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      Androgen Deprivation Therapy for Intracranial Metastasis of a Salivary Duct Carcinoma: Case Report

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          Abstract

          Salivary duct carcinoma (SDC) is a rare subtype of salivary cancers associated with androgen receptor and human epidermal growth factor receptor 2 (HER2/neu) overexpression. It shows a high propensity to give rise to distant metastases mainly to the lung, the bone, and the liver. Intracranial metastases are rare. We report the case of a 61-year-old male patient with SDC developing intracranial metastases. Unresponsive to radiotherapy and anti-HER/neu targeted therapy the intracranial metastases showed a very good partial remission to androgen deprivation therapy with goserelin acetate. This case demonstrates the potential of a highly targeted therapy with a relatively cheap and well-known drug in a patient with a rare disease without other good therapeutic options, which is a good example of modern, personalized medicine.

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          Androgen receptor-positive salivary duct carcinoma: a disease entity with promising new treatment options.

          Rafke Schoffelen, Pieter J Slootweg, Berit M. Verbist … (2011)
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            Salivary duct carcinoma: the predominance of apocrine morphology, prevalence of histologic variants, and androgen receptor expression.

            Lindsay Williams, Lester Thompson, Raja R. Seethala … (2015)
            Salivary duct carcinoma (SDC) is a prototypic aggressive salivary gland carcinoma. Our aim is to determine the prevalence of histologic variants (micropapillary, basal-like) and androgen receptor (AR) expression in a large multi-institutional series of SDC. AR status was determined by immunohistochemistry (IHC). Most SDCs were characterized by an apocrine phenotype and AR expression. Cases with a nonapocrine phenotype and AR-negative status were studied by additional IHC and fluorescence in situ hybridization for ETV6 or MYB/NFIB. The diagnosis of SDC was confirmed in 187 of 199 (94%) cases. Variant morphologies were identified in 12 cases: micropapillary (n=6), sarcomatoid (n=3), mucinous (n=2), and basal-like (n=1). AR IHC was performed in 183 cases, of which 179 (97.8%) showed AR expression. On the basis of morphologic appearance and results of additional studies, 12 cases were reclassified as squamous cell carcinoma (SCC) (n=4), epithelial-myoepithelial carcinoma with high-grade transformation (HGT) (n=2), myoepithelial carcinoma (n=2), mammary analogue secretory carcinoma, high grade (ETV6 translocated; n=1), adenoid cystic carcinoma with HGT (n=1), acinic cell carcinoma with HGT (n=1), and adenosquamous carcinoma (n=1). AR-negative SDC is extremely rare, and the majority of such cases are more accurately classified as other entities. HGTs of other salivary carcinomas and squamous cell carcinoma are the most common mimics of SDC. SDCs with variant morphologies still show at least a minor component of conventional apocrine appearance. Thus, apocrine morphology defines SDC.
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              Genetic and expression analysis of HER-2 and EGFR genes in salivary duct carcinoma: empirical and therapeutic significance.

              Merrill S. Kies, Mary Roberts, R Weber … (2010)
              Salivary duct carcinoma overexpresses epidermal growth factor receptor (EGFR) and HER-2, although the underlying mechanisms remain undefined. Because of the potential utilization of these markers as treatment targets, we evaluated protein and gene status by several techniques to determine complementary value. A tissue microarray of 66 salivary duct carcinomas was used for immunohistochemical analysis of HER-2 and EGFR expression (semiquantitatively evaluated into a three-tiered system), and fluorescence in situ hybridization for gene copy number, and chromosomes 7 and 17 ploidy status. Sequencing of exons 18, 19, and 21 of the EGFR gene for mutations was carried out. For EGFR, 46 (69.7%) of the 66 tumors showed some form of EGFR expression (17 at 3+, 17 at 2+, 12 at 1+) but none gene amplification. Five (9.4%) of 53 tumors showed mutations in exon 18 (n = 3) and exon 19 (n = 2). Polysomy of chromosome 7 (average >2.5 copies/cell) was detected in 15 (25.0%) of 60 tumors (6 at 3+, 5 at 2+, 2 at 1+, 2 at 0+ expression) and correlated with poor 3-year survival (P = 0.015). For HER-2, 17 (25.8%) of 66 tumors expressed HER-2 (10 at 3+, 3 at 2+, 4 at 1+). Eight tumors showed HER-2 gene amplification (6 at 3+, 1 at 1+, 1 at 0+ protein expression). Chromosome 17 polysomy was found in 8 (15.7%) of 51 tumors; two had HER-2 expression (3+, 1+). Our study shows that salivary duct carcinomas (a) harbor EGFR gene mutations in a subset of tumors that may guide therapy, (b) pursue an aggressive clinical course in cases with chromosome 7 polysomy and high EGFR expression, and (c) with HER-2 gene amplification and protein high expression, may be selected for targeted therapy.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Case Rep Oncol
                Journal ID (iso-abbrev): Case Rep Oncol
                Journal ID (hwp): CRO
                Journal ID (publisher-id): CRO
                Title: Case Reports in Oncology
                Publisher: S. Karger AG (Basel, Switzerland )
                ISSN (Electronic): 1662-6575
                Publication date (Electronic): 23 February 2023
                Publication date Collection: Jan-Dec 2023
                Publication date PMC-release: 23 February 2023
                Volume: 16
                Issue: 1
                Pages: 109-115
                Affiliations
                [a ]Department of Medical Oncology, Basel University Hospital, Basel, Switzerland
                [b ]Radiology Department, St. Claraspital, Basel, Switzerland
                [c ]Department of Pathology, University Hospital Basel, Basel, Switzerland
                [d ]Department of Medical Oncology, St. Claraspital, Basel, Switzerland
                Author notes
                Correspondence to: Martin Buess, martin.buess@claraspital.ch
                Article
                Publisher ID: 529470
                DOI: 10.1159/000529470
                PMC ID: 9950966
                PubMed ID: 36844935
                SO-VID: c7b12036-996a-481b-a1ff-de5f0449c761
                Copyright © © 2023 The Author(s). Published by S. Karger AG, Basel
                License:

                This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC) ( http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes requires written permission.

                History
                Date received : 14 October 2022
                Date accepted : 21 December 2022
                Date: 2023
                Page count
                Figures: 4, References: 15, Pages: 7
                Funding
                The submission and publishing of this case report are not sponsored, and the authors have no funding sources to declare.
                Categories
                Subject: Case Report

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: salivary duct carcinoma,androgen deprivation,intracranial metastasis,case report
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: salivary duct carcinoma, androgen deprivation, intracranial metastasis, case report

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