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Targeted molecular profiling of salivary duct carcinoma with rhabdoid features highlights parallels to other apocrine and discohesive neoplasms: which phenotype should drive classification?

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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.

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Data Availability

All data generated or analyzed during this study are included in this published article.

Code Availability

Not applicable.

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Funding

This study was funded in part by the Jane B. and Edwin P. Jenevein M.D Endowment for Pathology at UT Southwestern Medical Center. No external funding was obtained for this study.

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Authors and Affiliations

  1. Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Lisa M. Rooper

  2. Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Lisa M. Rooper

  3. Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Jeffrey Gagan & Justin A. Bishop

  4. The Johns Hopkins Medical Institutions, 401 N. Broadway, Weinberg 2242, 21231, Baltimore, MD, USA

    Lisa M. Rooper

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  1. Lisa M. Rooper
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  2. Jeffrey Gagan
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  3. Justin A. Bishop
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Contributions

LMR and JAB designed the study, contributed tumor samples, performed data collection and interpretation, and prepared the manuscript. JG performed data collection and interpretation. All authors read and approved the final paper.

Corresponding author

Correspondence to Lisa M. Rooper.

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All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript.

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All procedures performed in this retrospective data analysis involving human participants were in accordance with the ethical standards of the institutional review board (Johns Hopkins Medicine IRB 00176183 and UT Southwestern IRB 112017-073).

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Rooper, L.M., Gagan, J. & Bishop, J.A. Targeted molecular profiling of salivary duct carcinoma with rhabdoid features highlights parallels to other apocrine and discohesive neoplasms: which phenotype should drive classification?. Head and Neck Pathol 16, 1063–1072 (2022). https://doi.org/10.1007/s12105-022-01464-3

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