Novel Therapeutic Strategies in Salivary Gland Tumor

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: 30 April 2025 | Viewed by 8659

Special Issue Editors


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Guest Editor
1. Maxillofacial Surgery Operative Unit, Department of Medical, Surgical and Experimental Sciences, University of Sassari, 07100 Sassari, Italy
2. Biomedical Science Department, PhD School of Biomedical Science, University of Sassari, 07100 Sassari, Italy
Interests: oral and maxillofacial surgery; plastic surgery; otolaryngology
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Special Issue Information

Dear Colleagues,

Salivary gland tumors are rare, constituting 3–11% of all head and neck neoplasms and 0.2% of all malignant tumors. The likelihood that the tumor becomes malignant increases with a decreasing gland size, ranging from 15% to 30% for the parotid gland.

The clinical staging is often difficult, and for this reason, the Milan classification system for FNAC has been used; however, this tool has the disadvantage of ambiguous interpretation.

There has long been debate about which kind of diagnostic protocol to adopt, considering the costs of radiological investigations.

The traditional treatment of these lesions includes surgery, radiotherapy and chemotherapy. However, thanks to technological advances, endoscopic and robotic approaches are now being consolidated.

This Special Issue aims to discuss new therapeutic options for the treatment of salivary gland malignancies taking into account the diagnostic improvement obtained by the use of molecular pathological analysis methods, and the availability of targeted therapies that could ameliorate long-term outcomes.
Original research articles, case series, clinical trials and narrative and systematic reviews will all be considered. Articles dealing with any topic relevant to parotid gland surgery, including diagnosis, adjuvant treatment and molecular pathology, are welcome.

We look forward to receiving your contributions.

Dr. Giovanni Salzano
Dr. Arianna Di Stadio
Dr. Luigi Angelo Vaira
Guest Editors

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Keywords

  • parotid gland
  • parotid tumors
  • facial nerve
  • novel therapeutic options
  • distant metastasis
  • liquid biopsy
  • prognostic factors
  • parotid robotic surgery
  • microRNA
  • imaging

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Published Papers (6 papers)

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Research

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15 pages, 1999 KiB  
Article
Novel Detection of Pleomorphic Adenomas via Analysis of 68Ga-DOTATOC PET/CT Imaging
by Felix Johnson, Marcel Kloppenburg, Benedikt Hofauer, Barbara Wollenberg, Cosima C. Hoch, Fabian Stögbauer, Bernhard Haller, Andreas Knopf, Ulrich Strassen and Susan Notohamiprodjo
Cancers 2024, 16(15), 2624; https://doi.org/10.3390/cancers16152624 - 23 Jul 2024
Viewed by 801
Abstract
Introduction: Currently, the diagnosis of salivary gland tumors using imaging techniques is unreliable. Methods: In this monocentric retrospective study, we examined patients who received a 68Ga-DOTATOC PET/CT and subsequently underwent a salivary gland tumor resection between 1 January 2010 and 31 December [...] Read more.
Introduction: Currently, the diagnosis of salivary gland tumors using imaging techniques is unreliable. Methods: In this monocentric retrospective study, we examined patients who received a 68Ga-DOTATOC PET/CT and subsequently underwent a salivary gland tumor resection between 1 January 2010 and 31 December 2021. PET/CT image assessment was compared with somatostatin receptor (SSTR) expression and histology. Results: Thirteen patients (five pleomorphic adenoma (PA) and eight other parotid lesions (OPL)) received a 68Ga-DOTATOC PET/CT. Imaging displayed strong focal tracer uptake in all PA except for one with strong tumor to background discrimination. PA revealed higher SUVmax, SUVmean, liver and blood pool quotients than those of Warthin tumors (WT) and of OPL. In comparison to the contralateral parotid, SUVmax (p = 0.02), SUVmean (p = 0.02), liver quotient (p = 0.03) and blood pool quotient (p = 0.03) were all significantly higher. In contrast, WT and OPL showed in relation to the contralateral parotid no significant differences of SUVmax (WT p = 0.79; OPL p = 0.11), SUVmean (WT p = 1.0; OPL p = 0.08), liver quotient (WT p = 0.5; OPL p = 0.08) and blood pool quotient (WT p = 0.8; OPL p = 0.19). Two PA and one granuloma were not available for examination. In the immunohistochemal analysis, all PA demonstrated the highest intensity of SSTR2 expression (grade 3). Furthermore, PA had a high percentage of cells expressing SSTR2 (20%, 80% and 55%). Conclusions: A strong tracer uptake in PA was shown in 68Ga-DOTATOC PET/CT. This may allow physicians to utilize radioligated somatostatin analogue PET CT/MR imaging to accurately diagnose PA. Additionally, it may be possible in the future to treat the PA with a noninvasive peptide receptor radionuclide therapy or with somatostatin analogues. Full article
(This article belongs to the Special Issue Novel Therapeutic Strategies in Salivary Gland Tumor)
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15 pages, 1390 KiB  
Article
Immunoprofiles and Oncologic Outcomes of 15 Patients with Androgen Receptor-Positive Salivary Duct Carcinoma
by Emile Gogineni, Blake E. Sells, Khaled Dibs, Sachin R. Jhawar, Catherine T. Haring, Abberly L. Limbach, David J. Konieczkowski, Sung J. Ma, Simeng Zhu, Sujith Baliga, Darrion L. Mitchell, John C. Grecula, Marcelo Bonomi, Priyanka Bhateja, Matthew O. Old, Nolan B. Seim, Stephen Y. Kang, James W. Rocco, Arnab Chakravarti, Dukagjin M. Blakaj and Mauricio E. Gamezadd Show full author list remove Hide full author list
Cancers 2024, 16(6), 1204; https://doi.org/10.3390/cancers16061204 - 19 Mar 2024
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Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Novel Therapeutic Strategies in Salivary Gland Tumor)
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21 pages, 1043 KiB  
Article
A Retrospective Multicenter Italian Analysis of Epidemiological, Clinical and Histopathological Features in a Sample of Patients with Acinic Cell Carcinoma of the Parotid Gland
by Pietro De Luca, Arianna Di Stadio, Luca de Campora, Egidio De Bonis, Matteo Fermi, Gerardo Petruzzi, Francesca Atturo, Roberta Colangeli, Alfonso Scarpa, Alfredo Lo Manto, Andrea Colizza, Giulia Cintoli, Giulia Togo, Giovanni Salzano, Domenico Crescenzi, Massimo Ralli, Vincenzo Abbate, Filippo Ricciardiello, Luciano Magaldi, Aurelio D’Ecclesia, Gianluca di Massa, Leopoldo Costarelli, Elisabetta Merenda, Alessandro Corsi, Renato Covello, Rosa Maria Di Crescenzo, Loren Duda, Lucia Maria Dimitri, Alessandro Caputo, Gerardo Ferrara, Teresina Lucante, Francesco Longo, Domenico Tassone, Maurizio Iemma, Michele Cassano, Francesco Antonio Salzano, Luigi Califano, Daniele Marchioni, Raul Pellini, Marco de Vincentiis, Livio Presutti, Franco Ionna, Enrico de Campora, Marco Radici and Angelo Camaioniadd Show full author list remove Hide full author list
Cancers 2023, 15(22), 5456; https://doi.org/10.3390/cancers15225456 - 17 Nov 2023
Cited by 3 | Viewed by 1176
Abstract
Background. The acinic cell carcinoma (AciCC) of the parotid gland is a rare tumor with an indolent behavior; however, a subgroup of this tumor presents an aggressive behavior with a tendency to recur. The aim of this multicenter study was to identify and [...] Read more.
Background. The acinic cell carcinoma (AciCC) of the parotid gland is a rare tumor with an indolent behavior; however, a subgroup of this tumor presents an aggressive behavior with a tendency to recur. The aim of this multicenter study was to identify and stratify those patients with AciCC at high risk of tumor recurrence. Methods. A retrospective study was carried out involving 77 patients treated with surgery between January 2000 and September 2022, in different Italian referral centers. Data about tumor characteristics and its recurrence were collected. The histological specimens and slides were independently reviewed by a senior pathologist coordinator (L.C.) and the institution’s local head and neck pathologist. Results. The patients’ age average was 53.6 years, with a female prevalence in the group. The mean follow-up was 67.4 months (1-258, SD 59.39). The five-year overall survival (OS) was 83.2%. The 5-year disease-free survival (DFS) was 60% (95% CI 58.2–61.7). A high incidence of necrosis, extraglandular spread, lymphovascular invasion (LVI), atypical mitosis, and cellular pleomorphism was observed in the high-risk tumors compared to the low-risk ones. Conclusion. AciCC generally had an indolent behavior, optimal OS, DFS with few cervical node metastases, and rare distant relapses. This multicenter retrospective case series provides evidence of the need for clinical–epidemiological–histological stratification for patients at risk of poor outcomes. Our results suggest that the correct definition of high-risk AciCC should include tumor size, the presence of necrosis, extraglandular spread, LVI, atypical mitosis, and cellular pleomorphism. Full article
(This article belongs to the Special Issue Novel Therapeutic Strategies in Salivary Gland Tumor)
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Review

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20 pages, 591 KiB  
Review
Role of Exosomes in Salivary Gland Tumors and Technological Advances in Their Assessment
by Artur Nieszporek, Małgorzata Wierzbicka, Natalia Labedz, Weronika Zajac, Joanna Cybinska and Patrycja Gazinska
Cancers 2024, 16(19), 3298; https://doi.org/10.3390/cancers16193298 - 27 Sep 2024
Viewed by 718
Abstract
Backgroud: Salivary gland tumors (SGTs) are rare and diverse neoplasms, presenting significant challenges in diagnosis and management due to their rarity and complexity. Exosomes, lipid bilayer vesicles secreted by almost all cell types and present in all body fluids, have emerged as crucial [...] Read more.
Backgroud: Salivary gland tumors (SGTs) are rare and diverse neoplasms, presenting significant challenges in diagnosis and management due to their rarity and complexity. Exosomes, lipid bilayer vesicles secreted by almost all cell types and present in all body fluids, have emerged as crucial intercellular communication agents. They play multifaceted roles in tumor biology, including modulating the tumor microenvironment, promoting metastasis, and influencing immune responses. Results: This review focuses on the role of exosomes in SGT, hypothesizing that novel diagnostic and therapeutic approaches can be developed by exploring the mechanisms through which exosomes influence tumor occurrence and progression. By understanding these mechanisms, we can leverage exosomes as diagnostic and prognostic biomarkers, and target them for therapeutic interventions. The exploration of exosome-mediated pathways contributing to tumor progression and metastasis could lead to more effective treatments, transforming the management of SGT and improving patient outcomes. Ongoing research aims to elucidate the specific cargo and signaling pathways involved in exosome-mediated tumorigenesis and to develop standardized techniques for exosome-based liquid biopsies in clinical settings. Conclusions: Exosome-based liquid biopsies have shown promise as non-invasive, real-time systemic profiling tools for tumor diagnostics and prognosis, offering significant potential for enhancing patient care through precision and personalized medicine. Methods like fluorescence, electrochemical, colorimetric, and surface plasmon resonance (SPR) biosensors, combined with artificial intelligence, improve exosome analysis, providing rapid, precise, and clinically valid cancer diagnostics for difficult-to-diagnose cancers. Full article
(This article belongs to the Special Issue Novel Therapeutic Strategies in Salivary Gland Tumor)
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20 pages, 1872 KiB  
Review
Translational Insights in the Landscape of Salivary Gland Cancers: Ready for a New Era?
by Francesco Perri, Roberta Fusco, Francesco Sabbatino, Morena Fasano, Alessandro Ottaiano, Marco Cascella, Maria Luisa Marciano, Monica Pontone, Giovanni Salzano, Maria Elena Maiello, Massimo Montano, Ester Calogero, Roberta D’Aniello, Piera Maiolino, Fortunato Ciardiello, Alessia Zotta, Salvatore Alfieri and Franco Ionna
Cancers 2024, 16(5), 970; https://doi.org/10.3390/cancers16050970 - 28 Feb 2024
Cited by 1 | Viewed by 1351
Abstract
Salivary gland carcinomas (SGCs) are rare neoplasms, representing less than 10% of all head and neck tumors, but they are extremely heterogeneous from the histological point of view, their clinical behavior, and their genetics. The guidelines regarding their treatment include surgery in most [...] Read more.
Salivary gland carcinomas (SGCs) are rare neoplasms, representing less than 10% of all head and neck tumors, but they are extremely heterogeneous from the histological point of view, their clinical behavior, and their genetics. The guidelines regarding their treatment include surgery in most cases, which can also play an important role in oligometastatic disease. Where surgery cannot be used, systemic therapy comes into play. Systemic therapy for many years has been represented by polychemotherapy, but recently, with the affirmation of translational research, it can also count on targeted therapy, at least in some subtypes of SGCs. Interestingly, in some SGC histotypes, predominant mutations have been identified, which in some cases behave as “driver mutations”, namely mutations capable of governing the carcinogenesis process. Targeting these driver mutations may be an effective therapeutic strategy. Nonetheless, it is not always possible to have drugs suitable for targeting driver mutations—and targeting driver mutations is not always accompanied by a clinical benefit. In this review, we will analyze the main mutations predominant in the various histotypes of SGCs. Full article
(This article belongs to the Special Issue Novel Therapeutic Strategies in Salivary Gland Tumor)
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Other

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13 pages, 3877 KiB  
Systematic Review
Polymorphous Adenocarcinoma: A Systematic Review of the Literature and Presentation of Two Cases in a Less-Considered Anatomical Site
by Rodolfo Mauceri, Martina Coppini, Giuseppe Alecci, Adriana Cordova, Ada Maria Florena, Gaetano Magro, Corrado Toro and Giuseppina Campisi
Cancers 2024, 16(1), 220; https://doi.org/10.3390/cancers16010220 - 3 Jan 2024
Cited by 1 | Viewed by 2461
Abstract
Background: Polymorphous adenocarcinoma (PAC) is the second-most common malignant tumour of the minor salivary glands. Although PAC predominantly affects the palate, it can also involve the buccal mucosa. This systematic review aims to investigate the literature data about PAC. Furthermore, we report two [...] Read more.
Background: Polymorphous adenocarcinoma (PAC) is the second-most common malignant tumour of the minor salivary glands. Although PAC predominantly affects the palate, it can also involve the buccal mucosa. This systematic review aims to investigate the literature data about PAC. Furthermore, we report two cases of patients affected by PAC in an infrequently considered anatomical site. Methods: According to PRISMA guidelines, a systematic review search was conducted on PubMed, Scopus, and Web of Science. Observational studies conducted on patients with a histological diagnosis of PAC were selected and analysed. Furthermore, two cases of patients with PAC affecting the buccal mucosa were reported. Results: Twenty-nine studies were included, and 143 patients affected by PAC were analysed (62 males, 75 females, and 6 undefined, with a mean age of 57.4 ± 14.5 years). The palate was the most affected site (99/143, 69.2%), followed by the buccal mucosa (12/143, 8.4%). Moreover, we report two cases of patients with PAC affecting the buccal mucosa (one male and one female, with a mean age of 70.5 ± 2.5 years). Conclusions: The present study underscores the importance of considering the buccal mucosa as a possible location of minor salivary gland tumours; although it is a less-considered affliction, it is not uncommon. Full article
(This article belongs to the Special Issue Novel Therapeutic Strategies in Salivary Gland Tumor)
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