Lisa M Rooper1,2,3, Jeffrey Gagan4, Justin A Bishop4. 1. Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. rooper@jhmi.edu. 2. Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. rooper@jhmi.edu. 3. The Johns Hopkins Medical Institutions, 401 N. Broadway, Weinberg 2242, 21231, Baltimore, MD, USA. rooper@jhmi.edu. 4. Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Abstract
BACKGROUND: Salivary duct carcinoma with rhabdoid features (SDC-RF) is a recently-described salivary gland tumor that bears striking histologic similarity to lobular carcinoma of the breast. While this tumor has an apocrine phenotype that supports classification as a variant of SDC, it infrequently arises in association with conventional SDC. Furthermore, discohesive architecture can be seen in non-apocrine salivary carcinomas, raising the possibility that discohesive growth should define a separate entity. In this study, we aimed to perform comprehensive molecular profiling of SDC-RF to better understand its pathogenesis and classification. METHODS: We documented the clinicopathologic features of 9 cases of SDC-RF and performed immunostains including AR, GCDFP, and e-cadherin on all cases. We also performed targeted next generation sequencing (NGS) panels on 7 cases that had sufficient tissue available. RESULTS: The SDC-RF represented 8 men and 1 woman with a median age of 67 years (range 63-83 years) and included 6 parotid, 2 buccal, and 1 submandibular primary. All tumors were uniformly composed of discohesive cells with abundant eosinophilic cytoplasm; signet-ring cell features were seen in 2 cases. All tumors were also positive for AR (100%) and GCDFP (100%), and 7 tumors (78%) displayed lost or abnormal e-cadherin. NGS highlighted concomitant PIK3CA and HRAS mutations in 4 tumors, with additional cases harboring TP53, PTEN, and AKT1 mutations. Furthermore, CDH1 alterations were seen in 6 cases, including a novel CDH1::CORO7 fusion. Among 5 patients with follow-up available, 3 (60%) developed local recurrence and widespread distant metastasis and died of disease at a median 20 months (range 10-48 months). CONCLUSIONS: Overall, our findings confirm frequent CDH1 mutations and e-cadherin inactivation in SDC-RF, similar to discohesive tumors from other sites. We also highlight an apocrine molecular profile similar to conventional SDC. However, occasional AKT1 mutation and signet-ring features suggest SDC-RF may also be related to mucinous adenocarcinoma. As more salivary tumors with discohesive growth are identified, it may become clearer whether SDC-RF should remain in the SDC family or be recognized as a separate entity.
BACKGROUND: Salivary duct carcinoma with rhabdoid features (SDC-RF) is a recently-described salivary gland tumor that bears striking histologic similarity to lobular carcinoma of the breast. While this tumor has an apocrine phenotype that supports classification as a variant of SDC, it infrequently arises in association with conventional SDC. Furthermore, discohesive architecture can be seen in non-apocrine salivary carcinomas, raising the possibility that discohesive growth should define a separate entity. In this study, we aimed to perform comprehensive molecular profiling of SDC-RF to better understand its pathogenesis and classification. METHODS: We documented the clinicopathologic features of 9 cases of SDC-RF and performed immunostains including AR, GCDFP, and e-cadherin on all cases. We also performed targeted next generation sequencing (NGS) panels on 7 cases that had sufficient tissue available. RESULTS: The SDC-RF represented 8 men and 1 woman with a median age of 67 years (range 63-83 years) and included 6 parotid, 2 buccal, and 1 submandibular primary. All tumors were uniformly composed of discohesive cells with abundant eosinophilic cytoplasm; signet-ring cell features were seen in 2 cases. All tumors were also positive for AR (100%) and GCDFP (100%), and 7 tumors (78%) displayed lost or abnormal e-cadherin. NGS highlighted concomitant PIK3CA and HRAS mutations in 4 tumors, with additional cases harboring TP53, PTEN, and AKT1 mutations. Furthermore, CDH1 alterations were seen in 6 cases, including a novel CDH1::CORO7 fusion. Among 5 patients with follow-up available, 3 (60%) developed local recurrence and widespread distant metastasis and died of disease at a median 20 months (range 10-48 months). CONCLUSIONS: Overall, our findings confirm frequent CDH1 mutations and e-cadherin inactivation in SDC-RF, similar to discohesive tumors from other sites. We also highlight an apocrine molecular profile similar to conventional SDC. However, occasional AKT1 mutation and signet-ring features suggest SDC-RF may also be related to mucinous adenocarcinoma. As more salivary tumors with discohesive growth are identified, it may become clearer whether SDC-RF should remain in the SDC family or be recognized as a separate entity.
Authors: Lindsay Williams; Lester D R Thompson; Raja R Seethala; Ilan Weinreb; Adel M Assaad; Madalina Tuluc; Nasir Ud Din; Bibianna Purgina; Chi Lai; Christopher C Griffith; Simion I Chiosea Journal: Am J Surg Pathol Date: 2015-05 Impact factor: 6.394
Authors: Simion I Chiosea; Lindsay Williams; Christopher C Griffith; Lester D R Thompson; Ilan Weinreb; Julie E Bauman; Alyssa Luvison; Somak Roy; Raja R Seethala; Marina N Nikiforova Journal: Am J Surg Pathol Date: 2015-06 Impact factor: 6.394
Authors: Toshitaka Nagao; Thomas A Gaffey; Daniel W Visscher; Paul A Kay; Hiroshi Minato; Hiromi Serizawa; Jean E Lewis Journal: Am J Surg Pathol Date: 2004-03 Impact factor: 6.394