{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T12:17:48Z","timestamp":1769170668640,"version":"3.49.0"},"reference-count":18,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T00:00:00Z","timestamp":1614297600000},"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. Oncol."],"abstract":"<jats:p>Although cystadenocarcinoma is classified as a low-grade histological subtype of salivary gland carcinoma (SGC), recurrence and metastases sometimes develop. However, standard treatments for advanced cases have not yet been established. Here, we present a case of unresectable local recurrence and cervical lymph node metastases of cystadenocarcinoma of the parotid gland with multiple lung nodules, all of which showed complete response with only a single course of combined nivolumab and ipilimumab therapy. The patient's medical history of metastatic melanoma roused our suspicions that the multiple lung nodules were cystadenocarcinoma metastases or malignant melanoma. Combination therapy was used based on our suspected diagnosis of lung metastases of melanoma although histological examination of the lung nodules could not be performed. While various chemotherapies are used for advanced SGCs including cystadenocarcinoma, overall, the results are unsatisfactory. In contrast, there have not yet been any reports of advanced cystadenocarcinoma of the salivary gland treated with immune checkpoint inhibitors (ICIs). Given that, in our case, a single course of combined ICI therapy induced a complete response in the unresectable and lymph node metastases from the cystadenocarcinoma and the multiple lung nodules, ICIs, including combined therapy, could be a promising treatment for advanced cystadenocarcinoma.<\/jats:p>","DOI":"10.3389\/fonc.2021.618201","type":"journal-article","created":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T07:25:05Z","timestamp":1614324305000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Case Report: Complete Response of Recurrent and Metastatic Cystadenocarcinoma of the Parotid Gland With a Single Course of Combined Nivolumab and Ipilimumab Therapy"],"prefix":"10.3389","volume":"11","author":[{"given":"Yoshiyuki","family":"Nakamura","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiro","family":"Nakayama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bungo","family":"Nishimura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoko","family":"Okiyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryota","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yosuke","family":"Ishitsuka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shin","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhiro","family":"Fujisawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3946","DOI":"10.18632\/oncotarget.13952","article-title":"Management of salivary gland carcinomas - a review","volume":"8","author":"Wang","year":"2017","journal-title":"Oncotarget"},{"key":"B2","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1016\/j.anl.2015.08.012","article-title":"Cystadenocarcinoma of the salivary glands with potential lymph node metastasis","volume":"43","author":"Mukaigawa","year":"2016","journal-title":"Auris Nasus Larynx"},{"key":"B3","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1016\/j.jcms.2019.02.005","article-title":"The rare entity of cystadenocarcinoma (CAC) in parotid gland: a single-center experience","volume":"47","author":"Guo","year":"2019","journal-title":"J Craniomaxillofac Surg"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1016\/S1470-2045(19)30388-2","article-title":"Pembrolizumab versus ipilimumab in advanced melanoma (KEYNOTE-006): post-hoc 5-year results from an open-label, multicentre, randomised, controlled, phase 3 study","volume":"20","author":"Robert","year":"2019","journal-title":"Lancet Oncol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1056\/NEJMoa1412082","article-title":"Nivolumab in previously untreated melanoma without BRAF mutation","volume":"372","author":"Robert","year":"2015","journal-title":"N Engl J Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"2517","DOI":"10.1056\/NEJMoa1104621","article-title":"Ipilimumab plus dacarbazine for previously untreated metastatic melanoma","volume":"364","author":"Robert","year":"2011","journal-title":"N Engl J Med"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1535","DOI":"10.1056\/NEJMoa1910836","article-title":"Five-year survival with combined nivolumab and ipilimumab in advanced melanoma","volume":"381","author":"Larkin","year":"2019","journal-title":"N Engl J Med"},{"key":"B8","first-page":"E460","article-title":"Papillary cystadenoma and cystadenocarcinoma of salivary glands: two unusual entities","volume":"13","author":"Gallego","year":"2008","journal-title":"Med Oral Patol Oral Cir Bucal"},{"key":"B9","doi-asserted-by":"publisher","first-page":"6569","DOI":"10.2147\/OTT.S111247","article-title":"Clinicopathological characteristics, treatment, and survival outcomes of cystadenocarcinoma of the salivary gland: a population-based study","volume":"9","author":"Cai","year":"2016","journal-title":"Onco Targets Ther"},{"key":"B10","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/j.anl.2006.07.010","article-title":"Papillary cystadenocarcinoma: report of a case of high-grade histopathologic malignancy","volume":"34","author":"Cavalcante","year":"2007","journal-title":"Auris Nasus Larynx"},{"key":"B11","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.oraloncology.2016.12.016","article-title":"Systemic therapy in metastatic salivary gland carcinomas: a pathology-driven paradigm?","volume":"66","author":"Alfieri","year":"2017","journal-title":"Oral Oncol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1186\/2193-1801-2-679","article-title":"Cystadenocarcinoma of the parotid: case report of a BRAF inhibitor treatment","volume":"2","author":"Boyrie","year":"2013","journal-title":"Springerplus"},{"key":"B13","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/1758-3284-4-19","article-title":"Systemic therapy in the management of metastatic or advanced salivary gland cancers","volume":"4","author":"Lagha","year":"2012","journal-title":"Head Neck Oncol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1002\/jso.24266","article-title":"Programmed death ligand-1 expression is associated with poor disease free survival in salivary gland carcinomas","volume":"114","author":"Mukaigawa","year":"2016","journal-title":"J Surg Oncol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"2539","DOI":"10.1093\/annonc\/mdx399","article-title":"Comprehensive genomic profiles of metastatic and relapsed salivary gland carcinomas are associated with tumor type and reveal new routes to targeted therapies","volume":"28","author":"Ross","year":"2017","journal-title":"Ann Oncol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1097\/COC.0000000000000429","article-title":"Pembrolizumab for the treatment of advanced salivary gland carcinoma: findings of the phase 1b KEYNOTE-028 study","volume":"41","author":"Cohen","year":"2018","journal-title":"Am J Clin Oncol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"104359","DOI":"10.1016\/j.oraloncology.2019.07.002","article-title":"Nivolumab in patients with rare head and neck carcinomas: a single center's experience","volume":"101","author":"Kokkali","year":"2020","journal-title":"Oral Oncol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1158\/1078-0432.CCR-19-2214","article-title":"A phase II trial of pembrolizumab and vorinostat in recurrent metastatic head and neck squamous cell carcinomas and salivary gland cancer","volume":"26","author":"Rodriguez","year":"2020","journal-title":"Clin Cancer Res"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2021.618201\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T07:25:07Z","timestamp":1614324307000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2021.618201\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,26]]},"references-count":18,"alternative-id":["10.3389\/fonc.2021.618201"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2021.618201","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,26]]},"article-number":"618201"}}