Clinicopathologic Factors and Their Association with Outcomes of Salivary Duct Carcinoma: A Multicenter Experience

Laughlin, Brady S; Ebrahimi, Sasha; Voss, Molly M.; Patel, Samir H.; Foote, Robert L.; McGee, L.A.; García, Joaquín J.; Daniel, J.; Garces, Yolanda I.; Wittich, Michelle A. Neben; Price, Katharine A.; Schmitt, Alessandra C.; Zhai, Qihui; May, Byron C.; Nagel, Thomas H.; Hinni, Michael L.; Chintakuntlawar, Ashish V.; DeWees, T.A.; Rwigema, Jean‐Claude M.

doi:10.1016/j.adro.2023.101204

Cited by 2 publications

(3 citation statements)

References 27 publications

(53 reference statements)

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“…Oncologic and toxicity outcomes from our series compared favorably to other studies reporting outcomes of SDC, as shown in Table 3 [ 8 , 13 , 15 , 16 , 17 , 18 , 19 ]. These favorable outcomes may be related to the homogeneity of patients included in our study and may partially be due to our approach of treatment escalation, with a large percentage of patients receiving trimodality therapy.…”

Section: Discussionsupporting

confidence: 61%

“…Previous retrospective studies have demonstrated poor progression-free and overall survival (OS) for patients with SDC, with five-year survival ranging from 42% to 55% [ 8 , 11 , 12 , 13 ]. Unfortunately, the rarity of this tumor limits our ability to understand responsible molecular drivers and develop effective treatment strategies.…”

Section: Introductionmentioning

confidence: 99%

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Immunoprofiles and Oncologic Outcomes of 15 Patients with Androgen Receptor-Positive Salivary Duct Carcinoma

Gogineni,

Sells,

Dibs

et al. 2024

Cancers

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Background: Salivary duct carcinomas (SDC) are a rare and aggressive subtype of salivary gland neoplasm. They can present with distinct immunoprofiles, such as androgen receptor (AR) and HER-2/Neu-positivity. To date, no consensus exists on how to best manage this entity. Methods: All patients diagnosed with nonmetastatic AR+ SDC of the parotid from 2013 to 2019 treated with curative intent were included. Immunologic tumor profiling was conducted using 24 distinct markers. Kaplan–Meier analyses were used to estimate locoregional recurrence (LRR), distant control, and overall survival (OS). Results: Fifteen patients were included. Nine (60%) patients presented with T4 disease and eight (53%) had positive ipsilateral cervical lymphadenopathy. Ten (67%) patients underwent trimodality therapy, including surgery followed by adjuvant radiation and concurrent systemic therapy. The median follow-up was 5.5 years (interquartile range, 4.8–6.1). The estimated 5-year rates of LRR, distant progression, and OS were 6%, 13%, and 87%, respectively. Conclusion: Despite only including AR+ SDC of the parotid, immunoprofiles, such as expression of HER-2, were highly variable, highlighting the potential to tailor systemic regimens based on individual histologic profiles in the future. Studies with larger patient numbers using tumor-specific molecular profiling and tumor heterogeneity analyses are justified to better understand the biology of these tumors. Molecularly informed treatment approaches, including the potential use of AR- and HER-2/Neu-directed therapies upfront in the definitive setting, may hold future promise to further improve outcomes for these patients.

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Section: Discussionsupporting

confidence: 61%

Section: Introductionmentioning

confidence: 99%

Immunoprofiles and Oncologic Outcomes of 15 Patients with Androgen Receptor-Positive Salivary Duct Carcinoma

Gogineni,

Sells,

Dibs

et al. 2024

Cancers

View full text Add to dashboard Cite

show abstract

“…More recently, salivary duct carcinoma (SDC) has been associated with somatic CDH1 mutations. SDC represents less than 2% of all salivary gland cancers, which have been found to have incidence rates of 0.1 to 2.7 per 100,000 individuals worldwide ( 5 ). Given that SDC is an extremely rare malignancy, limited literature exists on its association with CDH1 .…”

Section: Introductionmentioning

confidence: 99%

Case report: Salivary duct carcinoma in a patient with a germline CDH1 pathogenic variant - expanding the spectrum of hereditary cancer predisposition syndromes

Desai,

Racila,

Fujioka

et al. 2024

Front. Oncol.

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IntroductionRecently, an entity known as salivary duct carcinoma with rhabdoid features (SDC-RF) has been associated with somatic CDH1 mutations. Here we present the first known case report of conventional SDC occurring in the setting of a germline CDH1 pathogenic variant accompanied by a somatic loss of heterozygosity at the CDH1 locus.Case discussionA 67-year-old man presented with chest and back pain and was found to have osteolytic lesions in the sternum and lumbar spine. Vertebral bone biopsies were positive for metastatic carcinoma of unknown primary. A molecular profiling assay consisting of both whole-exome next-generation sequencing (NGS) as well as immunohistochemistry (IHC) for select clinically-relevant proteins performed on the bone biopsy suggested a triple-negative (ER/PR/ERBB2 negative, by IHC), androgen receptor (AR IHC) positive tumor profile. Additionally, the assay uncovered a coding mutation in the CDH1 gene (c.1792C>T, p.R598*) with genomic loss of the second CDH1 allele. Germline testing returned positive for a heterozygous CDH1 pathogenic variant. PET-CT revealed a tumor in the neck suggestive of the primary malignancy consistent with that of salivary gland origin. The patient was initially treated with carboplatin and paclitaxel, then pembrolizumab, and finally with AR-directed therapy using leuprolide and enzalutamide. These treatments were not successful, and the patient eventually succumbed to his disease.ConclusionMolecular testing revealed that our patient had bi-allelic inactivation of the CDH1 gene. We believe our patient developed a somatic mutation in addition to his preexisting germline CDH1 mutation that ultimately predisposed him to SDC. While previous studies have found somatic CDH1 pathogenic variants in SDC-RF, our patient was found to have a germline CDH1 pathogenic variant in the setting of conventional SDC, without rhabdoid features. This case provokes questions regarding tumor genetics and molecular profiling of SDC in patients with germline CDH1 pathogenic variants. Moreover, this case supports the notion that SDC may be the salivary counterpart of other malignancies associated with germline CDH1 pathogenic variants and may possibly expand the spectrum of tumors that arise in this familial cancer-predisposition syndrome.

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Clinicopathologic Factors and Their Association with Outcomes of Salivary Duct Carcinoma: A Multicenter Experience

Cited by 2 publications

References 27 publications

Immunoprofiles and Oncologic Outcomes of 15 Patients with Androgen Receptor-Positive Salivary Duct Carcinoma

Immunoprofiles and Oncologic Outcomes of 15 Patients with Androgen Receptor-Positive Salivary Duct Carcinoma

Case report: Salivary duct carcinoma in a patient with a germline CDH1 pathogenic variant - expanding the spectrum of hereditary cancer predisposition syndromes

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