis, in the context of chromosomal abnormalities or malformations of the uterus or the vagina. VACs without DES exposition have a poor prognosis and a significantly worse outcome compared to vaginal squamous cell carcinomas or DES-associated VACs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>Here, we report the case of a primarily metastatic VAC, treated successfully with different lines of chemo-, antiangiogenic, antibody, and immunotherapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case<\/jats:title><jats:p>The 49-year-old patient presented in 5\/2018 with a primarily pulmonary metastatic VAC. Significant tumor reduction was seen after six cycles of carboplatin AUC5\/paclitaxel 175 mg\/m\u00b2\/bevacizumab 15 mg\/kg q3w. Bevacizumab maintenance therapy and later cisplatin mono 50 mg\/m\u00b2 q2w led to local and distant tumor progression. To identify a potential targeted therapy, new tumor biopsies were obtained. Immunohistochemistry revealed ERBB2 expression, and paclitaxel 80 mg\/m\u00b2 weekly plus trastuzumab 4 mg\/m\u00b2 respectively 2 mg\/m\u00b2 q3w was administered. Due to local and pulmonal tumor progression after 6 months and persistent ERBB2 positivity, the therapy was adjusted to trastuzumab emtansine (T-DM1) 3.6 mg\/kg q3w; however, the patient remained locally progressive after three cycles of T-DM1 and additionally showed a new bone metastasis. The new tumor biopsies revealed a combined positive score (CPS) of 2 regarding PD-L1, and pembrolizumab 200 mg q3w was initiated. The bone metastasis was radiated and treated with denosumab 120 mg q4w. Extreme tumor regression followed by stable disease was maintained for 9 months. Due to a slow locoregional progress only with new inguinal lymph node and pararectal lymph node metastases, a new tumor biopsy was taken. Molecular profiling showed an ARID1A mutation, a mutational burden of 5.1 mutations per megabase, and no genfusions. Based on these findings, therapy with PD-L1 antibodies, PD-1 antibodies, gemcitabine, or dasatinib was suggested. Therefore, administration of pembrolizumab was continued and local radiation therapy was performed. This led to a decrease in local tumor manifestations and a stable systemic disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our case demonstrates the diagnostic and therapeutic approach in a patient with primary metastatic vaginal adenocarcinoma. By tumorgenetic profiling, different lines of systemic therapy, namely, antiangiogenic therapy, monoclonal antibody therapy, immunotherapy, and local radiation therapy, were identified and successfully administered.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2021.686879","type":"journal-article","created":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T09:55:05Z","timestamp":1627034105000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Diagnostic and Therapeutic Approach in a Metastatic Vaginal Adenocarcinoma: A Case Report"],"prefix":"10.3389","volume":"12","author":[{"given":"Eva Katharina","family":"Egger","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Damian 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